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Genetic Epilepsy v0.2406 GLUD1 Zornitza Stark Marked gene: GLUD1 as ready
Genetic Epilepsy v0.2406 GLUD1 Zornitza Stark Gene: glud1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2406 GLUD1 Zornitza Stark Phenotypes for gene: GLUD1 were changed from to Hyperinsulinism-hyperammonemia syndrome, MIM# 606762
Genetic Epilepsy v0.2405 GLUD1 Zornitza Stark Publications for gene: GLUD1 were set to
Genetic Epilepsy v0.2404 GLUD1 Zornitza Stark Mode of inheritance for gene: GLUD1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2403 GLUD1 Zornitza Stark changed review comment from: Well established gene-disease association.; to: Well established gene-disease association. Hypoglycaemic seizures.
Genetic Epilepsy v0.2403 GLDC Zornitza Stark Marked gene: GLDC as ready
Genetic Epilepsy v0.2403 GLDC Zornitza Stark Gene: gldc has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2403 GLDC Zornitza Stark Phenotypes for gene: GLDC were changed from to Glycine encephalopathy (MIM#605899)
Genetic Epilepsy v0.2402 GLDC Zornitza Stark Publications for gene: GLDC were set to
Genetic Epilepsy v0.2401 GLDC Zornitza Stark Mode of inheritance for gene: GLDC was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2400 GLB1 Zornitza Stark Marked gene: GLB1 as ready
Genetic Epilepsy v0.2400 GLB1 Zornitza Stark Gene: glb1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2400 GLB1 Zornitza Stark Phenotypes for gene: GLB1 were changed from to GM1-gangliosidosis, type I MIM#230500; GM1-gangliosidosis, type II MIM# 230600
Genetic Epilepsy v0.2399 GLB1 Zornitza Stark Publications for gene: GLB1 were set to
Genetic Epilepsy v0.2398 GLB1 Zornitza Stark Mode of inheritance for gene: GLB1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2397 GFM1 Zornitza Stark Marked gene: GFM1 as ready
Genetic Epilepsy v0.2397 GFM1 Zornitza Stark Gene: gfm1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2397 GFM1 Zornitza Stark Phenotypes for gene: GFM1 were changed from to Combined oxidative phosphorylation deficiency 1 MIM#609060
Genetic Epilepsy v0.2396 GFM1 Zornitza Stark Publications for gene: GFM1 were set to
Genetic Epilepsy v0.2395 GFM1 Zornitza Stark Mode of inheritance for gene: GFM1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2394 GFAP Zornitza Stark Marked gene: GFAP as ready
Genetic Epilepsy v0.2394 GFAP Zornitza Stark Gene: gfap has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2394 GFAP Zornitza Stark Phenotypes for gene: GFAP were changed from to Alexander disease, MIM# 203450
Genetic Epilepsy v0.2393 GFAP Zornitza Stark Publications for gene: GFAP were set to
Genetic Epilepsy v0.2392 GFAP Zornitza Stark Mode of inheritance for gene: GFAP was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2391 GCH1 Zornitza Stark Marked gene: GCH1 as ready
Genetic Epilepsy v0.2391 GCH1 Zornitza Stark Gene: gch1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2391 GCH1 Zornitza Stark Phenotypes for gene: GCH1 were changed from to Hyperphenylalaninemia, BH4-deficient, B, MIM# 233910
Genetic Epilepsy v0.2390 GCH1 Zornitza Stark Publications for gene: GCH1 were set to
Genetic Epilepsy v0.2389 GCH1 Zornitza Stark Mode of inheritance for gene: GCH1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2388 GCH1 Zornitza Stark Deleted their comment
Genetic Epilepsy v0.2388 GCH1 Zornitza Stark edited their review of gene: GCH1: Added comment: Well established gene-disease association, seizures are part of the phenotype.; Changed publications: 7730309; Changed phenotypes: Hyperphenylalaninemia, BH4-deficient, B, MIM# 233910; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2388 GALC Zornitza Stark Marked gene: GALC as ready
Genetic Epilepsy v0.2388 GALC Zornitza Stark Gene: galc has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2388 GALC Zornitza Stark Phenotypes for gene: GALC were changed from to Krabbe disease, MIM# 245200; MONDO:0009499
Genetic Epilepsy v0.2387 GALC Zornitza Stark Publications for gene: GALC were set to
Genetic Epilepsy v0.2386 GALC Zornitza Stark Mode of inheritance for gene: GALC was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2385 GALC Zornitza Stark changed review comment from: Krabbe disease is an autosomal recessive lysosomal disorder affecting the white matter of the central and peripheral nervous systems. Most patients present within the first 6 months of life with 'infantile' or 'classic' disease manifest as extreme irritability, spasticity, and developmental delay. There is severe motor and mental deterioration, leading to decerebration and death by age 2 years. Approximately 10 to 15% of patients have a later onset, commonly differentiated as late-infantile (6 months to 3 years), juvenile (3 to 8 years), and even adult-onset forms. Multiple families reported.; to: Krabbe disease is an autosomal recessive lysosomal disorder affecting the white matter of the central and peripheral nervous systems. Most patients present within the first 6 months of life with 'infantile' or 'classic' disease manifest as extreme irritability, spasticity, and developmental delay. There is severe motor and mental deterioration, leading to decerebration and death by age 2 years. Approximately 10 to 15% of patients have a later onset, commonly differentiated as late-infantile (6 months to 3 years), juvenile (3 to 8 years), and even adult-onset forms. Multiple families reported.

Seizures are part of the phenotype.
Genetic Epilepsy v0.2385 FUCA1 Zornitza Stark Marked gene: FUCA1 as ready
Genetic Epilepsy v0.2385 FUCA1 Zornitza Stark Gene: fuca1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2385 FUCA1 Zornitza Stark Phenotypes for gene: FUCA1 were changed from to Fucosidosis, MIM# 230000; MONDO:0009254
Genetic Epilepsy v0.2384 FUCA1 Zornitza Stark Publications for gene: FUCA1 were set to
Genetic Epilepsy v0.2383 FUCA1 Zornitza Stark Mode of inheritance for gene: FUCA1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2382 FUCA1 Zornitza Stark changed review comment from: Fucosidosis is an autosomal recessive lysosomal storage disease caused by defective alpha-L-fucosidase with accumulation of fucose in the tissues. Clinical features include angiokeratoma, progressive psychomotor retardation, neurologic signs, coarse facial features, and dysostosis multiplex. Well established gene-disease association, multiple families reported.; to: Fucosidosis is an autosomal recessive lysosomal storage disease caused by defective alpha-L-fucosidase with accumulation of fucose in the tissues. Clinical features include angiokeratoma, progressive psychomotor retardation, neurologic signs, coarse facial features, and dysostosis multiplex. Well established gene-disease association, multiple families reported.

Seizures are part of the phenotype.
Genetic Epilepsy v0.2382 FRRS1L Zornitza Stark Marked gene: FRRS1L as ready
Genetic Epilepsy v0.2382 FRRS1L Zornitza Stark Gene: frrs1l has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2382 FRRS1L Zornitza Stark Phenotypes for gene: FRRS1L were changed from to Developmental and epileptic encephalopathy, 37 MONDO:0014859
Genetic Epilepsy v0.2381 FRRS1L Zornitza Stark Publications for gene: FRRS1L were set to
Genetic Epilepsy v0.2380 FRRS1L Zornitza Stark Mode of inheritance for gene: FRRS1L was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2379 DPM1 Zornitza Stark Marked gene: DPM1 as ready
Genetic Epilepsy v0.2379 DPM1 Zornitza Stark Gene: dpm1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2379 DPM1 Zornitza Stark Publications for gene: DPM1 were set to 23856421
Genetic Epilepsy v0.2378 DPM1 Zornitza Stark Phenotypes for gene: DPM1 were changed from to Congenital disorder of glycosylation, type Ie, 608799
Genetic Epilepsy v0.2377 DPM1 Zornitza Stark Publications for gene: DPM1 were set to
Genetic Epilepsy v0.2376 DPM1 Zornitza Stark Mode of inheritance for gene: DPM1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2375 DPM1 Zornitza Stark reviewed gene: DPM1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Congenital disorder of glycosylation, type Ie, 608799; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2375 DNM1L Zornitza Stark Marked gene: DNM1L as ready
Genetic Epilepsy v0.2375 DNM1L Zornitza Stark Gene: dnm1l has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2375 DNM1L Zornitza Stark Phenotypes for gene: DNM1L were changed from Encephalopathy, lethal, due to defective mitochondrial peroxisomal fission 1 - MIM#614388 (AD, AR) to Encephalopathy, lethal, due to defective mitochondrial peroxisomal fission 1 - MIM#614388 (AD, AR)
Genetic Epilepsy v0.2374 DNM1L Zornitza Stark Phenotypes for gene: DNM1L were changed from to Encephalopathy, lethal, due to defective mitochondrial peroxisomal fission 1 - MIM#614388 (AD, AR)
Genetic Epilepsy v0.2374 DNM1L Zornitza Stark Mode of inheritance for gene: DNM1L was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genetic Epilepsy v0.2373 DNM1L Zornitza Stark Mode of inheritance for gene: DNM1L was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Prepair 1000+ v1.5 ADPRHL2 Zornitza Stark Tag new gene name tag was added to gene: ADPRHL2.
Prepair 1000+ v1.5 ADPRHL2 Zornitza Stark Marked gene: ADPRHL2 as ready
Prepair 1000+ v1.5 ADPRHL2 Zornitza Stark Gene: adprhl2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.5 ADPRHL2 Zornitza Stark Classified gene: ADPRHL2 as Green List (high evidence)
Prepair 1000+ v1.5 ADPRHL2 Zornitza Stark Gene: adprhl2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.4 ADPRHL2 Zornitza Stark reviewed gene: ADPRHL2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures, MIM#618170; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1619 GNE Zornitza Stark Phenotypes for gene: GNE were changed from Nonaka myopathy 605820; Sialuria MIM#269921; ADUDP-GlcNAc epimerase/kinase deficiency (Disorders of multiple glycosylation and other glycosylation pathways) to Thrombocytopenia 12 with or without myopathy, MIM#620757; Nonaka myopathy 605820; Sialuria MIM#269921; ADUDP-GlcNAc epimerase/kinase deficiency (Disorders of multiple glycosylation and other glycosylation pathways)
Mendeliome v1.1618 GNE Zornitza Stark edited their review of gene: GNE: Changed phenotypes: Thrombocytopenia 12 with or without myopathy, MIM#620757, Nonaka myopathy 605820, Sialuria MIM#269921, ADUDP-GlcNAc epimerase/kinase deficiency (Disorders of multiple glycosylation and other glycosylation pathways)
Bleeding and Platelet Disorders v1.29 GNE Zornitza Stark Phenotypes for gene: GNE were changed from Thrombocytopaenia; Myopathy to Thrombocytopenia 12 with or without myopathy, MIM#620757
Bleeding and Platelet Disorders v1.28 GNE Zornitza Stark edited their review of gene: GNE: Changed phenotypes: Thrombocytopenia 12 with or without myopathy, MIM#620757
Cardiomyopathy_Paediatric v0.184 ANK2 Elena Savva Marked gene: ANK2 as ready
Cardiomyopathy_Paediatric v0.184 ANK2 Elena Savva Gene: ank2 has been classified as Red List (Low Evidence).
Cardiomyopathy_Paediatric v0.184 ANK2 Elena Savva Added comment: Comment on phenotypes: Association is disputed, gene associated to a neurodevelopmental disorder
Cardiomyopathy_Paediatric v0.184 ANK2 Elena Savva Phenotypes for gene: ANK2 were changed from to Cardiac arrhythmia, ankyrin-B-related MIM#600919; Long QT syndrome 4 MIM#600919
Cardiomyopathy_Paediatric v0.183 ANK2 Elena Savva Classified gene: ANK2 as Red List (low evidence)
Cardiomyopathy_Paediatric v0.183 ANK2 Elena Savva Gene: ank2 has been classified as Red List (Low Evidence).
Focal Epilepsy v0.14 ANK2 Elena Savva Classified gene: ANK2 as Green List (high evidence)
Focal Epilepsy v0.14 ANK2 Elena Savva Gene: ank2 has been classified as Green List (High Evidence).
Focal Epilepsy v0.13 ANK2 Elena Savva Marked gene: ANK2 as ready
Focal Epilepsy v0.13 ANK2 Elena Savva Gene: ank2 has been removed from the panel.
Genetic Epilepsy v0.2372 FOXG1 Zornitza Stark Marked gene: FOXG1 as ready
Genetic Epilepsy v0.2372 FOXG1 Zornitza Stark Gene: foxg1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2372 FOXG1 Zornitza Stark Phenotypes for gene: FOXG1 were changed from to Rett syndrome, congenital variant, MIM# 613454
Genetic Epilepsy v0.2371 FOXG1 Zornitza Stark Publications for gene: FOXG1 were set to
Genetic Epilepsy v0.2370 FOXG1 Zornitza Stark Mode of inheritance for gene: FOXG1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2369 FOXG1 Zornitza Stark reviewed gene: FOXG1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Rett syndrome, congenital variant, MIM# 613454; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2369 EXOSC3 Zornitza Stark Marked gene: EXOSC3 as ready
Genetic Epilepsy v0.2369 EXOSC3 Zornitza Stark Gene: exosc3 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2369 EXOSC3 Zornitza Stark Phenotypes for gene: EXOSC3 were changed from to Pontocerebellar hypoplasia, type 1B, MIM# 614678
Genetic Epilepsy v0.2368 EXOSC3 Zornitza Stark Publications for gene: EXOSC3 were set to
Genetic Epilepsy v0.2367 EXOSC3 Zornitza Stark Mode of inheritance for gene: EXOSC3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2366 EXOSC3 Zornitza Stark changed review comment from: Pontocerebellar hypoplasia type 1B is a severe autosomal recessive neurologic disorder characterized by a combination of cerebellar and spinal motor neuron degeneration beginning at birth. There is diffuse muscle weakness, progressive microcephaly, global developmental delay, and brainstem involvement. PCH1B can be divided into mild, moderate, and severe subgroups that vary in age at onset, progression, clinical and neuroradiologic severity, and survival. Multiple families reported.; to: Pontocerebellar hypoplasia type 1B is a severe autosomal recessive neurologic disorder characterized by a combination of cerebellar and spinal motor neuron degeneration beginning at birth. There is diffuse muscle weakness, progressive microcephaly, global developmental delay, and brainstem involvement. PCH1B can be divided into mild, moderate, and severe subgroups that vary in age at onset, progression, clinical and neuroradiologic severity, and survival. Multiple families reported.

Seizures are part of the phenotype.
Genetic Epilepsy v0.2366 EPM2A Zornitza Stark Marked gene: EPM2A as ready
Genetic Epilepsy v0.2366 EPM2A Zornitza Stark Gene: epm2a has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2366 EPM2A Zornitza Stark Phenotypes for gene: EPM2A were changed from Lafora disease MONDO:0009697 to Lafora disease MONDO:0009697
Genetic Epilepsy v0.2365 EPM2A Zornitza Stark Phenotypes for gene: EPM2A were changed from to Lafora disease MONDO:0009697
Genetic Epilepsy v0.2364 EPM2A Zornitza Stark Publications for gene: EPM2A were set to
Genetic Epilepsy v0.2363 EPM2A Zornitza Stark Mode of inheritance for gene: EPM2A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1618 SAMD7 Zornitza Stark Phenotypes for gene: SAMD7 were changed from Macular dystrophy, retinal, SAMD7-related MONDO:0031166 to Macular dystrophy with or without cone dysfunction, MIM# 620762
Mendeliome v1.1617 SAMD7 Zornitza Stark reviewed gene: SAMD7: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Macular dystrophy with or without cone dysfunction, MIM# 620762; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Macular Dystrophy/Stargardt Disease v0.45 SAMD7 Zornitza Stark Phenotypes for gene: SAMD7 were changed from Macular dystrophy, retinal, SAMD7-related MONDO:0031166 to Macular dystrophy with or without cone dysfunction, MIM# 620762
Macular Dystrophy/Stargardt Disease v0.44 SAMD7 Zornitza Stark reviewed gene: SAMD7: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Macular dystrophy with or without cone dysfunction, MIM# 620762; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1617 FHL2 Zornitza Stark Marked gene: FHL2 as ready
Mendeliome v1.1617 FHL2 Zornitza Stark Gene: fhl2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1617 FHL2 Zornitza Stark Classified gene: FHL2 as Amber List (moderate evidence)
Mendeliome v1.1617 FHL2 Zornitza Stark Gene: fhl2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1616 FHL2 Zornitza Stark gene: FHL2 was added
gene: FHL2 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: FHL2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FHL2 were set to 36854411; 25358972
Phenotypes for gene: FHL2 were set to Cardiomyopathy, MONDO:0004994, FHL2-related
Review for gene: FHL2 was set to AMBER
Added comment: Emerging evidence that variants in this gene may be associated with cardiomyopathy.

Reports of HCM and DCM.

c.391C>T (p.Arg131Cys) may be recurrent in early-onset DCM.
Sources: Expert Review
Cardiomyopathy_Paediatric v0.182 FHL2 Zornitza Stark Marked gene: FHL2 as ready
Cardiomyopathy_Paediatric v0.182 FHL2 Zornitza Stark Gene: fhl2 has been classified as Amber List (Moderate Evidence).
Cardiomyopathy_Paediatric v0.182 FHL2 Zornitza Stark Classified gene: FHL2 as Amber List (moderate evidence)
Cardiomyopathy_Paediatric v0.182 FHL2 Zornitza Stark Gene: fhl2 has been classified as Amber List (Moderate Evidence).
Cardiomyopathy_Paediatric v0.181 FHL2 Zornitza Stark gene: FHL2 was added
gene: FHL2 was added to Cardiomyopathy_Paediatric. Sources: Expert Review
Mode of inheritance for gene: FHL2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FHL2 were set to 36854411; 25358972
Phenotypes for gene: FHL2 were set to Cardiomyopathy, MONDO:0004994, FHL2-related
Review for gene: FHL2 was set to AMBER
Added comment: Emerging evidence that variants in this gene may be associated with cardiomyopathy.

Reports of HCM and DCM.

c.391C>T (p.Arg131Cys) may be recurrent in early-onset DCM.
Sources: Expert Review
Intellectual disability syndromic and non-syndromic v0.5724 ZFHX3 Zornitza Stark Publications for gene: ZFHX3 were set to 37292950
Intellectual disability syndromic and non-syndromic v0.5723 ZFHX3 Zornitza Stark edited their review of gene: ZFHX3: Added comment: Now published PMID 38412861; Changed publications: 38412861
Mendeliome v1.1615 ZFHX3 Zornitza Stark Publications for gene: ZFHX3 were set to
Mendeliome v1.1614 ZRSR2 Zornitza Stark Marked gene: ZRSR2 as ready
Mendeliome v1.1614 ZRSR2 Zornitza Stark Gene: zrsr2 has been classified as Green List (High Evidence).
Mendeliome v1.1614 ZRSR2 Zornitza Stark Classified gene: ZRSR2 as Green List (high evidence)
Mendeliome v1.1614 ZRSR2 Zornitza Stark Gene: zrsr2 has been classified as Green List (High Evidence).
Mendeliome v1.1613 ZRSR2 Zornitza Stark gene: ZRSR2 was added
gene: ZRSR2 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: ZRSR2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: ZRSR2 were set to 38158857
Phenotypes for gene: ZRSR2 were set to Orofacialdigital syndrome MONDO:0015375, ZRSR2-related
Review for gene: ZRSR2 was set to GREEN
Added comment: Oral-facial-digital (OFD) syndrome with brain anomalies ranging from alobar holoprosencephaly to pituitary anomalies.
Six unrelated families with two truncating variants and functional studies:
- p.(Gly404GlufsTer23): detected in one family with 2x affected males
- p.(Arg403GlyfsTer24): 5 unrelated families, both de novo and inherited
Sources: Expert Review
Intellectual disability syndromic and non-syndromic v0.5723 SLC32A1 Zornitza Stark Phenotypes for gene: SLC32A1 were changed from developmental and epileptic encephalopathy MONDO:0100062, SLC32A1-related to Generalized epilepsy with febrile seizures plus, type 12, MIM# 620755
Genetic Epilepsy v0.2362 SLC32A1 Zornitza Stark Phenotypes for gene: SLC32A1 were changed from Genetic epilepsy with febrile seizures plus; Developmental and epileptic encephalopathy MONDO:0100062, SLC32A1-related to Generalized epilepsy with febrile seizures plus, type 12, MIM# 620755
Genetic Epilepsy v0.2361 SLC32A1 Zornitza Stark edited their review of gene: SLC32A1: Changed phenotypes: Generalized epilepsy with febrile seizures plus, type 12, MIM# 620755
Mendeliome v1.1612 SLC32A1 Zornitza Stark Phenotypes for gene: SLC32A1 were changed from Genetic epilepsy with febrile seizures plus; Developmental and epileptic encephalopathy MONDO:0100062, SLC32A1-related to Generalized epilepsy with febrile seizures plus, type 12, MIM# 620755
Mendeliome v1.1611 SLC32A1 Zornitza Stark edited their review of gene: SLC32A1: Changed phenotypes: Generalized epilepsy with febrile seizures plus, type 12, MIM# 620755
Intellectual disability syndromic and non-syndromic v0.5722 PTRHD1 Zornitza Stark Phenotypes for gene: PTRHD1 were changed from Parkinsonism; Intellectual disability to Neurodevelopmental disorder with early-onset parkinsonism and behavioral abnormalities, MIM# 620747
Intellectual disability syndromic and non-syndromic v0.5721 PTRHD1 Zornitza Stark edited their review of gene: PTRHD1: Changed phenotypes: Neurodevelopmental disorder with early-onset parkinsonism and behavioral abnormalities, MIM# 620747
Mendeliome v1.1611 PTRHD1 Zornitza Stark Phenotypes for gene: PTRHD1 were changed from Parkinsonism; Intellectual disability to Neurodevelopmental disorder with early-onset parkinsonism and behavioral abnormalities, MIM# 620747
Early-onset Parkinson disease v0.295 PTRHD1 Zornitza Stark Phenotypes for gene: PTRHD1 were changed from early-onset parkinsonism; intellectual disability to Neurodevelopmental disorder with early-onset parkinsonism and behavioral abnormalities, MIM# 620747
Early-onset Parkinson disease v0.294 PTRHD1 Zornitza Stark reviewed gene: PTRHD1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with early-onset parkinsonism and behavioral abnormalities, MIM# 620747; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Osteopetrosis v0.34 DMP1 Zornitza Stark Marked gene: DMP1 as ready
Osteopetrosis v0.34 DMP1 Zornitza Stark Gene: dmp1 has been classified as Green List (High Evidence).
Osteopetrosis v0.34 DMP1 Zornitza Stark Classified gene: DMP1 as Green List (high evidence)
Osteopetrosis v0.34 DMP1 Zornitza Stark Gene: dmp1 has been classified as Green List (High Evidence).
Osteopetrosis v0.33 DMP1 Zornitza Stark gene: DMP1 was added
gene: DMP1 was added to Osteopetrosis. Sources: Expert Review
Mode of inheritance for gene: DMP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DMP1 were set to 17033625
Phenotypes for gene: DMP1 were set to Hypophosphataemic rickets, MIM#600980
Review for gene: DMP1 was set to GREEN
Added comment: Included due to phenotypic overlap: osteosclerotic changes on X-rays, severe in some individuals.
Sources: Expert Review
Mendeliome v1.1610 BBS4 Bryony Thompson reviewed gene: BBS4: Rating: RED; Mode of pathogenicity: None; Publications: 37588201; Phenotypes: autosomal dominant polycystic liver disease MONDO:0000447; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.1610 BBS4 Bryony Thompson Deleted their review
Mendeliome v1.1610 ZFHX3 Lucy Spencer reviewed gene: ZFHX3: Rating: GREEN; Mode of pathogenicity: None; Publications: 38412861; Phenotypes: Neurodevelopmental disorder (MONDO:0700092), ZFHX3-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.1610 EFEMP1 Zornitza Stark Phenotypes for gene: EFEMP1 were changed from Glaucoma 1, open angle, H, MIM# 611276; Doyne honeycomb degeneration of retina, MIM# 126600; EFEMP1-related connective tissue disorder to Glaucoma 1, open angle, H, MIM# 611276; Doyne honeycomb degeneration of retina, MIM# 126600; EFEMP1-related connective tissue disorder
Mendeliome v1.1609 EFEMP1 Zornitza Stark Phenotypes for gene: EFEMP1 were changed from Doyne honeycomb degeneration of retina, MIM# 126600; EFEMP1-related connective tissue disorder to Glaucoma 1, open angle, H, MIM# 611276; Doyne honeycomb degeneration of retina, MIM# 126600; EFEMP1-related connective tissue disorder
Mendeliome v1.1608 EFEMP1 Zornitza Stark edited their review of gene: EFEMP1: Changed phenotypes: Doyne honeycomb degeneration of retina, MIM# 126600, EFEMP1-related connective tissue disorder, Glaucoma 1, open angle, H, MIM# 611276
Glaucoma congenital v1.9 EFEMP1 Zornitza Stark Phenotypes for gene: EFEMP1 were changed from Juvenile-onset open angle glaucoma, MONDO:0020367, EFEMP1-related to Glaucoma 1, open angle, H, MIM# 611276
Glaucoma congenital v1.8 EFEMP1 Zornitza Stark reviewed gene: EFEMP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Glaucoma 1, open angle, H, MIM# 611276; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2361 DIAPH1 Zornitza Stark Marked gene: DIAPH1 as ready
Genetic Epilepsy v0.2361 DIAPH1 Zornitza Stark Gene: diaph1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2361 DIAPH1 Zornitza Stark Phenotypes for gene: DIAPH1 were changed from to Seizures, cortical blindness, microcephaly syndrome, MIM# 616632
Genetic Epilepsy v0.2360 DIAPH1 Zornitza Stark Publications for gene: DIAPH1 were set to
Genetic Epilepsy v0.2359 DIAPH1 Zornitza Stark Mode of inheritance for gene: DIAPH1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2358 DIAPH1 Zornitza Stark reviewed gene: DIAPH1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Seizures, cortical blindness, microcephaly syndrome, MIM# 616632; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2358 DHCR24 Zornitza Stark Marked gene: DHCR24 as ready
Genetic Epilepsy v0.2358 DHCR24 Zornitza Stark Gene: dhcr24 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2358 DHCR24 Zornitza Stark Phenotypes for gene: DHCR24 were changed from to Desmosterolosis, MIM# 602398
Genetic Epilepsy v0.2357 DHCR24 Zornitza Stark Publications for gene: DHCR24 were set to
Genetic Epilepsy v0.2356 DHCR24 Zornitza Stark Mode of inheritance for gene: DHCR24 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2355 DHCR24 Zornitza Stark changed review comment from: Clinical features include multiple congenital anomalies, including contractures and brain anomalies; intellectual disability; and elevated levels of the cholesterol precursor desmosterol in plasma, tissue, and cultured cells.

At least 10 unrelated families reported, mouse model.; to: Clinical features include multiple congenital anomalies, including contractures and brain anomalies; intellectual disability; and elevated levels of the cholesterol precursor desmosterol in plasma, tissue, and cultured cells.

At least 10 unrelated families reported, mouse model. Seizures are a feature.
Genetic Epilepsy v0.2355 DDX3X Zornitza Stark Marked gene: DDX3X as ready
Genetic Epilepsy v0.2355 DDX3X Zornitza Stark Gene: ddx3x has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2355 DDX3X Zornitza Stark Phenotypes for gene: DDX3X were changed from to Intellectual developmental disorder, X-linked, syndrome, Snijders Blok type MIM# 300958
Genetic Epilepsy v0.2354 DDX3X Zornitza Stark Publications for gene: DDX3X were set to
Genetic Epilepsy v0.2353 DDX3X Zornitza Stark Mode of inheritance for gene: DDX3X was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Genetic Epilepsy v0.2352 DDX3X Zornitza Stark changed review comment from: Syndromic X-linked mental retardation of the Snijders Blok type (MRXSSB), which occurs predominantly in females, is characterised by mildly to severely impaired intellectual development with variable other features including brain abnormalities, microcephaly, hypotonia, movement disorder and/or spasticity, ventricular enlargement, hypoplasia, and behavioural problems. Affected girls have de novo heterozygous mutations consistent with X-linked dominant inheritance. No consistent dysmorphic facial phenotype and onset in infancy.

Multiple unrelated families reported.; to: Syndromic X-linked mental retardation of the Snijders Blok type (MRXSSB), which occurs predominantly in females, is characterised by mildly to severely impaired intellectual development with variable other features including brain abnormalities, microcephaly, hypotonia, movement disorder and/or spasticity, ventricular enlargement, hypoplasia, and behavioural problems. Affected girls have de novo heterozygous mutations consistent with X-linked dominant inheritance. No consistent dysmorphic facial phenotype and onset in infancy.

Multiple unrelated families reported. Seizures are a feature.
Genetic Epilepsy v0.2352 DCX Zornitza Stark Marked gene: DCX as ready
Genetic Epilepsy v0.2352 DCX Zornitza Stark Gene: dcx has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2352 DCX Zornitza Stark Phenotypes for gene: DCX were changed from to Lissencephaly, X-linked, MIM# 300067; Subcortical laminal heterotopia, X-linked 300067
Genetic Epilepsy v0.2351 DCX Zornitza Stark Publications for gene: DCX were set to
Genetic Epilepsy v0.2350 DCX Zornitza Stark Mode of inheritance for gene: DCX was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Genetic Epilepsy v0.2349 DCX Zornitza Stark changed review comment from: DCX mutations cause classic lissencephaly with mental retardation in hemizygous males and a milder phenotype known as subcortical band heterotopia in females, sometimes in the same family. The subcortical lamina heterotopia found in heterozygous females is also referred to as 'double cortex' (DC) syndrome. Multiple affected families reported.; to: DCX mutations cause classic lissencephaly with mental retardation in hemizygous males and a milder phenotype known as subcortical band heterotopia in females, sometimes in the same family. The subcortical lamina heterotopia found in heterozygous females is also referred to as 'double cortex' (DC) syndrome. Multiple affected families reported. Seizures are a feature of the condition.
Genetic Epilepsy v0.2349 D2HGDH Zornitza Stark Marked gene: D2HGDH as ready
Genetic Epilepsy v0.2349 D2HGDH Zornitza Stark Gene: d2hgdh has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2349 D2HGDH Zornitza Stark Phenotypes for gene: D2HGDH were changed from to D-2-hydroxyglutaric aciduria MIM#600721
Genetic Epilepsy v0.2348 D2HGDH Zornitza Stark Publications for gene: D2HGDH were set to
Genetic Epilepsy v0.2347 D2HGDH Zornitza Stark Mode of inheritance for gene: D2HGDH was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2346 D2HGDH Zornitza Stark changed review comment from: More than 3 families reported.; to: More than 3 families reported, early onset encephalopathy is a key feature.
Genetic Epilepsy v0.2346 CTSD Zornitza Stark Marked gene: CTSD as ready
Genetic Epilepsy v0.2346 CTSD Zornitza Stark Gene: ctsd has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2346 CTSD Zornitza Stark Phenotypes for gene: CTSD were changed from to Ceroid lipofuscinosis, neuronal, 10, MIM# 610127; MONDO:0012414
Genetic Epilepsy v0.2345 CTSD Zornitza Stark Publications for gene: CTSD were set to
Genetic Epilepsy v0.2344 CTSD Zornitza Stark Mode of inheritance for gene: CTSD was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2343 CTSD Zornitza Stark changed review comment from: Neurodegenerative disorder though severe congenital forms also reported.; to: Neurodegenerative disorder though severe congenital forms also reported, seizures are a key feature.
Genetic Epilepsy v0.2343 COQ9 Zornitza Stark Marked gene: COQ9 as ready
Genetic Epilepsy v0.2343 COQ9 Zornitza Stark Gene: coq9 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2343 COQ9 Zornitza Stark Phenotypes for gene: COQ9 were changed from to Coenzyme Q10 deficiency, primary, 5, MIM#614654
Genetic Epilepsy v0.2342 COQ9 Zornitza Stark Publications for gene: COQ9 were set to
Genetic Epilepsy v0.2341 COQ9 Zornitza Stark Mode of inheritance for gene: COQ9 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2340 COQ9 Zornitza Stark reviewed gene: COQ9: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Coenzyme Q10 deficiency, primary, 5, MIM#614654; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2340 COQ4 Zornitza Stark Marked gene: COQ4 as ready
Genetic Epilepsy v0.2340 COQ4 Zornitza Stark Gene: coq4 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2340 COQ4 Zornitza Stark Phenotypes for gene: COQ4 were changed from to Coenzyme Q10 deficiency, primary, 7, MIM# 616276
Genetic Epilepsy v0.2339 COQ4 Zornitza Stark Publications for gene: COQ4 were set to
Genetic Epilepsy v0.2338 COQ4 Zornitza Stark Mode of inheritance for gene: COQ4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2337 COQ2 Zornitza Stark Marked gene: COQ2 as ready
Genetic Epilepsy v0.2337 COQ2 Zornitza Stark Gene: coq2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2337 COQ2 Zornitza Stark Phenotypes for gene: COQ2 were changed from to Coenzyme Q10 deficiency, primary, 1, MIM# 607426; MONDO:0011829
Genetic Epilepsy v0.2336 COQ2 Zornitza Stark Publications for gene: COQ2 were set to
Genetic Epilepsy v0.2335 COQ2 Zornitza Stark Mode of inheritance for gene: COQ2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.203 MYCN Zornitza Stark Phenotypes for gene: MYCN were changed from Feingold syndrome 1 (MIM#164280); Neurodevelopmental disorder (MONDO:0700092), MYCN-related to Feingold syndrome 1 (MIM#164280); Megalencephaly-polydactyly syndrome, MIM# 620748
Fetal anomalies v1.202 MYCN Zornitza Stark edited their review of gene: MYCN: Changed phenotypes: Feingold syndrome 1, MIM# 164280, Megalencephaly-polydactyly syndrome, MIM# 620748
Hand and foot malformations v0.73 MYCN Zornitza Stark Marked gene: MYCN as ready
Hand and foot malformations v0.73 MYCN Zornitza Stark Gene: mycn has been classified as Green List (High Evidence).
Hand and foot malformations v0.73 MYCN Zornitza Stark Phenotypes for gene: MYCN were changed from Feingold syndrome (Microcephaly-oculo-digito-esophageal-duodenal) 164280 to Megalencephaly-polydactyly syndrome, MIM# 620748; Feingold syndrome (Microcephaly-oculo-digito-esophageal-duodenal) 164280
Hand and foot malformations v0.72 MYCN Zornitza Stark reviewed gene: MYCN: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Megalencephaly-polydactyly syndrome, MIM# 620748; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Polydactyly v0.276 MYCN Zornitza Stark Phenotypes for gene: MYCN were changed from Neurodevelopmental disorder (MONDO:0700092), MYCN-related to Megalencephaly-polydactyly syndrome, MIM# 620748
Polydactyly v0.275 MYCN Zornitza Stark reviewed gene: MYCN: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Megalencephaly-polydactyly syndrome, MIM# 620748; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Macrocephaly_Megalencephaly v0.140 MYCN Zornitza Stark Phenotypes for gene: MYCN were changed from Neurodevelopmental disorder (MONDO:0700092), MYCN-related to Megalencephaly-polydactyly syndrome, MIM# 620748
Macrocephaly_Megalencephaly v0.139 MYCN Zornitza Stark reviewed gene: MYCN: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Megalencephaly-polydactyly syndrome, MIM# 620748; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5721 SLC4A10 Zornitza Stark Phenotypes for gene: SLC4A10 were changed from Neurodevelopmental disorderMONDO:0700092, SLC4A10-related to Neurodevelopmental disorder with hypotonia and characteristic brain abnormalities, MIM# 620746
Intellectual disability syndromic and non-syndromic v0.5720 SLC4A10 Zornitza Stark reviewed gene: SLC4A10: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with hypotonia and characteristic brain abnormalities, MIM# 620746; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Callosome v0.519 SLC4A10 Zornitza Stark Phenotypes for gene: SLC4A10 were changed from Neurodevelopmental disorderMONDO:0700092, SLC4A10-related to Neurodevelopmental disorder with hypotonia and characteristic brain abnormalities, MIM# 620746
Callosome v0.518 SLC4A10 Zornitza Stark reviewed gene: SLC4A10: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with hypotonia and characteristic brain abnormalities, MIM# 620746; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Muscular dystrophy and myopathy_Paediatric v1.21 SLC4A10 Zornitza Stark Phenotypes for gene: SLC4A10 were changed from Neurodevelopmental disorderMONDO:0700092, SLC4A10-related to Neurodevelopmental disorder with hypotonia and characteristic brain abnormalities, MIM# 620746
Muscular dystrophy and myopathy_Paediatric v1.20 SLC4A10 Zornitza Stark reviewed gene: SLC4A10: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with hypotonia and characteristic brain abnormalities, MIM# 620746; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v1.251 SLC4A10 Zornitza Stark Phenotypes for gene: SLC4A10 were changed from Neurodevelopmental disorderMONDO:0700092, SLC4A10-related to Neurodevelopmental disorder with hypotonia and characteristic brain abnormalities, MIM# 620746
Microcephaly v1.250 SLC4A10 Zornitza Stark reviewed gene: SLC4A10: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with hypotonia and characteristic brain abnormalities, MIM# 620746; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1608 SLC4A10 Zornitza Stark Phenotypes for gene: SLC4A10 were changed from Neurodevelopmental disorderMONDO:0700092, SLC4A10-related to Neurodevelopmental disorder with hypotonia and characteristic brain abnormalities, MIM# 620746
Mendeliome v1.1607 SLC4A10 Zornitza Stark reviewed gene: SLC4A10: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with hypotonia and characteristic brain abnormalities, MIM# 620746; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Autism v0.197 SLC4A10 Zornitza Stark Phenotypes for gene: SLC4A10 were changed from Neurodevelopmental disorderMONDO:0700092, SLC4A10-related to Neurodevelopmental disorder with hypotonia and characteristic brain abnormalities, MIM# 620746
Autism v0.196 SLC4A10 Zornitza Stark reviewed gene: SLC4A10: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with hypotonia and characteristic brain abnormalities, MIM# 620746; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1607 RREB1 Zornitza Stark Phenotypes for gene: RREB1 were changed from Noonan syndrome-like disorder to Rasopathy, MONDO:0021060, RREB1-related
Microcephaly v1.250 RGS6 Zornitza Stark Phenotypes for gene: RGS6 were changed from Cataract,MONDO:0005129; intellectual disability, MONDO:0001071; microcephaly, MONDO:0001149 to Neurodevelopmental disorder, MONDO:0700092, RGS6-related
Mendeliome v1.1606 RGS6 Zornitza Stark Phenotypes for gene: RGS6 were changed from Cataract,MONDO:0005129; intellectual disability, MONDO:0001071; microcephaly, MONDO:0001149 to Neurodevelopmental disorder, MONDO:0700092, RGS6-related
Cataract v0.364 RGS6 Zornitza Stark Phenotypes for gene: RGS6 were changed from Neurodevelopmental disorder, MONDO:0700092, RGS6-related to Neurodevelopmental disorder, MONDO:0700092, RGS6-related
Cataract v0.363 RGS6 Zornitza Stark Phenotypes for gene: RGS6 were changed from Cataract,MONDO:0005129; intellectual disability, MONDO:0001071; microcephaly, MONDO:0001149 to Neurodevelopmental disorder, MONDO:0700092, RGS6-related
Mendeliome v1.1605 ZSCAN10 Zornitza Stark Marked gene: ZSCAN10 as ready
Mendeliome v1.1605 ZSCAN10 Zornitza Stark Gene: zscan10 has been classified as Green List (High Evidence).
Mendeliome v1.1605 ZSCAN10 Zornitza Stark Classified gene: ZSCAN10 as Green List (high evidence)
Mendeliome v1.1605 ZSCAN10 Zornitza Stark Gene: zscan10 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.173 ZSCAN10 Zornitza Stark Marked gene: ZSCAN10 as ready
Deafness_IsolatedAndComplex v1.173 ZSCAN10 Zornitza Stark Gene: zscan10 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.173 ZSCAN10 Zornitza Stark Classified gene: ZSCAN10 as Green List (high evidence)
Deafness_IsolatedAndComplex v1.173 ZSCAN10 Zornitza Stark Gene: zscan10 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5720 ZSCAN10 Zornitza Stark Marked gene: ZSCAN10 as ready
Intellectual disability syndromic and non-syndromic v0.5720 ZSCAN10 Zornitza Stark Gene: zscan10 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5720 ZSCAN10 Zornitza Stark Classified gene: ZSCAN10 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5720 ZSCAN10 Zornitza Stark Gene: zscan10 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v1.20 SNUPN Zornitza Stark Phenotypes for gene: SNUPN were changed from autosomal recessive limb-girdle muscular dystrophy MONDO:0015152 to autosomal recessive limb-girdle muscular dystrophy MONDO:0015152, SNUPN-related
Mendeliome v1.1604 CORIN Zornitza Stark Phenotypes for gene: CORIN were changed from Preeclampsia/eclampsia 5 MIM#614595; ?Cardiomyopathy, familial hypertrophic, 30, atrial (MIM:620734) to Preeclampsia/eclampsia 5 MIM#614595; Cardiomyopathy, familial hypertrophic, 30, atrial (MIM:620734)
Mendeliome v1.1603 CORIN Zornitza Stark Publications for gene: CORIN were set to 22437503
Mendeliome v1.1602 CORIN Zornitza Stark Phenotypes for gene: CORIN were changed from Preeclampsia/eclampsia 5 MIM#614595 to Preeclampsia/eclampsia 5 MIM#614595; ?Cardiomyopathy, familial hypertrophic, 30, atrial (MIM:620734)
Genetic Epilepsy v0.2334 DIP2C Zornitza Stark Classified gene: DIP2C as Green List (high evidence)
Genetic Epilepsy v0.2334 DIP2C Zornitza Stark Gene: dip2c has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2333 DIP2C Zornitza Stark reviewed gene: DIP2C: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder (MONDO#0700092), DIP2C-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v1.202 CELSR3 Zornitza Stark Marked gene: CELSR3 as ready
Fetal anomalies v1.202 CELSR3 Zornitza Stark Gene: celsr3 has been classified as Green List (High Evidence).
Fetal anomalies v1.202 CELSR3 Zornitza Stark Classified gene: CELSR3 as Green List (high evidence)
Fetal anomalies v1.202 CELSR3 Zornitza Stark Gene: celsr3 has been classified as Green List (High Evidence).
Fetal anomalies v1.201 CELSR3 Zornitza Stark edited their review of gene: CELSR3: Changed rating: GREEN
Fetal anomalies v1.201 CELSR3 Zornitza Stark gene: CELSR3 was added
gene: CELSR3 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: CELSR3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CELSR3 were set to 38429302
Phenotypes for gene: CELSR3 were set to Neurodevelopmental disorder (MONDO#0700092), CELSR3-related
Added comment: PMID: 38429302:12 affected individuals from 11 families reported with bi-allelic variants. Phenotype ranged from CNS anomalies (7/12), CNS and CAKUT (3/12) and CAKUT only (2/12). 8/12 has ID/DD. Only missense variants reported and 1 inframe variant. Functional studies done in zebrafish demonstrate similar structural anomalies of the developing pronephros and neuronal abnormalities to affected individuals
Sources: Literature
Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic v0.138 CELSR3 Zornitza Stark Marked gene: CELSR3 as ready
Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic v0.138 CELSR3 Zornitza Stark Gene: celsr3 has been classified as Green List (High Evidence).
Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic v0.138 CELSR3 Zornitza Stark Classified gene: CELSR3 as Green List (high evidence)
Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic v0.138 CELSR3 Zornitza Stark Gene: celsr3 has been classified as Green List (High Evidence).
Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic v0.137 CELSR3 Zornitza Stark gene: CELSR3 was added
gene: CELSR3 was added to Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic. Sources: Literature
Mode of inheritance for gene: CELSR3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CELSR3 were set to 38429302
Phenotypes for gene: CELSR3 were set to Neurodevelopmental disorder (MONDO#0700092), CELSR3-related
Review for gene: CELSR3 was set to GREEN
Added comment: PMID: 38429302:12 affected individuals from 11 families reported with bi-allelic variants. Phenotype ranged from CNS anomalies (7/12), CNS and CAKUT (3/12) and CAKUT only (2/12). 8/12 has ID/DD. Only missense variants reported and 1 inframe variant. Functional studies done in zebrafish demonstrate similar structural anomalies of the developing pronephros and neuronal abnormalities to affected individuals.
Sources: Literature
Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic v0.136 CHD7 Zornitza Stark Marked gene: CHD7 as ready
Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic v0.136 CHD7 Zornitza Stark Gene: chd7 has been classified as Green List (High Evidence).
Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic v0.136 CHD7 Zornitza Stark Phenotypes for gene: CHD7 were changed from to CHARGE syndrome MIM#214800
Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic v0.135 CHD7 Zornitza Stark Mode of inheritance for gene: CHD7 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic v0.134 CHD7 Zornitza Stark reviewed gene: CHD7: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: CHARGE syndrome MIM#214800; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic v0.134 ACE Zornitza Stark Marked gene: ACE as ready
Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic v0.134 ACE Zornitza Stark Gene: ace has been classified as Green List (High Evidence).
Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic v0.134 ACE Zornitza Stark Deleted their review
Intellectual disability syndromic and non-syndromic v0.5719 CELSR3 Zornitza Stark Marked gene: CELSR3 as ready
Intellectual disability syndromic and non-syndromic v0.5719 CELSR3 Zornitza Stark Gene: celsr3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5719 CELSR3 Zornitza Stark Classified gene: CELSR3 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5719 CELSR3 Zornitza Stark Gene: celsr3 has been classified as Green List (High Evidence).
Mendeliome v1.1601 CELSR3 Zornitza Stark Marked gene: CELSR3 as ready
Mendeliome v1.1601 CELSR3 Zornitza Stark Gene: celsr3 has been classified as Green List (High Evidence).
Mendeliome v1.1601 CELSR3 Zornitza Stark Classified gene: CELSR3 as Green List (high evidence)
Mendeliome v1.1601 CELSR3 Zornitza Stark Gene: celsr3 has been classified as Green List (High Evidence).
Regression v0.547 CIAO1 Zornitza Stark Marked gene: CIAO1 as ready
Regression v0.547 CIAO1 Zornitza Stark Gene: ciao1 has been classified as Green List (High Evidence).
Regression v0.547 CIAO1 Zornitza Stark Classified gene: CIAO1 as Green List (high evidence)
Regression v0.547 CIAO1 Zornitza Stark Gene: ciao1 has been classified as Green List (High Evidence).
Regression v0.546 CIAO1 Zornitza Stark gene: CIAO1 was added
gene: CIAO1 was added to Regression. Sources: Literature
Mode of inheritance for gene: CIAO1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CIAO1 were set to 38411040; 38196629
Phenotypes for gene: CIAO1 were set to Neurodegenerative disease, MONDO:0005559, CIAO1-related
Review for gene: CIAO1 was set to GREEN
Added comment: PMID:38196629 (note pre-print) describes 4 unrelated patients with core features of progressive muscle weakness, respiratory insufficiency, joint hyperlaxity, ankle tightness, calf pseudohypertrophy, elevated CK, and larning disabilities/difficulties. 2 patients presented with increased iron deposition in the brain. Age of recognition of myopathic symptoms varied from early childhood to adolescence. Muscle biopsy showed variation in fiber size and an increase in internalized nuclei, as well as scattered degenerating/regenerating fibers and a mild to minimal increase in endomysial fibrosis. Electron microscopy revealed morphologically abnormal mitochondria.

PMID: 38411040 reports 2 unrelated patients. Patient 1 was born with microcephaly and borderline hypertonia, and died at 18 months of respiratory failure from bronchiolitis. Patient 2 presented with failure to thrive, a hyperkinetic movement disorder, and autism before deteriorating in late teens with muscle weakness, recurrent pneuomonia with respiratory insufficiency, and eventually death due to multi-organ failure with carnificating pneumonia, septic cardiomyopathy, and intracranial hemorrhages. Immune deficiency was ruled out.

All variants reported were homozygous or compound heterozygous missense variants, with the exception of one large in-frame deletion of exon 7. Cell line studies showed the variants resulted in reduced protein stability and downstream cellular defects which could be rescued by wild-type CIAO1.
Sources: Literature
Mendeliome v1.1600 CIAO1 Zornitza Stark Marked gene: CIAO1 as ready
Mendeliome v1.1600 CIAO1 Zornitza Stark Gene: ciao1 has been classified as Green List (High Evidence).
Mendeliome v1.1600 CIAO1 Zornitza Stark Phenotypes for gene: CIAO1 were changed from Neuromuscular disease, CIAO1-related (MONDO:0019056) to Neurodegenerative disease, MONDO:0005559, CIAO1-related
Mendeliome v1.1599 CIAO1 Zornitza Stark Classified gene: CIAO1 as Green List (high evidence)
Mendeliome v1.1599 CIAO1 Zornitza Stark Gene: ciao1 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v1.19 CIAO1 Zornitza Stark Phenotypes for gene: CIAO1 were changed from Neuromuscular disease, CIAO1-related (MONDO:0019056) to Neurodegenerative disease, MONDO:0005559, CIAO1-related
Muscular dystrophy and myopathy_Paediatric v1.18 CIAO1 Zornitza Stark Phenotypes for gene: CIAO1 were changed from Neurodegenerative disease, MONDO:0005559, CIAO1-related to Neuromuscular disease, CIAO1-related (MONDO:0019056)
Muscular dystrophy and myopathy_Paediatric v1.17 CIAO1 Zornitza Stark Marked gene: CIAO1 as ready
Muscular dystrophy and myopathy_Paediatric v1.17 CIAO1 Zornitza Stark Gene: ciao1 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v1.17 CIAO1 Zornitza Stark Phenotypes for gene: CIAO1 were changed from Neuromuscular disease, CIAO1-related (MONDO:0019056) to Neurodegenerative disease, MONDO:0005559, CIAO1-related
Muscular dystrophy and myopathy_Paediatric v1.16 CIAO1 Zornitza Stark Classified gene: CIAO1 as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v1.16 CIAO1 Zornitza Stark Gene: ciao1 has been classified as Green List (High Evidence).
Regression v0.545 MMS19 Zornitza Stark Marked gene: MMS19 as ready
Regression v0.545 MMS19 Zornitza Stark Gene: mms19 has been classified as Red List (Low Evidence).
Regression v0.545 MMS19 Zornitza Stark gene: MMS19 was added
gene: MMS19 was added to Regression. Sources: Literature
Mode of inheritance for gene: MMS19 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MMS19 were set to 38411040
Phenotypes for gene: MMS19 were set to Neurodegenerative disease, MONDO:0005559, MMS19-related
Review for gene: MMS19 was set to RED
Added comment: Single patient reported with postnatal microcephaly, bilateral cataracts, failure to thrive, progressive spastic tetraparesis, scoliosis, myoclonic epilepsy and precocious puberty. Cerebral MRI at age 4 years showed pontocerebellar atrophy and white matter abnormalities. Patient died age 13 after recurrent respiratory tract infections. A homozygous in-frame deletion p.(Glu213del) was identified. Cell line studies supported pathogenicity of the variant. A zebrafish knockout model showed Mms19 deficiency had detrimental effects on development.
Sources: Literature
Genetic Epilepsy v0.2333 MMS19 Zornitza Stark Marked gene: MMS19 as ready
Genetic Epilepsy v0.2333 MMS19 Zornitza Stark Gene: mms19 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2333 MMS19 Zornitza Stark Phenotypes for gene: MMS19 were changed from Neuromuscular disease, MMS19-related (MONDO:0019056) to Neurodegenerative disease, MONDO:0005559, MMS19-related
Genetic Epilepsy v0.2332 MMS19 Zornitza Stark Classified gene: MMS19 as Red List (low evidence)
Genetic Epilepsy v0.2332 MMS19 Zornitza Stark Gene: mms19 has been classified as Red List (Low Evidence).
Mendeliome v1.1598 MMS19 Zornitza Stark Marked gene: MMS19 as ready
Mendeliome v1.1598 MMS19 Zornitza Stark Gene: mms19 has been classified as Red List (Low Evidence).
Mendeliome v1.1598 MMS19 Zornitza Stark Phenotypes for gene: MMS19 were changed from Neuromuscular disease, MMS19-related (MONDO:0019056) to Neurodegenerative disease, MONDO:0005559, MMS19-related
Mendeliome v1.1597 MMS19 Zornitza Stark Classified gene: MMS19 as Red List (low evidence)
Mendeliome v1.1597 MMS19 Zornitza Stark Gene: mms19 has been classified as Red List (Low Evidence).
Muscular dystrophy and myopathy_Paediatric v1.15 MMS19 Zornitza Stark Classified gene: MMS19 as Red List (low evidence)
Muscular dystrophy and myopathy_Paediatric v1.15 MMS19 Zornitza Stark Gene: mms19 has been classified as Red List (Low Evidence).
Muscular dystrophy and myopathy_Paediatric v1.14 MMS19 Zornitza Stark Marked gene: MMS19 as ready
Muscular dystrophy and myopathy_Paediatric v1.14 MMS19 Zornitza Stark Gene: mms19 has been removed from the panel.
Muscular dystrophy and myopathy_Paediatric v1.14 MMS19 Zornitza Stark Phenotypes for gene: MMS19 were changed from Neuromuscular disease, MMS19-related (MONDO:0019056) to Neurodegenerative disease, MONDO:0005559, MMS19-related
Hereditary Neuropathy - complex v1.10 NARS Zornitza Stark changed review comment from: AR disorder: assessed as LIMITED by ClinGen (borderline MODERATE).; to: Both MOIs assessed as MODERATE by ClinGen.
Intellectual disability syndromic and non-syndromic v0.5718 NARS Zornitza Stark changed review comment from: AR disorder: assessed as LIMITED by ClinGen (borderline MODERATE).; to: Both MOIs assessed as MODERATE by ClinGen.
Genetic Epilepsy v0.2331 NARS Zornitza Stark changed review comment from: AR disorder: assessed as LIMITED by ClinGen (borderline MODERATE).; to: Both MOIs assessed as MODERATE by ClinGen.
Microcephaly v1.249 NARS Zornitza Stark changed review comment from: AR disorder: assessed as LIMITED by ClinGen (borderline MODERATE).; to: Both MOIs assessed as MODERATE by ClinGen.
Microcephaly v1.249 NARS Zornitza Stark edited their review of gene: NARS: Changed rating: GREEN
Mendeliome v1.1596 NARS Zornitza Stark changed review comment from: AR disorder: assessed as LIMITED by ClinGen (borderline MODERATE).; to: Both MOIs assessed as MODERATE by ClinGen.
Fetal anomalies v1.200 NARS Zornitza Stark edited their review of gene: NARS: Changed rating: GREEN
Fetal anomalies v1.200 NARS Zornitza Stark changed review comment from: AR disorder: assessed as LIMITED by ClinGen (borderline MODERATE).; to: Both MOIs assessed as MODERATE by ClinGen.
Muscular dystrophy and myopathy_Paediatric v1.13 MMS19 Paul De Fazio gene: MMS19 was added
gene: MMS19 was added to Muscular dystrophy and myopathy_Paediatric. Sources: Literature
Mode of inheritance for gene: MMS19 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MMS19 were set to 38411040
Phenotypes for gene: MMS19 were set to Neuromuscular disease, MMS19-related (MONDO:0019056)
Review for gene: MMS19 was set to RED
gene: MMS19 was marked as current diagnostic
Added comment: Single patient reported with postnatal microcephaly, bilateral cataracts, failure to thrive, progressive spastic tetraparesis, scoliosis, myoclonic epilepsy and precocious puberty. Cerebral MRI at age 4 years showed pontocerebellar atrophy and white matter abnormalities. Patient died age 13 after recurrent respiratory tract infections. A homozygous in-frame deletion p.(Glu213del) was identified. Cell line studies supported pathogenicity of the variant. A zebrafish knockout model showed Mms19 deficiency had detrimental effects on development.
Sources: Literature
Genetic Epilepsy v0.2331 MMS19 Paul De Fazio gene: MMS19 was added
gene: MMS19 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: MMS19 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MMS19 were set to 38411040
Phenotypes for gene: MMS19 were set to Neuromuscular disease, MMS19-related (MONDO:0019056)
Review for gene: MMS19 was set to RED
gene: MMS19 was marked as current diagnostic
Added comment: Single patient reported with postnatal microcephaly, bilateral cataracts, failure to thrive, progressive spastic tetraparesis, scoliosis, myoclonic epilepsy and precocious puberty. Cerebral MRI at age 4 years showed pontocerebellar atrophy and white matter abnormalities. Patient died age 13 after recurrent respiratory tract infections. A homozygous in-frame deletion p.(Glu213del) was identified. Cell line studies supported pathogenicity of the variant. A zebrafish knockout model showed Mms19 deficiency had detrimental effects on development.
Sources: Literature
Muscular dystrophy and myopathy_Paediatric v1.13 CIAO1 Paul De Fazio gene: CIAO1 was added
gene: CIAO1 was added to Muscular dystrophy and myopathy_Paediatric. Sources: Literature
Mode of inheritance for gene: CIAO1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CIAO1 were set to 38411040; 38196629
Phenotypes for gene: CIAO1 were set to Neuromuscular disease, CIAO1-related (MONDO:0019056)
Penetrance for gene: CIAO1 were set to unknown
Review for gene: CIAO1 was set to GREEN
gene: CIAO1 was marked as current diagnostic
Added comment: PMID:38196629 (note pre-print) describes 4 unrelated patients with core features of progressive muscle weakness, respiratory insufficiency, joint hyperlaxity, ankle tightness, calf pseudohypertrophy, elevated CK, and larning disabilities/difficulties. 2 patients presented with increased iron deposition in the brain. Age of recognition of myopathic symptoms varied from early childhood to adolescence. Muscle biopsy showed variation in fiber size and an increase in internalized nuclei, as well as scattered degenerating/regenerating fibers and a mild to minimal increase in endomysial fibrosis. Electron microscopy revealed morphologically abnormal mitochondria.

PMID: 38411040 reports 2 unrelated patients. Patient 1 was born with microcephaly and borderline hypertonia, and died at 18 months of respiratory failure from bronchiolitis. Patient 2 presented with failure to thrive, a hyperkinetic movement disorder, and autism before deteriorating in late teens with muscle weakness, recurrent pneuomonia with respiratory insufficiency, and eventually death due to multi-organ failure with carnificating pneumonia, septic cardiomyopathy, and intracranial hemorrhages. Immune deficiency was ruled out.

All variants reported were homozygous or compound heterozygous missense variants, with the exception of one large in-frame deletion of exon 7. Cell line studies showed the variants resulted in reduced protein stability and downstream cellular defects which could be rescued by wild-type CIAO1.
Sources: Literature
Mendeliome v1.1596 CIAO1 Paul De Fazio changed review comment from: PMID:38196629 (note pre-print) describes 4 unrelated patients with core features of progressive muscle weakness, respiratory insufficiency, joint hyperlaxity, ankle tightness, calf pseudohypertrophy, elevated CK, and larning disabilities/difficulties. 2 patients presented with increased iron deposition in the brain. Age of recognition of myopathic symptoms varied from early childhood to adolescence.

PMID: 38411040 reports 2 unrelated patients. Patient 1 was born with microcephaly and borderline hypertonia, and died at 18 months of respiratory failure from bronchiolitis. Patient 2 presented with failure to thrive, a hyperkinetic movement disorder, and autism before deteriorating in late teens with muscle weakness, recurrent pneuomonia with respiratory insufficiency, and eventually death due to multi-organ failure with carnificating pneumonia, septic cardiomyopathy, and intracranial hemorrhages. Immune deficiency was ruled out.

All variants reported were homozygous or compound heterozygous missense variants, with the exception of one large in-frame deletion of exon 7. Cell line studies showed the variants resulted in reduced protein stability and downstream cellular defects which could be rescued by wild-type CIAO1.
Sources: Literature; to: PMID:38196629 (note pre-print) describes 4 unrelated patients with core features of progressive muscle weakness, respiratory insufficiency, joint hyperlaxity, ankle tightness, calf pseudohypertrophy, elevated CK, and larning disabilities/difficulties. 2 patients presented with increased iron deposition in the brain. Age of recognition of myopathic symptoms varied from early childhood to adolescence. Muscle biopsy showed variation in fiber size and an increase in internalized nuclei, as well as scattered degenerating/regenerating fibers and a mild to minimal increase in endomysial fibrosis. Electron microscopy revealed morphologically abnormal mitochondria.

PMID: 38411040 reports 2 unrelated patients. Patient 1 was born with microcephaly and borderline hypertonia, and died at 18 months of respiratory failure from bronchiolitis. Patient 2 presented with failure to thrive, a hyperkinetic movement disorder, and autism before deteriorating in late teens with muscle weakness, recurrent pneuomonia with respiratory insufficiency, and eventually death due to multi-organ failure with carnificating pneumonia, septic cardiomyopathy, and intracranial hemorrhages. Immune deficiency was ruled out.

All variants reported were homozygous or compound heterozygous missense variants, with the exception of one large in-frame deletion of exon 7. Cell line studies showed the variants resulted in reduced protein stability and downstream cellular defects which could be rescued by wild-type CIAO1.
Mendeliome v1.1596 MMS19 Paul De Fazio gene: MMS19 was added
gene: MMS19 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MMS19 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MMS19 were set to 38411040
Phenotypes for gene: MMS19 were set to Neuromuscular disease, MMS19-related (MONDO:0019056)
Penetrance for gene: MMS19 were set to unknown
Review for gene: MMS19 was set to RED
gene: MMS19 was marked as current diagnostic
Added comment: Single patient reported with postnatal microcephaly, bilateral cataracts, failure to thrive, progressive spastic tetraparesis, scoliosis, myoclonic epilepsy and precocious puberty. Cerebral MRI at age 4 years showed pontocerebellar atrophy and white matter abnormalities. Patient died age 13 after recurrent respiratory tract infections. A homozygous in-frame deletion p.(Glu213del) was identified. Cell line studies supported pathogenicity of the variant. A zebrafish knockout model also showed a detrimental effect of Mms19 deficincy.
Sources: Literature
Mendeliome v1.1596 CIAO1 Paul De Fazio gene: CIAO1 was added
gene: CIAO1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CIAO1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CIAO1 were set to 38411040; 38196629
Phenotypes for gene: CIAO1 were set to Neuromuscular disease, CIAO1-related (MONDO:0019056)
Penetrance for gene: CIAO1 were set to unknown
Review for gene: CIAO1 was set to GREEN
gene: CIAO1 was marked as current diagnostic
Added comment: PMID:38196629 (note pre-print) describes 4 unrelated patients with core features of progressive muscle weakness, respiratory insufficiency, joint hyperlaxity, ankle tightness, calf pseudohypertrophy, elevated CK, and larning disabilities/difficulties. 2 patients presented with increased iron deposition in the brain. Age of recognition of myopathic symptoms varied from early childhood to adolescence.

PMID: 38411040 reports 2 unrelated patients. Patient 1 was born with microcephaly and borderline hypertonia, and died at 18 months of respiratory failure from bronchiolitis. Patient 2 presented with failure to thrive, a hyperkinetic movement disorder, and autism before deteriorating in late teens with muscle weakness, recurrent pneuomonia with respiratory insufficiency, and eventually death due to multi-organ failure with carnificating pneumonia, septic cardiomyopathy, and intracranial hemorrhages. Immune deficiency was ruled out.

All variants reported were homozygous or compound heterozygous missense variants, with the exception of one large in-frame deletion of exon 7. Cell line studies showed the variants resulted in reduced protein stability and downstream cellular defects which could be rescued by wild-type CIAO1.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5718 SLC12A9 Zornitza Stark Marked gene: SLC12A9 as ready
Intellectual disability syndromic and non-syndromic v0.5718 SLC12A9 Zornitza Stark Gene: slc12a9 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5718 SLC12A9 Zornitza Stark Classified gene: SLC12A9 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5718 SLC12A9 Zornitza Stark Gene: slc12a9 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5717 CELSR3 Crystle Lee gene: CELSR3 was added
gene: CELSR3 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: CELSR3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CELSR3 were set to PMID: 38429302
Phenotypes for gene: CELSR3 were set to Neurodevelopmental disorder (MONDO#0700092), CELSR3-related
Review for gene: CELSR3 was set to GREEN
Added comment: PMID: 38429302:12 affected individuals from 11 families reported with bi-allelic variants. Phenotype ranged from CNS anomalies (7/12), CNS and CAKUT (3/12) and CAKUT only (2/12). 8/12 has ID/DD. Only missense variants reported and 1 inframe variant. Functional studies done in zebrafish demonstrate similar structural anomalies of the developing pronephros and neuronal abnormalities to affected individuals
Sources: Literature
Genetic Epilepsy v0.2331 DIP2C Elena Savva Marked gene: DIP2C as ready
Genetic Epilepsy v0.2331 DIP2C Elena Savva Gene: dip2c has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2331 DIP2C Elena Savva Classified gene: DIP2C as Amber List (moderate evidence)
Genetic Epilepsy v0.2331 DIP2C Elena Savva Gene: dip2c has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1596 THBS2 Ain Roesley Phenotypes for gene: THBS2 were changed from {Lumbar disc herniation, susceptibility to} 603932 to {Lumbar disc herniation, susceptibility to} 603932; connective tissue disorder MONDO:0003900, THBS2-related
Mendeliome v1.1595 THBS2 Ain Roesley Publications for gene: THBS2 were set to
Mendeliome v1.1594 THBS2 Ain Roesley Mode of inheritance for gene: THBS2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.1594 THBS2 Ain Roesley Classified gene: THBS2 as Amber List (moderate evidence)
Mendeliome v1.1594 THBS2 Ain Roesley Gene: thbs2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1593 THBS2 Chris Ciotta reviewed gene: THBS2: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 38433265; Phenotypes: connective tissue disorder MONDO:0003900, THBS2-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Aortopathy_Connective Tissue Disorders v1.83 THBS2 Chris Ciotta Deleted their comment
Aortopathy_Connective Tissue Disorders v1.83 THBS2 Chris Ciotta Deleted their comment
Aortopathy_Connective Tissue Disorders v1.83 THBS2 Chris Ciotta Deleted their comment
Genetic Epilepsy v0.2330 DIP2C Melanie Marty reviewed gene: DIP2C: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 38421105; Phenotypes: Neurodevelopmental disorder (MONDO#0700092), DIP2C-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Aortopathy_Connective Tissue Disorders v1.83 THBS2 Chris Ciotta Deleted their comment
Genetic Epilepsy v0.2330 DIP2C Melanie Marty Deleted their review
Genetic Epilepsy v0.2330 DIP2C Melanie Marty gene: DIP2C was added
gene: DIP2C was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: DIP2C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DIP2C were set to PMID: 38421105
Phenotypes for gene: DIP2C were set to Neurodevelopmental disorder (MONDO#0700092), DIP2C-related
Review for gene: DIP2C was set to GREEN
Added comment: PMID: 38421105 - Twenty three patients with het DIP2C variants (10 de novo).
All patients had developmental delays affecting expressive language and speech, most had mild dev delay and ID. Four patients had seizures. Additional phenotypic findings were non-specific but recurrent anomalies did include a high anterior hair-line, prominent forehead, and a broad nasal tip. Four patients had cardiac defects (hypertrophic cardiomyopathy, atrial septal defects,and bicuspid aortic valve)
Sources: Literature
Mendeliome v1.1593 UBAP1L Seb Lunke Marked gene: UBAP1L as ready
Mendeliome v1.1593 UBAP1L Seb Lunke Gene: ubap1l has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v1.83 THBS2 Ain Roesley Phenotypes for gene: THBS2 were changed from connective tissue disorder MONDO:0003900, THBS2-related to connective tissue disorder MONDO:0003900, THBS2-related
Mendeliome v1.1593 UBAP1L Seb Lunke Classified gene: UBAP1L as Green List (high evidence)
Mendeliome v1.1593 UBAP1L Seb Lunke Gene: ubap1l has been classified as Green List (High Evidence).
Mendeliome v1.1592 UBAP1L Seb Lunke Classified gene: UBAP1L as Green List (high evidence)
Mendeliome v1.1592 UBAP1L Seb Lunke Gene: ubap1l has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v1.83 THBS2 Ain Roesley Marked gene: THBS2 as ready
Aortopathy_Connective Tissue Disorders v1.83 THBS2 Ain Roesley Gene: thbs2 has been classified as Amber List (Moderate Evidence).
Aortopathy_Connective Tissue Disorders v1.83 THBS2 Ain Roesley Phenotypes for gene: THBS2 were changed from connective tissue disorder MONDO:0003900, THBS2-related to connective tissue disorder MONDO:0003900, THBS2-related
Aortopathy_Connective Tissue Disorders v1.82 THBS2 Ain Roesley Phenotypes for gene: THBS2 were changed from Ehlers-Danlos syndrome to connective tissue disorder MONDO:0003900, THBS2-related
Mendeliome v1.1591 DIP2C Elena Savva Marked gene: DIP2C as ready
Mendeliome v1.1591 DIP2C Elena Savva Gene: dip2c has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v1.82 THBS2 Chris Ciotta edited their review of gene: THBS2: Added comment: One family with autosomal dominant inheritance of a THBS2 missense variant (NM_003247.5:c.2686T>C p.Cys896Arg). The index patient in this family presented with a history of multiple joint dislocations, easy bruising, prolonged wound healing and a diagnosis of bilateral greater saphenous vein insufficiency.

This individual's mother who also carries the variant was noted as having prolonged bleeding, thickened mitral valve and dilated aortic arch.

No other variants in 15 known EDS-related genes were identified in the index individual. Sanger sequencing confirmed this variants presence in the two other affected family members and its absence in an unaffected member.

Mouse knock-in of this variant demonstrated that mutant mice had hyper-flexibility of their tails and dramatically longer bleeding times when compared with wildtype mice.; Changed phenotypes: connective tissue disorder MONDO:0003900, THBS2-related
Intellectual disability syndromic and non-syndromic v0.5717 DIP2C Elena Savva Marked gene: DIP2C as ready
Intellectual disability syndromic and non-syndromic v0.5717 DIP2C Elena Savva Gene: dip2c has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5717 SLC12A9 Zornitza Stark Classified gene: SLC12A9 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5717 SLC12A9 Zornitza Stark Gene: slc12a9 has been classified as Green List (High Evidence).
Mendeliome v1.1591 APOLD1 Seb Lunke Marked gene: APOLD1 as ready
Mendeliome v1.1591 APOLD1 Seb Lunke Gene: apold1 has been classified as Amber List (Moderate Evidence).
Aortopathy_Connective Tissue Disorders v1.82 THBS2 Ain Roesley Classified gene: THBS2 as Amber List (moderate evidence)
Aortopathy_Connective Tissue Disorders v1.82 THBS2 Ain Roesley Gene: thbs2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5717 DIP2C Elena Savva Classified gene: DIP2C as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5717 DIP2C Elena Savva Gene: dip2c has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v1.82 THBS2 Ain Roesley Classified gene: THBS2 as Amber List (moderate evidence)
Aortopathy_Connective Tissue Disorders v1.82 THBS2 Ain Roesley Gene: thbs2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1591 TOGARAM2 Zornitza Stark Marked gene: TOGARAM2 as ready
Mendeliome v1.1591 TOGARAM2 Zornitza Stark Gene: togaram2 has been classified as Red List (Low Evidence).
Aortopathy_Connective Tissue Disorders v1.81 THBS2 Chris Ciotta commented on gene: THBS2: One family with autosomal dominant inheritance of a THBS2 missense variant (NM_003247.5:c.2686T>C p.Cys896Arg). The index patient in this family presented with a history of multiple joint dislocations, easy bruising, prolonged wound healing and a diagnosis of bilateral greater saphenous vein insufficiency.

This individual's mother who also carries the variant was noted as having prolonged bleeding, thickened mitral valve and dilated aortic arch.

No other variants in 15 known EDS-related genes were identified in the index individual. Sanger sequencing confirmed this variants presence in the two other affected family members and its absence in an unaffected member.

Mouse knock-in of this variant demonstrated that mutant mice had hyper-flexibility of their tails and dramatically longer bleeding times when compared with wildtype mice.
Intellectual disability syndromic and non-syndromic v0.5716 SLC12A9 Zornitza Stark Classified gene: SLC12A9 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5716 SLC12A9 Zornitza Stark Gene: slc12a9 has been classified as Green List (High Evidence).
Mendeliome v1.1591 APOLD1 Seb Lunke Classified gene: APOLD1 as Amber List (moderate evidence)
Mendeliome v1.1591 APOLD1 Seb Lunke Gene: apold1 has been classified as Amber List (Moderate Evidence).
Aortopathy_Connective Tissue Disorders v1.81 THBS2 Chris Ciotta commented on gene: THBS2: One family with autosomal dominant inheritance of a THBS2 missense variant (NM_003247.5:c.2686T>C p.Cys896Arg). The index patient in this family presented with a history of multiple joint dislocations, easy bruising, prolonged wound healing and a diagnosis of bilateral greater saphenous vein insufficiency.

This individual's mother who also carries the variant was noted as having prolonged bleeding, thickened mitral valve and dilated aortic arch.

No other variants in 15 known EDS-related genes were identified in the index individual. Sanger sequencing confirmed this variants presence in the two other affected family members and its absence in an unaffected member.

Mouse knock-in of this variant demonstrated that mutant mice had hyper-flexibility of their tails and dramatically longer bleeding times when compared with wildtype mice.
Mendeliome v1.1590 DIP2C Elena Savva Classified gene: DIP2C as Green List (high evidence)
Mendeliome v1.1590 DIP2C Elena Savva Gene: dip2c has been classified as Green List (High Evidence).
Mendeliome v1.1590 TOGARAM2 Zornitza Stark Classified gene: TOGARAM2 as Red List (low evidence)
Mendeliome v1.1590 TOGARAM2 Zornitza Stark Gene: togaram2 has been classified as Red List (Low Evidence).
Mendeliome v1.1589 UBAP1L Ee Ming Wong changed review comment from: - Twelve unrelated families with Hungary, the United States, Israel, Tunisia and the Netherlands with members presenting with autosomal recessive rod-cone or cone-rod dystrophy
- Reported variants included splice, nonsense, frameshift and in-frame del variants
- Age of disease onset was very variable, with some patients experiencing first symptoms during their fourth decade of life or later.
Sources: Literature; to: - Twelve unrelated families with Hungary, the United States, Israel, Tunisia and the Netherlands with members presenting with autosomal recessive rod-cone or cone-rod dystrophy
- Reported variants included splice, nonsense, frameshift and in-frame del variants
- Age of disease onset was very variable, with some patients experiencing first symptoms during their fourth decade of life or later.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5716 SNF8 Elena Savva Phenotypes for gene: SNF8 were changed from Neurodevelopmental disorder (MONDO:0700092), SNF8-related to Neurodevelopmental disorder (MONDO:0700092), SNF8-related
Aortopathy_Connective Tissue Disorders v1.81 THBS2 Chris Ciotta edited their review of gene: THBS2: Added comment: One family with autosomal dominant inheritance of a THBS2 missense variant (NM_003247.5:c.2686T>C p.Cys896Arg). The index patient in this family presented with a history of multiple joint dislocations, easy bruising, prolonged wound healing and a diagnosis of bilateral greater saphenous vein insufficiency.

This individual's mother who also carries the variant was noted as having prolonged bleeding, thickened mitral valve and dilated aortic arch.

No other variants in 15 known EDS-related genes were identified in the index individual. Sanger sequencing confirmed this variants presence in the two other affected family members and its absence in an unaffected member.

Mouse knock-in of this variant demonstrated that mutant mice had hyper-flexibility of their tails and dramatically longer bleeding times when compared with wildtype mice.; Changed phenotypes: connective tissue disorder MONDO:0003900
Mendeliome v1.1589 CORIN Daniel Flanagan reviewed gene: CORIN: Rating: RED; Mode of pathogenicity: None; Publications: 37913506, 15637153; Phenotypes: ?Cardiomyopathy, familial hypertrophic, 30, atrial (MIM:620734); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Muscular dystrophy and myopathy_Paediatric v1.13 SNUPN Seb Lunke Marked gene: SNUPN as ready
Muscular dystrophy and myopathy_Paediatric v1.13 SNUPN Seb Lunke Gene: snupn has been classified as Green List (High Evidence).
Mendeliome v1.1589 SNUPN Seb Lunke Marked gene: SNUPN as ready
Mendeliome v1.1589 SNUPN Seb Lunke Gene: snupn has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v1.81 THBS2 Ain Roesley Classified gene: THBS2 as Amber List (moderate evidence)
Aortopathy_Connective Tissue Disorders v1.81 THBS2 Ain Roesley Gene: thbs2 has been classified as Amber List (Moderate Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.27 SNUPN Seb Lunke Marked gene: SNUPN as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.27 SNUPN Seb Lunke Gene: snupn has been classified as Green List (High Evidence).
Bleeding and Platelet Disorders v1.28 APOLD1 Seb Lunke Marked gene: APOLD1 as ready
Bleeding and Platelet Disorders v1.28 APOLD1 Seb Lunke Gene: apold1 has been classified as Amber List (Moderate Evidence).
Atrial Fibrillation v1.2 CORIN Seb Lunke Marked gene: CORIN as ready
Atrial Fibrillation v1.2 CORIN Seb Lunke Gene: corin has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.5716 SLC12A9 Zornitza Stark Classified gene: SLC12A9 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5716 SLC12A9 Zornitza Stark Gene: slc12a9 has been classified as Green List (High Evidence).
Mendeliome v1.1589 TOGARAM2 Zornitza Stark Classified gene: TOGARAM2 as Red List (low evidence)
Mendeliome v1.1589 TOGARAM2 Zornitza Stark Gene: togaram2 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.5715 ZSCAN10 Rylee Peters gene: ZSCAN10 was added
gene: ZSCAN10 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: ZSCAN10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZSCAN10 were set to PMID: 38386308
Phenotypes for gene: ZSCAN10 were set to Syndromic disease MONDO:0002254
Review for gene: ZSCAN10 was set to GREEN
Added comment: Bi-allelic ZSCAN10 loss-of-function variants were identified in seven affected individuals from five unrelated families with syndromic neurodevelopmental disorder.

Highly consistent phenotypic features include global developmental delay, behavioural abnormalities, and variable facial asymmetry with outer and inner ear malformations leading to profound SNHL.

Facial asymmetry was recapitulated in the Zscan10 mouse model along with inner and outer ear malformations.
Sources: Literature
Atrial Fibrillation v1.2 CORIN Seb Lunke Classified gene: CORIN as Red List (low evidence)
Atrial Fibrillation v1.2 CORIN Seb Lunke Gene: corin has been classified as Red List (Low Evidence).
Muscular dystrophy and myopathy_Paediatric v1.13 SNUPN Seb Lunke Classified gene: SNUPN as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v1.13 SNUPN Seb Lunke Gene: snupn has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.27 SNUPN Seb Lunke Classified gene: SNUPN as Green List (high evidence)
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.27 SNUPN Seb Lunke Gene: snupn has been classified as Green List (High Evidence).
Mendeliome v1.1588 UBAP1L Ee Ming Wong gene: UBAP1L was added
gene: UBAP1L was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: UBAP1L was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: UBAP1L were set to PMID: 38293907; 38420906
Phenotypes for gene: UBAP1L were set to Cone-rod dystrophy (MONDO:0015993), UBAP1L-related
Review for gene: UBAP1L was set to GREEN
gene: UBAP1L was marked as current diagnostic
Added comment: - Twelve unrelated families with Hungary, the United States, Israel, Tunisia and the Netherlands with members presenting with autosomal recessive rod-cone or cone-rod dystrophy
- Reported variants included splice, nonsense, frameshift and in-frame del variants
- Age of disease onset was very variable, with some patients experiencing first symptoms during their fourth decade of life or later.
Sources: Literature
Bleeding and Platelet Disorders v1.28 APOLD1 Seb Lunke Classified gene: APOLD1 as Amber List (moderate evidence)
Bleeding and Platelet Disorders v1.28 APOLD1 Seb Lunke Gene: apold1 has been classified as Amber List (Moderate Evidence).
Deafness_Isolated v1.55 TOGARAM2 Zornitza Stark Marked gene: TOGARAM2 as ready
Deafness_Isolated v1.55 TOGARAM2 Zornitza Stark Gene: togaram2 has been classified as Red List (Low Evidence).
Aortopathy_Connective Tissue Disorders v1.81 THBS2 Ain Roesley Classified gene: THBS2 as Amber List (moderate evidence)
Aortopathy_Connective Tissue Disorders v1.81 THBS2 Ain Roesley Gene: thbs2 has been classified as Amber List (Moderate Evidence).
Deafness_Isolated v1.55 TOGARAM2 Zornitza Stark Classified gene: TOGARAM2 as Red List (low evidence)
Deafness_Isolated v1.55 TOGARAM2 Zornitza Stark Gene: togaram2 has been classified as Red List (Low Evidence).
Atrial Fibrillation v1.1 CORIN Daniel Flanagan gene: CORIN was added
gene: CORIN was added to Atrial Fibrillation. Sources: Expert list
Mode of inheritance for gene: CORIN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CORIN were set to 37913506; 15637153
Phenotypes for gene: CORIN were set to ?Cardiomyopathy, familial hypertrophic, 30, atrial (MIM:620734)
Review for gene: CORIN was set to RED
Added comment: Two siblings with a homozygous loss-of-function variant in CORIN. Both presented with left atrial hypertrophic cardiomyopathy, hypertension, fibrosis, and arrhythmia isolated to the left atrium. A plasma sample obtained from one of the siblings had no detectable levels of corin.

One sibling also had a het variant, p.(Ser571Thr), in PKP2 (associated with AD ARVC). The PKP2 variant is LP/VUS in ClinVar.

Cor-/- mice exhibit cardiac hypertrophy resulting in a mild decline in cardiac function later in life. Cor-/- mice also have spontaneous hypertension.
Sources: Expert list
Mendeliome v1.1588 SNUPN Seb Lunke Classified gene: SNUPN as Green List (high evidence)
Mendeliome v1.1588 SNUPN Seb Lunke Gene: snupn has been classified as Green List (High Evidence).
Mendeliome v1.1587 CELSR3 Crystle Lee gene: CELSR3 was added
gene: CELSR3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CELSR3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CELSR3 were set to PMID: 38429302
Phenotypes for gene: CELSR3 were set to Neurodevelopmental disorder (MONDO#0700092), CELSR3-related
Review for gene: CELSR3 was set to GREEN
Added comment: PMID: 38429302:12 affected individuals from 11 families reported with bi-allelic variants. Phenotype ranged from CNS anomalies (7/12), CNS and CAKUT (3/12) and CAKUT only (2/12). Only missense variants reported and 1 inframe variant. Functional studies done in zebrafish demonstrate similar structural anomalies of the developing pronephros and neuronal abnormalities to affected individuals

PMID: 34951123: 5 het missense variants reported in patients with febrile seizures (FS)/epilepsy. Arg3141Gln present in gnomAD (7 hets). No functional studies. Summarised as potentially associated with febrile seizures (FS)/epilepsy
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5715 SNF8 Elena Savva Phenotypes for gene: SNF8 were changed from Neurodevelopmental disorder (MONDO:0700092), SNF8-related to Neurodevelopmental disorder (MONDO:0700092), SNF8-related
Deafness_IsolatedAndComplex v1.172 ZSCAN10 Rylee Peters gene: ZSCAN10 was added
gene: ZSCAN10 was added to Deafness_IsolatedAndComplex. Sources: Literature
Mode of inheritance for gene: ZSCAN10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZSCAN10 were set to PMID: 38386308
Phenotypes for gene: ZSCAN10 were set to Syndromic disease MONDO:0002254
Review for gene: ZSCAN10 was set to GREEN
Added comment: Bi-allelic ZSCAN10 loss-of-function variants were identified in seven affected individuals from five unrelated families with syndromic neurodevelopmental disorder.

Highly consistent phenotypic features include global developmental delay, behavioural abnormalities, and variable facial asymmetry with outer and inner ear malformations leading to profound SNHL.

Facial asymmetry was recapitulated in the Zscan10 mouse model along with inner and outer ear malformations.
Sources: Literature
Cone-rod Dystrophy v0.54 UBAP1L Zornitza Stark Marked gene: UBAP1L as ready
Cone-rod Dystrophy v0.54 UBAP1L Zornitza Stark Gene: ubap1l has been classified as Green List (High Evidence).
Cone-rod Dystrophy v0.54 UBAP1L Zornitza Stark Classified gene: UBAP1L as Green List (high evidence)
Cone-rod Dystrophy v0.54 UBAP1L Zornitza Stark Gene: ubap1l has been classified as Green List (High Evidence).
Mendeliome v1.1587 APOLD1 Lucy Spencer changed review comment from: PMID: 35638551
1 family with an atypical inherited bleeding disorder characterised by severe spontaneous bleeding episodes in childhood and microcirculatory problems. 4 affected individuals across 2 generations have R49*in APOLD1, another affected individual from a third generation was not able to be sequenced = 4 meiosis. 4 unaffected individuals did not have the variant.

This gene has no NMD region, R49* would affect 82% of the protein. Paper is not using the MANE select transcript, alt p. in MANE select is R18* which affects 92% of the MANE select protein

Interestingly R49* is created by a delins/2 missense in cis, 1 common R49Q and 1 rare R49W, some UNaffected family members just have the common missense without the other in cis.

Immunofluorescence studies in patient platelets showed a 50% reduction of APOLD1 and disrupted cytoskeletal and junctional organization.
Sources: Literature; to: PMID: 35638551
1 family with an atypical inherited bleeding disorder characterised by severe spontaneous bleeding episodes in childhood and microcirculatory problems. 4 affected individuals across 2 generations have R49*in APOLD1, another affected individual from a third generation was not able to be sequenced = 4 meiosis. 4 unaffected individuals did not have the variant.

This gene has no NMD region, R49* would affect 82% of the protein. Paper is not using the MANE select transcript, alt p. in MANE select is R18* which affects 92% of the MANE select protein

Interestingly R49* is created by a delins/2 missense in cis, 1 common R49Q and 1 rare R49W, some UNaffected family members just have the common missense without the other in cis.

Immunofluorescence studies in patient platelets showed a 50% reduction of APOLD1 and disrupted cytoskeletal and junctional organization.

SiRNA silencing of APOLD1 in HBDEC cells resulted in altered cell shape and size, and were associated with endothelial cell junction dismantling. These cells were also almost devoid of VWF.
Sources: Literature
Bleeding and Platelet Disorders v1.27 APOLD1 Lucy Spencer changed review comment from: PMID: 35638551
1 family with an atypical inherited bleeding disorder characterised by severe spontaneous bleeding episodes in childhood and microcirculatory problems. 4 affected individuals across 2 generations have R49*in APOLD1, another affected individual from a third generation was not able to be sequenced = 4 meiosis. 4 unaffected individuals did not have the variant.

This gene has no NMD region, R49* would affect 82% of the protein. Paper is not using the MANE select transcript, alt p. in MANE select is R18* which affects 92% of the MANE select protein

Interestingly R49* is created by a delins/2 missense in cis, 1 common R49Q and 1 rare R49W, some UNaffected family members just have the common missense without the other in cis.

Immunofluorescence studies in patient platelets showed a 50% reduction of APOLD1 and disrupted cytoskeletal and junctional organization.
Sources: Literature; to: PMID: 35638551
1 family with an atypical inherited bleeding disorder characterised by severe spontaneous bleeding episodes in childhood and microcirculatory problems. 4 affected individuals across 2 generations have R49*in APOLD1, another affected individual from a third generation was not able to be sequenced = 4 meiosis. 4 unaffected individuals did not have the variant.

This gene has no NMD region, R49* would affect 82% of the protein. Paper is not using the MANE select transcript, alt p. in MANE select is R18* which affects 92% of the MANE select protein

Interestingly R49* is created by a delins/2 missense in cis, 1 common R49Q and 1 rare R49W, some UNaffected family members just have the common missense without the other in cis.

Immunofluorescence studies in patient platelets showed a 50% reduction of APOLD1 and disrupted cytoskeletal and junctional organization.

SiRNA silencing of APOLD1 in HBDEC cells resulted in altered cell shape and size, and were associated with endothelial cell junction dismantling. These cells were also almost devoid of VWF.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5715 SNF8 Elena Savva Phenotypes for gene: SNF8 were changed from Neurodevelopmental disorder (MONDO:0700092), SNF8-related to Neurodevelopmental disorder (MONDO:0700092), SNF8-related
Mendeliome v1.1587 ZSCAN10 Rylee Peters gene: ZSCAN10 was added
gene: ZSCAN10 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ZSCAN10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZSCAN10 were set to PMID: 38386308
Phenotypes for gene: ZSCAN10 were set to syndromic disease MONDO:0002254
Review for gene: ZSCAN10 was set to GREEN
Added comment: Bi-allelic ZSCAN10 loss-of-function variants were identified in seven affected individuals from five unrelated families with syndromic neurodevelopmental disorder.

Highly consistent phenotypic features include global developmental delay, behavioural abnormalities, and variable facial asymmetry with outer and inner ear malformations leading to profound SNHL.

Facial asymmetry was recapitulated in the Zscan10 mouse model along with inner and outer ear malformations.
Sources: Literature
Cone-rod Dystrophy v0.53 UBAP1L Ee Ming Wong gene: UBAP1L was added
gene: UBAP1L was added to Cone-rod Dystrophy. Sources: Literature
Mode of inheritance for gene: UBAP1L was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: UBAP1L were set to PMID: 38293907; 38420906
Phenotypes for gene: UBAP1L were set to Cone-rod dystrophy (MONDO:0015993), UBAP1L-related
Review for gene: UBAP1L was set to GREEN
gene: UBAP1L was marked as current diagnostic
Added comment: - Twelve unrelated families with Hungary, the United States, Israel, Tunisia and the Netherlands with members presenting with autosomal recessive rod-cone or cone-rod dystrophy
- Reported variants included splice, nonsense, frameshift and in-frame del variants
- Age of disease onset was very variable, with some patients experiencing first symptoms during their fourth decade of life or later.
Sources: Literature
Mendeliome v1.1587 SLC12A9 Zornitza Stark Marked gene: SLC12A9 as ready
Mendeliome v1.1587 SLC12A9 Zornitza Stark Gene: slc12a9 has been classified as Green List (High Evidence).
Mendeliome v1.1587 SLC12A9 Zornitza Stark Classified gene: SLC12A9 as Green List (high evidence)
Mendeliome v1.1587 SLC12A9 Zornitza Stark Gene: slc12a9 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5715 SNF8 Elena Savva Phenotypes for gene: SNF8 were changed from Severe developmental delay, epileptic encephalopathy, brain MRI abnormality; intellectual disability, childhood-onset optic atrophy, ataxia to Neurodevelopmental disorder (MONDO:0700092), SNF8-related
Genetic Epilepsy v0.2330 SNF8 Elena Savva Classified gene: SNF8 as Amber List (moderate evidence)
Genetic Epilepsy v0.2330 SNF8 Elena Savva Gene: snf8 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5715 POP1 Ain Roesley Publications for gene: POP1 were set to
Hypertrophic cardiomyopathy_HCM v0.177 CORIN Seb Lunke Marked gene: CORIN as ready
Hypertrophic cardiomyopathy_HCM v0.177 CORIN Seb Lunke Gene: corin has been classified as Red List (Low Evidence).
Mendeliome v1.1586 SNF8 Elena Savva Marked gene: SNF8 as ready
Mendeliome v1.1586 SNF8 Elena Savva Gene: snf8 has been classified as Green List (High Evidence).
Mendeliome v1.1586 SLC12A9 Zornitza Stark gene: SLC12A9 was added
gene: SLC12A9 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SLC12A9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC12A9 were set to 38334070
Phenotypes for gene: SLC12A9 were set to Neurodevelopmental disorder, MONDO:0700092, SLC12A9-related
Review for gene: SLC12A9 was set to GREEN
Added comment: Three individuals from unrelated families with bi-allelic LoF variants and a neurodevelopment phenotype, skeletal and brain abnormalities, hypopigmentation, dysmorphic features.
Sources: Literature
Callosome v0.518 SNF8 Elena Savva Phenotypes for gene: SNF8 were changed from Neurodevelopmental disorder (MONDO:0700092), SNF8-related to Neurodevelopmental disorder (MONDO:0700092), SNF8-related
Mendeliome v1.1586 SNF8 Elena Savva Classified gene: SNF8 as Green List (high evidence)
Mendeliome v1.1586 SNF8 Elena Savva Gene: snf8 has been classified as Green List (High Evidence).
Hypertrophic cardiomyopathy_HCM v0.177 CORIN Seb Lunke Classified gene: CORIN as Red List (low evidence)
Hypertrophic cardiomyopathy_HCM v0.177 CORIN Seb Lunke Gene: corin has been classified as Red List (Low Evidence).
Callosome v0.517 SNF8 Elena Savva Classified gene: SNF8 as Green List (high evidence)
Callosome v0.517 SNF8 Elena Savva Gene: snf8 has been classified as Green List (High Evidence).
Callosome v0.517 SNF8 Elena Savva Phenotypes for gene: SNF8 were changed from Severe developmental delay, epileptic encephalopathy, brain MRI abnormality; intellectual disability, childhood-onset optic atrophy, ataxia to Neurodevelopmental disorder (MONDO:0700092), SNF8-related
Muscular dystrophy and myopathy_Paediatric v1.12 TUBA4A Seb Lunke Classified gene: TUBA4A as Amber List (moderate evidence)
Muscular dystrophy and myopathy_Paediatric v1.12 TUBA4A Seb Lunke Gene: tuba4a has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5714 SLC12A9 Zornitza Stark gene: SLC12A9 was added
gene: SLC12A9 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: SLC12A9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC12A9 were set to 38334070
Phenotypes for gene: SLC12A9 were set to Neurodevelopmental disorder, MONDO:0700092, SLC12A9-related
Review for gene: SLC12A9 was set to GREEN
Added comment: Three individuals from unrelated families with bi-allelic LoF variants and a neurodevelopmental phenotype, skeletal abnormalities, brain abnormalities, hypopigmentation, dysmorphic features.
Sources: Literature
Genetic Epilepsy v0.2329 SNF8 Elena Savva Classified gene: SNF8 as Amber List (moderate evidence)
Genetic Epilepsy v0.2329 SNF8 Elena Savva Gene: snf8 has been classified as Amber List (Moderate Evidence).
Callosome v0.517 SNF8 Elena Savva Classified gene: SNF8 as Green List (high evidence)
Callosome v0.517 SNF8 Elena Savva Gene: snf8 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v1.12 TUBA4A Seb Lunke Marked gene: TUBA4A as ready
Muscular dystrophy and myopathy_Paediatric v1.12 TUBA4A Seb Lunke Gene: tuba4a has been classified as Amber List (Moderate Evidence).
Muscular dystrophy and myopathy_Paediatric v1.12 TUBA4A Seb Lunke Classified gene: TUBA4A as Amber List (moderate evidence)
Muscular dystrophy and myopathy_Paediatric v1.12 TUBA4A Seb Lunke Gene: tuba4a has been classified as Amber List (Moderate Evidence).
Callosome v0.516 SNF8 Elena Savva Marked gene: SNF8 as ready
Callosome v0.516 SNF8 Elena Savva Gene: snf8 has been removed from the panel.
Intellectual disability syndromic and non-syndromic v0.5714 SNF8 Elena Savva Marked gene: SNF8 as ready
Intellectual disability syndromic and non-syndromic v0.5714 SNF8 Elena Savva Gene: snf8 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5714 SNF8 Elena Savva Classified gene: SNF8 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5714 SNF8 Elena Savva Gene: snf8 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2329 SNF8 Elena Savva Classified gene: SNF8 as Amber List (moderate evidence)
Genetic Epilepsy v0.2329 SNF8 Elena Savva Gene: snf8 has been classified as Amber List (Moderate Evidence).
Optic Atrophy v1.30 SNF8 Elena Savva Marked gene: SNF8 as ready
Optic Atrophy v1.30 SNF8 Elena Savva Gene: snf8 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1585 SNF8 Chern Lim gene: SNF8 was added
gene: SNF8 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SNF8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SNF8 were set to 38423010
Phenotypes for gene: SNF8 were set to Neurodevelopmental disorder (MONDO:0700092), SNF8-related
Review for gene: SNF8 was set to GREEN
gene: SNF8 was marked as current diagnostic
Added comment: PMID: 38423010
- Nine individuals from six families presenting with a spectrum of neurodevelopmental/neurodegenerative features caused by bi-allelic variants in SNF8. In total, three putative LoF variants and four missense variants were identified.
- The phenotypic spectrum included four individuals with severe developmental and epileptic encephalopathy, massive reduction of white matter, hypo-/aplasia of the corpus callosum, neurodevelopmental arrest, and early death. A second cohort shows a milder phenotype with intellectual disability, childhood-onset optic atrophy, or ataxia. All mildly affected individuals shared the same hypomorphic variant, c.304G>A (p.Val102Ile) as compound heterozygous.
- Functional studies using fibroblasts derived from patients and zebrafish model showed LoF is the disease mech.
Sources: Literature
Aortopathy_Connective Tissue Disorders v1.80 THBS2 Chris Ciotta changed review comment from: One family with autosomal dominant inheritance of a THBS2 missense variant (NM_003247.5:c.2686T>C p.Cys896Arg). The index patient in this family presented with a history of multiple joint dislocations, easy bruising, prolonged wound healing and a diagnosis of bilateral greater saphenous vein insufficiency.

This individual's mother who also carries the variant was noted as having prolonged bleeding, thickened mitral valve and dilated aortic arch.

No other variants in 15 known EDS-related genes was identified in the index individual. Sanger sequencing confirmed this variants presence in the two other affected family members and its absence in an unaffected member.

Mouse knock-in of this variant demonstrated that mutant mice had hyper-flexibility of their tails and dramatically longer bleeding times when compared with wildtype mice.
Sources: Literature; to: One family with autosomal dominant inheritance of a THBS2 missense variant (NM_003247.5:c.2686T>C p.Cys896Arg). The index patient in this family presented with a history of multiple joint dislocations, easy bruising, prolonged wound healing and a diagnosis of bilateral greater saphenous vein insufficiency.

This individual's mother who also carries the variant was noted as having prolonged bleeding, thickened mitral valve and dilated aortic arch.

No other variants in 15 known EDS-related genes were identified in the index individual. Sanger sequencing confirmed this variants presence in the two other affected family members and its absence in an unaffected member.

Mouse knock-in of this variant demonstrated that mutant mice had hyper-flexibility of their tails and dramatically longer bleeding times when compared with wildtype mice.
Sources: Literature
Optic Atrophy v1.30 SNF8 Elena Savva Classified gene: SNF8 as Amber List (moderate evidence)
Optic Atrophy v1.30 SNF8 Elena Savva Gene: snf8 has been classified as Amber List (Moderate Evidence).
Aortopathy_Connective Tissue Disorders v1.80 THBS2 Chris Ciotta gene: THBS2 was added
gene: THBS2 was added to Aortopathy_Connective Tissue Disorders. Sources: Literature
Mode of inheritance for gene: THBS2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: THBS2 were set to PMID: 38433265
Phenotypes for gene: THBS2 were set to Ehlers-Danlos syndrome
Penetrance for gene: THBS2 were set to Complete
Review for gene: THBS2 was set to AMBER
Added comment: One family with autosomal dominant inheritance of a THBS2 missense variant (NM_003247.5:c.2686T>C p.Cys896Arg). The index patient in this family presented with a history of multiple joint dislocations, easy bruising, prolonged wound healing and a diagnosis of bilateral greater saphenous vein insufficiency.

This individual's mother who also carries the variant was noted as having prolonged bleeding, thickened mitral valve and dilated aortic arch.

No other variants in 15 known EDS-related genes was identified in the index individual. Sanger sequencing confirmed this variants presence in the two other affected family members and its absence in an unaffected member.

Mouse knock-in of this variant demonstrated that mutant mice had hyper-flexibility of their tails and dramatically longer bleeding times when compared with wildtype mice.
Sources: Literature
Genetic Epilepsy v0.2328 SNF8 Elena Savva Marked gene: SNF8 as ready
Genetic Epilepsy v0.2328 SNF8 Elena Savva Gene: snf8 has been removed from the panel.
Fetal anomalies v1.200 HSPG2 Ain Roesley Phenotypes for gene: HSPG2 were changed from Schwartz-Jampel syndrome, MONDO:0009717; Silverman-Handmaker type dyssegmental dysplasia, MONDO:0009140; Schwartz-Jampel syndrome, type 1, OMIM:255800; Dyssegmental dysplasia, Silverman-Handmaker type, OMIM:224410 to Dyssegmental dysplasia, Rolland-Desbuquois type (MONDO:0009139); Schwartz-Jampel syndrome, MONDO:0009717; Silverman-Handmaker type dyssegmental dysplasia, MONDO:0009140; Schwartz-Jampel syndrome, type 1, OMIM:255800; Dyssegmental dysplasia, Silverman-Handmaker type, OMIM:224410
Skeletal dysplasia v0.272 HSPG2 Ain Roesley Phenotypes for gene: HSPG2 were changed from Dyssegmental dysplasia, Silverman-Handmaker type 224410; Schwartz-Jampel syndrome, type 1 255800 to Dyssegmental dysplasia, Rolland-Desbuquois type (MONDO:0009139); Dyssegmental dysplasia, Silverman-Handmaker type 224410; Schwartz-Jampel syndrome, type 1 255800
Mendeliome v1.1585 TUBA4A Seb Lunke Marked gene: TUBA4A as ready
Mendeliome v1.1585 TUBA4A Seb Lunke Gene: tuba4a has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.199 HSPG2 Ain Roesley Publications for gene: HSPG2 were set to
Mendeliome v1.1585 TUBA4A Seb Lunke Classified gene: TUBA4A as Amber List (moderate evidence)
Mendeliome v1.1585 TUBA4A Seb Lunke Gene: tuba4a has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v0.272 HSPG2 Ain Roesley Publications for gene: HSPG2 were set to
Skeletal Dysplasia_Fetal v0.219 HSPG2 Ain Roesley Publications for gene: HSPG2 were set to
Fetal anomalies v1.198 HSPG2 Dean Phelan reviewed gene: HSPG2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38424183; Phenotypes: Dyssegmental dysplasia, Rolland-Desbuquois type (MONDO:0009139); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Optic Atrophy v1.29 SNF8 Chern Lim gene: SNF8 was added
gene: SNF8 was added to Optic Atrophy. Sources: Literature
Mode of inheritance for gene: SNF8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SNF8 were set to 38423010
Phenotypes for gene: SNF8 were set to Neurodevelopmental disorder (MONDO:0700092), SNF8-related
Review for gene: SNF8 was set to AMBER
gene: SNF8 was marked as current diagnostic
Added comment: PMID: 38423010
- Nine individuals from six families presenting with a spectrum of neurodevelopmental/neurodegenerative features caused by bi-allelic variants in SNF8. In total, three putative LoF variants and four missense variants were identified.
- The phenotypic spectrum included four individuals with severe developmental and epileptic encephalopathy, massive reduction of white matter, hypo-/aplasia of the corpus callosum, neurodevelopmental arrest, and early death. A second cohort shows a milder phenotype with intellectual disability, childhood-onset optic atrophy, or ataxia. All mildly affected individuals shared the same hypomorphic variant, c.304G>A (p.Val102Ile) as compound heterozygous.
- Three of the patients (from two families) with the milder phenotype also have optic atrophy.

- Functional studies using fibroblasts derived from patients and zebrafish model showed LoF is the disease mech.
Sources: Literature
Skeletal dysplasia v0.271 HSPG2 Dean Phelan reviewed gene: HSPG2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38424183; Phenotypes: Dyssegmental dysplasia, Rolland-Desbuquois type (MONDO:0009139); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal Dysplasia_Fetal v0.218 HSPG2 Ain Roesley Phenotypes for gene: HSPG2 were changed from to Schwartz-Jampel syndrome, type 1, MIM#255800; Dyssegmental dysplasia, Silverman-Handmaker type, MIM# 224410; Dyssegmental dysplasia, Rolland-Desbuquois type (MONDO:0009139)
Genetic Epilepsy v0.2328 SNF8 Chern Lim gene: SNF8 was added
gene: SNF8 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: SNF8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SNF8 were set to 38423010
Phenotypes for gene: SNF8 were set to Neurodevelopmental disorder (MONDO:0700092), SNF8-related
Review for gene: SNF8 was set to AMBER
gene: SNF8 was marked as current diagnostic
Added comment: PMID: 38423010
- Nine individuals from six families presenting with a spectrum of neurodevelopmental/neurodegenerative features caused by bi-allelic variants in SNF8. In total, three putative LoF variants and four missense variants were identified.
- The phenotypic spectrum included four individuals with severe developmental and epileptic encephalopathy, massive reduction of white matter, hypo-/aplasia of the corpus callosum, neurodevelopmental arrest, and early death. A second cohort shows a milder phenotype with intellectual disability, childhood-onset optic atrophy, or ataxia. All mildly affected individuals shared the same hypomorphic variant, c.304G>A (p.Val102Ile) as compound heterozygous.
- Two of the patients also had seizures.

- Functional studies using fibroblasts derived from patients and zebrafish model showed LoF is the disease mech.
Sources: Literature
Mendeliome v1.1584 HSPG2 Dean Phelan reviewed gene: HSPG2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38424183; Phenotypes: Dyssegmental dysplasia, Rolland-Desbuquois type (MONDO:0009139); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hypertrophic cardiomyopathy_HCM v0.176 CORIN Daniel Flanagan gene: CORIN was added
gene: CORIN was added to Hypertrophic cardiomyopathy_HCM. Sources: Expert list
Mode of inheritance for gene: CORIN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CORIN were set to 37913506; 15637153
Phenotypes for gene: CORIN were set to ?Cardiomyopathy, familial hypertrophic, 30, atrial (MIM:620734)
Review for gene: CORIN was set to RED
Added comment: Two siblings with a homozygous loss-of-function variant in CORIN. Both presented with left atrial hypertrophic cardiomyopathy, hypertension, fibrosis, and arrhythmia isolated to the left atrium. A plasma sample obtained from one of the siblings had no detectable levels of corin.

One sibling also had a het variant, p.(Ser571Thr), in PKP2 (associated with AD ARVC). The PKP2 variant is LP/VUS in ClinVar.

Cor-/- mice exhibit cardiac hypertrophy resulting in a mild decline in cardiac function later in life. Cor-/- mice also have spontaneous hypertension.
Sources: Expert list
Mendeliome v1.1584 SNUPN Suliman Khan gene: SNUPN was added
gene: SNUPN was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SNUPN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SNUPN were set to PMID: 38413582; PMID: 38366623
Phenotypes for gene: SNUPN were set to autosomal recessive limb-girdle muscular dystrophy MONDO:0015152
Review for gene: SNUPN was set to GREEN
Added comment: PMID: 38413582: reported 18 children from 15 unrelated families with muscular phenotypes, including proximal upper limb weakness, distal upper and lower limb weakness, and myopathy (EMG) with elevated serum creatinine kinase level. Exome sequencing revealed nine hypomorphic biallelic variants in the SNUPN gene, predominantly clustered in the last coding exon. Functional studies showed that mutant SPN1 failed to oligomerize leading to cytoplasmic aggregation in patients’ primary fibroblasts.

PMID: 38366623: reported five individuals from two unrelated families with limb-girdle muscular dystrophy.
Sources: Literature
Mendeliome v1.1584 APOLD1 Lucy Spencer gene: APOLD1 was added
gene: APOLD1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: APOLD1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: APOLD1 were set to 35638551
Phenotypes for gene: APOLD1 were set to Bleeding disorder, vascular-type (MIM#620715)
Review for gene: APOLD1 was set to AMBER
Added comment: PMID: 35638551
1 family with an atypical inherited bleeding disorder characterised by severe spontaneous bleeding episodes in childhood and microcirculatory problems. 4 affected individuals across 2 generations have R49*in APOLD1, another affected individual from a third generation was not able to be sequenced = 4 meiosis. 4 unaffected individuals did not have the variant.

This gene has no NMD region, R49* would affect 82% of the protein. Paper is not using the MANE select transcript, alt p. in MANE select is R18* which affects 92% of the MANE select protein

Interestingly R49* is created by a delins/2 missense in cis, 1 common R49Q and 1 rare R49W, some UNaffected family members just have the common missense without the other in cis.

Immunofluorescence studies in patient platelets showed a 50% reduction of APOLD1 and disrupted cytoskeletal and junctional organization.
Sources: Literature
Callosome v0.516 SNF8 Chern Lim edited their review of gene: SNF8: Changed phenotypes: Neurodevelopmental disorder (MONDO:0700092), SNF8-related
Intellectual disability syndromic and non-syndromic v0.5713 SNF8 Chern Lim edited their review of gene: SNF8: Changed phenotypes: Neurodevelopmental disorder (MONDO:0700092), SNF8-related
Mendeliome v1.1584 RGS6 Seb Lunke Marked gene: RGS6 as ready
Mendeliome v1.1584 RGS6 Seb Lunke Gene: rgs6 has been classified as Red List (Low Evidence).
Mendeliome v1.1584 RGS6 Seb Lunke gene: RGS6 was added
gene: RGS6 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RGS6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RGS6 were set to 38332109; 25525169
Phenotypes for gene: RGS6 were set to Cataract,MONDO:0005129; intellectual disability, MONDO:0001071; microcephaly, MONDO:0001149
Review for gene: RGS6 was set to RED
Added comment: Original paper from 2015 describes single consanguineous with two siblings affected by cataract, developmental delay, and microcephaly >3SD. A homozygous canonical splice variant predicted to lead to NMD in RGS6 was identified by WGS and linkage (rather than full WGS analysis). The 2024 paper speculates that the phenotype is driven by a change in RGS6 isoform balance rather than LoF using a knock-out mouse model. It is noted that the mice did not have microcephaly, and ID was assessed using social interaction. No mention of cataract in the mice.
Sources: Literature
Bleeding and Platelet Disorders v1.27 APOLD1 Lucy Spencer gene: APOLD1 was added
gene: APOLD1 was added to Bleeding and Platelet Disorders. Sources: Literature
Mode of inheritance for gene: APOLD1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: APOLD1 were set to 35638551
Phenotypes for gene: APOLD1 were set to Bleeding disorder, vascular-type (MIM#620715)
Review for gene: APOLD1 was set to AMBER
Added comment: PMID: 35638551
1 family with an atypical inherited bleeding disorder characterised by severe spontaneous bleeding episodes in childhood and microcirculatory problems. 4 affected individuals across 2 generations have R49*in APOLD1, another affected individual from a third generation was not able to be sequenced = 4 meiosis. 4 unaffected individuals did not have the variant.

This gene has no NMD region, R49* would affect 82% of the protein. Paper is not using the MANE select transcript, alt p. in MANE select is R18* which affects 92% of the MANE select protein

Interestingly R49* is created by a delins/2 missense in cis, 1 common R49Q and 1 rare R49W, some UNaffected family members just have the common missense without the other in cis.

Immunofluorescence studies in patient platelets showed a 50% reduction of APOLD1 and disrupted cytoskeletal and junctional organization.
Sources: Literature
Skeletal Dysplasia_Fetal v0.217 HSPG2 Ain Roesley Marked gene: HSPG2 as ready
Skeletal Dysplasia_Fetal v0.217 HSPG2 Ain Roesley Gene: hspg2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5713 DIP2C Melanie Marty gene: DIP2C was added
gene: DIP2C was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: DIP2C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DIP2C were set to PMID: 38421105
Phenotypes for gene: DIP2C were set to Neurodevelopmental disorder (MONDO#0700092), DIP2C-related
Review for gene: DIP2C was set to GREEN
Added comment: PMID: 38421105 - Twenty three patients with het DIP2C variants (10 de novo).
All patients had developmental delays affecting expressive language and speech, most had mild dev delay and ID. Four patients had seizures. Additional phenotypic findings were non-specific but recurrent anomalies did include a high anterior hair-line, prominent forehead, and a broad nasal tip. Four patients had cardiac defects (hypertrophic cardiomyopathy, atrial septal defects,and bicuspid aortic valve)
Sources: Literature
Cataract v0.362 RGS6 Seb Lunke Marked gene: RGS6 as ready
Cataract v0.362 RGS6 Seb Lunke Gene: rgs6 has been classified as Red List (Low Evidence).
Mendeliome v1.1583 TOGARAM2 Naomi Baker gene: TOGARAM2 was added
gene: TOGARAM2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TOGARAM2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TOGARAM2 were set to PMID:38374469
Phenotypes for gene: TOGARAM2 were set to Nonsyndromic genetic hearing loss (MONDO:0019497), TOGARAM2-related
Review for gene: TOGARAM2 was set to RED
Added comment: Paper reports one individual with bilateral profound hearing loss with a homozygous TOGARAM2 nonsense variant and demonstrated reduced mRNA expression in transfected cells.
Sources: Literature
Cataract v0.362 RGS6 Seb Lunke gene: RGS6 was added
gene: RGS6 was added to Cataract. Sources: Literature
Mode of inheritance for gene: RGS6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RGS6 were set to 38332109; 25525169
Phenotypes for gene: RGS6 were set to Cataract,MONDO:0005129; intellectual disability, MONDO:0001071; microcephaly, MONDO:0001149
Review for gene: RGS6 was set to RED
Added comment: Original paper from 2015 describes single consanguineous with two siblings affected by cataract, developmental delay, and microcephaly >3SD. A homozygous canonical splice variant predicted to lead to NMD in RGS6 was identified by WGS and linkage (rather than full WGS analysis). The 2024 paper speculates that the phenotype is driven by a change in RGS6 isoform balance rather than LoF using a knock-out mouse model. It is noted that the mice did not have microcephaly, and ID was assessed using social interaction. No mention of cataract in the mice.
Sources: Literature
Muscular dystrophy and myopathy_Paediatric v1.11 SNUPN Suliman Khan gene: SNUPN was added
gene: SNUPN was added to Muscular dystrophy and myopathy_Paediatric. Sources: Literature
Mode of inheritance for gene: SNUPN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SNUPN were set to PMID: 38413582; PMID: 38366623
Phenotypes for gene: SNUPN were set to autosomal recessive limb-girdle muscular dystrophy MONDO:0015152
Penetrance for gene: SNUPN were set to unknown
Added comment: PMID: 38413582: reported 18 children from 15 unrelated families with muscular phenotypes, including proximal upper limb weakness, distal upper and lower limb weakness, and myopathy (EMG) with elevated serum creatinine kinase level. Exome sequencing revealed nine hypomorphic biallelic variants in the SNUPN gene, predominantly clustered in the last coding exon. Functional studies showed that mutant SPN1 failed to oligomerize leading to cytoplasmic aggregation in patients’ primary fibroblasts.

PMID: 38366623: reported five individuals from two unrelated families with limb-girdle muscular dystrophy.
Sources: Literature
Mendeliome v1.1583 DIP2C Melanie Marty gene: DIP2C was added
gene: DIP2C was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: DIP2C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DIP2C were set to PMID: 38421105
Phenotypes for gene: DIP2C were set to Neurodevelopmental disorder (MONDO#0700092), DIP2C-related
Review for gene: DIP2C was set to GREEN
Added comment: PMID: 38421105 - Twenty three patients with het DIP2C variants (10 de novo).
All patients had developmental delays affecting expressive language and speech, most had mild dev delay and ID. Four patients had seizures. Additional phenotypic findings were non-specific but recurrent anomalies did include a high anterior hair-line, prominent forehead, and a broad nasal tip. Four patients had cardiac defects (hypertrophic cardiomyopathy, atrial septal defects,and bicuspid aortic valve)
Sources: Literature
Microcephaly v1.249 RGS6 Seb Lunke Marked gene: RGS6 as ready
Microcephaly v1.249 RGS6 Seb Lunke Gene: rgs6 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.5713 DENND5B Elena Savva Publications for gene: DENND5B were set to
Microcephaly v1.249 RGS6 Seb Lunke gene: RGS6 was added
gene: RGS6 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: RGS6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RGS6 were set to 38332109; 25525169
Phenotypes for gene: RGS6 were set to Cataract,MONDO:0005129; intellectual disability, MONDO:0001071; microcephaly, MONDO:0001149
Review for gene: RGS6 was set to RED
Added comment: Original paper from 2015 describes single consanguineous with two siblings affected by cataract, developmental delay, and microcephaly >3SD. A homozygous canonical splice variant predicted to lead to NMD in RGS6 was identified by WGS and linkage (rather than full WGS analysis). The 2024 paper speculates that the phenotype is driven by a change in RGS6 isoform balance rather than LoF using a knock-out mouse model. It is noted that the mice did not have microcephaly, and ID was assessed using social interaction. No mention of cataract in the mice.
Sources: Literature
Deafness_Isolated v1.54 TOGARAM2 Naomi Baker gene: TOGARAM2 was added
gene: TOGARAM2 was added to Deafness_Isolated. Sources: Literature
Mode of inheritance for gene: TOGARAM2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TOGARAM2 were set to PMID:38374469
Phenotypes for gene: TOGARAM2 were set to Nonsyndromic genetic hearing loss (MONDO:0019497), TOGARAM2-related
Review for gene: TOGARAM2 was set to RED
Added comment: Paper reports one individual with bilateral profound hearing loss with a homozygous TOGARAM2 nonsense variant and demonstrated reduced mRNA expression in transfected cells.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5713 DENND5B Elena Savva Mode of pathogenicity for gene: DENND5B was changed from None to None
Leukodystrophy - paediatric v0.306 DENND5B Elena Savva Publications for gene: DENND5B were set to
Mendeliome v1.1583 NIT1 Ain Roesley Marked gene: NIT1 as ready
Mendeliome v1.1583 NIT1 Ain Roesley Gene: nit1 has been classified as Green List (High Evidence).
Mendeliome v1.1583 NIT1 Zornitza Stark Marked gene: NIT1 as ready
Mendeliome v1.1583 NIT1 Zornitza Stark Gene: nit1 has been classified as Green List (High Evidence).
Mendeliome v1.1583 NIT1 Ain Roesley Classified gene: NIT1 as Green List (high evidence)
Mendeliome v1.1583 NIT1 Ain Roesley Gene: nit1 has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.26 SNUPN Suliman Khan gene: SNUPN was added
gene: SNUPN was added to Limb-Girdle Muscular Dystrophy and Distal Myopathy. Sources: Literature
Mode of inheritance for gene: SNUPN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SNUPN were set to PMID: 38413582; PMID: 38366623
Phenotypes for gene: SNUPN were set to autosomal recessive limb-girdle muscular dystrophy MONDO:0015152
Penetrance for gene: SNUPN were set to unknown
Review for gene: SNUPN was set to GREEN
Added comment: PMID: 38413582: reported 18 children from 15 unrelated families with muscular phenotypes, including proximal upper limb weakness, distal upper and lower limb weakness, and myopathy (EMG) with elevated serum creatinine kinase level. Exome sequencing revealed nine hypomorphic biallelic variants in the SNUPN gene, predominantly clustered in the last coding exon. Functional studies showed that mutant SPN1 failed to oligomerize leading to cytoplasmic aggregation in patients’ primary fibroblasts.

PMID: 38366623: reported five individuals from two unrelated families with limb-girdle muscular dystrophy.
Sources: Literature
Mendeliome v1.1582 NIT1 Zornitza Stark Classified gene: NIT1 as Green List (high evidence)
Mendeliome v1.1582 NIT1 Zornitza Stark Gene: nit1 has been classified as Green List (High Evidence).
Callosome v0.516 SNF8 Chern Lim gene: SNF8 was added
gene: SNF8 was added to Callosome. Sources: Literature
Mode of inheritance for gene: SNF8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SNF8 were set to 38423010
Phenotypes for gene: SNF8 were set to Severe developmental delay, epileptic encephalopathy, brain MRI abnormality; intellectual disability, childhood-onset optic atrophy, ataxia
Review for gene: SNF8 was set to GREEN
gene: SNF8 was marked as current diagnostic
Added comment: PMID: 38423010
- Nine individuals from six families presenting with a spectrum of neurodevelopmental/neurodegenerative features caused by bi-allelic variants in SNF8. In total, three putative LoF variants and four missense variants were identified.
- The phenotypic spectrum included four individuals with severe developmental and epileptic encephalopathy, massive reduction of white matter, hypo-/aplasia of the corpus callosum, neurodevelopmental arrest, and early death. A second cohort shows a milder phenotype with intellectual disability, childhood-onset optic atrophy, or ataxia. All mildly affected individuals shared the same hypomorphic variant, c.304G>A (p.Val102Ile) as compound heterozygous.
- Functional studies using fibroblasts derived from patients and zebrafish model showed LoF is the disease mech.
Sources: Literature
Mendeliome v1.1581 NIT1 Paul De Fazio edited their review of gene: NIT1: Changed rating: GREEN
Mendeliome v1.1581 TUBA4A Sarah Pantaleo gene: TUBA4A was added
gene: TUBA4A was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TUBA4A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TUBA4A were set to PMID: 38413182
Phenotypes for gene: TUBA4A were set to Congenital myopathy MONDO:0019952
Review for gene: TUBA4A was set to AMBER
Added comment: One novel TUBA4A variant in two unrelated Chinese patients with sporadic congenital myopathy.

Identified candidate genes using laser capture micro dissection, proteomics, WES, clinical data, myopathological changes, electrophysiological exams and thigh muscle MRIs.

The variant is de novo in both patients, c.679C>T, p.(Leu227Phe). The prominent myopathological changes in both patients were muscle fibres with focal myofibrillar disorganisation and rimmed vacuoles. Immunofluorescence showed ubiqution-positive TUBA4A protein aggregates in the muscle fibres with rimmed vacuoles. Overexpression of Leu227Phe resulted in cytoplasmic aggregates which colocalised with ubiquitin in cellular model.

Patient 1 is 14yo and had delayed motor development milestones since infancy. Myopathic face, high-arched palate, waddling gait, winged scapula and muscle weakness in four limbs with lower extremities and proximal muscle more severely affected. Follow up at 14yo showed slight improvement in motor function compared with 3yo.

Patient 2 is 6yo and presented with motor retardation since birth. At 3yo, presented with mild ptosis and ophthalmoparesis, high-arched palate and muscle weakness involving both proximal and distal in all limbs.

No likely pathogenic variants in 116 other protein-encoding genes. Variants confirmed by Sanger sequencing and absent from gnomAD. ACMG predicts likely pathogenic classification.
Sources: Literature
Mendeliome v1.1581 DENND5B Elena Savva Publications for gene: DENND5B were set to
Intellectual disability syndromic and non-syndromic v0.5712 SNF8 Chern Lim gene: SNF8 was added
gene: SNF8 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: SNF8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SNF8 were set to 38423010
Phenotypes for gene: SNF8 were set to Severe developmental delay, epileptic encephalopathy, brain MRI abnormality; intellectual disability, childhood-onset optic atrophy, ataxia
Review for gene: SNF8 was set to GREEN
gene: SNF8 was marked as current diagnostic
Added comment: PMID: 38423010
- Nine individuals from six families presenting with a spectrum of neurodevelopmental/neurodegenerative features caused by bi-allelic variants in SNF8. In total, three putative LoF variants and four missense variants were identified.
- The phenotypic spectrum included four individuals with severe developmental and epileptic encephalopathy, massive reduction of white matter, hypo-/aplasia of the corpus callosum, neurodevelopmental arrest, and early death. A second cohort shows a milder phenotype with intellectual disability, childhood-onset optic atrophy, or ataxia. All mildly affected individuals shared the same hypomorphic variant, c.304G>A (p.Val102Ile) as compound heterozygous.
- Functional studies using fibroblasts derived from patients and zebrafish model showed LoF is the disease mech.
Sources: Literature
Mendeliome v1.1580 NIT1 Paul De Fazio gene: NIT1 was added
gene: NIT1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NIT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NIT1 were set to 38430071
Phenotypes for gene: NIT1 were set to Cerebrovascular disorder, NIT1-related (MONDO:0011057)
Penetrance for gene: NIT1 were set to unknown
gene: NIT1 was marked as current diagnostic
Added comment: 5 unrelated families reported with recessively inherited cerebral small vessel disease had compound hetereozygous or homozygous variants in NIT1. 1 family (3 siblings) had p.(Ala68*) in trans with p.(Arg243Trp), the remaining 4 families (1 individual each) were all homozygous for p.(Arg243Trp).

Patients presented in mid-adulthood with progressive movement disorders (e.g. dystonia, chorea, bradykinesia and tremor, gait disturbance, dysarthria) and had abnormal brain MRI findings (honeycomb appearance of the basal ganglia-thalamus complex, due to numerous strongly dilated PVS). 3 patients had non-lobar intracerebral hemorrhage. Slowly progressive cognitive decline was also a key feature.

Metabolic analysis in urine confirmed loss of NIT1 enzymatic function.

Note p.(Arg243Trp) has 1 homozygote in gnomAD v4, but permitted due to later presentation in reported patients.
Sources: Literature
Mendeliome v1.1580 DENND5B Elena Savva reviewed gene: DENND5B: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38387458; Phenotypes: Neurodevelopmental disorder (MONDO#0700092), DENND5B-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Muscular dystrophy and myopathy_Paediatric v1.11 TUBA4A Sarah Pantaleo gene: TUBA4A was added
gene: TUBA4A was added to Muscular dystrophy and myopathy_Paediatric. Sources: Literature
Mode of inheritance for gene: TUBA4A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TUBA4A were set to PMID: 38413182
Phenotypes for gene: TUBA4A were set to Congenital myopathy MONDO:0019952
Review for gene: TUBA4A was set to AMBER
Added comment: One novel TUBA4A variant in two unrelated Chinese patients with sporadic congenital myopathy.

Identified candidate genes using laser capture micro dissection, proteomics, WES, clinical data, myopathological changes, electrophysiological exams and thigh muscle MRIs.

The variant is de novo in both patients, c.679C>T, p.(Leu227Phe). The prominent myopathological changes in both patients were muscle fibres with focal myofibrillar disorganisation and rimmed vacuoles. Immunofluorescence showed ubiqution-positive TUBA4A protein aggregates in the muscle fibres with rimmed vacuoles. Overexpression of Leu227Phe resulted in cytoplasmic aggregates which colocalised with ubiquitin in cellular model.

Patient 1 is 14yo and had delayed motor development milestones since infancy. Myopathic face, high-arched palate, waddling gait, winged scapula and muscle weakness in four limbs with lower extremities and proximal muscle more severely affected. Follow up at 14yo showed slight improvement in motor function compared with 3yo.

Patient 2 is 6yo and presented with motor retardation since birth. At 3yo, presented with mild ptosis and ophthalmoparesis, high-arched palate and muscle weakness involving both proximal and distal in all limbs.

No likely pathogenic variants in 116 other protein-encoding genes. Variants confirmed by Sanger sequencing and absent from gnomAD. ACMG predicts likely pathogenic classification.
Sources: Literature
Dystonia - isolated/combined v1.37 NIT1 Ain Roesley Marked gene: NIT1 as ready
Dystonia - isolated/combined v1.37 NIT1 Ain Roesley Gene: nit1 has been classified as Green List (High Evidence).
Dystonia - isolated/combined v1.37 NIT1 Ain Roesley Classified gene: NIT1 as Green List (high evidence)
Dystonia - isolated/combined v1.37 NIT1 Ain Roesley Gene: nit1 has been classified as Green List (High Evidence).
Stroke v1.16 NIT1 Ain Roesley Marked gene: NIT1 as ready
Stroke v1.16 NIT1 Ain Roesley Gene: nit1 has been classified as Green List (High Evidence).
Stroke v1.16 NIT1 Ain Roesley Classified gene: NIT1 as Green List (high evidence)
Stroke v1.16 NIT1 Ain Roesley Gene: nit1 has been classified as Green List (High Evidence).
Dystonia - isolated/combined v1.36 NIT1 Paul De Fazio gene: NIT1 was added
gene: NIT1 was added to Dystonia - isolated/combined. Sources: Literature
Mode of inheritance for gene: NIT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NIT1 were set to 38430071
Phenotypes for gene: NIT1 were set to Cerebrovascular disorder, NIT1-related (MONDO:0011057)
Penetrance for gene: NIT1 were set to unknown
Review for gene: NIT1 was set to GREEN
gene: NIT1 was marked as current diagnostic
Added comment: 5 unrelated families reported with recessively inherited cerebral small vessel disease had compound hetereozygous or homozygous variants in NIT1. 1 family (3 siblings) had p.(Ala68*) in trans with p.(Arg243Trp), the remaining 4 families (1 individual each) were all homozygous for p.(Arg243Trp).

Patients presented in mid-adulthood with progressive movement disorders (e.g. dystonia, chorea, bradykinesia and tremor, gait disturbance, dysarthria) and had abnormal brain MRI findings. 3 patients had non-lobar intracerebral hemorrhage. Metabolic analysis in urine confirmed loss of NIT1 enzymatic function.

Note p.(Arg243Trp) has 1 homozygote in gnomAD v4, but permitted due to later presentation in reported patients.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5712 RREB1 Zornitza Stark Marked gene: RREB1 as ready
Intellectual disability syndromic and non-syndromic v0.5712 RREB1 Zornitza Stark Gene: rreb1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5712 RREB1 Zornitza Stark Classified gene: RREB1 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.5712 RREB1 Zornitza Stark Gene: rreb1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5711 POP1 Belinda Chong reviewed gene: POP1: Rating: AMBER; Mode of pathogenicity: None; Publications: 38351533; Phenotypes: Anauxetic dysplasia 2, MIM#617396; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Skeletal Dysplasia_Fetal v0.217 HSPG2 Dean Phelan reviewed gene: HSPG2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38424183; Phenotypes: Dyssegmental dysplasia, Rolland-Desbuquois type (MONDO:0009139); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5711 RREB1 Zornitza Stark gene: RREB1 was added
gene: RREB1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: RREB1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RREB1 were set to 32938917; 38332451
Phenotypes for gene: RREB1 were set to Rasopathy, MONDO:0021060, RREB1-related
Review for gene: RREB1 was set to AMBER
Added comment: PMID 32938917: Single individual reported with Noonan syndrome-like features and a deletion encompassing RREB1. Overlapping deletions in publicly reported databases examined, and RREB1 postulated to be the key gene. Rreb1 hemizygous mice display orbital hypertelorism and age dependent cardiac hypertrophy. RREB1 recruits SIN3A and KDM1A to an RRE in target promoters in human and murine cells to control histone H3K4 methylation of MAPK pathway genes. In summary, single well phenotyped individual with a CNV and experimental data to support gene-disease association.

PMID 38332451: de novo LoF variant in an individual with phenotype consistent with the previous reports.
Sources: Literature
Stroke v1.15 NIT1 Paul De Fazio gene: NIT1 was added
gene: NIT1 was added to Stroke. Sources: Literature
Mode of inheritance for gene: NIT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NIT1 were set to 38430071
Phenotypes for gene: NIT1 were set to Cerebrovascular disorder, NIT1-related (MONDO:0011057)
Penetrance for gene: NIT1 were set to unknown
Review for gene: NIT1 was set to GREEN
gene: NIT1 was marked as current diagnostic
Added comment: 5 unrelated families reported with recessively inherited cerebral small vessel disease had compound hetereozygous or homozygous variants in NIT1. 1 family (3 siblings) had p.(Ala68*) in trans with p.(Arg243Trp), the remaining 4 families (1 individual each) were all homozygous for p.(Arg243Trp).

Patients presented in mid-adulthood with progressive movement disorders (e.g. dystonia, chorea, bradykinesia and tremor, gait disturbance, dysarthria) and had abnormal brain MRI findings. 3 patients had non-lobar intracerebral hemorrhage. Metabolic analysis in urine confirmed loss of NIT1 enzymatic function.

Note p.(Arg243Trp) has 1 homozygote in gnomAD v4, but permitted due to later presentation in reported patients.
Sources: Literature
Rasopathy v0.102 RREB1 Zornitza Stark Phenotypes for gene: RREB1 were changed from Noonan syndrome-like disorder to Rasopathy, MONDO:0021060, RREB1-related
Rasopathy v0.101 RREB1 Zornitza Stark Publications for gene: RREB1 were set to 32938917
Intellectual disability syndromic and non-syndromic v0.5710 FEZF2 Ain Roesley Marked gene: FEZF2 as ready
Intellectual disability syndromic and non-syndromic v0.5710 FEZF2 Ain Roesley Gene: fezf2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5710 FEZF2 Ain Roesley Classified gene: FEZF2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5710 FEZF2 Ain Roesley Gene: fezf2 has been classified as Green List (High Evidence).
Rasopathy v0.100 RREB1 Zornitza Stark Classified gene: RREB1 as Amber List (moderate evidence)
Rasopathy v0.100 RREB1 Zornitza Stark Gene: rreb1 has been classified as Amber List (Moderate Evidence).
Rasopathy v0.99 RREB1 Zornitza Stark edited their review of gene: RREB1: Added comment: PMID 38332451: de novo LoF variant in an individual with phenotype consistent with the previous reports.; Changed rating: AMBER; Changed publications: 32938917, 38332451; Changed phenotypes: Rasopathy, MONDO:0021060, RREB1-related
Intellectual disability syndromic and non-syndromic v0.5709 FEZF2 Ain Roesley gene: FEZF2 was added
gene: FEZF2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: FEZF2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FEZF2 were set to 38425142
Phenotypes for gene: FEZF2 were set to neurodevelopmental disorder MONDO:0700092, FEZF2-related
Review for gene: FEZF2 was set to GREEN
gene: FEZF2 was marked as current diagnostic
Added comment: - 7 indiv but 1 has whole gene deletion and 6x SNV (4x PTCs and 2x same missense Arg344Cys)
- of the 6x SNV, 4x de novo + 1x from affected father
- all have ID/ASD
- 1x seizures
- 1x hypotonia
- 1x motor coordination disorder
- 2x enuresis after 7yo
Sources: Literature
Mendeliome v1.1580 FEZF2 Ain Roesley Marked gene: FEZF2 as ready
Mendeliome v1.1580 FEZF2 Ain Roesley Gene: fezf2 has been classified as Green List (High Evidence).
Mendeliome v1.1580 RREB1 Zornitza Stark Publications for gene: RREB1 were set to 32938917
Mendeliome v1.1580 FEZF2 Ain Roesley Classified gene: FEZF2 as Green List (high evidence)
Mendeliome v1.1580 FEZF2 Ain Roesley Gene: fezf2 has been classified as Green List (High Evidence).
Mendeliome v1.1579 RREB1 Zornitza Stark Classified gene: RREB1 as Amber List (moderate evidence)
Mendeliome v1.1579 RREB1 Zornitza Stark Gene: rreb1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1578 RREB1 Zornitza Stark edited their review of gene: RREB1: Added comment: PMID 38332451: de novo LoF variant in an individual with phenotype consistent with the previous reports.; Changed rating: AMBER; Changed publications: 32938917, 38332451; Changed phenotypes: Rasopathy, MONDO:0021060, RREB1-related
Mendeliome v1.1578 FEZF2 Ain Roesley gene: FEZF2 was added
gene: FEZF2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: FEZF2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FEZF2 were set to 38425142
Phenotypes for gene: FEZF2 were set to neurodevelopmental disorder MONDO:0700092, FEZF2-related
Review for gene: FEZF2 was set to GREEN
gene: FEZF2 was marked as current diagnostic
Added comment: - 7 indiv but 1 has whole gene deletion and 6x SNV (4x PTCs and 2x same missense Arg344Cys)
- of the 6x SNV, 4x de novo + 1x from affected father
- all have ID/ASD
- 1x seizures
- 1x hypotonia
- 1x motor coordination disorder
- 2x enuresis after 7yo
Sources: Literature
Mendeliome v1.1577 ZFX Zornitza Stark Marked gene: ZFX as ready
Mendeliome v1.1577 ZFX Zornitza Stark Gene: zfx has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5708 ZFX Zornitza Stark Phenotypes for gene: ZFX were changed from X-linked neurodevelopmental disorder with recurrent facial gestalt to Neurodevelopmental disorder, MONDO:0700092, ZFX-related
Mendeliome v1.1577 ZFX Zornitza Stark Classified gene: ZFX as Green List (high evidence)
Mendeliome v1.1577 ZFX Zornitza Stark Gene: zfx has been classified as Green List (High Evidence).
Mendeliome v1.1576 ZFX Zornitza Stark gene: ZFX was added
gene: ZFX was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ZFX was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: ZFX were set to 26350204; 26740508; 38325380
Phenotypes for gene: ZFX were set to Neurodevelopmental disorder, MONDO:0700092, ZFX-related
Review for gene: ZFX was set to GREEN
Added comment: A single ZFX variant has been associated with a neurodevelopmental disorder, that has a Rett syndrome-like phenotype disorder, in a 14 year old male. The ZFX variant was allelic with another X-linked variant in SHROOM4. These variants were inherited from the mother, who had random X inactivation pattern (PMID: 26740508).
PMID: 38325380 reports 11 ZFX variants in 18 subjects from 16 unrelated families (14 males and 4 females) with an X-linked neurodevelopmental disorder with recurrent facial gestalt. Seven variants were truncating and the remaining were missense variants within the Zinc finger array. In the pedigree of family 6 (figure 3, PMID: 38325380), it was apparent that there were female carriers of the ZFX variant (GRCh38 chrX: 24229396A>G, c.2438A>G, p.Tyr774Cys) with hyperparathyroidism and two affected males and one affected female, with the neurodevelopmental disorder. It appeared that skewed X-inactivation in the female carriers was responsible for the different phenotypic features. The association between ZFX variants and a novel neurodevelopmental disorder, was further supported by functional studies showing altered transcriptional activity in missense variants and altered behavior in a zebrafish loss-of-function model.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5707 ZFX Zornitza Stark Marked gene: ZFX as ready
Intellectual disability syndromic and non-syndromic v0.5707 ZFX Zornitza Stark Gene: zfx has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5707 ZFX Zornitza Stark Classified gene: ZFX as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5707 ZFX Zornitza Stark Gene: zfx has been classified as Green List (High Evidence).
Fetal anomalies v1.198 NARS Zornitza Stark reviewed gene: NARS: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with microcephaly, impaired language, and gait abnormalities, autosomal recessive, MIM# 619091; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Neuropathy - complex v1.10 NARS Zornitza Stark commented on gene: NARS: AR disorder: assessed as LIMITED by ClinGen (borderline MODERATE).
Intellectual disability syndromic and non-syndromic v0.5706 NARS Zornitza Stark commented on gene: NARS: AR disorder: assessed as LIMITED by ClinGen (borderline MODERATE).
Genetic Epilepsy v0.2328 NARS Zornitza Stark commented on gene: NARS: AR disorder: assessed as LIMITED by ClinGen (borderline MODERATE).
Microcephaly v1.248 NARS Zornitza Stark reviewed gene: NARS: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with microcephaly, impaired language, and gait abnormalities, autosomal recessive, MIM# 619091; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1575 NARS Zornitza Stark commented on gene: NARS: AR disorder: assessed as LIMITED by ClinGen (borderline MODERATE).
Deafness_Isolated v1.54 STX4 Zornitza Stark Phenotypes for gene: STX4 were changed from Non-syndromic genetic hearing loss, MONDO:0019497, STX4-related to Deafness, autosomal recessive 123, MIM# 620745
Mendeliome v1.1575 STX4 Zornitza Stark Phenotypes for gene: STX4 were changed from Non-syndromic genetic hearing loss, MONDO:0019497, STX4-related. to Deafness, autosomal recessive 123, MIM# 620745
Mendeliome v1.1574 DES Zornitza Stark Mode of inheritance for gene: DES was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Dystonia - complex v0.234 PAH Natalie Lim gene: PAH was added
gene: PAH was added to Dystonia - complex. Sources: Expert Review
Mode of inheritance for gene: PAH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PAH were set to PMID: 25614310, PMID: 15390012, PMID: 30369906
Phenotypes for gene: PAH were set to Phenylketonuria MIM#261600
Review for gene: PAH was set to GREEN
Added comment: Reports of parkinsonism and dystonia have been documented as delayed manifestations amongst PKU patients although rare.
Sources: Expert Review
Intellectual disability syndromic and non-syndromic v0.5706 ZFX Sarah Leigh gene: ZFX was added
gene: ZFX was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: ZFX was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: ZFX were set to 26350204; 26740508; 38325380
Phenotypes for gene: ZFX were set to X-linked neurodevelopmental disorder with recurrent facial gestalt
Review for gene: ZFX was set to GREEN
Added comment: To date, germline variants in ZFX have not been associated with a phenotype in OMIM or Gen2Phen.
A single ZFX variant has been associated with a neurodevelopmental disorder, that has a Rett syndrome-like phenotype disorder, in a 14 year old male. The ZFX variant was allelic with another X-linked variant in SHROOM4. These variants were inherited from the mother, who had random X inactivation pattern (PMID: 26740508).
PMID: 38325380 reports 11 ZFX variants in 18 subjects from 16 unrelated families (14 males and 4 females) with an X-linked neurodevelopmental disorder with recurrent facial gestalt. Seven variants were truncating and the remaining were missense variants within the Zinc finger array. In the pedigree of family 6 (figure 3, PMID: 38325380), it was apparent that there were female carriers of the ZFX variant (GRCh38 chrX: 24229396A>G, c.2438A>G, p.Tyr774Cys) with hyperparathyroidism and two affected males and one affected female, with the neurodevelopmental disorder. It appeared that skewed X-inactivation in the female carriers was responsible for the different phenotypic features. The association between ZFX variants and a novel neurodevelopmental disorder, was further supported by functional studies showing altered transcriptional activity in missense variants and altered behavior in a zebrafish loss-of-function model.
Sources: Literature
Inflammatory bowel disease v0.118 ELF4 Peter McNaughton gene: ELF4 was added
gene: ELF4 was added to Inflammatory bowel disease. Sources: Literature
Mode of inheritance for gene: ELF4 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: ELF4 were set to PMID: 38231408
Phenotypes for gene: ELF4 were set to Inflammatory bowel disease
Review for gene: ELF4 was set to GREEN
Added comment: Cohort of 14 patients from 13 families with many presenting with gastrointestinal inflammation and ulceration. Frequently patients had been labelled with IBD prior to diagnosis of ELF4.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5706 PI4K2A Zornitza Stark Phenotypes for gene: PI4K2A were changed from complex neurodevelopmental disorder with motor features, PI4K2A-related, MONDO:0100516 to Neurodevelopmental disorder with hyperkinetic movements, seizures and structural brain abnormalities, MIM# 620732
Genetic Epilepsy v0.2328 PI4K2A Zornitza Stark Phenotypes for gene: PI4K2A were changed from complex neurodevelopmental disorder with motor features, PI4K2A-related, MONDO:0100516 to Neurodevelopmental disorder with hyperkinetic movements, seizures and structural brain abnormalities, MIM# 620732
Mendeliome v1.1573 PI4K2A Zornitza Stark Phenotypes for gene: PI4K2A were changed from complex neurodevelopmental disorder with motor features, PI4K2A-related, MONDO:0100516; Cutis laxa, intellectual disability, movement disorder to Neurodevelopmental disorder with hyperkinetic movements, seizures and structural brain abnormalities, MIM# 620732; Cutis laxa, intellectual disability, movement disorder
Genetic Epilepsy v0.2327 ALDH3A2 Zornitza Stark Mode of inheritance for gene: ALDH3A2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Mendelian susceptibility to Immune Disorders v0.49 USP18 Peter McNaughton gene: USP18 was added
gene: USP18 was added to Mendelian susceptibility to Immune Disorders. Sources: Literature
Mode of inheritance for gene: USP18 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: USP18 were set to PMID: 35258551
Phenotypes for gene: USP18 were set to Susceptibility to mycobacterial disease
Review for gene: USP18 was set to AMBER
Added comment: Partial USP18 deficiency in three siblings from a consanguineous family from Morocco presented with localized fistulizing lymphadenopathies after BCG vaccination
Sources: Literature
Mendeliome v1.1572 KLF14 Bryony Thompson Marked gene: KLF14 as ready
Mendeliome v1.1572 KLF14 Bryony Thompson Gene: klf14 has been classified as Red List (Low Evidence).
Mendeliome v1.1572 KLF14 Bryony Thompson Classified gene: KLF14 as Red List (low evidence)
Mendeliome v1.1572 KLF14 Bryony Thompson Gene: klf14 has been classified as Red List (Low Evidence).
Mendeliome v1.1571 NOTCH2NL Bryony Thompson Tag STR tag was added to gene: NOTCH2NL.
Mendeliome v1.1571 NLRP12 Bryony Thompson Publications for gene: NLRP12 were set to 18230725; 21360512; 24064030; 27633793
Fetal anomalies v1.198 THSD1 Zornitza Stark Marked gene: THSD1 as ready
Fetal anomalies v1.198 THSD1 Zornitza Stark Gene: thsd1 has been classified as Green List (High Evidence).
Fetal anomalies v1.198 THSD1 Zornitza Stark Classified gene: THSD1 as Green List (high evidence)
Fetal anomalies v1.198 THSD1 Zornitza Stark Gene: thsd1 has been classified as Green List (High Evidence).
Fetal anomalies v1.197 THSD1 Zornitza Stark gene: THSD1 was added
gene: THSD1 was added to Fetal anomalies. Sources: Expert Review
Mode of inheritance for gene: THSD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: THSD1 were set to 33569873; 27895300
Phenotypes for gene: THSD1 were set to Lymphatic malformation 13, MIM# 620244
Review for gene: THSD1 was set to GREEN
Added comment: PMID: 33569873 - 1 fetus with a homozygous PTC and nonimmune hydrops fetalis (NIHF), congenital heart disease and hemangiomas. FHx of 1/3 triplets with severe hydrops fetalis, not sequenced.
- Paper reviews previous NIHF cases and reports another homozygous PTC in two families ( and a recurring homozygous missense (p.Cys206Tyr) in three families.


PMID: 27895300- Mouse model has hydrocephaly with poor perfusion.
Sources: Expert Review
Intellectual disability syndromic and non-syndromic v0.5705 CBL Hali Van Niel reviewed gene: CBL: Rating: GREEN; Mode of pathogenicity: None; Publications: 20694012, 20543203, 11315197; Phenotypes: CBL-related disorder MONDO:0013308; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5705 CACNA1A Hali Van Niel reviewed gene: CACNA1A: Rating: GREEN; Mode of pathogenicity: None; Publications: 27476654, 33985586; Phenotypes: developmental and epileptic encephalopathy, 42 MONDO:0014917; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5705 C12orf65 Hali Van Niel reviewed gene: C12orf65: Rating: GREEN; Mode of pathogenicity: None; Publications: 24284555, 20598281, 23188110, 24080142, PMID: 3479531; Phenotypes: hereditary spastic paraplegia 55 MONDO:0014020; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5705 BTD Hali Van Niel reviewed gene: BTD: Rating: GREEN; Mode of pathogenicity: None; Publications: 7550325, 9375914, 37751899, 32741581; Phenotypes: biotinidase deficiency MONDO:0009665; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5705 BSCL2 Hali Van Niel reviewed gene: BSCL2: Rating: GREEN; Mode of pathogenicity: None; Publications: 12362029, 26072926, 28916377; Phenotypes: congenital generalized lipodystrophy type 2 MONDO:0010020; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.1570 PCSK2 Bryony Thompson Classified gene: PCSK2 as Red List (low evidence)
Mendeliome v1.1570 PCSK2 Bryony Thompson Gene: pcsk2 has been classified as Red List (Low Evidence).
Maturity-onset Diabetes of the Young v1.17 RFX6 Bryony Thompson changed review comment from: At least 3 unrelated cases with heterozygous variants and a suspected diagnosis of MODY. Null mouse model demonstrates abnormal pancreatic islet cells.
Sources: Expert list; to: At least 3 unrelated cases with heterozygous variants and a suspected diagnosis of MODY. Expected to have reduced penetrance. Null mouse model demonstrates abnormal pancreatic islet cells.
Sources: Expert list
Maturity-onset Diabetes of the Young v1.17 RFX6 Bryony Thompson edited their review of gene: RFX6: Changed rating: GREEN
Maturity-onset Diabetes of the Young v1.17 RFX6 Bryony Thompson Classified gene: RFX6 as Green List (high evidence)
Maturity-onset Diabetes of the Young v1.17 RFX6 Bryony Thompson Gene: rfx6 has been classified as Green List (High Evidence).
Maturity-onset Diabetes of the Young v1.16 RFX6 Bryony Thompson Phenotypes for gene: RFX6 were changed from Maturity-onset diabetes of the young to maturity-onset diabetes of the young MONDO:0018911
Maturity-onset Diabetes of the Young v1.15 WFS1 Bryony Thompson Publications for gene: WFS1 were set to 27185633
Maturity-onset Diabetes of the Young v1.14 RFX6 Bryony Thompson Publications for gene: RFX6 were set to 20148032; 25048417; 27185633; 29026101; 31001871
Maturity-onset Diabetes of the Young v1.13 RFX6 Bryony Thompson Classified gene: RFX6 as Amber List (moderate evidence)
Maturity-onset Diabetes of the Young v1.13 RFX6 Bryony Thompson Gene: rfx6 has been classified as Amber List (Moderate Evidence).
Maturity-onset Diabetes of the Young v1.12 RFX6 Bryony Thompson edited their review of gene: RFX6: Added comment: PMID: 36208030 - a study using the UK Biobank comparing individuals with and without diabetes found heterozygous variants (mainly LoF) in RFX6 were ‘Inconclusive’ with being highly penetrant for diabetes (met one of two statistical criteria - met enrichment criteria & failed comparison to maximum credible allele frequency); Changed rating: AMBER; Changed publications: 20148032, 25048417, 27185633, 29026101, 31001871, 36208030
Intellectual disability syndromic and non-syndromic v0.5705 BCS1L Hali Van Niel reviewed gene: BCS1L: Rating: GREEN; Mode of pathogenicity: None; Publications: 9777342, 17314340, 11528392, 30582773, 30582773, 25914718; Phenotypes: Bjornstad syndrome MONDO:0009872; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5705 BCKDHB Hali Van Niel reviewed gene: BCKDHB: Rating: GREEN; Mode of pathogenicity: None; Publications: 7672509, 11509994, 14742428; Phenotypes: maple syrup urine disease type 1B MONDO:0023692; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5705 BCKDHA Hali Van Niel reviewed gene: BCKDHA: Rating: GREEN; Mode of pathogenicity: None; Publications: 7883996, 7672509, 34288399; Phenotypes: maple syrup urine disease type 1A MONDO:0023691; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5705 BBS2 Hali Van Niel reviewed gene: BBS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 11285252, 11567139; Phenotypes: Bardet-Biedl syndrome 2 MONDO:0014432; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5705 BBS12 Hali Van Niel reviewed gene: BBS12: Rating: GREEN; Mode of pathogenicity: None; Publications: 17160889, 20827784; Phenotypes: Bardet-Biedl syndrome 12 MONDO:0014440; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5705 BBS10 Hali Van Niel reviewed gene: BBS10: Rating: GREEN; Mode of pathogenicity: None; Publications: 16582908, 20805367, 27245532; Phenotypes: Phenotype: Bardet-Biedl syndrome 10 MONDO:0014438; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5705 BBS1 Hali Van Niel reviewed gene: BBS1: Rating: GREEN; Mode of pathogenicity: None; Publications: 12118255, 12677556, 12567324; Phenotypes: Bardet-Biedl syndrome 1 MONDO:0008854; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.1569 RFX6 Bryony Thompson Added comment: Comment on mode of inheritance: Mitchell-Riley syndrome is AR and MODY is AD
Mendeliome v1.1569 RFX6 Bryony Thompson Mode of inheritance for gene: RFX6 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Maturity-onset Diabetes of the Young v1.12 WFS1 Bryony Thompson Marked gene: WFS1 as ready
Maturity-onset Diabetes of the Young v1.12 WFS1 Bryony Thompson Gene: wfs1 has been classified as Red List (Low Evidence).
Maturity-onset Diabetes of the Young v1.12 WFS1 Bryony Thompson Classified gene: WFS1 as Red List (low evidence)
Maturity-onset Diabetes of the Young v1.12 WFS1 Bryony Thompson Gene: wfs1 has been classified as Red List (Low Evidence).
Maturity-onset Diabetes of the Young v1.11 WFS1 Bryony Thompson reviewed gene: WFS1: Rating: RED; Mode of pathogenicity: None; Publications: 30014265, 36208030; Phenotypes: maturity-onset diabetes of the young MONDO:0018911; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.1568 PPP2R2B Bryony Thompson Tag STR tag was added to gene: PPP2R2B.
Mendeliome v1.1568 SAMD12 Bryony Thompson Tag STR tag was added to gene: SAMD12.
Maturity-onset Diabetes of the Young v1.11 GATA6 Bryony Thompson Marked gene: GATA6 as ready
Maturity-onset Diabetes of the Young v1.11 GATA6 Bryony Thompson Gene: gata6 has been classified as Red List (Low Evidence).
Maturity-onset Diabetes of the Young v1.11 GATA6 Bryony Thompson Classified gene: GATA6 as Red List (low evidence)
Maturity-onset Diabetes of the Young v1.11 GATA6 Bryony Thompson Gene: gata6 has been classified as Red List (Low Evidence).
Monogenic Diabetes v0.50 APPL1 Bryony Thompson Publications for gene: APPL1 were set to 26073777
Monogenic Diabetes v0.49 APPL1 Bryony Thompson Classified gene: APPL1 as Red List (low evidence)
Monogenic Diabetes v0.49 APPL1 Bryony Thompson Gene: appl1 has been classified as Red List (Low Evidence).
Monogenic Diabetes v0.48 APPL1 Bryony Thompson Deleted their comment
Monogenic Diabetes v0.48 APPL1 Bryony Thompson edited their review of gene: APPL1: Added comment: PMID: 36208030 - a study using the UK Biobank comparing individuals with and without diabetes found LoF variants in APPL1 were ‘Inconsistent’ with being high penetrant for diabetes (failed both statistical criteria - enrichment & comparison to maximum credible allele frequency). Refutes previous study.; Changed rating: RED; Changed publications: 26073777, 36208030
Mendeliome v1.1568 APPL1 Bryony Thompson Publications for gene: APPL1 were set to 26073777
Maturity-onset Diabetes of the Young v1.10 APPL1 Bryony Thompson Deleted their comment
Mendeliome v1.1567 APPL1 Bryony Thompson Classified gene: APPL1 as Red List (low evidence)
Mendeliome v1.1567 APPL1 Bryony Thompson Gene: appl1 has been classified as Red List (Low Evidence).
Mendeliome v1.1566 APPL1 Bryony Thompson Deleted their comment
Mendeliome v1.1566 APPL1 Bryony Thompson edited their review of gene: APPL1: Added comment: PMID: 36208030 - a study using the UK Biobank comparing individuals with and without diabetes found LoF variants in APPL1 were ‘Inconsistent’ with being high penetrant for diabetes (failed both statistical criteria - enrichment & comparison to maximum credible allele frequency). Refutes previous study.; Changed rating: RED; Changed publications: 26073777, 36208030
Maturity-onset Diabetes of the Young v1.10 APPL1 Bryony Thompson Marked gene: APPL1 as ready
Maturity-onset Diabetes of the Young v1.10 APPL1 Bryony Thompson Gene: appl1 has been classified as Red List (Low Evidence).
Maturity-onset Diabetes of the Young v1.10 APPL1 Bryony Thompson Publications for gene: APPL1 were set to 26073777
Maturity-onset Diabetes of the Young v1.9 APPL1 Bryony Thompson Classified gene: APPL1 as Red List (low evidence)
Maturity-onset Diabetes of the Young v1.9 APPL1 Bryony Thompson Gene: appl1 has been classified as Red List (Low Evidence).
Maturity-onset Diabetes of the Young v1.8 APPL1 Bryony Thompson edited their review of gene: APPL1: Added comment: PMID: 36208030 - a study using the UK Biobank comparing individuals with and without diabetes found LoF variants in APPL1 were ‘Inconsistent’ with being high penetrant for diabetes (failed both statistical criteria - enrichment & comparison to maximum credible allele frequency). Refutes previous study.; Changed rating: RED; Changed publications: 26073777, 36208030
Monogenic Diabetes v0.48 KLF11 Bryony Thompson Marked gene: KLF11 as ready
Monogenic Diabetes v0.48 KLF11 Bryony Thompson Gene: klf11 has been classified as Red List (Low Evidence).
Monogenic Diabetes v0.48 KLF11 Bryony Thompson Publications for gene: KLF11 were set to 15774581; 26248217; 23589285; 31124255
Monogenic Diabetes v0.47 KLF11 Bryony Thompson Classified gene: KLF11 as Red List (low evidence)
Monogenic Diabetes v0.47 KLF11 Bryony Thompson Added comment: Comment on list classification: Association with monogenic diabetes now Refuted Classification - 02/08/2023. ClinGen Monogenic Diabetes GCEP - https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_b1e38a49-7c12-4514-a2a1-109e04da146f-2023-02-08T170000.000Z?page=1&size=25&search=
Monogenic Diabetes v0.47 KLF11 Bryony Thompson Gene: klf11 has been classified as Red List (Low Evidence).
Maturity-onset Diabetes of the Young v1.8 KLF11 Bryony Thompson Publications for gene: KLF11 were set to
Maturity-onset Diabetes of the Young v1.7 KLF11 Bryony Thompson Classified gene: KLF11 as Red List (low evidence)
Maturity-onset Diabetes of the Young v1.7 KLF11 Bryony Thompson Added comment: Comment on list classification: Association with monogenic diabetes now Refuted Classification - 02/08/2023. ClinGen Monogenic Diabetes GCEP - https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_b1e38a49-7c12-4514-a2a1-109e04da146f-2023-02-08T170000.000Z?page=1&size=25&search=
Maturity-onset Diabetes of the Young v1.7 KLF11 Bryony Thompson Gene: klf11 has been classified as Red List (Low Evidence).
Mendeliome v1.1566 KLF11 Bryony Thompson Publications for gene: KLF11 were set to 15774581; 26248217; 23589285; 31124255
Mendeliome v1.1565 KLF11 Bryony Thompson Classified gene: KLF11 as Red List (low evidence)
Mendeliome v1.1565 KLF11 Bryony Thompson Added comment: Comment on list classification: Association with monogenic diabetes now Refuted
Classification - 02/08/2023. ClinGen Monogenic Diabetes GCEP - https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_b1e38a49-7c12-4514-a2a1-109e04da146f-2023-02-08T170000.000Z?page=1&size=25&search=
Mendeliome v1.1565 KLF11 Bryony Thompson Gene: klf11 has been classified as Red List (Low Evidence).
Maturity-onset Diabetes of the Young v1.6 SLC19A2 Bryony Thompson Marked gene: SLC19A2 as ready
Maturity-onset Diabetes of the Young v1.6 SLC19A2 Bryony Thompson Gene: slc19a2 has been classified as Red List (Low Evidence).
Maturity-onset Diabetes of the Young v1.6 SLC19A2 Bryony Thompson Classified gene: SLC19A2 as Red List (low evidence)
Maturity-onset Diabetes of the Young v1.6 SLC19A2 Bryony Thompson Gene: slc19a2 has been classified as Red List (Low Evidence).
Maturity-onset Diabetes of the Young v1.5 GATA6 Hali Van Niel gene: GATA6 was added
gene: GATA6 was added to Maturity-onset Diabetes of the Young. Sources: Other
Mode of inheritance for gene: GATA6 was set to Unknown
Publications for gene: GATA6 were set to 27185633
Review for gene: GATA6 was set to RED
Added comment: 1 patient with clinically diagnosed MODY with GATA6 variant
Sources: Other
Monogenic Diabetes v0.46 PPARG Hali Van Niel reviewed gene: PPARG: Rating: RED; Mode of pathogenicity: None; Publications: 30207237, 34900790; Phenotypes: diabetes mellitus MONDO:0005015; Mode of inheritance: Unknown
Maturity-onset Diabetes of the Young v1.5 WFS1 Hali Van Niel gene: WFS1 was added
gene: WFS1 was added to Maturity-onset Diabetes of the Young. Sources: Other
Mode of inheritance for gene: WFS1 was set to Unknown
Publications for gene: WFS1 were set to 27185633
Phenotypes for gene: WFS1 were set to maturity-onset diabetes of the young MONDO:0018911
Review for gene: WFS1 was set to RED
Added comment: 1 patient with clinically established MODY with WFS1 variant
Sources: Other
Maturity-onset Diabetes of the Young v1.5 SLC19A2 Hali Van Niel gene: SLC19A2 was added
gene: SLC19A2 was added to Maturity-onset Diabetes of the Young. Sources: Other
Mode of inheritance for gene: SLC19A2 was set to Unknown
Publications for gene: SLC19A2 were set to 27185633
Phenotypes for gene: SLC19A2 were set to maturity-onset diabetes of the young MONDO:0018911
Review for gene: SLC19A2 was set to RED
Added comment: 1 patient with clinically established MODY with SLC19A2 variant
Sources: Other
Mendeliome v1.1564 KLF14 Hali Van Niel changed review comment from: PMID: 33389382
Case-sibling study of 92 healthy individuals and 92 type 2 diabetes patients found KLF14 SNPs associated with susceptibility to type 2 diabetes

PMID: 35081256
Large scale association analysis found type 2 susceptibility of KLF14 SNPS appearing to be driven by reduced insulin sensitivity

PMID: 24486580
Global Meta-analysis found risk allele SNP associated with increased risk of type 2 diabetes (in global population)
Sources: Other; to: Cannot find any evidence of association with mendelian disease

PMID: 33389382
Case-sibling study of 92 healthy individuals and 92 type 2 diabetes patients found KLF14 SNPs associated with susceptibility to type 2 diabetes

PMID: 35081256
Large scale association analysis found type 2 susceptibility of KLF14 SNPS appearing to be driven by reduced insulin sensitivity

PMID: 24486580
Global Meta-analysis found risk allele SNP associated with increased risk of type 2 diabetes (in global population)
Sources: Other
Mendeliome v1.1564 KLF14 Hali Van Niel gene: KLF14 was added
gene: KLF14 was added to Mendeliome. Sources: Other
Mode of inheritance for gene: KLF14 was set to Unknown
Publications for gene: KLF14 were set to 33389382; 35081256; 24486580
Phenotypes for gene: KLF14 were set to diabetes mellitus MONDO:0005015
Review for gene: KLF14 was set to RED
Added comment: PMID: 33389382
Case-sibling study of 92 healthy individuals and 92 type 2 diabetes patients found KLF14 SNPs associated with susceptibility to type 2 diabetes

PMID: 35081256
Large scale association analysis found type 2 susceptibility of KLF14 SNPS appearing to be driven by reduced insulin sensitivity

PMID: 24486580
Global Meta-analysis found risk allele SNP associated with increased risk of type 2 diabetes (in global population)
Sources: Other
Mendeliome v1.1564 PCSK2 Hali Van Niel gene: PCSK2 was added
gene: PCSK2 was added to Mendeliome. Sources: Other
Mode of inheritance for gene: PCSK2 was set to Unknown
Publications for gene: PCSK2 were set to 26607656; 7698505; 17618154
Phenotypes for gene: PCSK2 were set to diabetes mellitus MONDO:0005015
Review for gene: PCSK2 was set to RED
Added comment: Cannot find any evidence of association with mendelian disease

PMID: 26607656

10 SNPs genotyped, genetic polymorphisms responsible for glucose homeostasis and incidental diabetes

PMID: 7698505
DNA polymorphism found in 11% of non insulin dependent diabetes patients (out of 152 japanese patients) vs 4% in health population (out of 102 japanese patients).

PMID: 17618154
29 SNPS analysed across PCSK2, 4 SNPS associated type 2 diabetes in african american population
Sources: Other
Mendeliome v1.1564 ACO2 Zornitza Stark Publications for gene: ACO2 were set to 22405087; 25351951; 30689204; 32519519; 25351951
Mendeliome v1.1563 ACO2 Zornitza Stark Mode of inheritance for gene: ACO2 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Optic Atrophy v1.29 ACO2 Zornitza Stark Publications for gene: ACO2 were set to 25351951; 22405087
Optic Atrophy v1.28 ACO2 Zornitza Stark Mode of inheritance for gene: ACO2 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mitochondrial disease v0.918 ACO2 Zornitza Stark Publications for gene: ACO2 were set to 22405087; 25351951; 30689204; 32519519; 25351951
Mitochondrial disease v0.917 ACO2 Zornitza Stark Mode of inheritance for gene: ACO2 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Genetic Epilepsy v0.2326 TSEN34 Zornitza Stark Marked gene: TSEN34 as ready
Genetic Epilepsy v0.2326 TSEN34 Zornitza Stark Added comment: Comment when marking as ready: No publications specifically reporting seizures identified.
Genetic Epilepsy v0.2326 TSEN34 Zornitza Stark Gene: tsen34 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2326 TSEN34 Zornitza Stark Marked gene: TSEN34 as ready
Genetic Epilepsy v0.2326 TSEN34 Zornitza Stark Gene: tsen34 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2326 WDFY3 Zornitza Stark Phenotypes for gene: WDFY3 were changed from ?Microcephaly 18, primary, autosomal dominant MIM#617520 to Microcephaly 18, primary, autosomal dominant MIM#617520
Mendeliome v1.1562 YEATS2 Zornitza Stark Tag STR tag was added to gene: YEATS2.
Genetic Epilepsy v0.2325 YEATS2 Zornitza Stark Tag STR tag was added to gene: YEATS2.
Genetic Epilepsy v0.2325 ZMIZ1 Zornitza Stark Classified gene: ZMIZ1 as Amber List (moderate evidence)
Genetic Epilepsy v0.2325 ZMIZ1 Zornitza Stark Gene: zmiz1 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2324 ZMIZ1 Zornitza Stark reviewed gene: ZMIZ1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with dysmorphic facies and distal skeletal anomalies MIM#618659; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2324 ZSWIM6 Elena Savva Marked gene: ZSWIM6 as ready
Genetic Epilepsy v0.2324 ZSWIM6 Elena Savva Gene: zswim6 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2324 ZSWIM6 Elena Savva Classified gene: ZSWIM6 as Green List (high evidence)
Genetic Epilepsy v0.2324 ZSWIM6 Elena Savva Gene: zswim6 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2323 ZSWIM6 Elena Savva gene: ZSWIM6 was added
gene: ZSWIM6 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: ZSWIM6 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ZSWIM6 were set to PMID: 29198722; 33958584
Phenotypes for gene: ZSWIM6 were set to Acromelic frontonasal dysostosis MIM#603671; Neurodevelopmental disorder with movement abnormalities, abnormal gait, and autistic features MIM#617865
Review for gene: ZSWIM6 was set to GREEN
Added comment: Seizures listed in OMIM as a feature of both conditions.

PMID: 29198722 - seven unrelated individuals with a recurrent de novo nonsense variant p.Arg913* in the penultimate exon. 4/7 confirmed to have seizures or possible seizures.

PMID: 33958584 - Japanese male patient with severe neurodevelopmental delay, epilepsy, distinctive facial features, microcephaly, growth deficiency, abnormal behavior, and frequent vomiting but without frontonasal or limb malformations. Proband had the same de novo p.Arg913* variant
Sources: Literature
Genetic Epilepsy v0.2322 ZMIZ1 Elena Savva Marked gene: ZMIZ1 as ready
Genetic Epilepsy v0.2322 ZMIZ1 Elena Savva Gene: zmiz1 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2322 ZMIZ1 Elena Savva gene: ZMIZ1 was added
gene: ZMIZ1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: ZMIZ1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ZMIZ1 were set to PMID: 30639322
Phenotypes for gene: ZMIZ1 were set to Neurodevelopmental disorder with dysmorphic facies and distal skeletal anomalies MIM#618659
Review for gene: ZMIZ1 was set to RED
Added comment: Seizures (rare) listed in OMIM

PMID: 30639322 - gene-disease establishing paper. Cohort of 19 probands (16 unrelated), where 3 were reported with seizures.
Sources: Literature
Genetic Epilepsy v0.2321 ZIC2 Elena Savva Marked gene: ZIC2 as ready
Genetic Epilepsy v0.2321 ZIC2 Elena Savva Gene: zic2 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2321 ZIC2 Elena Savva gene: ZIC2 was added
gene: ZIC2 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: ZIC2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: ZIC2 were set to Holoprosencephaly 5 MIM#609637
Review for gene: ZIC2 was set to RED
Added comment: No evidence of SNVs in this gene causing epilepsy/seizures.

This gene was listed in the Oliver list.
Sources: Literature
Genetic Epilepsy v0.2320 YEATS2 Elena Savva Marked gene: YEATS2 as ready
Genetic Epilepsy v0.2320 YEATS2 Elena Savva Gene: yeats2 has been classified as Red List (Low Evidence).
Mendeliome v1.1562 YEATS2 Elena Savva Marked gene: YEATS2 as ready
Mendeliome v1.1562 YEATS2 Elena Savva Gene: yeats2 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2320 YEATS2 Elena Savva gene: YEATS2 was added
gene: YEATS2 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: YEATS2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: YEATS2 were set to PMID: 22713812; 31539032
Phenotypes for gene: YEATS2 were set to ?Epilepsy, myoclonic, familial adult, 4 MIM#615127
Review for gene: YEATS2 was set to RED
Added comment: PMID: 22713812 - 13 members of a single family with Benign Adult Familial Myoclonic Epilepsy (BAFME). The average age of onset was 19.5 (range 10–33) years for tremor and 25 (range 19–33) years for seizures.
PMID: 31539032 - Expansions of TTTTA and insertions of TTTCA repeats in intron 1 of YEATS2 segregated in the same family ^.
Sources: Literature
Mendeliome v1.1562 YEATS2 Elena Savva gene: YEATS2 was added
gene: YEATS2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: YEATS2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: YEATS2 were set to PMID: 22713812; 31539032
Phenotypes for gene: YEATS2 were set to ?Epilepsy, myoclonic, familial adult, 4 MIM#615127
Review for gene: YEATS2 was set to RED
Added comment: PMID: 22713812 - 13 members of a single family with Benign Adult Familial Myoclonic Epilepsy (BAFME). The average age of onset was 19.5 (range 10–33) years for tremor and 25 (range 19–33) years for seizures.
PMID: 31539032 - Expansions of TTTTA and insertions of TTTCA repeats in intron 1 of YEATS2 segregated in the same family ^.
Sources: Literature
Genetic Epilepsy v0.2319 XPR1 Elena Savva Marked gene: XPR1 as ready
Genetic Epilepsy v0.2319 XPR1 Elena Savva Gene: xpr1 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2319 XPR1 Elena Savva Classified gene: XPR1 as Amber List (moderate evidence)
Genetic Epilepsy v0.2319 XPR1 Elena Savva Gene: xpr1 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2318 XPR1 Elena Savva gene: XPR1 was added
gene: XPR1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: XPR1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: XPR1 were set to PMID: 33433330
Phenotypes for gene: XPR1 were set to Basal ganglia calcification, idiopathic, 6 MIM#616413
Review for gene: XPR1 was set to AMBER
Added comment: Seizures (in some patients) listed in OMIM

PMID: 33433330
- chet proband (PTC, missense) with paroxysmal kinesigenic dyskinesia with infantile convulsions, and generalized tonic-clonic seizures (GTCS) at the age of 2 years. Both parents were unaffected.
- Only missense in AD disease had been reported.
- Reviews literature, notes seizures 2/12 unrelated individuals, where an additional proband was ?seizures?
Sources: Literature
Genetic Epilepsy v0.2317 WDFY3 Elena Savva Marked gene: WDFY3 as ready
Genetic Epilepsy v0.2317 WDFY3 Elena Savva Gene: wdfy3 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2317 WDFY3 Elena Savva gene: WDFY3 was added
gene: WDFY3 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: WDFY3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: WDFY3 were set to PMID: 31327001
Phenotypes for gene: WDFY3 were set to ?Microcephaly 18, primary, autosomal dominant MIM#617520
Review for gene: WDFY3 was set to RED
Added comment: PMID: 31327001 - cohort of 13 probands and mouse model, NONE had reported to have epilepsy/seizures.

Gene was listed as part of the Oliver review for genes associated with epilepsy
Sources: Literature
Genetic Epilepsy v0.2316 WASHC4 Elena Savva Marked gene: WASHC4 as ready
Genetic Epilepsy v0.2316 WASHC4 Elena Savva Gene: washc4 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2316 WASHC4 Elena Savva gene: WASHC4 was added
gene: WASHC4 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: WASHC4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WASHC4 were set to PMID: 34599609
Phenotypes for gene: WASHC4 were set to Intellectual developmental disorder, autosomal recessive 43 MIM#615817
Review for gene: WASHC4 was set to RED
Added comment: PMID: 34599609 - two siblings, only 1 sibling presented with epilepsy with generalized tonic–clonic seizures and received oxcarbazepine (seizure-free on therapy). They were homozygous for a missense, some functional studies supporting pathogenicity.
Review of previous reports did NOT describe any other reports of seizures.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5705 WASHC4 Elena Savva Phenotypes for gene: WASHC4 were changed from ?Mental retardation, autosomal recessive 43; OMIM #615817 to Intellectual developmental disorder, autosomal recessive 43 MIM#615817
Mendeliome v1.1561 WASHC4 Elena Savva Phenotypes for gene: WASHC4 were changed from Mental retardation, autosomal recessive 43, MIM #615817 to Intellectual developmental disorder, autosomal recessive 43 MIM#615817
Genetic Epilepsy v0.2315 WAC Elena Savva Marked gene: WAC as ready
Genetic Epilepsy v0.2315 WAC Elena Savva Gene: wac has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2315 WAC Elena Savva Classified gene: WAC as Green List (high evidence)
Genetic Epilepsy v0.2315 WAC Elena Savva Gene: wac has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2314 WAC Elena Savva gene: WAC was added
gene: WAC was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: WAC was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: WAC were set to PMID: 36420948
Phenotypes for gene: WAC were set to Desanto-Shinawi syndrome MIM#616708
Review for gene: WAC was set to GREEN
Added comment: Seizures (in some patients) listed in OMIM

PMID: 36420948 - reviews literature, describes seizures in 10/33 probands
Sources: Literature
Mendeliome v1.1560 UGGT1 Elena Savva Marked gene: UGGT1 as ready
Mendeliome v1.1560 UGGT1 Elena Savva Gene: uggt1 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2313 UGGT1 Elena Savva Marked gene: UGGT1 as ready
Genetic Epilepsy v0.2313 UGGT1 Elena Savva Gene: uggt1 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2313 UGGT1 Elena Savva gene: UGGT1 was added
gene: UGGT1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: UGGT1 was set to Unknown
Review for gene: UGGT1 was set to RED
Added comment: Gene was on the Oliver list for epilepsy genes.

No gene-disease association paper has been published.

GnomAD NOT constrained for LOF variants.
Sources: Literature
Mendeliome v1.1560 UGGT1 Elena Savva gene: UGGT1 was added
gene: UGGT1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: UGGT1 was set to Unknown
Review for gene: UGGT1 was set to RED
Added comment: Gene was on the Oliver list for epilepsy genes.

No gene-disease association paper has been published.

GnomAD NOT constrained for LOF variants.
Sources: Literature
Genetic Epilepsy v0.2312 UBTF Elena Savva Classified gene: UBTF as Amber List (moderate evidence)
Genetic Epilepsy v0.2312 UBTF Elena Savva Gene: ubtf has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2312 UBTF Elena Savva Classified gene: UBTF as Amber List (moderate evidence)
Genetic Epilepsy v0.2312 UBTF Elena Savva Gene: ubtf has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2311 UBTF Elena Savva Marked gene: UBTF as ready
Genetic Epilepsy v0.2311 UBTF Elena Savva Gene: ubtf has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2311 UBTF Elena Savva gene: UBTF was added
gene: UBTF was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: UBTF was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: UBTF were set to PMID: 30517966
Phenotypes for gene: UBTF were set to Neurodegeneration, childhood-onset, with brain atrophy MIM#617672
Review for gene: UBTF was set to AMBER
Added comment: PMID: 30517966 - recurring de novo missense p.Glu210Lys, observed in 11 probands with neurodegeneration. 3/11 had seizures. Paper had an additional proband with this variant and drug-resistant epilepsy.
Sources: Literature
Fetal anomalies v1.196 FZD5 Zornitza Stark Phenotypes for gene: FZD5 were changed from Autosomal Dominant Coloboma to Microphthalmia/coloboma 11, MIM# 620731
Fetal anomalies v1.195 FZD5 Zornitza Stark Classified gene: FZD5 as Amber List (moderate evidence)
Fetal anomalies v1.195 FZD5 Zornitza Stark Gene: fzd5 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.194 FZD5 Zornitza Stark edited their review of gene: FZD5: Changed rating: AMBER
Fetal anomalies v1.194 FZD5 Zornitza Stark edited their review of gene: FZD5: Changed phenotypes: Microphthalmia/coloboma 11, MIM# 620731
Mendeliome v1.1559 FZD5 Zornitza Stark Phenotypes for gene: FZD5 were changed from Coloboma MONDO:0001476 to Microphthalmia/coloboma 11, MIM# 620731
Mendeliome v1.1558 FZD5 Zornitza Stark edited their review of gene: FZD5: Changed phenotypes: Microphthalmia/coloboma 11, MIM# 620731
Anophthalmia_Microphthalmia_Coloboma v1.39 FZD5 Zornitza Stark Phenotypes for gene: FZD5 were changed from Coloboma (MONDO:0001476), FZD5-related to Microphthalmia/coloboma 11, MIM# 620731
Anophthalmia_Microphthalmia_Coloboma v1.38 FZD5 Zornitza Stark edited their review of gene: FZD5: Changed phenotypes: Microphthalmia/coloboma 11, MIM# 620731
Metal Metabolism Disorders v0.37 STAB1 Zornitza Stark Phenotypes for gene: STAB1 were changed from Iron metabolism metabolism, MONDO:0002279, STAB1-related; Hyperferritinaemia without iron overload to Hyperferritinemia, MIM# 620729
Metal Metabolism Disorders v0.36 STAB1 Zornitza Stark reviewed gene: STAB1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Hyperferritinemia, MIM# 620729; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1558 STAB1 Zornitza Stark Phenotypes for gene: STAB1 were changed from Iron metabolism disease (MONDO:0002279), STAB1-related to Hyperferritinemia, MIM# 620729
Mendeliome v1.1557 STAB1 Zornitza Stark reviewed gene: STAB1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Hyperferritinemia, MIM# 620729; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Dystonia - complex v0.234 NAA15 Shekeeb Mohammad gene: NAA15 was added
gene: NAA15 was added to Dystonia - complex. Sources: Literature
Mode of inheritance for gene: NAA15 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NAA15 were set to 38380600
Phenotypes for gene: NAA15 were set to dystonia; neurodevelopmental delay
Penetrance for gene: NAA15 were set to unknown
Review for gene: NAA15 was set to GREEN
Added comment: previous 3 cases in literature referenced in 38380600
Sources: Literature
Genetic Epilepsy v0.2310 PUM1 Zornitza Stark Phenotypes for gene: PUM1 were changed from Neurodevelopmental disorder with motor abnormalities, seizures, and facial dysmorphism, MIM# 620719; Spinocerebellar ataxia 47, MIM# 617931 to Neurodevelopmental disorder with motor abnormalities, seizures, and facial dysmorphism, MIM# 620719
Intellectual disability syndromic and non-syndromic v0.5704 PUM1 Zornitza Stark Phenotypes for gene: PUM1 were changed from Spinocerebellar ataxia 47, MIM#617931; intellectual disability; epilepsy to Neurodevelopmental disorder with motor abnormalities, seizures, and facial dysmorphism, MIM# 620719
Intellectual disability syndromic and non-syndromic v0.5703 PUM1 Zornitza Stark edited their review of gene: PUM1: Changed phenotypes: Neurodevelopmental disorder with motor abnormalities, seizures, and facial dysmorphism, MIM# 620719
Intellectual disability syndromic and non-syndromic v0.5703 PUM1 Zornitza Stark edited their review of gene: PUM1: Changed phenotypes: Spinocerebellar ataxia 47, MIM#617931, Neurodevelopmental disorder with motor abnormalities, seizures, and facial dysmorphism, MIM# 620719
Genetic Epilepsy v0.2309 PUM1 Zornitza Stark Phenotypes for gene: PUM1 were changed from intellectual disability; epilepsy; Spinocerebellar ataxia 47, MIM# 617931 to Neurodevelopmental disorder with motor abnormalities, seizures, and facial dysmorphism, MIM# 620719; Spinocerebellar ataxia 47, MIM# 617931
Genetic Epilepsy v0.2308 PUM1 Zornitza Stark edited their review of gene: PUM1: Changed phenotypes: Neurodevelopmental disorder with motor abnormalities, seizures, and facial dysmorphism, MIM# 620719
Mendeliome v1.1557 PUM1 Zornitza Stark Phenotypes for gene: PUM1 were changed from Spinocerebellar ataxia 47, MIM# 617931; Neurodevelopmental disorder, MONDO:0700092, PUM1-related to Spinocerebellar ataxia 47, MIM# 617931; Neurodevelopmental disorder with motor abnormalities, seizures, and facial dysmorphism, MIM# 620719
Mendeliome v1.1556 PUM1 Zornitza Stark Publications for gene: PUM1 were set to 29474920; 25768905; 30903679; 31859446
Mendeliome v1.1555 PUM1 Zornitza Stark edited their review of gene: PUM1: Changed phenotypes: Spinocerebellar ataxia 47, MIM# 617931, Neurodevelopmental disorder with motor abnormalities, seizures, and facial dysmorphism, MIM# 620719
Genetic Epilepsy v0.2308 TWNK Elena Savva Classified gene: TWNK as Green List (high evidence)
Genetic Epilepsy v0.2308 TWNK Elena Savva Gene: twnk has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2307 TWNK Elena Savva Marked gene: TWNK as ready
Genetic Epilepsy v0.2307 TWNK Elena Savva Gene: twnk has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2307 TWNK Elena Savva gene: TWNK was added
gene: TWNK was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: TWNK was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: TWNK were set to PMID: 19304794
Phenotypes for gene: TWNK were set to Mitochondrial DNA depletion syndrome 7 (hepatocerebral type) MIM#271245; Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3 MIM#609286
Review for gene: TWNK was set to GREEN
Added comment: PMID: 19304794 - reviews, notes epilepsia partialis continua occurred in 15 patients leading to generalized epileptic statuses in 13/15. Probands had biallelic variants

OMIM lists Seizures (uncommon) as a phenotype for AD disease
Sources: Literature
Genetic Epilepsy v0.2306 TSEN34 Elena Savva gene: TSEN34 was added
gene: TSEN34 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: TSEN34 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TSEN34 were set to Pontocerebellar hypoplasia type 2C, MIM#612390
Review for gene: TSEN34 was set to RED
Added comment: Gene was part of the Oliver list, no new publications
Sources: Literature
Genetic Epilepsy v0.2305 TSEN15 Elena Savva Marked gene: TSEN15 as ready
Genetic Epilepsy v0.2305 TSEN15 Elena Savva Gene: tsen15 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2305 TSEN15 Elena Savva Classified gene: TSEN15 as Amber List (moderate evidence)
Genetic Epilepsy v0.2305 TSEN15 Elena Savva Gene: tsen15 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2304 TSEN15 Elena Savva gene: TSEN15 was added
gene: TSEN15 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: TSEN15 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TSEN15 were set to PMID: 27392077
Phenotypes for gene: TSEN15 were set to Pontocerebellar hypoplasia, type 2F MIM#617026
Review for gene: TSEN15 was set to AMBER
Added comment: Few patients reported with disease for this gene

PMID: 27392077 - 2/4 probands had seizures, onset <1 year old. Probands had homozygous missense, none had homs in v4 gnomAD. Functional studies support missense pathogenicity.
Sources: Literature
Mitochondrial disease v0.916 ACO2 Rylee Peters reviewed gene: ACO2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 34056600; Phenotypes: Optic atrophy 9, MIM# 616289; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Optic Atrophy v1.27 ACO2 Rylee Peters reviewed gene: ACO2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 34056600; Phenotypes: Optic atrophy 9, MIM# 616289; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v1.1555 ACO2 Rylee Peters reviewed gene: ACO2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 34056600; Phenotypes: Optic atrophy 9, MIM# 616289; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Genetic Epilepsy v0.2303 TRMT1 Elena Savva Classified gene: TRMT1 as Green List (high evidence)
Genetic Epilepsy v0.2303 TRMT1 Elena Savva Gene: trmt1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2302 TRMT1 Elena Savva Classified gene: TRMT1 as Green List (high evidence)
Genetic Epilepsy v0.2302 TRMT1 Elena Savva Gene: trmt1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2301 TRMT1 Elena Savva Marked gene: TRMT1 as ready
Genetic Epilepsy v0.2301 TRMT1 Elena Savva Gene: trmt1 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2301 TRMT1 Elena Savva gene: TRMT1 was added
gene: TRMT1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: TRMT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRMT1 were set to PMID: 31898845; 26308914; 30289604
Phenotypes for gene: TRMT1 were set to Intellectual developmental disorder, autosomal recessive 68 MIM#618302
Review for gene: TRMT1 was set to GREEN
Added comment: Rarely reported gene

Seizures (in some patients) described in OMIM.

PMID: 31898845 - homozygous missense in a proband with developmental delay, ID, and epilepsy. Functional studies support pathogenicity of the missense.

PMID: 26308914 - family with a homozygous PTC. The patients did not manifest any other neurological problems, ie. NO seizures.

PMID: 30289604 - two families (total 4 affected) with hom PTC and canonical splice. All had seizures.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5703 TRMT1 Elena Savva Phenotypes for gene: TRMT1 were changed from Mental retardation, autosomal recessive 68; OMIM #618302 to Intellectual developmental disorder, autosomal recessive 68 MIM#618302
Mendeliome v1.1555 TRMT1 Elena Savva Phenotypes for gene: TRMT1 were changed from Mental retardation, autosomal recessive 68; OMIM #618302 to Intellectual developmental disorder, autosomal recessive 68 MIM#618302
Genetic Epilepsy v0.2300 TRIT1 Elena Savva Marked gene: TRIT1 as ready
Genetic Epilepsy v0.2300 TRIT1 Elena Savva Gene: trit1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2300 TRIT1 Elena Savva Classified gene: TRIT1 as Green List (high evidence)
Genetic Epilepsy v0.2300 TRIT1 Elena Savva Gene: trit1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2299 TRIT1 Elena Savva gene: TRIT1 was added
gene: TRIT1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: TRIT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRIT1 were set to PMID: 36047296; 36049610
Phenotypes for gene: TRIT1 were set to Combined oxidative phosphorylation deficiency 35 MIM#617873
Review for gene: TRIT1 was set to GREEN
Added comment: PMID: 36047296 - two probands with tonic–clonic seizures, as well as myoclonic seizures in patient 1. Both probands had chet PTC/missense.

PMID: 36049610 - two probands with seizures. Both probands had chet PTC/missense. Reviews, seizures reported in 100% (20/20) patients, including myoclonic epilepsy and febrile convulsions
Sources: Literature
Genetic Epilepsy v0.2298 TRIP12 Elena Savva Marked gene: TRIP12 as ready
Genetic Epilepsy v0.2298 TRIP12 Elena Savva Gene: trip12 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2298 TRIP12 Elena Savva Classified gene: TRIP12 as Amber List (moderate evidence)
Genetic Epilepsy v0.2298 TRIP12 Elena Savva Gene: trip12 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2297 TRIP12 Elena Savva gene: TRIP12 was added
gene: TRIP12 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: TRIP12 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: TRIP12 were set to PMID: 36275919; 32424948
Phenotypes for gene: TRIP12 were set to Intellectual developmental disorder, autosomal dominant 49 MIM#617752
Review for gene: TRIP12 was set to AMBER
Added comment: Seizures described as a rare feature in OMIM

PMID: 36275919 - patient with GDD, hypotonia and intermittent seizures. De novo synonymous variant with proven splice outcome found.

PMID: 32424948 - reviews, epilepsy observed in 21% (5/24) patients
Sources: Literature
Genetic Epilepsy v0.2296 TRIO Elena Savva Classified gene: TRIO as Green List (high evidence)
Genetic Epilepsy v0.2296 TRIO Elena Savva Gene: trio has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2295 TRIO Elena Savva Marked gene: TRIO as ready
Genetic Epilepsy v0.2295 TRIO Elena Savva Gene: trio has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2295 TRIO Elena Savva gene: TRIO was added
gene: TRIO was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: TRIO was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: TRIO were set to Intellectual developmental disorder, autosomal dominant 44, with microcephaly MIM#617061; Intellectual developmental disorder, autosomal dominant 63, with macrocephaly MIM#618825
Review for gene: TRIO was set to GREEN
Added comment: Seizures described in OMIM as a rare feature of both AR and AD disease

GeneReviews: seizures described in 7/19 probands with GOF variants, and 7/29 in individuals with LOF variants. Only one in ten individuals with a TRIO missense variant in the GEFD1 domain had seizures
Sources: Literature
Genetic Epilepsy v0.2294 TREM2 Elena Savva Classified gene: TREM2 as Green List (high evidence)
Genetic Epilepsy v0.2294 TREM2 Elena Savva Gene: trem2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2294 TREM2 Elena Savva Classified gene: TREM2 as Green List (high evidence)
Genetic Epilepsy v0.2294 TREM2 Elena Savva Gene: trem2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2293 TREM2 Elena Savva Marked gene: TREM2 as ready
Genetic Epilepsy v0.2293 TREM2 Elena Savva Gene: trem2 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2293 TREM2 Elena Savva gene: TREM2 was added
gene: TREM2 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: TREM2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TREM2 were set to PMID: 36820836; 24910390
Phenotypes for gene: TREM2 were set to Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 2 MIM#618193
Review for gene: TREM2 was set to GREEN
Added comment: PMID: 36820836 - adult with repetitive seizures with a homozygous missense variant. Sibling also affected. No functional studies.

PMID: 24910390 - two siblings with a hom missense, no seizures reported. Summary of literature notes epilepsy in 75% of probands.

Seizures listed in OMIM
Sources: Literature
Genetic Epilepsy v0.2292 TPK1 Elena Savva Marked gene: TPK1 as ready
Genetic Epilepsy v0.2292 TPK1 Elena Savva Gene: tpk1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2292 TPK1 Elena Savva Classified gene: TPK1 as Green List (high evidence)
Genetic Epilepsy v0.2292 TPK1 Elena Savva Gene: tpk1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2291 TPK1 Elena Savva gene: TPK1 was added
gene: TPK1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: TPK1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TPK1 were set to PMID: 37622082
Phenotypes for gene: TPK1 were set to Thiamine metabolism dysfunction syndrome 5 (episodic encephalopathy type) MIM#614458
Review for gene: TPK1 was set to GREEN
Added comment: PMID: 37622082
- proband 1 had a single convulsive seizure after fever, rashes. Diagnosed with leigh syndrome. Was chet for a PTC and missense.
- proband 2 had frequent tonic seizures, Was chet for a PTC and missense.
Review of literature found seizure (10/28, 35.71%) of reported cases
Sources: Literature
Neurodegeneration with brain iron accumulation v0.32 Bryony Thompson Panel name changed from Neuroferritinopathies to Neurodegeneration with brain iron accumulation
Early-onset Parkinson disease v0.294 FTL Bryony Thompson Publications for gene: FTL were set to 23447832; 20301320
Early-onset Parkinson disease v0.293 FTL Bryony Thompson Publications for gene: FTL were set to
Early-onset Parkinson disease v0.292 FTL Bryony Thompson Mode of inheritance for gene: FTL was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.291 FTL Bryony Thompson Classified gene: FTL as Green List (high evidence)
Early-onset Parkinson disease v0.291 FTL Bryony Thompson Added comment: Comment on list classification: Parkinsonism can be a presenting feature of the condition
Early-onset Parkinson disease v0.291 FTL Bryony Thompson Gene: ftl has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.291 FTL Bryony Thompson Classified gene: FTL as Green List (high evidence)
Early-onset Parkinson disease v0.291 FTL Bryony Thompson Added comment: Comment on list classification: Parkinsonism can be a presenting feature of the condition
Early-onset Parkinson disease v0.291 FTL Bryony Thompson Gene: ftl has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.290 TAF1 Bryony Thompson Tag STR tag was added to gene: TAF1.
Early-onset Parkinson disease v0.290 FBXO7 Bryony Thompson Marked gene: FBXO7 as ready
Early-onset Parkinson disease v0.290 FBXO7 Bryony Thompson Gene: fbxo7 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.290 FBXO7 Bryony Thompson Publications for gene: FBXO7 were set to
Early-onset Parkinson disease v0.289 FBXO7 Bryony Thompson Phenotypes for gene: FBXO7 were changed from to parkinsonian-pyramidal syndrome MONDO:0009830
Early-onset Parkinson disease v0.288 FBXO7 Bryony Thompson Mode of inheritance for gene: FBXO7 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.287 DNAJC6 Bryony Thompson Marked gene: DNAJC6 as ready
Early-onset Parkinson disease v0.287 DNAJC6 Bryony Thompson Gene: dnajc6 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.287 DNAJC6 Bryony Thompson Phenotypes for gene: DNAJC6 were changed from to juvenile onset Parkinson disease 19A MONDO:0014231
Early-onset Parkinson disease v0.286 DNAJC6 Bryony Thompson Publications for gene: DNAJC6 were set to
Early-onset Parkinson disease v0.285 DNAJC6 Bryony Thompson Mode of inheritance for gene: DNAJC6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.284 DCTN1 Bryony Thompson Marked gene: DCTN1 as ready
Early-onset Parkinson disease v0.284 DCTN1 Bryony Thompson Gene: dctn1 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.284 DCTN1 Bryony Thompson Phenotypes for gene: DCTN1 were changed from Perry syndrome MONDO:0008201 to Perry syndrome MONDO:0008201
Early-onset Parkinson disease v0.283 DCTN1 Bryony Thompson Phenotypes for gene: DCTN1 were changed from to Perry syndrome MONDO:0008201
Early-onset Parkinson disease v0.282 DCTN1 Bryony Thompson Publications for gene: DCTN1 were set to 20945553
Early-onset Parkinson disease v0.282 DCTN1 Bryony Thompson Publications for gene: DCTN1 were set to
Early-onset Parkinson disease v0.281 DCTN1 Bryony Thompson Mode of inheritance for gene: DCTN1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.281 DCTN1 Bryony Thompson Mode of inheritance for gene: DCTN1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.280 DCTN1 Bryony Thompson Mode of inheritance for gene: DCTN1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.280 DCTN1 Bryony Thompson Classified gene: DCTN1 as Green List (high evidence)
Early-onset Parkinson disease v0.280 DCTN1 Bryony Thompson Added comment: Comment on list classification: Parkinsonism is a characteristic feature of Perry syndrome
Early-onset Parkinson disease v0.280 DCTN1 Bryony Thompson Gene: dctn1 has been classified as Green List (High Evidence).
Fetal anomalies v1.194 NEK1 Zornitza Stark Phenotypes for gene: NEK1 were changed from Short-rib thoracic dysplasia 6 with or without polydactyly, MIM# 263520 to Short-rib thoracic dysplasia 6 with or without polydactyly, MIM# 263520; Orofaciodigital syndrome II , MIM# 252100
Fetal anomalies v1.193 NEK1 Zornitza Stark Publications for gene: NEK1 were set to 21211617; 22499340; 25492405; 28123176
Fetal anomalies v1.192 NEK1 Zornitza Stark edited their review of gene: NEK1: Added comment: Single family with OFD phenotype.; Changed publications: 21211617, 22499340, 25492405, 28123176, 27530628; Changed phenotypes: Short-rib thoracic dysplasia 6 with or without polydactyly, MIM# 263520, Orofaciodigital syndrome II , MIM# 252100
Clefting disorders v0.252 NEK1 Zornitza Stark Marked gene: NEK1 as ready
Clefting disorders v0.252 NEK1 Zornitza Stark Gene: nek1 has been classified as Green List (High Evidence).
Clefting disorders v0.252 NEK1 Zornitza Stark Phenotypes for gene: NEK1 were changed from SHORT-RIB THORACIC DYSPLASIA 6 WITH OR WITHOUT POLYDACTYLY; SRTD6 to Short-rib thoracic dysplasia 6 with or without polydactyly, MIM# 263520; Orofaciodigital syndrome II , MIM# 252100
Clefting disorders v0.251 NEK1 Zornitza Stark Publications for gene: NEK1 were set to
Clefting disorders v0.250 NEK1 Zornitza Stark reviewed gene: NEK1: Rating: GREEN; Mode of pathogenicity: None; Publications: 21211617, 22499340, 25492405, 28123176, 27530628; Phenotypes: Short-rib thoracic dysplasia 6 with or without polydactyly, MIM# 263520, Orofaciodigital syndrome II , MIM# 252100; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1554 NEK1 Zornitza Stark Phenotypes for gene: NEK1 were changed from Short-rib thoracic dysplasia 6 with or without polydactyly, MIM# 263520; Amyotrophic lateral sclerosis, susceptibility to, 24, MIM# 617892 to Short-rib thoracic dysplasia 6 with or without polydactyly, MIM# 263520; Orofaciodigital syndrome II , MIM# 252100; Amyotrophic lateral sclerosis, susceptibility to, 24, MIM# 617892
Mendeliome v1.1553 NEK1 Zornitza Stark Publications for gene: NEK1 were set to 21211617; 22499340; 25492405; 28123176; 33445179
Mendeliome v1.1552 NEK1 Zornitza Stark edited their review of gene: NEK1: Added comment: PMID 27530628: two brothers with OFD phenotype.; Changed publications: 21211617, 22499340, 25492405, 28123176, 27530628; Changed phenotypes: Short-rib thoracic dysplasia 6 with or without polydactyly, MIM# 263520, Orofaciodigital syndrome II , MIM# 252100, Amyotrophic lateral sclerosis, susceptibility to, 24, MIM# 617892
Ciliopathies v1.51 NEK1 Zornitza Stark Phenotypes for gene: NEK1 were changed from Short-rib thoracic dysplasia 6 with or without polydactyly, MIM# 263520 to Short-rib thoracic dysplasia 6 with or without polydactyly, MIM# 263520; Orofaciodigital syndrome II , MIM# 252100
Ciliopathies v1.50 NEK1 Zornitza Stark Publications for gene: NEK1 were set to 21211617; 22499340; 25492405; 28123176
Ciliopathies v1.49 NEK1 Zornitza Stark edited their review of gene: NEK1: Added comment: PMID 27530628: two brothers with OFD phenotype.; Changed publications: 21211617, 22499340, 25492405, 28123176, 27530628; Changed phenotypes: Short-rib thoracic dysplasia 6 with or without polydactyly, MIM# 263520, Orofaciodigital syndrome II , MIM# 252100
Mendeliome v1.1552 HMBS Zornitza Stark Phenotypes for gene: HMBS were changed from Porphyria, acute intermittent, MIM#176000; Porphyria, acute intermittent, non-erythroid variant, MIM#176000 to Porphyria, acute intermittent, MIM#176000; Porphyria, acute intermittent, non-erythroid variant, MIM#176000; Encephalopathy, porphyria-related MIM#620704; Leukoencephalopathy, porphyria-related, MIM#620711
Mendeliome v1.1551 HMBS Zornitza Stark edited their review of gene: HMBS: Changed phenotypes: Porphyria, acute intermittent, MIM#176000, Porphyria, acute intermittent, non-erythroid variant, MIM#176000, Encephalopathy, porphyria-related MIM#620704, Leukoencephalopathy, porphyria-related, MIM#620711
Regression v0.544 HMBS Zornitza Stark Marked gene: HMBS as ready
Regression v0.544 HMBS Zornitza Stark Gene: hmbs has been classified as Green List (High Evidence).
Regression v0.544 HMBS Zornitza Stark Phenotypes for gene: HMBS were changed from to Encephalopathy, porphyria-related MIM#620704; Leukoencephalopathy, porphyria-related, MIM#620711
Regression v0.543 HMBS Zornitza Stark Mode of inheritance for gene: HMBS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Regression v0.542 HMBS Zornitza Stark reviewed gene: HMBS: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Encephalopathy, porphyria-related MIM#620704, Leukoencephalopathy, porphyria-related, MIM#620711; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5702 HMBS Zornitza Stark Marked gene: HMBS as ready
Intellectual disability syndromic and non-syndromic v0.5702 HMBS Zornitza Stark Gene: hmbs has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5702 HMBS Zornitza Stark Publications for gene: HMBS were set to 15534187
Intellectual disability syndromic and non-syndromic v0.5701 HMBS Zornitza Stark Classified gene: HMBS as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5701 HMBS Zornitza Stark Gene: hmbs has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5700 HMBS Zornitza Stark edited their review of gene: HMBS: Changed publications: 15534187, 34089223; Changed phenotypes: Encephalopathy, porphyria-related MIM#620704, Leukoencephalopathy, porphyria-related, MIM#620711
Intellectual disability syndromic and non-syndromic v0.5700 HMBS Zornitza Stark gene: HMBS was added
gene: HMBS was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review
Mode of inheritance for gene: HMBS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HMBS were set to 15534187
Phenotypes for gene: HMBS were set to Encephalopathy, porphyria-related MIM#620704; Leukoencephalopathy, porphyria-related, MIM#620711
Review for gene: HMBS was set to GREEN
Added comment: Several families reported with encephalopathy/leukoencephalopathy and ballelic variants in this gene.
Sources: Expert Review
Leukodystrophy - paediatric v0.305 HMBS Zornitza Stark Phenotypes for gene: HMBS were changed from Porphyria, acute intermittent, MIM#176000; Acute intermittent porphyria-related leukoencephalopathy to Leukoencephalopathy, porphyria-related, MIM# 620711
Leukodystrophy - paediatric v0.304 HMBS Zornitza Stark edited their review of gene: HMBS: Changed phenotypes: Leukoencephalopathy, porphyria-related, MIM# 620711
Intellectual disability syndromic and non-syndromic v0.5699 DDX3X Abhijit Kulkarni edited their review of gene: DDX3X: Changed publications: PMID: 32135084, 32852922
Intellectual disability syndromic and non-syndromic v0.5699 DDX3X Abhijit Kulkarni changed review comment from: Genotype-Phenotype Correlations

Females. Affected females with a subset of missense variants generally are more severely affected than those with truncating variants [Lennox et al 2020].

Polymicrogyria has been associated with missense or in-frame deletions [Lennox et al 2020].

Males. While all affected males have had missense DDX3X variants (see Table 6), their female relatives who are heterozygous for the same DDX3X variant do not manifest an atypical neurodevelopmental phenotype.; to: Genotype-Phenotype Correlations

Females. Affected females with a subset of missense variants generally are more severely affected than those with truncating variants PMID: 32135084

Polymicrogyria has been associated with missense or in-frame deletions PMID: 32135084

Males. While all affected males have had missense DDX3X variants , their female relatives who are heterozygous for the same DDX3X variant do not manifest an atypical neurodevelopmental phenotype.
Intellectual disability syndromic and non-syndromic v0.5699 DDX3X Abhijit Kulkarni commented on gene: DDX3X
Mendeliome v1.1551 LCP2 Achchuthan Shanmugasundram reviewed gene: LCP2: Rating: GREEN; Mode of pathogenicity: None; Publications: 37211057; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v1.172 MYO3A Zornitza Stark Phenotypes for gene: MYO3A were changed from Deafness, autosomal recessive 30, MIM# 607101; dominant deafness to Deafness, autosomal recessive 30, MIM# 607101; Deafness, autosomal dominant 90, MIM# 620722
Deafness_IsolatedAndComplex v1.171 MYO3A Zornitza Stark edited their review of gene: MYO3A: Changed phenotypes: Deafness, autosomal recessive 30, MIM# 607101, Deafness, autosomal dominant 90, MIM# 620722
Mendeliome v1.1551 MYO3A Zornitza Stark Phenotypes for gene: MYO3A were changed from Deafness, autosomal recessive 30 OMIM:607101; autosomal recessive nonsyndromic deafness 30 MONDO:0011774; dominant deafness to Deafness, autosomal recessive 30, MIM# 607101; Deafness, autosomal dominant 90, MIM# 620722
Mendeliome v1.1550 MYO3A Zornitza Stark edited their review of gene: MYO3A: Changed phenotypes: Deafness, autosomal recessive 30, MIM# 607101, Deafness, autosomal dominant 90, MIM# 620722
Deafness_Isolated v1.53 TMTC2 Zornitza Stark Phenotypes for gene: TMTC2 were changed from Deafness to Deafness, autosomal dominant; Deafness, autosomal recessive 122, MIM# 620714
Deafness_Isolated v1.52 TMTC2 Zornitza Stark Publications for gene: TMTC2 were set to 29671961; 27311106
Deafness_Isolated v1.51 TMTC2 Zornitza Stark Mode of inheritance for gene: TMTC2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Deafness_Isolated v1.50 TMTC2 Zornitza Stark edited their review of gene: TMTC2: Added comment: Single family reported with bi-allelic variants. Mouse model.; Changed publications: 29671961, 27311106, 37943620, 30188326; Changed phenotypes: Deafness, autosomal dominant, Deafness, autosomal recessive 122, MIM# 620714; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v1.171 TMTC2 Zornitza Stark Phenotypes for gene: TMTC2 were changed from Deafness, autosomal dominant to Deafness, autosomal dominant; Deafness, autosomal recessive 122, MIM# 620714
Deafness_IsolatedAndComplex v1.170 TMTC2 Zornitza Stark Publications for gene: TMTC2 were set to
Deafness_IsolatedAndComplex v1.169 TMTC2 Zornitza Stark Mode of inheritance for gene: TMTC2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v1.168 TMTC2 Zornitza Stark commented on gene: TMTC2: Single family reported with bi-allelic variants. Mouse model.
Deafness_IsolatedAndComplex v1.168 TMTC2 Zornitza Stark edited their review of gene: TMTC2: Changed publications: 29671961, 27311106, 37943620, 30188326; Changed phenotypes: Deafness, autosomal recessive 122, MIM# 620714; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.1550 TMTC2 Zornitza Stark Phenotypes for gene: TMTC2 were changed from Deafness to Deafness, autosomal recessive 122, MIM# 620714
Mendeliome v1.1549 TMTC2 Zornitza Stark Publications for gene: TMTC2 were set to 29671961; 27311106
Mendeliome v1.1548 TMTC2 Zornitza Stark Mode of inheritance for gene: TMTC2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.1547 TMTC2 Zornitza Stark edited their review of gene: TMTC2: Added comment: Single family reported with bi-allelic variants.

Mouse model.; Changed publications: 29671961, 27311106, 37943620, 30188326; Changed phenotypes: Deafness, autosomal recessive 122, MIM# 620714; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Autism v0.196 TMLHE Bryony Thompson Classified gene: TMLHE as Red List (low evidence)
Autism v0.196 TMLHE Bryony Thompson Added comment: Comment on list classification: ClinGen Disputed gene-disease association Classification - 03/02/2021 by ID & Autism GCEP: https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_7a780ea6-ad4e-417a-a596-27188e327aad-2021-03-02T050000.000Z?page=1&size=25&search=
Autism v0.196 TMLHE Bryony Thompson Gene: tmlhe has been classified as Red List (Low Evidence).
Mendeliome v1.1547 TMLHE Bryony Thompson Classified gene: TMLHE as Red List (low evidence)
Mendeliome v1.1547 TMLHE Bryony Thompson Added comment: Comment on list classification: ClinGen Disputed gene-disease association Classification - 03/02/2021 by ID & Autism GCEP: https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_7a780ea6-ad4e-417a-a596-27188e327aad-2021-03-02T050000.000Z?page=1&size=25&search=
Mendeliome v1.1547 TMLHE Bryony Thompson Gene: tmlhe has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.5699 TMLHE Bryony Thompson Classified gene: TMLHE as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.5699 TMLHE Bryony Thompson Added comment: Comment on list classification: ClinGen Disputed gene-disease association Classification - 03/02/2021 by ID & Autism GCEP: https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_7a780ea6-ad4e-417a-a596-27188e327aad-2021-03-02T050000.000Z?page=1&size=25&search=
Intellectual disability syndromic and non-syndromic v0.5699 TMLHE Bryony Thompson Gene: tmlhe has been classified as Red List (Low Evidence).
Early-onset Parkinson disease v0.279 CSF1R Bryony Thompson Marked gene: CSF1R as ready
Early-onset Parkinson disease v0.279 CSF1R Bryony Thompson Gene: csf1r has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.279 CSF1R Bryony Thompson Phenotypes for gene: CSF1R were changed from to leukoencephalopathy, diffuse hereditary, with spheroids 1 MONDO:0800027
Early-onset Parkinson disease v0.278 CSF1R Bryony Thompson Publications for gene: CSF1R were set to
Early-onset Parkinson disease v0.277 CSF1R Bryony Thompson Mode of inheritance for gene: CSF1R was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.276 CSF1R Bryony Thompson Classified gene: CSF1R as Green List (high evidence)
Early-onset Parkinson disease v0.276 CSF1R Bryony Thompson Added comment: Comment on list classification: Parkinsonian signs can be a feature on the condition
Early-onset Parkinson disease v0.276 CSF1R Bryony Thompson Gene: csf1r has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.275 C19orf12 Bryony Thompson Marked gene: C19orf12 as ready
Early-onset Parkinson disease v0.275 C19orf12 Bryony Thompson Gene: c19orf12 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.275 C19orf12 Bryony Thompson Phenotypes for gene: C19orf12 were changed from to neurodegeneration with brain iron accumulation 4 MONDO:0013674
Early-onset Parkinson disease v0.274 C19orf12 Bryony Thompson Publications for gene: C19orf12 were set to
Early-onset Parkinson disease v0.273 C19orf12 Bryony Thompson Mode of inheritance for gene: C19orf12 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.272 ATP1A3 Bryony Thompson Marked gene: ATP1A3 as ready
Early-onset Parkinson disease v0.272 ATP1A3 Bryony Thompson Gene: atp1a3 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.272 ATP1A3 Bryony Thompson Phenotypes for gene: ATP1A3 were changed from to ATP1A3-associated neurological disorder MONDO:0700002
Early-onset Parkinson disease v0.271 ATP1A3 Bryony Thompson Publications for gene: ATP1A3 were set to
Early-onset Parkinson disease v0.270 ATP1A3 Bryony Thompson Mode of inheritance for gene: ATP1A3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.269 ATP1A3 Bryony Thompson Classified gene: ATP1A3 as Green List (high evidence)
Early-onset Parkinson disease v0.269 ATP1A3 Bryony Thompson Added comment: Comment on list classification: Parkinsonism is a major feature of the condition
Early-onset Parkinson disease v0.269 ATP1A3 Bryony Thompson Gene: atp1a3 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.268 ATP13A2 Bryony Thompson Marked gene: ATP13A2 as ready
Early-onset Parkinson disease v0.268 ATP13A2 Bryony Thompson Gene: atp13a2 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.268 ATP13A2 Bryony Thompson Phenotypes for gene: ATP13A2 were changed from to parkinsonism due to ATP13A2 deficiency MONDO:0017809
Early-onset Parkinson disease v0.267 ATP13A2 Bryony Thompson Publications for gene: ATP13A2 were set to
Early-onset Parkinson disease v0.266 ATP13A2 Bryony Thompson Mode of inheritance for gene: ATP13A2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.275 RAB34 Zornitza Stark Phenotypes for gene: RAB34 were changed from Multiple congenital anomalies, (MONDO:0019042), RAB34-related to Orofaciodigital syndrome 20, MIM#620718
Skeletal dysplasia v0.271 RAB34 Zornitza Stark Phenotypes for gene: RAB34 were changed from Multiple congenital anomalies, (MONDO:0019042), RAB34-related to Orofaciodigital syndrome 20, MIM#620718
Skeletal Dysplasia_Fetal v0.217 LFNG Elena Savva Marked gene: LFNG as ready
Skeletal Dysplasia_Fetal v0.217 LFNG Elena Savva Gene: lfng has been classified as Green List (High Evidence).
Spondylocostal Dysostosis v0.10 LFNG Elena Savva Phenotypes for gene: LFNG were changed from Spondylocostal dysostosis 3, autosomal recessive MIM#609813 to Spondylocostal dysostosis 3, autosomal recessive MIM#609813
Spondylocostal Dysostosis v0.10 LFNG Elena Savva Phenotypes for gene: LFNG were changed from to Spondylocostal dysostosis 3, autosomal recessive MIM#609813
Spondylocostal Dysostosis v0.9 LFNG Elena Savva Marked gene: LFNG as ready
Spondylocostal Dysostosis v0.9 LFNG Elena Savva Gene: lfng has been classified as Green List (High Evidence).
Skeletal Dysplasia_Fetal v0.217 LFNG Elena Savva Phenotypes for gene: LFNG were changed from to Spondylocostal dysostosis 3, autosomal recessive, MIM#609813
Skeletal Dysplasia_Fetal v0.216 LFNG Elena Savva Publications for gene: LFNG were set to
Skeletal Dysplasia_Fetal v0.216 LFNG Elena Savva Mode of inheritance for gene: LFNG was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v0.270 LFNG Elena Savva Marked gene: LFNG as ready
Skeletal dysplasia v0.270 LFNG Elena Savva Gene: lfng has been classified as Green List (High Evidence).
Skeletal dysplasia v0.270 LFNG Elena Savva Publications for gene: LFNG were set to 30196550; 16385447
Skeletal dysplasia v0.270 LFNG Elena Savva Phenotypes for gene: LFNG were changed from Spondylocostal dysostosis 3, autosomal recessive 609813 to Spondylocostal dysostosis 3, autosomal recessive MIM#609813
Skeletal dysplasia v0.269 LFNG Elena Savva Classified gene: LFNG as Green List (high evidence)
Skeletal dysplasia v0.269 LFNG Elena Savva Gene: lfng has been classified as Green List (High Evidence).
Polydactyly v0.274 RAB34 Elena Savva Classified gene: RAB34 as Green List (high evidence)
Polydactyly v0.274 RAB34 Elena Savva Gene: rab34 has been classified as Green List (High Evidence).
Polydactyly v0.273 RAB34 Elena Savva Classified gene: RAB34 as Green List (high evidence)
Polydactyly v0.273 RAB34 Elena Savva Gene: rab34 has been classified as Green List (High Evidence).
Polydactyly v0.272 RAB34 Elena Savva Marked gene: RAB34 as ready
Polydactyly v0.272 RAB34 Elena Savva Gene: rab34 has been classified as Red List (Low Evidence).
Polydactyly v0.272 RAB34 Elena Savva gene: RAB34 was added
gene: RAB34 was added to Polydactyly. Sources: Literature
Mode of inheritance for gene: RAB34 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RAB34 were set to 37619988; 37384395
Phenotypes for gene: RAB34 were set to Multiple congenital anomalies, (MONDO:0019042), RAB34-related
Review for gene: RAB34 was set to GREEN
Added comment: PMID: 37619988
- Compound heterozygous variants identified in a fetus with multiple malformations, including a combination of rarely occurring pre- and postaxial polydactyly.
- Rab34-/- mice displayed polydactyly.

PMID: 37384395
- Biallelic variants in RAB34 were identified in 3 unrelated families. All affected individuals presented a novel form of OFDS accompanied by prexial and central polydactyly/bilateral polysyndactyly
Sources: Literature
Skeletal dysplasia v0.268 RAB34 Elena Savva Marked gene: RAB34 as ready
Skeletal dysplasia v0.268 RAB34 Elena Savva Gene: rab34 has been classified as Green List (High Evidence).
Skeletal dysplasia v0.268 RAB34 Elena Savva Classified gene: RAB34 as Green List (high evidence)
Skeletal dysplasia v0.268 RAB34 Elena Savva Gene: rab34 has been classified as Green List (High Evidence).
Skeletal dysplasia v0.267 RAB34 Elena Savva gene: RAB34 was added
gene: RAB34 was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: RAB34 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RAB34 were set to 37619988; 37384395
Phenotypes for gene: RAB34 were set to Multiple congenital anomalies, (MONDO:0019042), RAB34-related
Review for gene: RAB34 was set to GREEN
Added comment: PMID: 37619988
- Compound heterozygous variants identified in RAB34 in a fetus with multiple malformations, including posterior neck edema, micrognathia, low-set and small ears, auricular hypoplasia, cleft lip and palate, short extremities, and a combination of rarely occurring pre- and postaxial polydactyly.
- Rab34-/- mice displayed a ciliopathy phenotype with cleft palate and polydactyly.

PMID: 37384395
- Biallelic variants in RAB34 were identified in 3 unrelated families. Affected individuals presented a novel form of OFDS accompanied by cardiac, cerebral, skeletal (eg. Shortening of long bones), and anorectal defects. Onset is prenatal (multiple developmental defects including short femur, polydactyly, heart malformations, kidney malformations, and brain malformations), resulting in medical termination for three probands.
Sources: Literature
Skeletal Dysplasia_Fetal v0.215 KIAA0586 Elena Savva Publications for gene: KIAA0586 were set to
Skeletal dysplasia v0.266 KIAA0586 Elena Savva Classified gene: KIAA0586 as Green List (high evidence)
Skeletal dysplasia v0.266 KIAA0586 Elena Savva Gene: kiaa0586 has been classified as Green List (High Evidence).
Skeletal Dysplasia_Fetal v0.214 KIAA0586 Elena Savva Phenotypes for gene: KIAA0586 were changed from to Joubert syndrome 23 MIM#616490; Short-rib thoracic dysplasia 14 with polydactyly MIM#616546
Skeletal dysplasia v0.266 KIAA0586 Elena Savva Classified gene: KIAA0586 as Green List (high evidence)
Skeletal dysplasia v0.266 KIAA0586 Elena Savva Gene: kiaa0586 has been classified as Green List (High Evidence).
Skeletal Dysplasia_Fetal v0.214 KIAA0586 Elena Savva Mode of inheritance for gene: KIAA0586 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v0.265 KIAA0586 Elena Savva Marked gene: KIAA0586 as ready
Skeletal dysplasia v0.265 KIAA0586 Elena Savva Gene: kiaa0586 has been classified as Red List (Low Evidence).
Skeletal dysplasia v0.265 KIAA0586 Elena Savva gene: KIAA0586 was added
gene: KIAA0586 was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: KIAA0586 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIAA0586 were set to PMID: 36538006; 26096313; 26166481
Phenotypes for gene: KIAA0586 were set to Joubert syndrome 23 MIM#616490; Short-rib thoracic dysplasia 14 with polydactyly MIM#616546
Review for gene: KIAA0586 was set to GREEN
Added comment: PMID: 36538006 - fetus with post-axial polydactyly, short limbs and persistent left superior vena cava (PLSVC) with a dilated coronary sinus. Chet variants c.3940+1G>A
and c.3303G>A (synonymous) were identified. Functional studies support an impact for both variants.

PMID: 26096313 - 9 unrelated families with Joubert syndrome. MRI shows the molar tooth sign in 3/3 scanned patients. Patients tended to have biallelic PTCs, though missense also reported. p.Arg143Lysfs*4 appears to be a recurring mutation, seen in patients either as a homozygote or in chet with another unique mutation in 7/9 families. Interestingly these 7 families were of different ethnicity

PMID: 26166481 - Four unrelated families reported with a severe neurological/skeletal phenotype. However, note same variant identified in three of the families, indicative of founder effect. Gene is also associated with Joubert syndrome.
Sources: Literature
Skeletal dysplasia v0.264 HYLS1 Elena Savva Marked gene: HYLS1 as ready
Skeletal dysplasia v0.264 HYLS1 Elena Savva Gene: hyls1 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v0.264 HYLS1 Elena Savva Phenotypes for gene: HYLS1 were changed from to Hydrolethalus syndrome MIM#236680
Skeletal dysplasia v0.264 HYLS1 Elena Savva Publications for gene: HYLS1 were set to
Skeletal dysplasia v0.263 HYLS1 Elena Savva Classified gene: HYLS1 as Amber List (moderate evidence)
Skeletal dysplasia v0.263 HYLS1 Elena Savva Gene: hyls1 has been classified as Amber List (Moderate Evidence).
Skeletal Dysplasia_Fetal v0.213 HYLS1 Elena Savva Publications for gene: HYLS1 were set to 15843405; 18648327; 19400947; 19656802; 32509774; 26830932
Skeletal Dysplasia_Fetal v0.212 HYLS1 Elena Savva edited their review of gene: HYLS1: Added comment: PMID: 34212369 - additional two fetuses with a phenotype of HLS with brain abnormalities, limbs malformations with pre and postaxial hexadactyly and abnormal genitalia. Probands were het for the Finnish founder variant (p.Asp211Gly) but each chet with a novel variant (p.(Arg221Pro, p.(Arg205*)). One fetus had occipital meningocele
molar tooth sign, the other craniorachischisis; Changed publications: PMID: 26830932, 34212369, 15843405, 18648327, 19400947, 19656802, 32509774; Changed phenotypes: Hydrolethalus syndrome MIM#236680
Prepair 1000+ v1.4 PIEZO1 Crystle Lee gene: PIEZO1 was added
gene: PIEZO1 was added to Prepair 1000+. Sources: Literature
Mode of inheritance for gene: PIEZO1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PIEZO1 were set to PMID: 26333996
Phenotypes for gene: PIEZO1 were set to Lymphatic malformation 6, MIM#616843
Review for gene: PIEZO1 was set to GREEN
Added comment: Biallelic mutations in PIEZO1 reported in 10 patients from 6 families with generalized lymphatic dysplasia (GLD) This is characterized by a uniform, widespread lymphedema affecting all segments of the body, with systemic involvement such as intestinal and/or pulmonary lymphangiectasia, pleural effusions, chylothoraces and/or pericardial effusions.
Sources: Literature
Mendeliome v1.1546 ANKZF1 Zornitza Stark reviewed gene: ANKZF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28302725, 36857589; Phenotypes: Infantile-onset inflammatory bowel disease, MONDO:0005265, ANKZF1-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Inflammatory bowel disease v0.118 ANKZF1 Zornitza Stark Publications for gene: ANKZF1 were set to 28302725
Inflammatory bowel disease v0.117 ANKZF1 Zornitza Stark Mode of inheritance for gene: ANKZF1 was changed from BIALLELIC, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Inflammatory bowel disease v0.116 ANKZF1 Zornitza Stark Classified gene: ANKZF1 as Green List (high evidence)
Inflammatory bowel disease v0.116 ANKZF1 Zornitza Stark Gene: ankzf1 has been classified as Green List (High Evidence).
Mendeliome v1.1546 CARD8 Zornitza Stark Classified gene: CARD8 as Amber List (moderate evidence)
Mendeliome v1.1546 CARD8 Zornitza Stark Gene: card8 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1545 CARD8 Zornitza Stark edited their review of gene: CARD8: Added comment: Additional individual reported with JRA and IBD.; Changed rating: AMBER; Changed publications: 29408806, 37724393
Inflammatory bowel disease v0.115 CARD8 Zornitza Stark Classified gene: CARD8 as Amber List (moderate evidence)
Inflammatory bowel disease v0.115 CARD8 Zornitza Stark Gene: card8 has been classified as Amber List (Moderate Evidence).
Inflammatory bowel disease v0.114 HSPA1L Zornitza Stark Marked gene: HSPA1L as ready
Inflammatory bowel disease v0.114 HSPA1L Zornitza Stark Gene: hspa1l has been classified as Amber List (Moderate Evidence).
Inflammatory bowel disease v0.114 HSPA1L Zornitza Stark Classified gene: HSPA1L as Amber List (moderate evidence)
Inflammatory bowel disease v0.114 HSPA1L Zornitza Stark Gene: hspa1l has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.192 RAB34 Zornitza Stark Phenotypes for gene: RAB34 were changed from Multiple congenital anomalies, (MONDO:0019042), RAB34-related to Orofaciodigital syndrome 20, MIM#620718
Clefting disorders v0.250 RAB34 Zornitza Stark Phenotypes for gene: RAB34 were changed from Multiple congenital anomalies, (MONDO:0019042), RAB34-related to Orofaciodigital syndrome 20, MIM#620718
Callosome v0.516 RAB34 Zornitza Stark Phenotypes for gene: RAB34 were changed from Multiple congenital anomalies, (MONDO:0019042), RAB34-related to Orofaciodigital syndrome 20, MIM#620718
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v1.12 RAB34 Zornitza Stark Phenotypes for gene: RAB34 were changed from Orofaciodigital syndrome 20, MIM#620718 to Orofaciodigital syndrome 20, MIM#620718
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v1.11 RAB34 Zornitza Stark Phenotypes for gene: RAB34 were changed from Multiple congenital anomalies, (MONDO:0019042), RAB34-related to Orofaciodigital syndrome 20, MIM#620718
Radial Ray Abnormalities v1.10 RAB34 Zornitza Stark Phenotypes for gene: RAB34 were changed from Multiple congenital anomalies, (MONDO:0019042), RAB34-related to Orofaciodigital syndrome 20, MIM#620718
Mendeliome v1.1545 RAB34 Zornitza Stark Phenotypes for gene: RAB34 were changed from Multiple congenital anomalies, (MONDO:0019042), RAB34-related to Orofaciodigital syndrome 20, MIM#620718
Ciliopathies v1.49 RAB34 Zornitza Stark Phenotypes for gene: RAB34 were changed from Multiple congenital anomalies, (MONDO:0019042), RAB34-related to Orofaciodigital syndrome 20, MIM#620718
Skeletal Dysplasia_Fetal v0.212 RAB34 Zornitza Stark Phenotypes for gene: RAB34 were changed from Multiple congenital anomalies, (MONDO:0019042), RAB34-related to Orofaciodigital syndrome 20, MIM#620718
Skeletal Dysplasia_Fetal v0.211 RAB34 Zornitza Stark reviewed gene: RAB34: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Orofaciodigital syndrome 20, MIM#620718; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1544 ONECUT1 Bryony Thompson Marked gene: ONECUT1 as ready
Mendeliome v1.1544 ONECUT1 Bryony Thompson Gene: onecut1 has been classified as Green List (High Evidence).
Mendeliome v1.1544 ONECUT1 Bryony Thompson Classified gene: ONECUT1 as Green List (high evidence)
Mendeliome v1.1544 ONECUT1 Bryony Thompson Gene: onecut1 has been classified as Green List (High Evidence).
Mendeliome v1.1543 ONECUT1 Bryony Thompson gene: ONECUT1 was added
gene: ONECUT1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ONECUT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ONECUT1 were set to 37639628; 34663987; 10825208
Phenotypes for gene: ONECUT1 were set to Neonatal diabetes mellitus MONDO:0016391
Review for gene: ONECUT1 was set to GREEN
Added comment: 3 unrelated neonatal diabetes cases with homozygous variants & supporting iPSC/mouse models
PMID: 37639628 - UK biobank study of ONECUT1 variants in neonatal diabetes mellitus (NDM), MODY, and type 2 diabetes. Identified a case with syndromic NDM with a homozygous frameshift (p.Met289Argfs*8). Rare heterozygous variants were not enriched in individuals with suspected MODY (n=484). Heterozygous null variants were significantly associated with type 2 diabetes (p=0.006) as a potential susceptibility gene.

PMID: 34663987 - 2 consanguineous families with homozygous variants (Glu231Ter or Glu231Asp) in cases with syndromic ND. Directed differentiation of human pluripotent stem cells revealed that loss of ONECUT1 impairs pancreatic progenitor formation.

PMID: 10825208 - Hnf6 (old gene name) null mice have diabetes
Sources: Literature
Monogenic Diabetes v0.46 ONECUT1 Bryony Thompson Marked gene: ONECUT1 as ready
Monogenic Diabetes v0.46 ONECUT1 Bryony Thompson Gene: onecut1 has been classified as Green List (High Evidence).
Monogenic Diabetes v0.46 ONECUT1 Bryony Thompson Phenotypes for gene: ONECUT1 were changed from Syndromic diabetes to Syndromic diabetes; Neonatal diabetes mellitus MONDO:0016391
Monogenic Diabetes v0.45 ONECUT1 Bryony Thompson Publications for gene: ONECUT1 were set to PMID: 34663987
Monogenic Diabetes v0.44 ONECUT1 Bryony Thompson Classified gene: ONECUT1 as Green List (high evidence)
Monogenic Diabetes v0.44 ONECUT1 Bryony Thompson Gene: onecut1 has been classified as Green List (High Evidence).
Monogenic Diabetes v0.43 ONECUT1 Bryony Thompson reviewed gene: ONECUT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 37639628, 34663987, 10825208; Phenotypes: Neonatal diabetes mellitus MONDO:0016391; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Inflammatory bowel disease v0.113 HSPA1L Zornitza Stark gene: HSPA1L was added
gene: HSPA1L was added to Inflammatory bowel disease. Sources: Literature
Mode of inheritance for gene: HSPA1L was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HSPA1L were set to 28126021
Phenotypes for gene: HSPA1L were set to inflammatory bowel disease, MONDO:0005265, HSPA1L-related
Review for gene: HSPA1L was set to AMBER
Added comment: PMID:28126021 reported the identification of a heterozygous de novo variant (p.Ser277Leu) in HSPA1L in a patient with inflammatory bowel disease. In addition, five additional rare HSPA1L variants (p.Gly77Ser, p.Leu172del, p.Thr267Ile, p.Ala268Thr, p.Glu558Asp) were identified in six patients from a cohort of 136 IBD patients with WES data. Functional studies showed that all six HSPA1L variant proteins showed decreased chaperone activity in vitro. Moreover, three variants demonstrated dominant negative effects on HSPA1L and HSPA1A protein activity.

However, the variants identified are present at relatively high frequencies in gnomad V4, in particular p.Thr267Ile is present in 281 individuals, and the p.Ala268Thr is present in 4,753 individuals.
Sources: Literature
Mendeliome v1.1542 HSPA1L Zornitza Stark Marked gene: HSPA1L as ready
Mendeliome v1.1542 HSPA1L Zornitza Stark Gene: hspa1l has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1542 HSPA1L Zornitza Stark Classified gene: HSPA1L as Amber List (moderate evidence)
Mendeliome v1.1542 HSPA1L Zornitza Stark Gene: hspa1l has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1541 HSPA1L Zornitza Stark reviewed gene: HSPA1L: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: inflammatory bowel disease, MONDO:0005265; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Systemic Autoinflammatory Disease_Periodic Fever v1.34 SCGN Zornitza Stark Marked gene: SCGN as ready
Systemic Autoinflammatory Disease_Periodic Fever v1.34 SCGN Zornitza Stark Gene: scgn has been classified as Amber List (Moderate Evidence).
Systemic Autoinflammatory Disease_Periodic Fever v1.34 SCGN Zornitza Stark Classified gene: SCGN as Amber List (moderate evidence)
Systemic Autoinflammatory Disease_Periodic Fever v1.34 SCGN Zornitza Stark Gene: scgn has been classified as Amber List (Moderate Evidence).
Systemic Autoinflammatory Disease_Periodic Fever v1.33 SCGN Zornitza Stark gene: SCGN was added
gene: SCGN was added to Systemic Autoinflammatory Disease_Periodic Fever. Sources: Literature
Mode of inheritance for gene: SCGN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SCGN were set to 31663849
Phenotypes for gene: SCGN were set to ulcerative colitis, MONDO:0005101
Review for gene: SCGN was set to AMBER
Added comment: PMID:31663849 reported three siblings with homozygous missense SCGN variant and with early-onset ulcerative colitis. Functional studies demonstrated that SCGN variant identified impacted the localisation of the SNARE complex partner, SNAP25, leading to impaired hormone release. In addition, SCGN knockout mouse model recapitulated impaired hormone release and susceptibility to DSS-induced colitis.
Sources: Literature
Mendeliome v1.1541 SCGN Zornitza Stark Marked gene: SCGN as ready
Mendeliome v1.1541 SCGN Zornitza Stark Gene: scgn has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1541 SCGN Zornitza Stark Classified gene: SCGN as Amber List (moderate evidence)
Mendeliome v1.1541 SCGN Zornitza Stark Gene: scgn has been classified as Amber List (Moderate Evidence).
Systemic Autoinflammatory Disease_Periodic Fever v1.32 SIRT1 Zornitza Stark Marked gene: SIRT1 as ready
Systemic Autoinflammatory Disease_Periodic Fever v1.32 SIRT1 Zornitza Stark Gene: sirt1 has been classified as Red List (Low Evidence).
Systemic Autoinflammatory Disease_Periodic Fever v1.32 SIRT1 Zornitza Stark gene: SIRT1 was added
gene: SIRT1 was added to Systemic Autoinflammatory Disease_Periodic Fever. Sources: Literature
Mode of inheritance for gene: SIRT1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SIRT1 were set to 23473037
Phenotypes for gene: SIRT1 were set to autoimmune disease, MONDO:0007179, SIRT1-related
Review for gene: SIRT1 was set to RED
Added comment: PMID:23473037 reported the identification of a missense SIRT1 variant (p.Leu107Pro) in five members of a single family and all five of them had autoimmune disorder, four had type I diabetes and one had ulcerative colitis.
Sources: Literature
Mendeliome v1.1540 SIRT1 Zornitza Stark Marked gene: SIRT1 as ready
Mendeliome v1.1540 SIRT1 Zornitza Stark Gene: sirt1 has been classified as Red List (Low Evidence).
Mendeliome v1.1540 SIRT1 Zornitza Stark Classified gene: SIRT1 as Red List (low evidence)
Mendeliome v1.1540 SIRT1 Zornitza Stark Gene: sirt1 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2290 TNRC6A Zornitza Stark Marked gene: TNRC6A as ready
Genetic Epilepsy v0.2290 TNRC6A Zornitza Stark Gene: tnrc6a has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2290 TNRC6A Zornitza Stark Phenotypes for gene: TNRC6A were changed from ?Epilepsy, familial adult myoclonic, 6 MIM#618074 to Epilepsy, familial adult myoclonic, 6 MIM#618074
Mendeliome v1.1539 TNRC6A Elena Savva Marked gene: TNRC6A as ready
Mendeliome v1.1539 TNRC6A Elena Savva Gene: tnrc6a has been classified as Red List (Low Evidence).
Mendeliome v1.1539 TNRC6A Elena Savva gene: TNRC6A was added
gene: TNRC6A was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TNRC6A was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: TNRC6A were set to PMID: 29507423; 33040085
Phenotypes for gene: TNRC6A were set to ?Epilepsy, familial adult myoclonic, 6 MIM#618074
Review for gene: TNRC6A was set to RED
Added comment: PMID: 29507423;33040085 - intronic expansion in a cohort with familial myoclonic epilepsy, also observed in controls but enriched in the affect cohort.

Gene was listed in the Oliver list
Sources: Literature
Genetic Epilepsy v0.2289 TNRC6A Elena Savva gene: TNRC6A was added
gene: TNRC6A was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: TNRC6A was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: TNRC6A were set to PMID: 29507423; 33040085
Phenotypes for gene: TNRC6A were set to ?Epilepsy, familial adult myoclonic, 6 MIM#618074
Review for gene: TNRC6A was set to RED
Added comment: PMID: 29507423;33040085 - intronic expansion in a cohort with familial myoclonic epilepsy, also observed in controls but enriched in the affect cohort.

Gene was listed in the Oliver list
Sources: Literature
Genetic Epilepsy v0.2289 TNRC6A Elena Savva gene: TNRC6A was added
gene: TNRC6A was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: TNRC6A was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: TNRC6A were set to PMID: 29507423; 33040085
Phenotypes for gene: TNRC6A were set to ?Epilepsy, familial adult myoclonic, 6 MIM#618074
Review for gene: TNRC6A was set to RED
Added comment: PMID: 29507423;33040085 - intronic expansion in a cohort with familial myoclonic epilepsy, also observed in controls but enriched in the affect cohort.

Gene was listed in the Oliver list
Sources: Literature
Genetic Epilepsy v0.2288 TLK2 Elena Savva Marked gene: TLK2 as ready
Genetic Epilepsy v0.2288 TLK2 Elena Savva Gene: tlk2 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2288 TLK2 Elena Savva Classified gene: TLK2 as Amber List (moderate evidence)
Genetic Epilepsy v0.2288 TLK2 Elena Savva Gene: tlk2 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2287 TLK2 Elena Savva gene: TLK2 was added
gene: TLK2 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: TLK2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: TLK2 were set to 37662408; 31558842
Phenotypes for gene: TLK2 were set to Intellectual developmental disorder, autosomal dominant 57 MIM#618050
Review for gene: TLK2 was set to AMBER
Added comment: Seizures (13%) in OMIM

PMID: 37662408 - NOT PEER REVIEWED. Patient presenting with ID, seizures, global developmental delay, hypothyroidism, and primary immunodeficiency. De novo missense found, but also another de novo PTC in MDM1. Functional studies support missense pathogenicity

PMID: 31558842 - HOM missense patient with a severe neurodev disorder, parents are clinically unaffected. She presented with epileptic spasms at the age of 6 months. Her EEG showed hypsarrhythmia suggesting West syndrome. She has been seizure-free since 3 years of age.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5698 FBXO31 Lucy Spencer reviewed gene: FBXO31: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Intellectual developmental disorder, autosomal recessive 45 (MIM#615979); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1538 FBXO31 Lucy Spencer reviewed gene: FBXO31: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Intellectual developmental disorder, autosomal recessive 45 (MIM#615979); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1538 SIRT1 Achchuthan Shanmugasundram gene: SIRT1 was added
gene: SIRT1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SIRT1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SIRT1 were set to 23473037
Phenotypes for gene: SIRT1 were set to autoimmune disease, MONDO:0007179
Review for gene: SIRT1 was set to RED
Added comment: PMID:23473037 reported the identification of a missense SIRT1 variant (p.Leu107Pro) in five members of a single family and all five of them had autoimmune disorder, four had type I diabetes and one had ulcerative colitis.
Sources: Literature
Mendeliome v1.1538 SCGN Achchuthan Shanmugasundram gene: SCGN was added
gene: SCGN was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SCGN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SCGN were set to 31663849
Phenotypes for gene: SCGN were set to ulcerative colitis, MONDO:0005101
Review for gene: SCGN was set to AMBER
Added comment: PMID:31663849 reported three siblings with homozygous missense SCGN variant and with early-onset ulcerative colitis. Functional studies demonstrated that SCGN variant identified impacted the localisation of the SNARE complex partner, SNAP25, leading to impaired hormone release. In addition, SCGN knockout mouse model recapitulated impaired hormone release and susceptibility to DSS-induced colitis.
Sources: Literature
Mendeliome v1.1538 HSPA1L Achchuthan Shanmugasundram gene: HSPA1L was added
gene: HSPA1L was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: HSPA1L was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HSPA1L were set to 28126021
Phenotypes for gene: HSPA1L were set to inflammatory bowel disease, MONDO:0005265
Review for gene: HSPA1L was set to GREEN
Added comment: PMID:28126021 reported the identification of a heterozygous de novo variant (p.Ser277Leu) in HSPA1L in a patient with inflammatory bowel disease. In addition, five additional rare HSPA1L variants (p.Gly77Ser, p.Leu172del, p.Thr267Ile, p.Ala268Thr, p.Glu558Asp) were identified in six patients from a cohort of 136 IBD patients with WES data.

Functional studies showed that all six HSPA1L variant proteins showed decreased chaperone activity in vitro. Moreover, three variants demonstrated dominant negative effects on HSPA1L and HSPA1A protein activity.
Sources: Literature
Inflammatory bowel disease v0.112 CARD8 Achchuthan Shanmugasundram reviewed gene: CARD8: Rating: AMBER; Mode of pathogenicity: None; Publications: 37724393; Phenotypes: ?Inflammatory bowel disease (Crohn disease) 30, OMIM:619079; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Inflammatory bowel disease v0.112 ANKZF1 Achchuthan Shanmugasundram reviewed gene: ANKZF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28302725, 36857589; Phenotypes: inflammatory bowel disease, MONDO:0005265; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Neurodegeneration with brain iron accumulation v0.31 DDHD1 Shekeeb Mohammad gene: DDHD1 was added
gene: DDHD1 was added to Neuroferritinopathies. Sources: Literature
Mode of inheritance for gene: DDHD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DDHD1 were set to 28818478
Phenotypes for gene: DDHD1 were set to spastic paraplegia; sensory neuropathy
Review for gene: DDHD1 was set to GREEN
gene: DDHD1 was marked as current diagnostic
Added comment: Sources: Literature
Neurodegeneration with brain iron accumulation v0.31 THAP1 Shekeeb Mohammad gene: THAP1 was added
gene: THAP1 was added to Neuroferritinopathies. Sources: Literature
Mode of inheritance for gene: THAP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: THAP1 were set to 38094642; 33665847
Phenotypes for gene: THAP1 were set to cervical dystonia; dystonia; dystonic tremor
Review for gene: THAP1 was set to GREEN
gene: THAP1 was marked as current diagnostic
Added comment: 3 published cases; 1 under clinical care with a pathogenic THAP1 variant.
Sources: Literature
Neurodegeneration with brain iron accumulation v0.31 SQSTM1 Shekeeb Mohammad gene: SQSTM1 was added
gene: SQSTM1 was added to Neuroferritinopathies. Sources: Literature
Mode of inheritance for gene: SQSTM1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SQSTM1 were set to 27545679
Phenotypes for gene: SQSTM1 were set to ataxia; dystonia; gaze palsy; neuroregression; cognitive decline; childhood dementia
Review for gene: SQSTM1 was set to GREEN
gene: SQSTM1 was marked as current diagnostic
Added comment: Sources: Literature
Neurodegeneration with brain iron accumulation v0.31 ATP7B Shekeeb Mohammad reviewed gene: ATP7B: Rating: GREEN; Mode of pathogenicity: None; Publications: 33680437, 28376267, 34289020; Phenotypes: ; Mode of inheritance: None; Current diagnostic: yes
Genetic Epilepsy v0.2286 FLNA Zornitza Stark Marked gene: FLNA as ready
Genetic Epilepsy v0.2286 FLNA Zornitza Stark Gene: flna has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2286 FLNA Zornitza Stark Phenotypes for gene: FLNA were changed from to Heterotopia, periventricular, 1, MIM# 300049
Genetic Epilepsy v0.2285 FLNA Zornitza Stark Publications for gene: FLNA were set to
Genetic Epilepsy v0.2284 FLNA Zornitza Stark Mode of inheritance for gene: FLNA was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Genetic Epilepsy v0.2283 FKTN Zornitza Stark Marked gene: FKTN as ready
Genetic Epilepsy v0.2283 FKTN Zornitza Stark Gene: fktn has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2283 FKTN Zornitza Stark Phenotypes for gene: FKTN were changed from to Muscular dystrophy-dystroglycanopathy MONDO:0018276
Genetic Epilepsy v0.2282 FKTN Zornitza Stark Publications for gene: FKTN were set to
Genetic Epilepsy v0.2281 FKTN Zornitza Stark Mode of inheritance for gene: FKTN was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2280 FKTN Zornitza Stark reviewed gene: FKTN: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Muscular dystrophy-dystroglycanopathy MONDO:0018276; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2280 FBXL4 Zornitza Stark Marked gene: FBXL4 as ready
Genetic Epilepsy v0.2280 FBXL4 Zornitza Stark Gene: fbxl4 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2280 FBXL4 Zornitza Stark Phenotypes for gene: FBXL4 were changed from to Mitochondrial DNA depletion syndrome 13 (encephalomyopathic type) MIM#615471
Genetic Epilepsy v0.2279 FBXL4 Zornitza Stark Publications for gene: FBXL4 were set to
Genetic Epilepsy v0.2278 FBXL4 Zornitza Stark Mode of inheritance for gene: FBXL4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2277 FBXL4 Zornitza Stark reviewed gene: FBXL4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Mitochondrial DNA depletion syndrome 13 (encephalomyopathic type) MIM#615471; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2277 FARS2 Zornitza Stark Marked gene: FARS2 as ready
Genetic Epilepsy v0.2277 FARS2 Zornitza Stark Gene: fars2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2277 FARS2 Zornitza Stark Phenotypes for gene: FARS2 were changed from to combined oxidative phosphorylation defect type 14 MONDO:0013986
Genetic Epilepsy v0.2276 FARS2 Zornitza Stark Publications for gene: FARS2 were set to
Genetic Epilepsy v0.2275 FARS2 Zornitza Stark Mode of inheritance for gene: FARS2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2274 TET3 Zornitza Stark Marked gene: TET3 as ready
Genetic Epilepsy v0.2274 TET3 Zornitza Stark Gene: tet3 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2274 TET3 Zornitza Stark Classified gene: TET3 as Green List (high evidence)
Genetic Epilepsy v0.2274 TET3 Zornitza Stark Gene: tet3 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2273 TET3 Zornitza Stark reviewed gene: TET3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Beck-Fahrner syndrome MIM#618798; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v1.191 THOC2 Zornitza Stark Phenotypes for gene: THOC2 were changed from Mental retardation, X-linked 12/35 MIM#300957 to Mental retardation, X-linked 12/35 MIM#300957; Arthrogryposis (MONDO:0008779), THOC2-related
Fetal anomalies v1.190 THOC2 Zornitza Stark Publications for gene: THOC2 were set to 26166480; 32116545; 29851191; 32960281
Fetal anomalies v1.189 THOC2 Zornitza Stark edited their review of gene: THOC2: Added comment: PMID: 34976470 - arthrogryposis multiplex congenita phenotype (AMC) in two male fetuses in a family, caused by splice deletion c.2482-1_2484delGTCA which was mat inherited. No splice studies conducted, mother was normal. Postulate that amorphic or severe null pathogenic variants (possible complete loss of function) lead to AMC phenotype

PMID: 37945483 - a proband with AMC and the same splice site mutation ^ above, but de novo. Cytoplasmic bodies also detected in muscle; Changed publications: 29851191, 34976470, 37945483; Changed phenotypes: Mental retardation, X-linked 12/35 MIM#300957, Arthrogryposis (MONDO:0008779), THOC2-related
Genetic Epilepsy v0.2273 TK2 Elena Savva Marked gene: TK2 as ready
Genetic Epilepsy v0.2273 TK2 Elena Savva Gene: tk2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2273 TK2 Elena Savva Classified gene: TK2 as Green List (high evidence)
Genetic Epilepsy v0.2273 TK2 Elena Savva Gene: tk2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2272 TK2 Elena Savva gene: TK2 was added
gene: TK2 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: TK2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TK2 were set to 25446393; 16504786
Phenotypes for gene: TK2 were set to Mitochondrial DNA depletion syndrome 2 (myopathic type), MIM#609560; Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 3, MIM# 617069
Review for gene: TK2 was set to GREEN
Added comment: GeneReviews: Seizures 11/34 (32%) in infantile onset cases

PMID: 25446393 - two siblings with chet missense, presenting with early onset myopathy with profound loss of muscle mass, axonal neuropathy, respiratory failure as well as severe brain atrophy with status epilepticus.

PMID: 16504786 - five children in two families reported with infantile encephalomyopathy with biallelic missense. Generalised seizures described in 2/3 siblings from one family
Sources: Literature
Genetic Epilepsy v0.2271 THOC2 Elena Savva Marked gene: THOC2 as ready
Genetic Epilepsy v0.2271 THOC2 Elena Savva Gene: thoc2 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2271 THOC2 Elena Savva Classified gene: THOC2 as Amber List (moderate evidence)
Genetic Epilepsy v0.2271 THOC2 Elena Savva Gene: thoc2 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2270 THOC2 Elena Savva gene: THOC2 was added
gene: THOC2 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: THOC2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: THOC2 were set to PMID: 26166480; 29851191
Phenotypes for gene: THOC2 were set to Intellectual developmental disorder, X-linked 12 MIM#300957
Review for gene: THOC2 was set to AMBER
Added comment: Seizures (in some patients) described in OMIM

PMID: 26166480 - gene-disease establishing paper, epilepsy described in 5/20 individuals where affected individuals were from three families. Only missense reported but all segregated well in families and had backing functional studies.

PMID: 29851191 - overlapping authors with ^, expanded cohort. Only 1/7 probands had epilepsy with an additional proband "suspected"
Sources: Literature
Arthrogryposis v0.405 THOC2 Elena Savva Classified gene: THOC2 as Amber List (moderate evidence)
Arthrogryposis v0.405 THOC2 Elena Savva Gene: thoc2 has been classified as Amber List (Moderate Evidence).
Arthrogryposis v0.405 THOC2 Elena Savva Classified gene: THOC2 as Amber List (moderate evidence)
Arthrogryposis v0.405 THOC2 Elena Savva Gene: thoc2 has been classified as Amber List (Moderate Evidence).
Arthrogryposis v0.404 THOC2 Elena Savva Classified gene: THOC2 as Amber List (moderate evidence)
Arthrogryposis v0.404 THOC2 Elena Savva Gene: thoc2 has been classified as Amber List (Moderate Evidence).
Arthrogryposis v0.403 THOC2 Elena Savva Marked gene: THOC2 as ready
Arthrogryposis v0.403 THOC2 Elena Savva Gene: thoc2 has been classified as Red List (Low Evidence).
Arthrogryposis v0.403 THOC2 Elena Savva gene: THOC2 was added
gene: THOC2 was added to Arthrogryposis. Sources: Literature
Mode of inheritance for gene: THOC2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: THOC2 were set to PMID: 34976470; 37945483
Phenotypes for gene: THOC2 were set to Arthrogryposis (MONDO:0008779), THOC2-related
Review for gene: THOC2 was set to AMBER
Added comment: PMID: 34976470 - arthrogryposis multiplex congenita phenotype (AMC) in two male fetuses in a family, caused by splice deletion c.2482-1_2484delGTCA which was mat inherited. No splice studies conducted, mother was normal.
Postulate that amorphic or severe null pathogenic variants (possible complete loss of function) lead to AMC phenotype

PMID: 37945483 - a proband with AMC and the same splice site mutation ^ above, but de novo. Cytoplasmic bodies also detected in muscle
Sources: Literature
Genetic Epilepsy v0.2269 TGIF1 Elena Savva Marked gene: TGIF1 as ready
Genetic Epilepsy v0.2269 TGIF1 Elena Savva Gene: tgif1 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2269 TGIF1 Elena Savva gene: TGIF1 was added
gene: TGIF1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: TGIF1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: TGIF1 were set to Holoprosencephaly 4 MIM#142946
Review for gene: TGIF1 was set to RED
Added comment: Gene was listed in the Oliver list
Sources: Literature
Genetic Epilepsy v0.2268 TET3 Elena Savva gene: TET3 was added
gene: TET3 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: TET3 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: TET3 were set to 36192301
Phenotypes for gene: TET3 were set to Beck-Fahrner syndrome MIM#618798
Review for gene: TET3 was set to AMBER
Added comment: Seizures (in some patients) noted in OMIM

GeneReviews: seizure disorder described in 9/24 patients

PMID: 36192301 - de novo PTC, generalized tonic-clonic seizures began at 5yo

Difficulty finding additional literature stating patient phenotypes
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5698 TET3 Elena Savva Phenotypes for gene: TET3 were changed from Intellectual disability; dysmorphic features; abnormal growth; movement disorders to Beck-Fahrner syndrome MIM#618798
Mendeliome v1.1538 TET3 Elena Savva Phenotypes for gene: TET3 were changed from Intellectual disability; dysmorphic features; abnormal growth; movement disorders to Beck-Fahrner syndrome MIM#618798
Genetic Epilepsy v0.2267 TBC1D7 Elena Savva Marked gene: TBC1D7 as ready
Genetic Epilepsy v0.2267 TBC1D7 Elena Savva Gene: tbc1d7 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2267 TBC1D7 Elena Savva gene: TBC1D7 was added
gene: TBC1D7 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: TBC1D7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TBC1D7 were set to 23687350; 24515783
Phenotypes for gene: TBC1D7 were set to Macrocephaly/megalencephaly syndrome, autosomal recessive MIM#248000
Review for gene: TBC1D7 was set to RED
Added comment: PMID: 23687350 - There is no history of seizures in two siblings, but EEG recording showed some epileptic activity in the right temporal lobe

PMID: 24515783 - There is no history of seizures; EEG and brain SPECT were normal.

Gene was listed in the Oliver list
Sources: Literature
Genetic Epilepsy v0.2266 EIF2B4 Zornitza Stark Marked gene: EIF2B4 as ready
Genetic Epilepsy v0.2266 EIF2B4 Zornitza Stark Added comment: Comment when marking as ready: Seizures are a feature.
Genetic Epilepsy v0.2266 EIF2B4 Zornitza Stark Gene: eif2b4 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2266 EIF2B4 Zornitza Stark Phenotypes for gene: EIF2B4 were changed from to leukoencephalopathy with vanishing white matter MONDO:0011380
Genetic Epilepsy v0.2265 EIF2B4 Zornitza Stark Publications for gene: EIF2B4 were set to
Genetic Epilepsy v0.2264 EIF2B4 Zornitza Stark Mode of inheritance for gene: EIF2B4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2263 EIF2B3 Zornitza Stark Marked gene: EIF2B3 as ready
Genetic Epilepsy v0.2263 EIF2B3 Zornitza Stark Gene: eif2b3 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2263 EIF2B3 Zornitza Stark Phenotypes for gene: EIF2B3 were changed from to leukoencephalopathy with vanishing white matter MONDO:0011380
Genetic Epilepsy v0.2262 EIF2B3 Zornitza Stark Publications for gene: EIF2B3 were set to
Genetic Epilepsy v0.2261 EIF2B3 Zornitza Stark Mode of inheritance for gene: EIF2B3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2260 EIF2B2 Zornitza Stark Marked gene: EIF2B2 as ready
Genetic Epilepsy v0.2260 EIF2B2 Zornitza Stark Gene: eif2b2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2260 EIF2B2 Zornitza Stark Phenotypes for gene: EIF2B2 were changed from to Leukoencephalopathy with vanishing white matter, MIM#603896; Ovarioleukodystrophy, MIM# 603896
Genetic Epilepsy v0.2259 EIF2B2 Zornitza Stark Publications for gene: EIF2B2 were set to
Genetic Epilepsy v0.2258 EIF2B2 Zornitza Stark Mode of inheritance for gene: EIF2B2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2257 EIF2B1 Zornitza Stark Marked gene: EIF2B1 as ready
Genetic Epilepsy v0.2257 EIF2B1 Zornitza Stark Gene: eif2b1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2257 EIF2B1 Zornitza Stark Phenotypes for gene: EIF2B1 were changed from to Leukoencephalopathy with vanishing white matter MIM#603896; Neonatal diabetes mellitus, MONDO:0016391, EIF2B1-related
Genetic Epilepsy v0.2256 EIF2B1 Zornitza Stark Publications for gene: EIF2B1 were set to
Genetic Epilepsy v0.2255 EIF2B1 Zornitza Stark Mode of inheritance for gene: EIF2B1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genetic Epilepsy v0.2254 POMK Zornitza Stark Marked gene: POMK as ready
Genetic Epilepsy v0.2254 POMK Zornitza Stark Gene: pomk has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2254 POMK Zornitza Stark Classified gene: POMK as Amber List (moderate evidence)
Genetic Epilepsy v0.2254 POMK Zornitza Stark Gene: pomk has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2253 POMK Zornitza Stark reviewed gene: POMK: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 12 MIM#615249; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1537 PRDM8 Zornitza Stark Marked gene: PRDM8 as ready
Mendeliome v1.1537 PRDM8 Zornitza Stark Gene: prdm8 has been classified as Red List (Low Evidence).
Mendeliome v1.1537 PRDM8 Zornitza Stark gene: PRDM8 was added
gene: PRDM8 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: PRDM8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PRDM8 were set to 2296154; 35034233
Phenotypes for gene: PRDM8 were set to Epilepsy, progressive myoclonic, 10 MIM#616640
Review for gene: PRDM8 was set to RED
Added comment: - PMID:22961547, 3 individuals from one family, all with myoclonic epilepsy, all had the Phe261Leu variant. This variant is absent from gnomAD V4.
- PMID: 35034233, Two individuals from one family, no clinical seizures but presented with myoclonus and abnormal EEG (generalised epileptiform charges), these individuals had the Ala230Gly missense change, which has currently been reported as a VUS.
Sources: Expert list
Genetic Epilepsy v0.2253 PRDM8 Zornitza Stark Marked gene: PRDM8 as ready
Genetic Epilepsy v0.2253 PRDM8 Zornitza Stark Gene: prdm8 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2253 PRDM8 Zornitza Stark Classified gene: PRDM8 as Red List (low evidence)
Genetic Epilepsy v0.2253 PRDM8 Zornitza Stark Gene: prdm8 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2252 PRDM8 Zornitza Stark Classified gene: PRDM8 as Red List (low evidence)
Genetic Epilepsy v0.2252 PRDM8 Zornitza Stark Gene: prdm8 has been classified as Red List (Low Evidence).
Mendeliome v1.1536 PRIMA1 Zornitza Stark Marked gene: PRIMA1 as ready
Mendeliome v1.1536 PRIMA1 Zornitza Stark Gene: prima1 has been classified as Red List (Low Evidence).
Mendeliome v1.1536 PRIMA1 Zornitza Stark gene: PRIMA1 was added
gene: PRIMA1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: PRIMA1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PRIMA1 were set to 26339676
Phenotypes for gene: PRIMA1 were set to Frontal Lobe Epilepsy MONDO:0002612
Review for gene: PRIMA1 was set to RED
Added comment: - 2/3 siblings from unaffected parents in PMID: 26339676 were diagnosed with nocturnal frontal lobe epilepsy, which was confirmed by EEG. The affected siblings were homozygous for the c.93+2T>C variant canonical splice site variant. This variant was demonstrated by mini-gene assay to skip exon 2 of PRIMA1. Overall 1 family, 2 individuals with epilepsy and high impact variants in PRIMA1.
Sources: Expert list
Genetic Epilepsy v0.2251 PRIMA1 Zornitza Stark Marked gene: PRIMA1 as ready
Genetic Epilepsy v0.2251 PRIMA1 Zornitza Stark Gene: prima1 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2251 PRIMA1 Zornitza Stark Classified gene: PRIMA1 as Red List (low evidence)
Genetic Epilepsy v0.2251 PRIMA1 Zornitza Stark Gene: prima1 has been classified as Red List (Low Evidence).
Fetal anomalies v1.189 MAX Zornitza Stark Phenotypes for gene: MAX were changed from Syndromic disease (MONDO:0002254), MAX-related to Polydactyly-macrocephaly syndrome, MIM# 620712
Fetal anomalies v1.188 MAX Zornitza Stark reviewed gene: MAX: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Polydactyly-macrocephaly syndrome, MIM# 620712; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5697 MAX Zornitza Stark Phenotypes for gene: MAX were changed from Syndromic disease (MONDO:0002254), MAX-related to Polydactyly-macrocephaly syndrome, MIM# 620712
Polydactyly v0.271 MAX Zornitza Stark Phenotypes for gene: MAX were changed from Syndromic disease (MONDO:0002254), MAX-related to Polydactyly-macrocephaly syndrome, MIM# 620712
Polydactyly v0.270 MAX Zornitza Stark reviewed gene: MAX: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Polydactyly-macrocephaly syndrome, MIM# 620712; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.1535 MAX Zornitza Stark Phenotypes for gene: MAX were changed from {Pheochromocytoma, susceptibility to}, MIM# 171300; Syndromic disease (MONDO:0002254), MAX-related to {Pheochromocytoma, susceptibility to}, MIM# 171300; Polydactyly-macrocephaly syndrome, MIM# 620712
Macrocephaly_Megalencephaly v0.139 MAX Zornitza Stark Phenotypes for gene: MAX were changed from Syndromic disease (MONDO:0002254), MAX-related to Polydactyly-macrocephaly syndrome, MIM# 620712
Macrocephaly_Megalencephaly v0.138 MAX Zornitza Stark reviewed gene: MAX: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Polydactyly-macrocephaly syndrome, MIM# 620712; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2250 PPP2R5D Zornitza Stark Marked gene: PPP2R5D as ready
Genetic Epilepsy v0.2250 PPP2R5D Zornitza Stark Gene: ppp2r5d has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2250 PPP2R5D Zornitza Stark Publications for gene: PPP2R5D were set to
Genetic Epilepsy v0.2249 PPP2R5D Zornitza Stark Classified gene: PPP2R5D as Green List (high evidence)
Genetic Epilepsy v0.2249 PPP2R5D Zornitza Stark Gene: ppp2r5d has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2248 POMGNT2 Zornitza Stark Marked gene: POMGNT2 as ready
Genetic Epilepsy v0.2248 POMGNT2 Zornitza Stark Gene: pomgnt2 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2248 POMGNT2 Zornitza Stark Classified gene: POMGNT2 as Amber List (moderate evidence)
Genetic Epilepsy v0.2248 POMGNT2 Zornitza Stark Gene: pomgnt2 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2247 POMGNT2 Zornitza Stark reviewed gene: POMGNT2: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 8 MIM#614830; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2247 POGZ Zornitza Stark Marked gene: POGZ as ready
Genetic Epilepsy v0.2247 POGZ Zornitza Stark Gene: pogz has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2247 POGZ Zornitza Stark Classified gene: POGZ as Green List (high evidence)
Genetic Epilepsy v0.2247 POGZ Zornitza Stark Gene: pogz has been classified as Green List (High Evidence).
Mendeliome v1.1534 PLXNC1 Zornitza Stark Marked gene: PLXNC1 as ready
Mendeliome v1.1534 PLXNC1 Zornitza Stark Gene: plxnc1 has been classified as Red List (Low Evidence).
Mendeliome v1.1534 PLXNC1 Zornitza Stark gene: PLXNC1 was added
gene: PLXNC1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: PLXNC1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PLXNC1 were set to 36808730
Phenotypes for gene: PLXNC1 were set to Malformations of cortical development
Review for gene: PLXNC1 was set to RED
Added comment: This gene was included in the genes4epilepsy resource (PMID:36808730) and was reported as being associated with the clinical phenotype "malformations of cortical development". There are no current PubMed articles linking this gene with epilepsy however
Sources: Expert list
Genetic Epilepsy v0.2246 PLXNC1 Zornitza Stark Marked gene: PLXNC1 as ready
Genetic Epilepsy v0.2246 PLXNC1 Zornitza Stark Gene: plxnc1 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2246 PLXNC1 Zornitza Stark Classified gene: PLXNC1 as Red List (low evidence)
Genetic Epilepsy v0.2246 PLXNC1 Zornitza Stark Gene: plxnc1 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2245 PEX13 Zornitza Stark Marked gene: PEX13 as ready
Genetic Epilepsy v0.2245 PEX13 Zornitza Stark Gene: pex13 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2245 PEX13 Zornitza Stark Classified gene: PEX13 as Green List (high evidence)
Genetic Epilepsy v0.2245 PEX13 Zornitza Stark Gene: pex13 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2244 PEX10 Zornitza Stark Marked gene: PEX10 as ready
Genetic Epilepsy v0.2244 PEX10 Zornitza Stark Gene: pex10 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2244 PEX10 Zornitza Stark Classified gene: PEX10 as Red List (low evidence)
Genetic Epilepsy v0.2244 PEX10 Zornitza Stark Gene: pex10 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2243 PCLO Zornitza Stark Marked gene: PCLO as ready
Genetic Epilepsy v0.2243 PCLO Zornitza Stark Gene: pclo has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2243 PCLO Zornitza Stark Classified gene: PCLO as Red List (low evidence)
Genetic Epilepsy v0.2243 PCLO Zornitza Stark Gene: pclo has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2242 PAX6 Zornitza Stark Marked gene: PAX6 as ready
Genetic Epilepsy v0.2242 PAX6 Zornitza Stark Gene: pax6 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2242 PAX6 Zornitza Stark Classified gene: PAX6 as Amber List (moderate evidence)
Genetic Epilepsy v0.2242 PAX6 Zornitza Stark Gene: pax6 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2241 PAK3 Zornitza Stark Marked gene: PAK3 as ready
Genetic Epilepsy v0.2241 PAK3 Zornitza Stark Gene: pak3 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2241 PAK3 Zornitza Stark Classified gene: PAK3 as Amber List (moderate evidence)
Genetic Epilepsy v0.2241 PAK3 Zornitza Stark Gene: pak3 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2240 OFD1 Zornitza Stark Marked gene: OFD1 as ready
Genetic Epilepsy v0.2240 OFD1 Zornitza Stark Gene: ofd1 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2240 OFD1 Zornitza Stark Classified gene: OFD1 as Amber List (moderate evidence)
Genetic Epilepsy v0.2240 OFD1 Zornitza Stark Gene: ofd1 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2239 NR2F1 Zornitza Stark Marked gene: NR2F1 as ready
Genetic Epilepsy v0.2239 NR2F1 Zornitza Stark Gene: nr2f1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2239 NR2F1 Zornitza Stark Classified gene: NR2F1 as Green List (high evidence)
Genetic Epilepsy v0.2239 NR2F1 Zornitza Stark Gene: nr2f1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2238 NF1 Zornitza Stark Marked gene: NF1 as ready
Genetic Epilepsy v0.2238 NF1 Zornitza Stark Gene: nf1 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2238 NF1 Zornitza Stark Classified gene: NF1 as Amber List (moderate evidence)
Genetic Epilepsy v0.2238 NF1 Zornitza Stark Gene: nf1 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2237 MCM3AP Zornitza Stark Marked gene: MCM3AP as ready
Genetic Epilepsy v0.2237 MCM3AP Zornitza Stark Gene: mcm3ap has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2237 MCM3AP Zornitza Stark Classified gene: MCM3AP as Red List (low evidence)
Genetic Epilepsy v0.2237 MCM3AP Zornitza Stark Gene: mcm3ap has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2236 LRPPRC Zornitza Stark Marked gene: LRPPRC as ready
Genetic Epilepsy v0.2236 LRPPRC Zornitza Stark Gene: lrpprc has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2236 LRPPRC Zornitza Stark Classified gene: LRPPRC as Amber List (moderate evidence)
Genetic Epilepsy v0.2236 LRPPRC Zornitza Stark Gene: lrpprc has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2235 COL3A1 Zornitza Stark Marked gene: COL3A1 as ready
Genetic Epilepsy v0.2235 COL3A1 Zornitza Stark Gene: col3a1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2235 COL3A1 Zornitza Stark Classified gene: COL3A1 as Green List (high evidence)
Genetic Epilepsy v0.2235 COL3A1 Zornitza Stark Gene: col3a1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2234 CHD1 Zornitza Stark Marked gene: CHD1 as ready
Genetic Epilepsy v0.2234 CHD1 Zornitza Stark Gene: chd1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2234 CHD1 Zornitza Stark Classified gene: CHD1 as Green List (high evidence)
Genetic Epilepsy v0.2234 CHD1 Zornitza Stark Gene: chd1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2233 SERAC1 Zornitza Stark Classified gene: SERAC1 as Green List (high evidence)
Genetic Epilepsy v0.2233 SERAC1 Zornitza Stark Gene: serac1 has been classified as Green List (High Evidence).
Mendeliome v1.1533 CASZ1 Zornitza Stark Marked gene: CASZ1 as ready
Mendeliome v1.1533 CASZ1 Zornitza Stark Gene: casz1 has been classified as Green List (High Evidence).
Mendeliome v1.1533 CASZ1 Zornitza Stark Classified gene: CASZ1 as Green List (high evidence)
Mendeliome v1.1533 CASZ1 Zornitza Stark Gene: casz1 has been classified as Green List (High Evidence).
Mendeliome v1.1532 CASZ1 Zornitza Stark gene: CASZ1 was added
gene: CASZ1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: CASZ1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CASZ1 were set to 28099117; 36293425; 31268246
Phenotypes for gene: CASZ1 were set to Dilated cardiomyopathy, MONDO:0005021, CASZ1-related; left ventricular non compaction
Review for gene: CASZ1 was set to GREEN
Added comment: Rare cause of paeditric onsent DCM. at least 3 papers report LoF variants, 2 of which each report a novel de novo frameshift variant in children diagnosed with DCM less than 1 and who died at 11 mths ( PMID: 31268246; Guo 2019) and 22mths (PMID: 36293425, Orlova 2022). Another paper (PMID: 28099117, Qiu 2017) reported a nonsense variant that segregated with DCM in a family in an AD fashion (full text not available).
Sources: Expert list
Cardiomyopathy_Paediatric v0.180 CASZ1 Zornitza Stark Marked gene: CASZ1 as ready
Cardiomyopathy_Paediatric v0.180 CASZ1 Zornitza Stark Gene: casz1 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v0.180 CASZ1 Zornitza Stark Phenotypes for gene: CASZ1 were changed from dilated cardiomyopathy, left ventricular non compaction to Dilated cardiomyopathy, MONDO:0005021, CASZ1-related; left ventricular non compaction
Cardiomyopathy_Paediatric v0.179 CASZ1 Zornitza Stark Classified gene: CASZ1 as Green List (high evidence)
Cardiomyopathy_Paediatric v0.179 CASZ1 Zornitza Stark Gene: casz1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2232 SRCAP Zornitza Stark Classified gene: SRCAP as Green List (high evidence)
Genetic Epilepsy v0.2232 SRCAP Zornitza Stark Gene: srcap has been classified as Green List (High Evidence).
Mendeliome v1.1531 SMC3 Zornitza Stark Publications for gene: SMC3 were set to 18996922; 25655089; 31334757
Genetic Epilepsy v0.2231 SYNE1 Zornitza Stark Phenotypes for gene: SYNE1 were changed from Arthrogryposis multiplex congenita 3, myogenic type MIM#618484; Emery-Dreifuss muscular dystrophy 4, autosomal dominant MIM#612998; Spinocerebellar ataxia, autosomal recessive 8 MIM#610743 to Neurodevelopmental disorder, MONDO:0700092
Genetic Epilepsy v0.2230 SYNE1 Zornitza Stark Mode of inheritance for gene: SYNE1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5696 TAF1C Zornitza Stark Marked gene: TAF1C as ready
Intellectual disability syndromic and non-syndromic v0.5696 TAF1C Zornitza Stark Gene: taf1c has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2229 TAOK1 Zornitza Stark Marked gene: TAOK1 as ready
Genetic Epilepsy v0.2229 TAOK1 Zornitza Stark Gene: taok1 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.5696 NDUFB9 Zornitza Stark Publications for gene: NDUFB9 were set to 22200994
Intellectual disability syndromic and non-syndromic v0.5695 NDUFB9 Zornitza Stark edited their review of gene: NDUFB9: Added comment: PMID: 38129218: Thr144Met, listed as ACMG-P, hom in 1x pt with mito complex I deficiency and leukodystrophy, no functional studies, both parents are het. However, this variant has 2 homozygotes in gnomADv4, so unlikely pathogenic.; Changed publications: 22200994, 38129218
Mitochondrial disease v0.916 NDUFB9 Zornitza Stark Publications for gene: NDUFB9 were set to
Mendeliome v1.1530 NDUFB9 Zornitza Stark Publications for gene: NDUFB9 were set to 22200994
Mendeliome v1.1529 NDUFB9 Zornitza Stark edited their review of gene: NDUFB9: Added comment: PMID: 38129218: Thr144Met, listed as ACMG-P, hom in 1x pt with mito complex I deficiency and leukodystrophy, no functional studies, both parents are het.

However, this variant has 2 homozygotes in gnomADv4 so unlikely pathogenic.; Changed publications: 22200994, 38129218
Mitochondrial disease v0.915 NDUFB9 Chern Lim reviewed gene: NDUFB9: Rating: AMBER; Mode of pathogenicity: None; Publications: 38129218; Phenotypes: Mitochondrial complex I deficiency, nuclear type 24, MIM#618245; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Renal Macrocystic Disease v0.68 NEK8 Elena Savva Classified gene: NEK8 as Green List (high evidence)
Renal Macrocystic Disease v0.68 NEK8 Elena Savva Gene: nek8 has been classified as Green List (High Evidence).
Renal Macrocystic Disease v0.67 NEK8 Elena Savva Publications for gene: NEK8 were set to Unpublished ESHG presentation
Mendeliome v1.1529 DNM2 Bryony Thompson reviewed gene: DNM2: Rating: RED; Mode of pathogenicity: None; Publications: 23092955; Phenotypes: fetal akinesia-cerebral and retinal hemorrhage syndrome MONDO:0014149; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2229 NALCN Zornitza Stark Marked gene: NALCN as ready
Genetic Epilepsy v0.2229 NALCN Zornitza Stark Gene: nalcn has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2229 NALCN Zornitza Stark Classified gene: NALCN as Green List (high evidence)
Genetic Epilepsy v0.2229 NALCN Zornitza Stark Gene: nalcn has been classified as Green List (High Evidence).
Renal Macrocystic Disease v0.66 NEK8 Lauren Rogers reviewed gene: NEK8: Rating: GREEN; Mode of pathogenicity: None; Publications: 37598857; Phenotypes: Familial cystic renal disease MONDO:0019741; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2228 TAOK1 Elena Savva gene: TAOK1 was added
gene: TAOK1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: TAOK1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: TAOK1 were set to Developmental delay with or without intellectual impairment or behavioral abnormalities MIM#619575
Review for gene: TAOK1 was set to RED
Added comment: No reports found of patients with seizures/epilepsy.

Gene was listed in the Oliver list
Sources: Literature
Genetic Epilepsy v0.2228 TAOK1 Elena Savva gene: TAOK1 was added
gene: TAOK1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: TAOK1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: TAOK1 were set to Developmental delay with or without intellectual impairment or behavioral abnormalities MIM#619575
Review for gene: TAOK1 was set to RED
Added comment: No reports found of patients with seizures/epilepsy.

Gene was listed in the Oliver list
Sources: Literature
Genetic Epilepsy v0.2227 TANC2 Elena Savva Marked gene: TANC2 as ready
Genetic Epilepsy v0.2227 TANC2 Elena Savva Gene: tanc2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2227 TANC2 Elena Savva Classified gene: TANC2 as Green List (high evidence)
Genetic Epilepsy v0.2227 TANC2 Elena Savva Gene: tanc2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2226 TANC2 Elena Savva gene: TANC2 was added
gene: TANC2 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: TANC2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: TANC2 were set to PMID: 31616000
Phenotypes for gene: TANC2 were set to Intellectual developmental disorder with autistic features and language delay, with or without seizures MIM#618906
Review for gene: TANC2 was set to GREEN
Added comment: PMID: 31616000 - 11/20 individuals had either a formal diagnosis of epilepsy (n = 9) or suffered from recurrent seizures (n = 2).
Sources: Literature
Genetic Epilepsy v0.2225 TAF1C Elena Savva Marked gene: TAF1C as ready
Intellectual disability syndromic and non-syndromic v0.5695 TAF1C Elena Savva Phenotypes for gene: TAF1C were changed from Global developmental delay; Intellectual disability; Spasticity; Strabismus; Seizures; Abnormality of nervous system morphology to Neurodevelopmental disorder (MONDO#0700092), TAF1C-related
Genetic Epilepsy v0.2225 TAF1C Elena Savva Gene: taf1c has been classified as Red List (Low Evidence).
Mendeliome v1.1529 TAF1C Elena Savva Phenotypes for gene: TAF1C were changed from Global developmental delay; Intellectual disability; Spasticity; Strabismus; Seizures; Abnormality of nervous system morphology to Neurodevelopmental disorder (MONDO#0700092), TAF1C-related
Genetic Epilepsy v0.2225 TAF1C Elena Savva gene: TAF1C was added
gene: TAF1C was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: TAF1C was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TAF1C were set to 32779182
Phenotypes for gene: TAF1C were set to Neurodevelopmental disorder (MONDO#0700092), TAF1C-related
Review for gene: TAF1C was set to RED
Added comment: Knuutinen et al (2020 - PMID: 32779182) report on 2 individuals from 2 consanguineous families, homozygous for TAF1C missense variants. Both presented with an early onset neurological phenotype with severe global DD, ID (2/2 - moderate and profound), spasticity (2/2), ophthalmic findings (strabismus 2/2, nystagmus 1/2). Epilepsy, abnormal brain MRI (cerebral and cerebellar atrophy and white matter hyperintensities) as well and additional findings were reported in one (always the same individual).

NO hom PTCs in gnomAD v4
Sources: Literature
Genetic Epilepsy v0.2224 SYNE1 Elena Savva Marked gene: SYNE1 as ready
Genetic Epilepsy v0.2224 SYNE1 Elena Savva Gene: syne1 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2224 SYNE1 Elena Savva gene: SYNE1 was added
gene: SYNE1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: SYNE1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: SYNE1 were set to PMID: 31703138; 37096302; 30573412
Phenotypes for gene: SYNE1 were set to Arthrogryposis multiplex congenita 3, myogenic type MIM#618484; Emery-Dreifuss muscular dystrophy 4, autosomal dominant MIM#612998; Spinocerebellar ataxia, autosomal recessive 8 MIM#610743
Review for gene: SYNE1 was set to RED
Added comment: PMID: 31703138 - PTC in a child featuring infantile epilepsy and developmental disorder, inherited from a father with a history of convulsions in infancy

PMID: 37096302;30573412 - review, no reports noted of patients with seizures/epilepsy.

Gene was listed in the Oliver list
Sources: Literature
Genetic Epilepsy v0.2223 SUMF1 Elena Savva Marked gene: SUMF1 as ready
Genetic Epilepsy v0.2223 SUMF1 Elena Savva Gene: sumf1 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2223 SUMF1 Elena Savva gene: SUMF1 was added
gene: SUMF1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: SUMF1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SUMF1 were set to 36980153; 36959582
Phenotypes for gene: SUMF1 were set to Multiple sulfatase deficiency MIM#272200
Review for gene: SUMF1 was set to RED
Added comment: PMID: 36980153 - review, no patients described with seizures/epilepsy

PMID: 36959582 - review, no patients described with seizures/epilepsy. Single proband in the study reported to have intractable epilepsy during sleep EEG study

Gene was listed in the Oliver list
Sources: Literature
Mendeliome v1.1528 SMC3 Bryony Thompson reviewed gene: SMC3: Rating: GREEN; Mode of pathogenicity: None; Publications: 38297832; Phenotypes: Cornelia de Lange syndrome MONDO:0016033; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Genetic Epilepsy v0.2222 SRCAP Elena Savva Classified gene: SRCAP as Amber List (moderate evidence)
Genetic Epilepsy v0.2222 SRCAP Elena Savva Gene: srcap has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2222 SRCAP Elena Savva Marked gene: SRCAP as ready
Genetic Epilepsy v0.2222 SRCAP Elena Savva Gene: srcap has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2222 SRCAP Elena Savva Classified gene: SRCAP as Amber List (moderate evidence)
Genetic Epilepsy v0.2222 SRCAP Elena Savva Gene: srcap has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2221 SRCAP Elena Savva gene: SRCAP was added
gene: SRCAP was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: SRCAP was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SRCAP were set to 23193612; 23621943
Phenotypes for gene: SRCAP were set to Developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities MIM#619595; Floating-Harbor syndrome MIM#136140
Review for gene: SRCAP was set to AMBER
Added comment: OMIM: Seizures listed as a rare trait for both conditions

GeneReviews: Seizures have been observed in seven of 73 individuals.

PMID: 23621943: review, 6/52 patients reported with seizures
Sources: Literature
Genetic Epilepsy v0.2220 SOX11 Elena Savva Mode of pathogenicity for gene: SOX11 was changed from None to None
Genetic Epilepsy v0.2219 SOX11 Elena Savva Marked gene: SOX11 as ready
Genetic Epilepsy v0.2219 SOX11 Elena Savva Gene: sox11 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2219 SOX11 Elena Savva gene: SOX11 was added
gene: SOX11 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: SOX11 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: SOX11 were set to Intellectual developmental disorder with microcephaly and with or without ocular malformations or hypogonadotropic hypogonadism MIM#615866
Review for gene: SOX11 was set to RED
Added comment: No reports found of patients with seizures/epilepsy.

Gene was listed in the Oliver list
Sources: Literature
Genetic Epilepsy v0.2218 SON Elena Savva Classified gene: SON as Green List (high evidence)
Genetic Epilepsy v0.2218 SON Elena Savva Gene: son has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2217 SON Elena Savva Classified gene: SON as Green List (high evidence)
Genetic Epilepsy v0.2217 SON Elena Savva Gene: son has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2217 SON Elena Savva Classified gene: SON as Green List (high evidence)
Genetic Epilepsy v0.2217 SON Elena Savva Gene: son has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2216 SON Elena Savva Marked gene: SON as ready
Genetic Epilepsy v0.2216 SON Elena Savva Gene: son has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2216 SON Elena Savva gene: SON was added
gene: SON was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: SON was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SON were set to PMID: 37488749; 27545680
Phenotypes for gene: SON were set to ZTTK syndrome MIM#617140
Review for gene: SON was set to GREEN
Added comment: Seizures (in some patients) noted in OMIM

PMID: 37488749 - review of 79 patients, seizures not described

PMID: 27545680 - 11 of 20 individuals developed seizures and/or epilepsy with an age of onset ranging from 1 to 6 years
Sources: Literature
Cardiomyopathy_Paediatric v0.178 CASZ1 Ivan Macciocca gene: CASZ1 was added
gene: CASZ1 was added to Cardiomyopathy_Paediatric. Sources: Literature
Mode of inheritance for gene: CASZ1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CASZ1 were set to PMID: 28099117; 36293425; 31268246
Phenotypes for gene: CASZ1 were set to dilated cardiomyopathy, left ventricular non compaction
Penetrance for gene: CASZ1 were set to unknown
Review for gene: CASZ1 was set to GREEN
Added comment: rare cause of paeditric onsent DCM.
at least 3 papers report LoF variants, 2 of which each report a novel de novo frameshift variant in children diagnosed with DCM less than 1 and who died at 11 mths ( PMID: 31268246; Guo 2019) and 22mths (PMID: 36293425, Orlova 2022). Another paper (PMID: 28099117, Qiu 2017) reported a nonsense variant that segregated with DCM in a family in an AD fashion (full text not available).
Sources: Literature
Genetic Epilepsy v0.2215 BET1 Zornitza Stark Phenotypes for gene: BET1 were changed from Muscular dystrophy MONDO:0020121 to Muscular dystrophy, congenital, with rapid progression, MIM# 254100
Genetic Epilepsy v0.2214 BET1 Zornitza Stark edited their review of gene: BET1: Changed phenotypes: Muscular dystrophy, congenital, with rapid progression, MIM# 254100
Muscular dystrophy and myopathy_Paediatric v1.11 BET1 Zornitza Stark Phenotypes for gene: BET1 were changed from Muscular dystrophy; Epilepsy to Muscular dystrophy, congenital, with rapid progression, MIM# 254100
Muscular dystrophy and myopathy_Paediatric v1.10 BET1 Zornitza Stark edited their review of gene: BET1: Changed phenotypes: Muscular dystrophy, congenital, with rapid progression, MIM# 254100
Mendeliome v1.1528 BET1 Zornitza Stark Phenotypes for gene: BET1 were changed from Muscular dystrophy, MONDO:0019950, BET1-related; Epilepsy to Muscular dystrophy, congenital, with rapid progression, MIM# 254100
Mendeliome v1.1527 BET1 Zornitza Stark edited their review of gene: BET1: Changed phenotypes: Muscular dystrophy, congenital, with rapid progression, MIM# 254100
Intellectual disability syndromic and non-syndromic v0.5694 CSTF2 Zornitza Stark Phenotypes for gene: CSTF2 were changed from Intellectual disability to Intellectual developmental disorder, X-linked 113, MIM# 301116
Intellectual disability syndromic and non-syndromic v0.5693 CSTF2 Zornitza Stark edited their review of gene: CSTF2: Changed phenotypes: Intellectual developmental disorder, X-linked 113, MIM# 301116
Mendeliome v1.1527 CSTF2 Zornitza Stark Phenotypes for gene: CSTF2 were changed from Intellectual disability to Intellectual developmental disorder, X-linked 113, MIM# 301116
Mendeliome v1.1526 CSTF2 Zornitza Stark edited their review of gene: CSTF2: Changed phenotypes: Intellectual developmental disorder, X-linked 113, MIM# 301116
Hypertrophic cardiomyopathy_HCM v0.176 TTR Zornitza Stark Tag treatable tag was added to gene: TTR.
Mendeliome v1.1526 TTR Zornitza Stark Tag treatable tag was added to gene: TTR.
Fetal anomalies v1.188 NARS Zornitza Stark Marked gene: NARS as ready
Fetal anomalies v1.188 NARS Zornitza Stark Gene: nars has been classified as Green List (High Evidence).
Fetal anomalies v1.188 NARS Zornitza Stark Classified gene: NARS as Green List (high evidence)
Fetal anomalies v1.188 NARS Zornitza Stark Gene: nars has been classified as Green List (High Evidence).
Congenital Heart Defect v0.412 DLG5 Zornitza Stark Marked gene: DLG5 as ready
Congenital Heart Defect v0.412 DLG5 Zornitza Stark Gene: dlg5 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.412 DLG5 Zornitza Stark Classified gene: DLG5 as Green List (high evidence)
Congenital Heart Defect v0.412 DLG5 Zornitza Stark Gene: dlg5 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.411 DLG5 Zornitza Stark gene: DLG5 was added
gene: DLG5 was added to Congenital Heart Defect. Sources: Expert list
Mode of inheritance for gene: DLG5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DLG5 were set to 32631816
Phenotypes for gene: DLG5 were set to Yuksel-Vogel-Bauer syndrome, MIM#620703
Review for gene: DLG5 was set to GREEN
Added comment: Four unrelated families reported, supportive Xenopus animal model data. Cystic kidneys, nephrotic syndrome, hydrocephalus, limb abnormalities, congenital heart disease and craniofacial malformations.
Sources: Expert list
Renal Ciliopathies and Nephronophthisis v1.22 DLG5 Zornitza Stark Marked gene: DLG5 as ready
Renal Ciliopathies and Nephronophthisis v1.22 DLG5 Zornitza Stark Gene: dlg5 has been classified as Green List (High Evidence).
Renal Ciliopathies and Nephronophthisis v1.22 DLG5 Zornitza Stark Classified gene: DLG5 as Green List (high evidence)
Renal Ciliopathies and Nephronophthisis v1.22 DLG5 Zornitza Stark Gene: dlg5 has been classified as Green List (High Evidence).
Renal Ciliopathies and Nephronophthisis v1.21 DLG5 Zornitza Stark gene: DLG5 was added
gene: DLG5 was added to Renal Ciliopathies and Nephronophthisis. Sources: Expert Review
Mode of inheritance for gene: DLG5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DLG5 were set to 32631816
Phenotypes for gene: DLG5 were set to Yuksel-Vogel-Bauer syndrome, MIM#620703
Review for gene: DLG5 was set to GREEN
Added comment: Four unrelated families reported, supportive Xenopus animal model data. Cystic kidneys, nephrotic syndrome, hydrocephalus, limb abnormalities, congenital heart disease and craniofacial malformations.
Sources: Expert Review
Hydrocephalus_Ventriculomegaly v0.123 DLG5 Zornitza Stark Marked gene: DLG5 as ready
Hydrocephalus_Ventriculomegaly v0.123 DLG5 Zornitza Stark Gene: dlg5 has been classified as Green List (High Evidence).
Hydrocephalus_Ventriculomegaly v0.123 DLG5 Zornitza Stark Classified gene: DLG5 as Green List (high evidence)
Hydrocephalus_Ventriculomegaly v0.123 DLG5 Zornitza Stark Gene: dlg5 has been classified as Green List (High Evidence).
Hydrocephalus_Ventriculomegaly v0.122 DLG5 Zornitza Stark gene: DLG5 was added
gene: DLG5 was added to Hydrocephalus_Ventriculomegaly. Sources: Expert Review
Mode of inheritance for gene: DLG5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DLG5 were set to 32631816
Phenotypes for gene: DLG5 were set to Yuksel-Vogel-Bauer syndrome, MIM#620703
Review for gene: DLG5 was set to GREEN
Added comment: Four unrelated families reported, supportive Xenopus animal model data. Cystic kidneys, nephrotic syndrome, hydrocephalus, limb abnormalities, congenital heart disease and craniofacial malformations.
Sources: Expert Review
Fetal anomalies v1.187 DLG5 Zornitza Stark Marked gene: DLG5 as ready
Fetal anomalies v1.187 DLG5 Zornitza Stark Gene: dlg5 has been classified as Green List (High Evidence).
Fetal anomalies v1.187 DLG5 Zornitza Stark Classified gene: DLG5 as Green List (high evidence)
Fetal anomalies v1.187 DLG5 Zornitza Stark Gene: dlg5 has been classified as Green List (High Evidence).
Fetal anomalies v1.186 DLG5 Zornitza Stark gene: DLG5 was added
gene: DLG5 was added to Fetal anomalies. Sources: Expert Review
Mode of inheritance for gene: DLG5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DLG5 were set to 32631816
Phenotypes for gene: DLG5 were set to Yuksel-Vogel-Bauer syndrome, MIM#620703
Review for gene: DLG5 was set to GREEN
Added comment: Four unrelated families reported, supportive Xenopus animal model data. Cystic kidneys, nephrotic syndrome, hydrocephalus, limb abnormalities, congenital heart disease and craniofacial malformations.
Sources: Expert Review
Mendeliome v1.1526 DLG5 Zornitza Stark Phenotypes for gene: DLG5 were changed from Ciliopathy, MONDO:0016044, DLG5-related; Cystic kidneys, nephrotic syndrome, hydrocephalus, limb abnormalities, congenital heart disease and craniofacial malformations to Yuksel-Vogel-Bauer syndrome, MIM#620703
Mendeliome v1.1525 DLG5 Zornitza Stark edited their review of gene: DLG5: Changed phenotypes: Yuksel-Vogel-Bauer syndrome, MIM#620703
Mendeliome v1.1525 DLG5 Zornitza Stark changed review comment from: Four unrelated families reported, supportive Xenopus animal model data.
Sources: Literature; to: Four unrelated families reported, supportive Xenopus animal model data. Cystic kidneys, nephrotic syndrome, hydrocephalus, limb abnormalities, congenital heart disease and craniofacial malformations.
Sources: Literature
Ciliopathies v1.48 DLG5 Zornitza Stark Phenotypes for gene: DLG5 were changed from Ciliopathy, MONDO:0016044, DLG5-related; Cystic kidneys, nephrotic syndrome, hydrocephalus, limb abnormalities, congenital heart disease and craniofacial malformations to Yuksel-Vogel-Bauer syndrome, MIM#620703
Ciliopathies v1.47 DLG5 Zornitza Stark edited their review of gene: DLG5: Changed phenotypes: Yuksel-Vogel-Bauer syndrome, MIM#620703
Ciliopathies v1.47 DLG5 Zornitza Stark changed review comment from: Four unrelated families reported, supportive Xenopus animal model data.
Sources: Literature; to: Four unrelated families reported, supportive Xenopus animal model data. Cystic kidneys, nephrotic syndrome, hydrocephalus, limb abnormalities, congenital heart disease and craniofacial malformations.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5693 ASCC3 Zornitza Stark Marked gene: ASCC3 as ready
Intellectual disability syndromic and non-syndromic v0.5693 ASCC3 Zornitza Stark Gene: ascc3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5693 ASCC3 Zornitza Stark Classified gene: ASCC3 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5693 ASCC3 Zornitza Stark Gene: ascc3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5692 ASCC3 Zornitza Stark gene: ASCC3 was added
gene: ASCC3 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review
Mode of inheritance for gene: ASCC3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ASCC3 were set to 21937992; 35047834
Phenotypes for gene: ASCC3 were set to Intellectual developmental disorder, autosomal recessive 81, MIM# 620700
Review for gene: ASCC3 was set to GREEN
Added comment: Combined neuromuscular and neurobehavioral phenotype.

11 individuals from 7 unrelated families with homozygous (missense) or compound heterozygous variants (missense with a presumed LoF variant or 2 missense, no biallelic LoF) with a neurologic phenotype that ranges from severe developmental delay to muscle fatigue
Sources: Expert Review
Muscular dystrophy and myopathy_Paediatric v1.10 ASCC3 Zornitza Stark Phenotypes for gene: ASCC3 were changed from Congenital Myopathy (MONDO:0019952); Neuromuscular Symptoms to Intellectual developmental disorder, autosomal recessive 81, MIM# 620700
Muscular dystrophy and myopathy_Paediatric v1.9 ASCC3 Zornitza Stark Publications for gene: ASCC3 were set to 35047834
Muscular dystrophy and myopathy_Paediatric v1.8 ASCC3 Zornitza Stark reviewed gene: ASCC3: Rating: GREEN; Mode of pathogenicity: None; Publications: 35047834; Phenotypes: Intellectual developmental disorder, autosomal recessive 81, MIM# 620700; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1525 ASCC3 Zornitza Stark Phenotypes for gene: ASCC3 were changed from Neuromuscular syndrome; congenital myopathy to Intellectual developmental disorder, autosomal recessive 81, MIM# 620700
Mendeliome v1.1524 ASCC3 Zornitza Stark Publications for gene: ASCC3 were set to 21937992; https://doi.org/10.1016/j.xhgg.2021.100024
Mendeliome v1.1523 ASCC3 Zornitza Stark reviewed gene: ASCC3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Intellectual developmental disorder, autosomal recessive 81, MIM# 620700; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5691 GIGYF1 Zornitza Stark Phenotypes for gene: GIGYF1 were changed from Autism, Intellectual disability, GIGYF1-related (MONDO#0001071) to Autism spectrum disorder (MONDO:0005258), GIGYF1-related
Mendeliome v1.1523 GIGYF1 Zornitza Stark Phenotypes for gene: GIGYF1 were changed from Autism, Intellectual disability, GIGYF1-related (MONDO#0001071) to Autism spectrum disorder (MONDO:0005258), GIGYF1-related
Intellectual disability syndromic and non-syndromic v0.5690 SYN1 Zornitza Stark Mode of inheritance for gene: SYN1 was changed from BIALLELIC, autosomal or pseudoautosomal to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Genetic Epilepsy v0.2214 SNAP29 Elena Savva Marked gene: SNAP29 as ready
Genetic Epilepsy v0.2214 SNAP29 Elena Savva Gene: snap29 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2214 SNAP29 Elena Savva Classified gene: SNAP29 as Green List (high evidence)
Genetic Epilepsy v0.2214 SNAP29 Elena Savva Gene: snap29 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2213 SNAP29 Elena Savva gene: SNAP29 was added
gene: SNAP29 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: SNAP29 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SNAP29 were set to PMID: 33977139
Phenotypes for gene: SNAP29 were set to Cerebral dysgenesis, neuropathy, ichthyosis, and palmoplantar keratoderma syndrome MIM#609528
Review for gene: SNAP29 was set to GREEN
Added comment: Seizures (in some patients) noted in OMIM

PMID: 33977139 - cohort of 6 probands, seizures detected in 3/6. Paper reviews previous reports, notes seizures in another cohort of 7/19
Sources: Literature
Genetic Epilepsy v0.2212 SMARCE1 Elena Savva Marked gene: SMARCE1 as ready
Genetic Epilepsy v0.2212 SMARCE1 Elena Savva Gene: smarce1 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2212 SMARCE1 Elena Savva gene: SMARCE1 was added
gene: SMARCE1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: SMARCE1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SMARCE1 were set to PMID: 30548424
Phenotypes for gene: SMARCE1 were set to Coffin-Siris syndrome 5 MIM#616938
Review for gene: SMARCE1 was set to RED
Added comment: PMID: 30548424 - Proband with a de novo splice variant (proven to result in inframe exon skipping), presented with seizures, hypotonia, GDD, ataxia etc.

No other literature showing SNVs in this gene and epilepsy/seizures. Gene was listed in the Oliver review
Sources: Literature
Genetic Epilepsy v0.2211 SLC19A3 Elena Savva Marked gene: SLC19A3 as ready
Genetic Epilepsy v0.2211 SLC19A3 Elena Savva Gene: slc19a3 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2211 SLC19A3 Elena Savva Classified gene: SLC19A3 as Green List (high evidence)
Genetic Epilepsy v0.2211 SLC19A3 Elena Savva Gene: slc19a3 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2210 SLC19A3 Elena Savva gene: SLC19A3 was added
gene: SLC19A3 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: SLC19A3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC19A3 were set to PMID: 37670342; 23269594; 26863430
Phenotypes for gene: SLC19A3 were set to Thiamine metabolism dysfunction syndrome 2 (biotin- or thiamine-responsive encephalopathy type 2) MIM#607483
Review for gene: SLC19A3 was set to GREEN
Added comment: Seizures noted in OMIM

PMID: 37670342 - 1/21 probands had absence seizure on Depakene. Hom missense but many families in this paper had the same variant (likely founder).

PMID: 23269594 - 8/10 patients had acute-subacute onset consisting of ataxia, seizures, and encephalopathy. All probands had the same recurring missense described in PMID: 37670342.

PMID: 26863430 - two siblings with early-onset encephalopathy dystonia and epilepsy,
Sources: Literature
Genetic Epilepsy v0.2209 SHANK3 Elena Savva Marked gene: SHANK3 as ready
Genetic Epilepsy v0.2209 SHANK3 Elena Savva Gene: shank3 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2209 SHANK3 Elena Savva Classified gene: SHANK3 as Green List (high evidence)
Genetic Epilepsy v0.2209 SHANK3 Elena Savva Gene: shank3 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2209 SHANK3 Elena Savva Classified gene: SHANK3 as Green List (high evidence)
Genetic Epilepsy v0.2209 SHANK3 Elena Savva Gene: shank3 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2208 SHANK3 Elena Savva gene: SHANK3 was added
gene: SHANK3 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: SHANK3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SHANK3 were set to PMID: 37655421
Phenotypes for gene: SHANK3 were set to Phelan-McDermid syndrome MIM#606232
Review for gene: SHANK3 was set to GREEN
Added comment: Seizures listed in OMIM, SHANK3 is often involved in a 22q13.3 deletion

PMID: 37655421 - Proband with a PTC, presenting with epileptic seizures, impaired speech development

PMID: 36967043 - large review, considered patients who had the 22q13.3 deletion as well as SNVs. Prevalence of epilepsy ranged from 17-70% in one study, 27% in another study and 41% in another. Seizure type was highly variable, ranging from atypical absent, tonic, atonic, tonic-clonic and myoclonic.
Sources: Literature
Genetic Epilepsy v0.2207 SERAC1 Elena Savva Marked gene: SERAC1 as ready
Genetic Epilepsy v0.2207 SERAC1 Elena Savva Gene: serac1 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2207 SERAC1 Elena Savva Classified gene: SERAC1 as Amber List (moderate evidence)
Genetic Epilepsy v0.2207 SERAC1 Elena Savva Gene: serac1 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2206 SERAC1 Elena Savva gene: SERAC1 was added
gene: SERAC1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: SERAC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SERAC1 were set to PMID: 27186703; 24997715
Phenotypes for gene: SERAC1 were set to 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome MIM#614739
Review for gene: SERAC1 was set to AMBER
Added comment: Seizures (less common) listed in OMIM

PMID: 27186703 - two sibling patients who presented with 3-methylglutaconic acid and 3-methylglutaric aciduria, microcephaly, growth retardation, dysmorphic features, severe sensorineural deafness, progressive spasticity, dystonia, seizures and basal ganglia involvement.

PMID: 24997715 - Proband with biallelic PTCs, presented with 3-methylglutaconic aciduria, sensorineural hearing loss, encephalopathy, and Leigh-like pattern on MRI, as well as developmental delay and developmental regression, bilateral optic nerve atrophy, microcephaly, and myoclonic epilepsy.

GeneReviews - 38% of patients have seizures (febrile, myoclonic)
Sources: Literature
Mendeliome v1.1522 HNRNPC Zornitza Stark Phenotypes for gene: HNRNPC were changed from Neurodevelopmental disorder (MONDO:0700092), HNRNPC-related to Intellectual developmental disorder-74, MIM#620688
Mendeliome v1.1521 HNRNPC Zornitza Stark edited their review of gene: HNRNPC: Changed phenotypes: intellectual developmental disorder-74, MIM#620688
Intellectual disability syndromic and non-syndromic v0.5689 HNRNPC Zornitza Stark Phenotypes for gene: HNRNPC were changed from Neurodevelopmental disorder (MONDO:0700092), HNRNPC-related to intellectual developmental disorder-74, MIM#620688
Intellectual disability syndromic and non-syndromic v0.5688 HNRNPC Zornitza Stark edited their review of gene: HNRNPC: Changed phenotypes: intellectual developmental disorder-74, MIM#620688
Genetic Epilepsy v0.2205 SCN10A Elena Savva Marked gene: SCN10A as ready
Genetic Epilepsy v0.2205 SCN10A Elena Savva Gene: scn10a has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2205 SCN10A Elena Savva gene: SCN10A was added
gene: SCN10A was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: SCN10A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SCN10A were set to PMID: 28078312
Phenotypes for gene: SCN10A were set to Episodic pain syndrome, familial, 2 MIM#615551; Neurodevelopmental disorder (MONDO#0700092), SCN10A-related
Review for gene: SCN10A was set to RED
Added comment: PMID: 28078312 - three families (2x biallelic missense, hom PTC).
- family 1 had progressive neuromuscular disease, severe cognitive impairment, muscle weakness, upper motor neuron lesion, anhydrosis, facial dysmorphism, and recurrent seizures
- family 2 had neonatal hypotonia, bradycardia, and recurrent seizures
- family 3 had febrile infection-related epilepsy syndrome (FIRES)
- Additional 5 probands reported with biallelic missense and Lennox–Gastaut syndrome, epilepsy databases and autism databases
- Het carriers of PTC were NOT affected, but LOF is NOT a known mechanism of AD disease

Red for biallelic disease - none of the missense had functional studies to support pathogenicity. More evidence needed.
Sources: Literature
Genetic Epilepsy v0.2204 SACS Elena Savva Classified gene: SACS as Amber List (moderate evidence)
Genetic Epilepsy v0.2204 SACS Elena Savva Gene: sacs has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2203 SACS Elena Savva Classified gene: SACS as Amber List (moderate evidence)
Genetic Epilepsy v0.2203 SACS Elena Savva Gene: sacs has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2202 SACS Elena Savva Marked gene: SACS as ready
Genetic Epilepsy v0.2202 SACS Elena Savva Gene: sacs has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2202 SACS Elena Savva gene: SACS was added
gene: SACS was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: SACS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SACS were set to PMID: 27871429; 35386405
Phenotypes for gene: SACS were set to Spastic ataxia, Charlevoix-Saguenay type MIM#270550
Review for gene: SACS was set to AMBER
Added comment: PMID: 27871429 - two consanguinous families (8 affecteds) with homozygous PTCs. Epilepsy observed for all 4/4 members of a single family. Authors note seizures may be present in 10% of SACS patients

PMID: 35386405 - Review of chinese patients, found 4/27 patients had epilepsy (one was questionable)
Sources: Literature
Genetic Epilepsy v0.2201 TMEM5 Elena Savva Marked gene: TMEM5 as ready
Genetic Epilepsy v0.2201 TMEM5 Elena Savva Gene: tmem5 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2201 TMEM5 Elena Savva gene: TMEM5 was added
gene: TMEM5 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: TMEM5 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TMEM5 were set to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 10 MIM#615041
Review for gene: TMEM5 was set to RED
Added comment: Alt, gene name RXYLT1

No literature showing SNVs in this gene and epilepsy/seizures. Gene was listed in the Oliver review
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5688 WDR44 Zornitza Stark Marked gene: WDR44 as ready
Intellectual disability syndromic and non-syndromic v0.5688 WDR44 Zornitza Stark Gene: wdr44 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5688 WDR44 Zornitza Stark Classified gene: WDR44 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5688 WDR44 Zornitza Stark Gene: wdr44 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5687 WDR44 Zornitza Stark gene: WDR44 was added
gene: WDR44 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: WDR44 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: WDR44 were set to 38191484
Phenotypes for gene: WDR44 were set to Ciliopathy, MONDO:0005308, WDR44-related
Review for gene: WDR44 was set to GREEN
Added comment: 11 male patients with 6 missense and 1 nonsense variant in WDR44 displaying a wide range of cognitive impairment and variable congenital anomalies associated with primary cilium dysfunction. All patients had learning difficulties with 8 labelled as intellectually disabled (mild-moderate). Other clinical features included anomalies of craniofacial, musculoskeletal, brain, renal and cardiac development.
WDR44 is a negative regulator of ciliogenesis. Increased binding is hypothesised to underlie the pathogenicity of WDR44 variants identified in this cohort. Functional data supported impaired ciliogenesis initiation in patient fibroblasts and a zebrafish model. A zebrafish model recapitulated the human phenotype when morphants expressed WDR44 L668S, D669N, S764F, G782C, H839R, and R733* variants. Of note, D648G or N840S did not recapitulate the phenotype in the zebrafish model.
The studies supported a GoF mechanism, but the authors could not rule out that LoF of WDR44 contributes to the ciliopathy-like phenotype observed, because protein expression data was only available for a limited number of patients.
Sources: Literature
Mendeliome v1.1521 RIC1 Zornitza Stark Phenotypes for gene: RIC1 were changed from Cleft lip; cataract; tooth abnormality; intellectual disability; facial dysmorphism; ADHD to Cleft lip/palate MONDO:0016044, RIC1-related; Cleft lip; cataract; tooth abnormality; intellectual disability; facial dysmorphism; ADHD
Mendeliome v1.1520 RIC1 Zornitza Stark Publications for gene: RIC1 were set to 31932796
Mendeliome v1.1519 RIC1 Zornitza Stark Mode of inheritance for gene: RIC1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.1518 RIC1 Zornitza Stark Classified gene: RIC1 as Green List (high evidence)
Mendeliome v1.1518 RIC1 Zornitza Stark Gene: ric1 has been classified as Green List (High Evidence).
Fetal anomalies v1.185 MYMK Zornitza Stark Deleted their comment
Fetal anomalies v1.185 MYMK Zornitza Stark Classified gene: MYMK as Green List (high evidence)
Fetal anomalies v1.185 MYMK Zornitza Stark Gene: mymk has been classified as Green List (High Evidence).
Fetal anomalies v1.184 MYMK Zornitza Stark edited their review of gene: MYMK: Added comment: Cleft palate, micrognathia, microcephaly, talipes are features detectable on fetal ultrasound.; Changed rating: GREEN
Clefting disorders v0.249 MYMK Zornitza Stark Marked gene: MYMK as ready
Clefting disorders v0.249 MYMK Zornitza Stark Gene: mymk has been classified as Green List (High Evidence).
Clefting disorders v0.249 MYMK Zornitza Stark Phenotypes for gene: MYMK were changed from Carey-Fineman-Ziter syndrome 254940 to Carey-Fineman-Ziter syndrome, MIM# 254940
Clefting disorders v0.248 MYMK Zornitza Stark reviewed gene: MYMK: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Carey-Fineman-Ziter syndrome, MIM# 254940; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Clefting disorders v0.248 FBXO11 Zornitza Stark Marked gene: FBXO11 as ready
Clefting disorders v0.248 FBXO11 Zornitza Stark Gene: fbxo11 has been classified as Amber List (Moderate Evidence).
Clefting disorders v0.248 FBXO11 Zornitza Stark reviewed gene: FBXO11: Rating: AMBER; Mode of pathogenicity: None; Publications: 30057029; Phenotypes: intellectual developmental disorder with dysmorphic facies and behavioral abnormalities, MIM# 618089; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Clefting disorders v0.248 FOXP2 Zornitza Stark Marked gene: FOXP2 as ready
Clefting disorders v0.248 FOXP2 Zornitza Stark Gene: foxp2 has been classified as Red List (Low Evidence).
Clefting disorders v0.248 FOXP2 Zornitza Stark Phenotypes for gene: FOXP2 were changed from Speech-language disorder-1, 602081 to Speech-language disorder-1, MIM# 602081
Clefting disorders v0.247 FOXP2 Zornitza Stark Classified gene: FOXP2 as Red List (low evidence)
Clefting disorders v0.247 FOXP2 Zornitza Stark Gene: foxp2 has been classified as Red List (Low Evidence).
Clefting disorders v0.246 FOXP2 Zornitza Stark reviewed gene: FOXP2: Rating: RED; Mode of pathogenicity: None; Publications: 36328423; Phenotypes: Speech-language disorder-1, MIM# 602081; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5686 ACACA Zornitza Stark Marked gene: ACACA as ready
Intellectual disability syndromic and non-syndromic v0.5686 ACACA Zornitza Stark Gene: acaca has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5686 ACACA Zornitza Stark Classified gene: ACACA as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.5686 ACACA Zornitza Stark Gene: acaca has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5685 ACACA Zornitza Stark gene: ACACA was added
gene: ACACA was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: ACACA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ACACA were set to 34552920; 10677481; 16717184; 36709796
Phenotypes for gene: ACACA were set to Acetyl-CoA carboxylase deficiency, MIM# 613933
Review for gene: ACACA was set to AMBER
Added comment: Two families with molecular testing, missense variants, supportive functional data.
Sources: Literature
Mendeliome v1.1517 ACACA Zornitza Stark Classified gene: ACACA as Amber List (moderate evidence)
Mendeliome v1.1517 ACACA Zornitza Stark Gene: acaca has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1516 ACACA Zornitza Stark reviewed gene: ACACA: Rating: AMBER; Mode of pathogenicity: None; Publications: 36709796; Phenotypes: Acetyl-CoA carboxylase deficiency, MIM# 613933; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebral vascular malformations v0.38 ANO1 Zornitza Stark Phenotypes for gene: ANO1 were changed from Moyamoya disease, MONDO:0016820, ANO1 related to Moyamoya disease 7, MIM# 620687
Cerebral vascular malformations v0.37 ANO1 Zornitza Stark reviewed gene: ANO1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Moyamoya disease 7, MIM# 620687; Mode of inheritance: None
Stroke v1.15 ANO1 Zornitza Stark Phenotypes for gene: ANO1 were changed from moyamoya; cerebral arteriopathy; stroke; MONDO:0016820 to Moyamoya disease 7, MIM# 620687
Stroke v1.14 ANO1 Zornitza Stark reviewed gene: ANO1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Moyamoya disease 7, MIM# 620687; Mode of inheritance: None
Mendeliome v1.1516 ANO1 Zornitza Stark Phenotypes for gene: ANO1 were changed from Intestinal dysmotility syndrome, MIM# 620045; Moyamoya disease, MONDO:0016820, ANO1 related to Intestinal dysmotility syndrome, MIM# 620045; Moyamoya disease 7, MIM# 620687
Mendeliome v1.1515 ANO1 Zornitza Stark edited their review of gene: ANO1: Changed phenotypes: Intestinal dysmotility syndrome, MIM# 620045, Moyamoya disease 7, MIM# 620687
Proteinuria v0.222 NUP160 Zornitza Stark Classified gene: NUP160 as Green List (high evidence)
Proteinuria v0.222 NUP160 Zornitza Stark Gene: nup160 has been classified as Green List (High Evidence).
Proteinuria v0.221 NUP160 Zornitza Stark Deleted their comment
Proteinuria v0.221 NUP160 Zornitza Stark edited their review of gene: NUP160: Changed rating: GREEN
Proteinuria v0.221 NUP160 Zornitza Stark commented on gene: NUP160: PMID: 30910934 1 x patient with familial steroid-resistant nephrotic syndrome (SRNS) and FSGS carried novel compound-heterozygous variants in NUP160 (R1173X and E803K).

Silencing of Drosophila NUP160 specifically in nephrocytes (fly renal cells) led to functional abnormalities, reduced cell size and nuclear volume, and disorganized nuclear membrane structure. These defects were completely rescued by the expression of the wild-type human NUP160 gene in nephrocytes.

PMID: 30179222 1 x family (2 sibs) with compound het variants E803K and Arg910X. 1 Sib had SRNS and FSGS, the other had proteinuria.

PMID: 33456446 1 x family (2 sibs) with SRNS and chronic kidney disease. Homozygous for NUP160 c.1179+5G>A, confirmed by RT-PCR to cause abnormal splicing [r.1102_1179del;p.(Phe368_Gln393del)]. These individuals also had additional neurological features of intellectual disability and epilepsy.

PMID: 38224683 Generated a podocyte-specific Nup160 knockout (Nup160podKO) mouse model using CRISPR/Cas9 and Cre/loxP technologies. They showed that Nup160podKO mice develop typical signs of NS.
Proteinuria v0.221 NUP160 Zornitza Stark edited their review of gene: NUP160: Added comment: PMID: 30910934 1 x patient with familial steroid-resistant nephrotic syndrome (SRNS) and FSGS carried novel compound-heterozygous variants in NUP160 (R1173X and E803K).

Silencing of Drosophila NUP160 specifically in nephrocytes (fly renal cells) led to functional abnormalities, reduced cell size and nuclear volume, and disorganized nuclear membrane structure. These defects were completely rescued by the expression of the wild-type human NUP160 gene in nephrocytes.

PMID: 30179222 1 x family (2 sibs) with compound het variants E803K and Arg910X. 1 Sib had SRNS and FSGS, the other had proteinuria.

PMID: 33456446 1 x family (2 sibs) with SRNS and chronic kidney disease. Homozygous for NUP160 c.1179+5G>A, confirmed by RT-PCR to cause abnormal splicing [r.1102_1179del;p.(Phe368_Gln393del)]. These individuals also had additional neurological features of intellectual disability and epilepsy.

PMID: 38224683 Generated a podocyte-specific Nup160 knockout (Nup160podKO) mouse model using CRISPR/Cas9 and Cre/loxP technologies. They showed that Nup160podKO mice develop typical signs of NS.; Changed publications: 30910934, 30179222, 33456446, 38224683
Mendeliome v1.1515 NUP160 Zornitza Stark Publications for gene: NUP160 were set to 30179222
Mendeliome v1.1514 NUP160 Zornitza Stark Classified gene: NUP160 as Green List (high evidence)
Mendeliome v1.1514 NUP160 Zornitza Stark Gene: nup160 has been classified as Green List (High Evidence).
Mendeliome v1.1513 NUP160 Melanie Marty changed review comment from: PMID: 30910934 1 x patient with familial steroid-resistant nephrotic syndrome (SRNS) and FSGS carried novel compound-heterozygous variants in NUP160 (R1173X and E803K). Silencing of Drosophila NUP160 specifically in nephrocytes (fly renal cells) led to functional abnormalities, reduced cell size and nuclear volume, and disorganized nuclear membrane structure. These defects were completely rescued by the expression of the wild-type human NUP160 gene in nephrocytes.

PMID: 30179222 1 x family (2 sibs) with compound het variants E803K and Arg910X. 1 Sib had SRNS and FSGS, the other had proteinuria.

PMID: 33456446 1 x family (2 sibs) with steroid-resistant nephrotic syndrome and chronic kidney disease. Homozygous for NUP160 c.1179+5G>A, confirmed by RT-PCR to cause abnormal splicing [r.1102_1179del;p.(Phe368_Gln393del)]. These individuals also had additional neurological features of intellectual disability and epilepsy.

PMID: 38224683 Generated a podocyte-specific Nup160 knockout (Nup160podKO) mouse mode using CRISPR/Cas9 and Cre/loxP technologies. They showed that Nup160podKO mice develop typical signs of NS.; to: PMID: 30910934 1 x patient with familial steroid-resistant nephrotic syndrome (SRNS) and FSGS carried novel compound-heterozygous variants in NUP160 (R1173X and E803K). Silencing of Drosophila NUP160 specifically in nephrocytes (fly renal cells) led to functional abnormalities, reduced cell size and nuclear volume, and disorganized nuclear membrane structure. These defects were completely rescued by the expression of the wild-type human NUP160 gene in nephrocytes.

PMID: 30179222 1 x family (2 sibs) with compound het variants E803K and Arg910X. 1 Sib had SRNS and FSGS, the other had proteinuria.

PMID: 33456446 1 x family (2 sibs) with SRNS and chronic kidney disease. Homozygous for NUP160 c.1179+5G>A, confirmed by RT-PCR to cause abnormal splicing [r.1102_1179del;p.(Phe368_Gln393del)]. These individuals also had additional neurological features of intellectual disability and epilepsy.

PMID: 38224683 Generated a podocyte-specific Nup160 knockout (Nup160podKO) mouse model using CRISPR/Cas9 and Cre/loxP technologies. They showed that Nup160podKO mice develop typical signs of NS.
Mendeliome v1.1513 NUP160 Melanie Marty reviewed gene: NUP160: Rating: GREEN; Mode of pathogenicity: None; Publications: 30910934, 30179222, 33456446, 38224683; Phenotypes: Steroid-resistant nephrotic syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5684 SP9 Zornitza Stark Marked gene: SP9 as ready
Intellectual disability syndromic and non-syndromic v0.5684 SP9 Zornitza Stark Gene: sp9 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5684 SP9 Zornitza Stark Classified gene: SP9 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5684 SP9 Zornitza Stark Gene: sp9 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5683 SP9 Suliman Khan gene: SP9 was added
gene: SP9 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: SP9 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SP9 were set to PMID: 38288683
Phenotypes for gene: SP9 were set to neurodevelopmental disorder MONDO:0700092
Review for gene: SP9 was set to GREEN
Added comment: PMID: 38288683: reported 5 unrelated patients with de novo heterozygous variants (missense and PTV) in SP9 gene. In silico and in vitro studies suggested a novel form of interneuronopathy with variable severity depending on the presence of loss or gain of function variants. Patients with loss-of-function variants had ID, ASD, and epilepsy, whereas missense variants in the second C2H2 binding domain result in hypomorphic and neomorphic DNA binding functions that cause severe epileptic encephalopathy. The author suggested a novel form of interneuronopathy with variable severity depending on the presence of loss or gain of function variants.
Sources: Literature
Mendeliome v1.1513 SP9 Zornitza Stark Marked gene: SP9 as ready
Mendeliome v1.1513 SP9 Zornitza Stark Gene: sp9 has been classified as Green List (High Evidence).
Mendeliome v1.1513 SP9 Suliman Khan commented on gene: SP9: PMID: 38288683: reported 5 unrelated patients with de novo heterozygous variants (missense and PTV) in SP9 gene. In silico and in vitro studies suggested a novel form of interneuronopathy with variable severity depending on the presence of loss or gain of function variants. Patients with loss-of-function variants had ID, ASD, and epilepsy, whereas missense variants in the second C2H2 binding domain result in hypomorphic and neomorphic DNA binding functions that cause severe epileptic encephalopathy. The author suggested a novel form of interneuronopathy with variable severity depending on the presence of loss or gain of function variants.
Mendeliome v1.1513 SP9 Zornitza Stark Phenotypes for gene: SP9 were changed from neurodevelopmental disorder MONDO:0700092 to neurodevelopmental disorder MONDO:0700092, SP9-related
Mendeliome v1.1512 SP9 Zornitza Stark Classified gene: SP9 as Green List (high evidence)
Mendeliome v1.1512 SP9 Zornitza Stark Gene: sp9 has been classified as Green List (High Evidence).
Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic v0.134 WDR44 Seb Lunke Marked gene: WDR44 as ready
Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic v0.134 WDR44 Seb Lunke Added comment: Comment when marking as ready: GoF mentioned but not well supported.
Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic v0.134 WDR44 Seb Lunke Gene: wdr44 has been classified as Green List (High Evidence).
Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic v0.134 WDR44 Seb Lunke Classified gene: WDR44 as Green List (high evidence)
Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic v0.134 WDR44 Seb Lunke Gene: wdr44 has been classified as Green List (High Evidence).
Mendeliome v1.1511 SP9 Suliman Khan gene: SP9 was added
gene: SP9 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SP9 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SP9 were set to PMID: 38288683
Phenotypes for gene: SP9 were set to neurodevelopmental disorder MONDO:0700092
Review for gene: SP9 was set to GREEN
Added comment: Sources: Literature
Genetic Epilepsy v0.2200 SP9 Zornitza Stark Marked gene: SP9 as ready
Genetic Epilepsy v0.2200 SP9 Zornitza Stark Gene: sp9 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2200 SP9 Zornitza Stark Phenotypes for gene: SP9 were changed from neurodevelopmental disorder MONDO:0700092 to neurodevelopmental disorder MONDO:0700092, SP9-related
Genetic Epilepsy v0.2199 SP9 Zornitza Stark Classified gene: SP9 as Green List (high evidence)
Genetic Epilepsy v0.2199 SP9 Zornitza Stark Gene: sp9 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2198 SP9 Suliman Khan gene: SP9 was added
gene: SP9 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: SP9 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SP9 were set to PMID: 38288683
Phenotypes for gene: SP9 were set to neurodevelopmental disorder MONDO:0700092
Penetrance for gene: SP9 were set to Incomplete
Review for gene: SP9 was set to GREEN
Added comment: PMID: 38288683: reported 5 unrelated patients with de novo heterozygous variants (missense and PTV) in SP9 gene. In silico and in vitro studies suggested a novel form of interneuronopathy with variable severity depending on the presence of loss or gain of function variants. Patients with loss-of-function variants had ID, ASD, and epilepsy, whereas missense variants in the second C2H2 binding domain result in hypomorphic and neomorphic DNA binding functions that cause severe epileptic encephalopathy. The author suggested a novel form of interneuronopathy with variable severity depending on the presence of loss or gain of function variants.
Sources: Literature
Mendeliome v1.1511 MEI4 Lisa Norbart edited their review of gene: MEI4: Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1511 MEI4 Lisa Norbart changed review comment from: PMID: 38252283 - 5x compound heterozygous missense variants and 1x homozygous missense variant seen in five individuals across 4 unrelated families affected with female infertility characterised by preimplantation embryonic arrest. Includes one family with two affected sisters with the same compound heterozygous variants. 2/4 families showed inheritance, parental data not available for other two families. Homozygous variant in the consanguineous family appears with a more severe phenotype.

In vitro evidence shows variants reduced the interactions between MEI4 and DNA, but no effects on protein levels. In vivo knock-out mouse model showed female mice were infertile, characterised by developmental defects during oogenesis.
Sources: Literature; to: PMID: 38252283 - 5x compound heterozygous missense variants and 1x homozygous missense variant seen in five individuals across 4 unrelated families affected with female infertility characterised by preimplantation embryonic arrest. Includes one family with two affected sisters with the same compound heterozygous variants. 2/4 families showed inheritance, parental data not available for other two families. Homozygous variant in the consanguineous family appears with a more severe phenotype.

In vitro evidence shows variants reduced the interactions between MEI4 and DNA, but no effects on protein levels. In vivo knock-out mouse model showed female mice were infertile, characterised by developmental defects during oogenesis.
Sources: Literature
Genetic Epilepsy v0.2198 CCDC88C Rylee Peters reviewed gene: CCDC88C: Rating: AMBER; Mode of pathogenicity: None; Publications: 38173219; Phenotypes: monogenic epilepsy MONDO:0015653, CCDC88C-related; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v1.1511 CCDC88C Rylee Peters reviewed gene: CCDC88C: Rating: AMBER; Mode of pathogenicity: None; Publications: 38173219; Phenotypes: monogenic epilepsy MONDO:0015653, CCDC88C-related; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v1.1511 RHOXF1 Zornitza Stark Marked gene: RHOXF1 as ready
Mendeliome v1.1511 RHOXF1 Zornitza Stark Gene: rhoxf1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1511 RHOXF1 Zornitza Stark Classified gene: RHOXF1 as Amber List (moderate evidence)
Mendeliome v1.1511 RHOXF1 Zornitza Stark Gene: rhoxf1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.184 CELSR1 Chern Lim edited their review of gene: CELSR1: Changed rating: GREEN
Hydrops fetalis v0.308 CELSR1 Chern Lim edited their review of gene: CELSR1: Changed rating: GREEN
Mendeliome v1.1510 MEI4 Zornitza Stark Marked gene: MEI4 as ready
Mendeliome v1.1510 MEI4 Zornitza Stark Gene: mei4 has been classified as Green List (High Evidence).
Mendeliome v1.1510 RHOXF1 Chris Ciotta gene: RHOXF1 was added
gene: RHOXF1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RHOXF1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: RHOXF1 were set to PMID: 38258527
Phenotypes for gene: RHOXF1 were set to Spermatogenic failure, MONDO:0004983, RHOXF1-related
Review for gene: RHOXF1 was set to AMBER
Added comment: In a cohort of 1,201 men from China with oligozoospermia and azoospermia, hemizygous RHOXF1 variants were identified in 4 unrelated individuals.

Three of these variants were missense variants (V130M, A91V & A156V), all were absent from gnomAD (including version 4) and had deleterious in silicos.

The one other variant was a nonsense variant (R160X) which is predicted to escape NMD and truncate the protein. This is seen in gnomAD version 4 in 1 heterozygote female, and absent in other versions.

In vitro functional evidence for these variants was provided, the V130M, A156V and R160X mutants demonstrated impaired protein localisation with an increase in the protein in the cytoplasm and impaired nuclear entry, the A91V mutant protein did not share these localisation defects.

Further, The V130M mutant protein decreased DMRT1 promotor activity, DMRT1 is considered essential for testicular development and spermatogenesis. However, the R160X variant demonstrated increased activation, three times higher than WT. The two other missense variants had no effect.
Sources: Literature
Mendeliome v1.1510 PRDM6 Elena Savva Marked gene: PRDM6 as ready
Mendeliome v1.1510 PRDM6 Elena Savva Gene: prdm6 has been classified as Green List (High Evidence).
Mendeliome v1.1510 PRDM6 Elena Savva Classified gene: PRDM6 as Green List (high evidence)
Mendeliome v1.1510 PRDM6 Elena Savva Gene: prdm6 has been classified as Green List (High Evidence).
Mendeliome v1.1509 PRDM6 Elena Savva gene: PRDM6 was added
gene: PRDM6 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PRDM6 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PRDM6 were set to 38071433; 27716515; 27181681
Phenotypes for gene: PRDM6 were set to Patent ductus arteriosus 3 MIM#617039
Review for gene: PRDM6 was set to GREEN
Added comment: Gene is established for patent ductus arteriosus. Only missense reported but supported by functional studies suggesting LOF.

PMID: 38071433 - Two families (3 affected, 6 affected) with patent ductus arteriosus with/without additional coarctation of the aorta. Family 1 had a missense, family 2 had a PTC - both regarded as VUSs

Additional papers PMID: 27716515;27181681 describe nonsyndromic patent ductus arteriosus for the first time
Sources: Literature
Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic v0.133 WDR44 Andrew Fennell gene: WDR44 was added
gene: WDR44 was added to Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic. Sources: Literature
Mode of inheritance for gene: WDR44 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: WDR44 were set to PMID: 38191484
Phenotypes for gene: WDR44 were set to Ciliopathy, MONDO:0005308, WDR44-related
Review for gene: WDR44 was set to GREEN
Added comment: 11 male patients with 6 missense and 1 nonsense variant in WDR44 displaying a wide range of cognitive impairment and variable congenital anomalies associated with primary cilium dysfunction.
3 patients had renal anomalies including 1 with unilateral cystic kidney disease; and nephritis, and kidney hypoplasia resulting in renal failure in two patients.
All patients had learning difficulties with 8 labelled as intellectually disabled (mild-moderate). Other clinical features included anomalies of craniofacial, musculoskeletal, brain, and cardiac development.
WDR44 is a negative regulator of ciliogenesis. Increased binding is hypothesised to underlie the pathogenicity of WDR44 variants identified in this cohort. Functional data supported impaired ciliogenesis initiation in patient fibroblasts and a zebrafish model. A zebrafish model recapitulated the human phenotype when morphants expressed WDR44 L668S, D669N, S764F, G782C, H839R, and R733* variants. Of note, D648G or N840S did not recapitulate the phenotype in the zebrafish model.
The studies supported a GoF mechanism, but the authors could not rule out that LoF of WDR44 contributes to the ciliopathy-like phenotype observed, because protein expression data was only available for a limited number of patients.
Sources: Literature
Mendeliome v1.1508 MEI4 Zornitza Stark Classified gene: MEI4 as Green List (high evidence)
Mendeliome v1.1508 MEI4 Zornitza Stark Gene: mei4 has been classified as Green List (High Evidence).
Mendeliome v1.1507 MEI4 Lisa Norbart gene: MEI4 was added
gene: MEI4 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MEI4 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: MEI4 were set to 38252283
Phenotypes for gene: MEI4 were set to Infertility disorder, MONDO:0005047, MEI4-related
Review for gene: MEI4 was set to GREEN
Added comment: PMID: 38252283 - 5x compound heterozygous missense variants and 1x homozygous missense variant seen in five individuals across 4 unrelated families affected with female infertility characterised by preimplantation embryonic arrest. Includes one family with two affected sisters with the same compound heterozygous variants. 2/4 families showed inheritance, parental data not available for other two families. Homozygous variant in the consanguineous family appears with a more severe phenotype.

In vitro evidence shows variants reduced the interactions between MEI4 and DNA, but no effects on protein levels. In vivo knock-out mouse model showed female mice were infertile, characterised by developmental defects during oogenesis.
Sources: Literature
Hydrops fetalis v0.308 CELSR1 Ain Roesley Phenotypes for gene: CELSR1 were changed from Lymphatic malformation 9, MIM# 619319 to Lymphatic malformation 9, MIM# 619319
Hydrops fetalis v0.307 CELSR1 Ain Roesley changed review comment from: Comment on phenotypes: Presentation of hydrod is a phenotypic expansion on Lymphatic malformation; to: Comment on phenotypes: Presentation of hydrops is a phenotypic expansion on Lymphatic malformation
Hydrops fetalis v0.307 CELSR1 Ain Roesley Marked gene: CELSR1 as ready
Hydrops fetalis v0.307 CELSR1 Ain Roesley Gene: celsr1 has been classified as Green List (High Evidence).
Hydrops fetalis v0.307 CELSR1 Ain Roesley Added comment: Comment on phenotypes: Presentation of hydrod is a phenotypic expansion on Lymphatic malformation
Hydrops fetalis v0.307 CELSR1 Ain Roesley Phenotypes for gene: CELSR1 were changed from hydrops fetalis (MONDO:0015193), CELSR1-related to Lymphatic malformation 9, MIM# 619319
Mendeliome v1.1507 WDR44 Seb Lunke Marked gene: WDR44 as ready
Mendeliome v1.1507 WDR44 Seb Lunke Added comment: Comment when marking as ready: GoF mentioned but not well established.
Mendeliome v1.1507 WDR44 Seb Lunke Gene: wdr44 has been classified as Green List (High Evidence).
Hydrops fetalis v0.306 CELSR1 Ain Roesley Classified gene: CELSR1 as Green List (high evidence)
Hydrops fetalis v0.306 CELSR1 Ain Roesley Gene: celsr1 has been classified as Green List (High Evidence).
Mendeliome v1.1507 WDR44 Seb Lunke Classified gene: WDR44 as Green List (high evidence)
Mendeliome v1.1507 WDR44 Seb Lunke Gene: wdr44 has been classified as Green List (High Evidence).
Fetal anomalies v1.184 PIEZO1 Naomi Baker reviewed gene: PIEZO1: Rating: RED; Mode of pathogenicity: None; Publications: PMID:38184690; Phenotypes: Prune belly syndrome (MONDO:0007032), PIEZO1-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.184 WDR44 Seb Lunke Marked gene: WDR44 as ready
Fetal anomalies v1.184 WDR44 Seb Lunke Added comment: Comment when marking as ready: GoF mentioned but not well established.
Fetal anomalies v1.184 WDR44 Seb Lunke Gene: wdr44 has been classified as Green List (High Evidence).
Fetal anomalies v1.184 CELSR1 Ain Roesley Publications for gene: CELSR1 were set to 31215153; 31403174; 26855770
Fetal anomalies v1.184 WDR44 Seb Lunke Classified gene: WDR44 as Green List (high evidence)
Fetal anomalies v1.184 WDR44 Seb Lunke Gene: wdr44 has been classified as Green List (High Evidence).
Fetal anomalies v1.183 CELSR1 Ain Roesley Classified gene: CELSR1 as Green List (high evidence)
Fetal anomalies v1.183 CELSR1 Ain Roesley Gene: celsr1 has been classified as Green List (High Evidence).
Mendeliome v1.1506 WDR44 Andrew Fennell gene: WDR44 was added
gene: WDR44 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: WDR44 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: WDR44 were set to PMID: 38191484
Phenotypes for gene: WDR44 were set to Ciliopathy, MONDO:0005308, WDR44-related
Review for gene: WDR44 was set to GREEN
Added comment: 11 male patients with 6 missense and 1 nonsense variant in WDR44 displaying a wide range of cognitive impairment and variable congenital anomalies associated with primary cilium dysfunction. All patients had learning difficulties with 8 labelled as intellectually disabled (mild-moderate). Other clinical features included anomalies of craniofacial, musculoskeletal, brain, renal and cardiac development.
WDR44 is a negative regulator of ciliogenesis. Increased binding is hypothesised to underlie the pathogenicity of WDR44 variants identified in this cohort. Functional data supported impaired ciliogenesis initiation in patient fibroblasts and a zebrafish model. A zebrafish model recapitulated the human phenotype when morphants expressed WDR44 L668S, D669N, S764F, G782C, H839R, and R733* variants. Of note, D648G or N840S did not recapitulate the phenotype in the zebrafish model.
The studies supported a GoF mechanism, but the authors could not rule out that LoF of WDR44 contributes to the ciliopathy-like phenotype observed, because protein expression data was only available for a limited number of patients.
Sources: Literature
Fetal anomalies v1.182 WDR44 Andrew Fennell gene: WDR44 was added
gene: WDR44 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: WDR44 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: WDR44 were set to PMID: 38191484
Phenotypes for gene: WDR44 were set to Ciliopathy, MONDO:0005308, WDR44-related
Review for gene: WDR44 was set to GREEN
Added comment: 11 male patients with 6 missense and 1 nonsense variant in WDR44 displaying a wide range of cognitive impairment and variable congenital anomalies associated with primary cilium dysfunction. All patients had learning difficulties with 8 labelled as intellectually disabled (mild-moderate). Other clinical features included anomalies of craniofacial, musculoskeletal, brain, renal and cardiac development.
WDR44 is a negative regulator of ciliogenesis. Increased binding is hypothesised to underlie the pathogenicity of WDR44 variants identified in this cohort. Functional data supported impaired ciliogenesis initiation in patient fibroblasts and a zebrafish model. A zebrafish model recapitulated the human phenotype when morphants expressed WDR44 L668S, D669N, S764F, G782C, H839R, and R733* variants. Of note, D648G or N840S did not recapitulate the phenotype in the zebrafish model.
The studies supported a GoF mechanism, but the authors could not rule out that LoF of WDR44 contributes to the ciliopathy-like phenotype observed, because protein expression data was only available for a limited number of patients.
Sources: Literature
Macular Dystrophy/Stargardt Disease v0.44 SAMD7 Zornitza Stark Marked gene: SAMD7 as ready
Macular Dystrophy/Stargardt Disease v0.44 SAMD7 Zornitza Stark Gene: samd7 has been classified as Green List (High Evidence).
Macular Dystrophy/Stargardt Disease v0.44 SAMD7 Zornitza Stark Classified gene: SAMD7 as Green List (high evidence)
Macular Dystrophy/Stargardt Disease v0.44 SAMD7 Zornitza Stark Gene: samd7 has been classified as Green List (High Evidence).
Bone Marrow Failure v1.86 SH2B3 Ain Roesley Marked gene: SH2B3 as ready
Bone Marrow Failure v1.86 SH2B3 Ain Roesley Gene: sh2b3 has been classified as Green List (High Evidence).
Bone Marrow Failure v1.86 SH2B3 Ain Roesley Classified gene: SH2B3 as Green List (high evidence)
Bone Marrow Failure v1.86 SH2B3 Ain Roesley Gene: sh2b3 has been classified as Green List (High Evidence).
Mendeliome v1.1506 SAMD7 Zornitza Stark Marked gene: SAMD7 as ready
Mendeliome v1.1506 SAMD7 Zornitza Stark Gene: samd7 has been classified as Green List (High Evidence).
Ciliopathies v1.47 WDR44 Seb Lunke Marked gene: WDR44 as ready
Ciliopathies v1.47 WDR44 Seb Lunke Added comment: Comment when marking as ready: GoF mentioned but not well supported.
Ciliopathies v1.47 WDR44 Seb Lunke Gene: wdr44 has been classified as Green List (High Evidence).
Mendeliome v1.1506 SAMD7 Zornitza Stark Classified gene: SAMD7 as Green List (high evidence)
Mendeliome v1.1506 SAMD7 Zornitza Stark Gene: samd7 has been classified as Green List (High Evidence).
Ciliopathies v1.47 WDR44 Seb Lunke Classified gene: WDR44 as Green List (high evidence)
Ciliopathies v1.47 WDR44 Seb Lunke Gene: wdr44 has been classified as Green List (High Evidence).
Bone Marrow Failure v1.85 SH2B3 Ain Roesley gene: SH2B3 was added
gene: SH2B3 was added to Bone Marrow Failure. Sources: Literature
Mode of inheritance for gene: SH2B3 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: SH2B3 were set to 37206266; 23908464; 38152053; 37206266; 38152053
Phenotypes for gene: SH2B3 were set to Predisposition to haematological malignancies; Myeloproliferation and multi-organ autoimmunity; juvenile myelomonocytic leukemia MONDO:001190, SH2B3-related
Review for gene: SH2B3 was set to GREEN
gene: SH2B3 was marked as current diagnostic
Added comment: PMID:37206266
2x families
- hom missense variant Val402Met:
functional performed on patient's fibroblasts demonstrated increased basal pSTAT5, pSTAT3 and increased pJAK2 + pSTAT5 after stimulation with IL-3, GH, GM-CSF and EPO

- hom fs Arg148Profs*40
functional performed in zebrafish demonstrated increased number of macrophages and thrombocytes

PMID:23908464;
1 fam with 2 affecteds with dev delay + autoimmunity + (1x) ALL, hom for Asp231Gly fs*3

PMID:38152053;
JMML cohort - 2x hom missense + 2x het PTCs
Sources: Literature
Fetal anomalies v1.182 CELSR1 Chern Lim reviewed gene: CELSR1: Rating: AMBER; Mode of pathogenicity: None; Publications: 38272662; Phenotypes: hydrops fetalis (MONDO:0015193), CELSR1-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Hydrops fetalis v0.305 CELSR1 Chern Lim gene: CELSR1 was added
gene: CELSR1 was added to Hydrops fetalis. Sources: Literature
Mode of inheritance for gene: CELSR1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CELSR1 were set to 38272662
Phenotypes for gene: CELSR1 were set to hydrops fetalis (MONDO:0015193), CELSR1-related
Review for gene: CELSR1 was set to AMBER
gene: CELSR1 was marked as current diagnostic
Added comment: PMID: 38272662:
- Het de novo missense variants in two unrelated cases of fetal pleural effusions leading to severe fetal hydrops - Cys1318Tyr, Cys1349Arg.
- Both variants lie within the same protein domain.
- Functional studies performed for only one of the variants, p.(Cys1318Tyr): the variant affected CELSR1 protein cell membrane localisation compared with wild-type CELSR1 protein in both a plasmid-based overexpression system and the patient fibroblast cells. Bulk RNA-seq of RNA samples extracted from the proband and the mother’s fibroblast cells demonstrated that in the proband mRNA samples, the amount of CELSR1 mRNA was significantly decreased.
- No functional testing was performed on the p.(Cys1349Arg) variant.
Sources: Literature
Mendeliome v1.1505 SH2B3 Ain Roesley Phenotypes for gene: SH2B3 were changed from Predisposition to haematological malignancies to Predisposition to haematological malignancies; Myeloproliferation and multi-organ autoimmunity; juvenile myelomonocytic leukemia MONDO:001190, SH2B3-related
Mendeliome v1.1504 SH2B3 Ain Roesley Publications for gene: SH2B3 were set to 26457647; 23908464; 31102422; 31173385
Mendeliome v1.1503 SH2B3 Ain Roesley Mode of inheritance for gene: SH2B3 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Ciliopathies v1.46 WDR44 Andrew Fennell changed review comment from: 11 male patients with 6 missense and 1 nonsense variant in WDR44 displaying a wide range of cognitive impairment and variable congenital anomalies associated with primary cilium dysfunction. All patients had learning difficulties with 8 labelled as intellectually disabled (mild-moderate). Other clinical features included anomalies of craniofacial, musculoskeletal, brain, renal and cardiac development.
WDR44 is a negative regulator of ciliogenesis. Increased binding is hypothesised to underlie the pathogenicity of WDR44 variants identified in this cohort. Functional data supported impaired ciliogenesis initiation in patient fibroblasts and a zebrafish model. A zebrafish model recaptulated the human phenotype when morphants expressed WDR44 L668S, D669N, S764F, G782C, H839R, and R733* variants. Of note, D648G or N840S did not recapitulate the phenotype in the zebrafish model.
The studies supported a GoF mechanism, but the authors could not rule out that LoF of WDR44 contributes to the ciliopathy-like phenotype observed, because protein expression data was only available for a limited number of patients.
Sources: Literature; to: 11 male patients with 6 missense and 1 nonsense variant in WDR44 displaying a wide range of cognitive impairment and variable congenital anomalies associated with primary cilium dysfunction. All patients had learning difficulties with 8 labelled as intellectually disabled (mild-moderate). Other clinical features included anomalies of craniofacial, musculoskeletal, brain, renal and cardiac development.
WDR44 is a negative regulator of ciliogenesis. Increased binding is hypothesised to underlie the pathogenicity of WDR44 variants identified in this cohort. Functional data supported impaired ciliogenesis initiation in patient fibroblasts and a zebrafish model. A zebrafish model recapitulated the human phenotype when morphants expressed WDR44 L668S, D669N, S764F, G782C, H839R, and R733* variants. Of note, D648G or N840S did not recapitulate the phenotype in the zebrafish model.
The studies supported a GoF mechanism, but the authors could not rule out that LoF of WDR44 contributes to the ciliopathy-like phenotype observed, because protein expression data was only available for a limited number of patients.
Sources: Literature
Ciliopathies v1.46 WDR44 Andrew Fennell gene: WDR44 was added
gene: WDR44 was added to Ciliopathies. Sources: Literature
Mode of inheritance for gene: WDR44 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: WDR44 were set to PMID: 38191484
Phenotypes for gene: WDR44 were set to Ciliopathy, MONDO:0005308, WDR44-related
Review for gene: WDR44 was set to GREEN
Added comment: 11 male patients with 6 missense and 1 nonsense variant in WDR44 displaying a wide range of cognitive impairment and variable congenital anomalies associated with primary cilium dysfunction. All patients had learning difficulties with 8 labelled as intellectually disabled (mild-moderate). Other clinical features included anomalies of craniofacial, musculoskeletal, brain, renal and cardiac development.
WDR44 is a negative regulator of ciliogenesis. Increased binding is hypothesised to underlie the pathogenicity of WDR44 variants identified in this cohort. Functional data supported impaired ciliogenesis initiation in patient fibroblasts and a zebrafish model. A zebrafish model recaptulated the human phenotype when morphants expressed WDR44 L668S, D669N, S764F, G782C, H839R, and R733* variants. Of note, D648G or N840S did not recapitulate the phenotype in the zebrafish model.
The studies supported a GoF mechanism, but the authors could not rule out that LoF of WDR44 contributes to the ciliopathy-like phenotype observed, because protein expression data was only available for a limited number of patients.
Sources: Literature
Mendeliome v1.1502 SH2B3 Ain Roesley Deleted their comment
Mendeliome v1.1502 SH2B3 Ain Roesley commented on gene: SH2B3: PMID:37206266
2x families
- hom missense variant Val402Met:
functional performed on patient's fibroblasts demonstrated increased basal pSTAT5, pSTAT3 and increased pJAK2 + pSTAT5 after stimulation with IL-3, GH, GM-CSF and EPO

- hom fs Arg148Profs*40
functional performed in zebrafish demonstrated increased number of macrophages and thrombocytes

PMID:23908464;
1 fam with 2 affecteds with dev delay + autoimmunity + (1x) ALL, hom for Asp231Gly fs*3

PMID:38152053;
JMML cohort - 2x hom missense + 2x het PTCs
Mendeliome v1.1502 SH2B3 Ain Roesley reviewed gene: SH2B3: Rating: GREEN; Mode of pathogenicity: None; Publications: 37206266, 23908464, 38152053; Phenotypes: Myeloproliferation and multi-organ autoimmunity, juvenile myelomonocytic leukemia MONDO:001190, SH2B3-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v1.1502 SAMD7 Paul De Fazio gene: SAMD7 was added
gene: SAMD7 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SAMD7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SAMD7 were set to 38272031
Phenotypes for gene: SAMD7 were set to Macular dystrophy, retinal, SAMD7-related MONDO:0031166
Review for gene: SAMD7 was set to GREEN
gene: SAMD7 was marked as current diagnostic
Added comment: Five biallelic variants were identified in eight individuals from six families with macular dystrophy with or without cone dysfunction. Three families were consanguineous. Mean age at first presentation was 34.8 years, range 14 to 51.

Four variants affected splicing, while one missense variant impaired the repressive activity of SAMD7. All functional work was performed using in vitro assays.
Sources: Literature
Macular Dystrophy/Stargardt Disease v0.43 SAMD7 Paul De Fazio gene: SAMD7 was added
gene: SAMD7 was added to Macular Dystrophy/Stargardt Disease. Sources: Literature
Mode of inheritance for gene: SAMD7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SAMD7 were set to 38272031
Phenotypes for gene: SAMD7 were set to Macular dystrophy, retinal, SAMD7-related MONDO:0031166
Review for gene: SAMD7 was set to GREEN
gene: SAMD7 was marked as current diagnostic
Added comment: Five biallelic variants were identified in eight individuals from six families with macular dystrophy with or without cone dysfunction. Three families were consanguineous. Mean age at first presentation was 34.8 years, range 14 to 51.

Four variants affected splicing, while one missense variant impaired the repressive activity of SAMD7. All functional work was performed using in vitro assays.
Sources: Literature
Genetic Epilepsy v0.2198 CAMK2D Elena Savva Classified gene: CAMK2D as Amber List (moderate evidence)
Genetic Epilepsy v0.2198 CAMK2D Elena Savva Gene: camk2d has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2198 CAMK2D Elena Savva Classified gene: CAMK2D as Amber List (moderate evidence)
Genetic Epilepsy v0.2198 CAMK2D Elena Savva Gene: camk2d has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2197 CAMK2D Elena Savva Marked gene: CAMK2D as ready
Genetic Epilepsy v0.2197 CAMK2D Elena Savva Gene: camk2d has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2197 CAMK2D Elena Savva gene: CAMK2D was added
gene: CAMK2D was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: CAMK2D was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CAMK2D were set to 38272033
Phenotypes for gene: CAMK2D were set to Neurodevelopmental disorder (MONDO#0700092), CAMK2D-related
Review for gene: CAMK2D was set to AMBER
Added comment: PMID: 38272033
- 8 patients (5/8 de novo) with mostly missense and a single splice site variant, ages range from 5 weeks to 20 years old
- Most variants functionally shown to have a GOF mechanism causing addition DCM phenotype, LOF is only neurological
- Phenotypes include dev delay (mild-severe) (7/7 patients), skeletal anomalies (7/8, scoliosis, kyphosis, involving spine/hands/feet/palate), DCM (6/8), seizures (3/8), visual anomalies (astigmatism, cortical vision impairment, myopia, strabismus 5/5), enlarged brain ventricles (3/5)
Sources: Literature
Cardiomyopathy_Paediatric v0.178 CAMK2D Elena Savva Marked gene: CAMK2D as ready
Cardiomyopathy_Paediatric v0.178 CAMK2D Elena Savva Gene: camk2d has been classified as Green List (High Evidence).
Mendeliome v1.1502 CAMK2D Elena Savva Marked gene: CAMK2D as ready
Mendeliome v1.1502 CAMK2D Elena Savva Gene: camk2d has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v0.178 CAMK2D Elena Savva Classified gene: CAMK2D as Green List (high evidence)
Cardiomyopathy_Paediatric v0.178 CAMK2D Elena Savva Gene: camk2d has been classified as Green List (High Evidence).
Mendeliome v1.1502 CAMK2D Elena Savva Classified gene: CAMK2D as Green List (high evidence)
Mendeliome v1.1502 CAMK2D Elena Savva Gene: camk2d has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v0.177 CAMK2D Elena Savva changed review comment from: PMID: 38272033
- 8 patients (5/8 de novo) with mostly missense and a single splice site variant, ages range from 5 weeks to 20 years old
- Most variants functionally shown to have a GOF mechanism causing addition DCM phenotype, LOF is only neurological
- Phenotypes include dev delay (mild-severe) (7/7 patients), skeletal anomalies (7/8, scoliosis, kyphosis, involving spine/hands/feet/palate), DCM (6/8), seizures (3/8), visual anomalies (astigmatism, cortical vision impairment, myopia, strabismus 5/5), enlarged brain ventricles (3/5)
Sources: Literature; to: PMID: 38272033
- 8 patients (5/8 de novo) with mostly missense and a single splice site variant, ages range from 5 weeks to 20 years old
- Most variants functionally shown to have a GOF mechanism causing addition DCM phenotype, LOF is only neurological
- Phenotypes include dev delay (mild-severe) (7/7 patients), skeletal anomalies (7/8, scoliosis, kyphosis, involving spine/hands/feet/palate), DCM (6/8), seizures (3/8), visual anomalies (astigmatism, cortical vision impairment, myopia, strabismus 5/5), enlarged brain ventricles (3/5)
Sources: Literature
Mendeliome v1.1501 CAMK2D Elena Savva gene: CAMK2D was added
gene: CAMK2D was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CAMK2D was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CAMK2D were set to 38272033
Phenotypes for gene: CAMK2D were set to Neurodevelopmental disorder (MONDO#0700092), CAMK2D-related
Added comment: PMID: 38272033
- 8 patients (5/8 de novo) with mostly missense and a single splice site variant, ages range from 5 weeks to 20 years old
- Most variants functionally shown to have a GOF mechanism causing addition DCM phenotype, LOF is only neurological
- Phenotypes include dev delay (mild-severe) (7/7 patients), skeletal anomalies (7/8, scoliosis, kyphosis, involving spine/hands/feet/palate), DCM (6/8), seizures (3/8), visual anomalies (astigmatism, cortical vision impairment, myopia, strabismus 5/5), enlarged brain ventricles (3/5)
Sources: Literature
Cardiomyopathy_Paediatric v0.177 CAMK2D Elena Savva gene: CAMK2D was added
gene: CAMK2D was added to Cardiomyopathy_Paediatric. Sources: Literature
Mode of inheritance for gene: CAMK2D was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CAMK2D were set to 38272033
Phenotypes for gene: CAMK2D were set to Neurodevelopmental disorder (MONDO#0700092), CAMK2D-related
Review for gene: CAMK2D was set to GREEN
Added comment: PMID: 38272033
- 8 patients (5/8 de novo) with mostly missense and a single splice site variant, ages range from 5 weeks to 20 years old
- Most variants functionally shown to have a GOF mechanism causing addition DCM phenotype, LOF is only neurological
- Phenotypes include dev delay (mild-severe) (7/7 patients), skeletal anomalies (7/8, scoliosis, kyphosis, involving spine/hands/feet/palate), DCM (6/8), seizures (3/8), visual anomalies (astigmatism, cortical vision impairment, myopia, strabismus 5/5), enlarged brain ventricles (3/5)
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5683 CAMK2D Elena Savva Marked gene: CAMK2D as ready
Intellectual disability syndromic and non-syndromic v0.5683 CAMK2D Elena Savva Gene: camk2d has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5683 CAMK2D Elena Savva Classified gene: CAMK2D as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5683 CAMK2D Elena Savva Gene: camk2d has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5682 CAMK2D Elena Savva gene: CAMK2D was added
gene: CAMK2D was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: CAMK2D was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CAMK2D were set to PMID: 38272033
Phenotypes for gene: CAMK2D were set to Neurodevelopmental disorder (MONDO#0700092), CAMK2D-related
Review for gene: CAMK2D was set to GREEN
Added comment: PMID: 38272033
- 8 patients (5/8 de novo) with mostly missense and a single splice site variant, ages range from 5 weeks to 20 years old
- Most variants functionally shown to have a GOF mechanism causing addition DCM phenotype, LOF is only neurological
- Phenotypes include dev delay (mild-severe) (7/7 patients), skeletal anomalies (7/8, scoliosis, kyphosis, involving spine/hands/feet/palate), DCM (6/8), seizures (3/8), visual anomalies (astigmatism, cortical vision impairment, myopia, strabismus 5/5), enlarged brain ventricles (3/5)
Sources: Literature
Mendeliome v1.1500 ERG Zornitza Stark Phenotypes for gene: ERG were changed from Lymphatic malformation 14, MIM# 620602 to Lymphatic malformation 14, MIM# 620602; Myelodysplasia syndrome, MONDO:0018881, ERG-related
Bone Marrow Failure v1.84 ERG Zornitza Stark Phenotypes for gene: ERG were changed from https://ash.confex.com/ash/2023/webprogram/Paper191986.html to Myelodysplasia syndrome, MONDO:0018881, ERG-related
Bone Marrow Failure v1.83 ERG Zornitza Stark Publications for gene: ERG were set to
Bone Marrow Failure v1.82 ERG Zornitza Stark edited their review of gene: ERG: Changed phenotypes: Myelodysplasia syndrome, MONDO:0018881, ERG-related
Mendeliome v1.1499 ERG Zornitza Stark edited their review of gene: ERG: Changed rating: AMBER; Changed publications: s://ash.confex.com/ash/2023/webprogram/Paper191986.html; Changed phenotypes: Myelodysplasia syndrome, MONDO:0018881, ERG-related; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Bone Marrow Failure v1.82 ERG Zornitza Stark edited their review of gene: ERG: Changed publications: https://ash.confex.com/ash/2023/webprogram/Paper191986.html
Bone Marrow Failure v1.82 ERG Zornitza Stark changed review comment from: Conference abstract:

15 heterozygous variants in the ERG gene, 13 of which are missense and 2 truncating variants, in 17 individuals with cytopenia and/or HM (mainly myeloid) or lympheedema. Onset of hematological symptoms ranged from birth to 38 years for truncating and constrained ETS domain variants.
Sources: Literature; to: Conference abstract:

15 heterozygous variants in the ERG gene, 13 of which are missense and 2 truncating variants, in 17 individuals with cytopenia and/or HM (mainly myeloid) or lymphoedema. Onset of hematological symptoms ranged from birth to 38 years for truncating and constrained ETS domain variants.
Sources: Literature
Bone Marrow Failure v1.82 ERG Zornitza Stark Marked gene: ERG as ready
Bone Marrow Failure v1.82 ERG Zornitza Stark Gene: erg has been classified as Amber List (Moderate Evidence).
Bone Marrow Failure v1.82 ERG Zornitza Stark Classified gene: ERG as Amber List (moderate evidence)
Bone Marrow Failure v1.82 ERG Zornitza Stark Gene: erg has been classified as Amber List (Moderate Evidence).
Bone Marrow Failure v1.81 ERG Zornitza Stark gene: ERG was added
gene: ERG was added to Bone Marrow Failure. Sources: Literature
Mode of inheritance for gene: ERG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: ERG were set to https://ash.confex.com/ash/2023/webprogram/Paper191986.html
Review for gene: ERG was set to AMBER
Added comment: Conference abstract:

15 heterozygous variants in the ERG gene, 13 of which are missense and 2 truncating variants, in 17 individuals with cytopenia and/or HM (mainly myeloid) or lympheedema. Onset of hematological symptoms ranged from birth to 38 years for truncating and constrained ETS domain variants.
Sources: Literature
Mendeliome v1.1499 RBMX Zornitza Stark Phenotypes for gene: RBMX were changed from Intellectual developmental disorder, syndromic 11, Shashi type, MIM#300238 to Intellectual developmental disorder, syndromic 11, Shashi type, MIM#300238; Gustavson syndrome, MIM# 309555
Mendeliome v1.1498 RBMX Zornitza Stark Publications for gene: RBMX were set to 25256757; 34260915
Mendeliome v1.1497 RBMX Zornitza Stark edited their review of gene: RBMX: Added comment: PMID 37277488: In-frame deletion reported in a large multiplex Swedish family; Changed publications: 25256757, 34260915, 37277488; Changed phenotypes: Intellectual developmental disorder, syndromic 11, Shashi type, MIM#300238, Gustavson syndrome, MIM# 309555
Intellectual disability syndromic and non-syndromic v0.5681 RBMX Zornitza Stark Phenotypes for gene: RBMX were changed from Intellectual developmental disorder, syndromic 11, Shashi type, MIM#300238 to Intellectual developmental disorder, syndromic 11, Shashi type, MIM#300238; Gustavson syndrome, MIM# 309555
Intellectual disability syndromic and non-syndromic v0.5680 RBMX Zornitza Stark Publications for gene: RBMX were set to 25256757; 34260915
Intellectual disability syndromic and non-syndromic v0.5679 RBMX Zornitza Stark edited their review of gene: RBMX: Added comment: PMID 37277488: In-frame deletion reported in a large multiplex Swedish family; Changed publications: 25256757, 34260915, 37277488; Changed phenotypes: Intellectual developmental disorder, syndromic 11, Shashi type, MIM#300238, Gustavson syndrome, MIM# 309555
Genetic Epilepsy v0.2196 LMX1B Elena Savva Marked gene: LMX1B as ready
Genetic Epilepsy v0.2196 LMX1B Elena Savva Gene: lmx1b has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2196 LMX1B Elena Savva gene: LMX1B was added
gene: LMX1B was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: LMX1B was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: LMX1B were set to Focal segmental glomerulosclerosis 10 MIM#256020; Nail-patella syndrome MIM#161200
Review for gene: LMX1B was set to RED
Added comment: GeneReviews - Epilepsy was reported in 6% of affected individuals in one large study [Sweeney et al 2003].

No new literature describing SNVs in this gene and epilepsy/seizures.

Gene was listed on Oliver's list
Sources: Literature
Genetic Epilepsy v0.2195 LMNB2 Elena Savva gene: LMNB2 was added
gene: LMNB2 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: LMNB2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LMNB2 were set to PMID: 33783721; 25954030; 34466237
Phenotypes for gene: LMNB2 were set to ?Epilepsy, progressive myoclonic, 9 MIM#616540
Review for gene: LMNB2 was set to AMBER
Added comment: PMID: 33783721 - hom missense p.(Arg158Trp) in a proband with Progressive myoclonus epilepsies. No functional studies to validate the missense variant

PMID: 25954030 - hom missense p.(His157Tyr) in a proband with Progressive myoclonus epilepsies. In vitro assembly analysis of mutant lamin B2 protein revealed a distinct defect in the assembly of the highly ordered fibrous arrays typically formed by wild-type lamin B2, variant segregated in the affected sister

PMID: 34466237 - Hom missense p.(Arg158Leu) in a 5yo boy with progressive wide-based ataxic gait and intractable myoclonic seizure. All unaffected relatives (13) were het or wildtype

Association to epilepsy is amber and biallelic
Seizures noted as a rare feature of dominant disease in OMIM
Sources: Literature
Genetic Epilepsy v0.2194 L2HGDH Elena Savva Classified gene: L2HGDH as Green List (high evidence)
Genetic Epilepsy v0.2194 L2HGDH Elena Savva Gene: l2hgdh has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2193 L2HGDH Elena Savva Classified gene: L2HGDH as Green List (high evidence)
Genetic Epilepsy v0.2193 L2HGDH Elena Savva Gene: l2hgdh has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2192 L2HGDH Elena Savva Marked gene: L2HGDH as ready
Genetic Epilepsy v0.2192 L2HGDH Elena Savva Gene: l2hgdh has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2192 L2HGDH Elena Savva gene: L2HGDH was added
gene: L2HGDH was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: L2HGDH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: L2HGDH were set to PMID: 37113859
Phenotypes for gene: L2HGDH were set to L-2-hydroxyglutaric aciduria MIM#236792
Review for gene: L2HGDH was set to GREEN
Added comment: PMID: 37113859 - two sisters with a hom PTC, features included delayed milestones, both had generalised tonic clonic seizures associated with fever in childhood. Reviews literature, notes seizures observed in 26% of patients
Sources: Literature
Genetic Epilepsy v0.2191 KRIT1 Elena Savva Classified gene: KRIT1 as Green List (high evidence)
Genetic Epilepsy v0.2191 KRIT1 Elena Savva Gene: krit1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2191 KRIT1 Elena Savva Classified gene: KRIT1 as Green List (high evidence)
Genetic Epilepsy v0.2191 KRIT1 Elena Savva Gene: krit1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2190 KRIT1 Elena Savva Marked gene: KRIT1 as ready
Genetic Epilepsy v0.2190 KRIT1 Elena Savva Gene: krit1 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2190 KRIT1 Elena Savva gene: KRIT1 was added
gene: KRIT1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: KRIT1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: KRIT1 were set to 35836010; 35444609
Phenotypes for gene: KRIT1 were set to Hyperkeratotic cutaneous capillary-venous malformations associated with cerebral capillary malformations MIM#116860; Cavernous malformations of CNS and retina MIM#116860; Cerebral cavernous malformations-1 MIM#116860
Review for gene: KRIT1 was set to GREEN
Added comment: Seizures noted as a feature in OMIM

PMID: 35836010 - proband presenting with seizures, nausea and vomiting, tachycardia, and bulging fontanelles

PMID: 35444609 - Family with CCM, segregated extensively. Only a single relative had seizures, but infrequently. Review, notes ~60% of individuals with cavernous hemangioma will experience seizures

GeneReviews - "The cumulative incidence of childhood seizures is ~20% (~60% by age 80 yrs)."
Sources: Literature
Genetic Epilepsy v0.2189 KMT2B Elena Savva Marked gene: KMT2B as ready
Genetic Epilepsy v0.2189 KMT2B Elena Savva Gene: kmt2b has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2189 KMT2B Elena Savva gene: KMT2B was added
gene: KMT2B was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: KMT2B was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: KMT2B were set to PMID: 34477219; 37309110
Phenotypes for gene: KMT2B were set to Dystonia 28, childhood-onset MIM#617284; Intellectual developmental disorder, autosomal dominant 68 MIM#619934
Review for gene: KMT2B was set to RED
Added comment: PMID: 34477219 - Single 30yo patient with a canonical splice variant resulting in inframe exon 8 skipping. Presented with adult-onset cerebellar ataxia, minor dystonia, neuropathy and seizure

PMID: 37309110 - large review study, no patients specified to have seizures/epilepsy

Gene was listed in the Oliver review
Sources: Literature
Genetic Epilepsy v0.2188 KMT2A Elena Savva Classified gene: KMT2A as Green List (high evidence)
Genetic Epilepsy v0.2188 KMT2A Elena Savva Gene: kmt2a has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2188 KMT2A Elena Savva Classified gene: KMT2A as Green List (high evidence)
Genetic Epilepsy v0.2188 KMT2A Elena Savva Gene: kmt2a has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2187 KMT2A Elena Savva Marked gene: KMT2A as ready
Genetic Epilepsy v0.2187 KMT2A Elena Savva Gene: kmt2a has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2187 KMT2A Elena Savva gene: KMT2A was added
gene: KMT2A was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: KMT2A was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: KMT2A were set to PMID: 37075569
Phenotypes for gene: KMT2A were set to Wiedemann-Steiner syndrome MIM#605130
Review for gene: KMT2A was set to GREEN
Added comment: OMIM notes seizures were observed in a single patient

PMID: 37075569 - couldnt access paper, but abstract notes five patients with DEE, where epilepsy ranged from drug resistant to self-limited. Reviews literature and notes 33 patients with epilepsy, but limited clinical details.
Sources: Literature
Mendelian susceptibility to Immune Disorders v0.49 MCTS1 Zornitza Stark Phenotypes for gene: MCTS1 were changed from Inherited susceptibility to mycobacterial diseases, MONDO:0019146, MCTS1-related to Immunodeficiency 118, mycobacteriosis, MIM# 301115
Mendeliome v1.1497 MCTS1 Zornitza Stark Phenotypes for gene: MCTS1 were changed from Inherited susceptibility to mycobacterial diseases, MONDO:0019146, MCTS1-related to Immunodeficiency 118, mycobacteriosis, MIM# 301115
Mendeliome v1.1496 MCTS1 Zornitza Stark edited their review of gene: MCTS1: Changed phenotypes: Immunodeficiency 118, mycobacteriosis, MIM# 301115
Hereditary Neuropathy - complex v1.10 PLA2G16 Zornitza Stark Phenotypes for gene: PLA2G16 were changed from Lipodystrophy (MONDO:0006573), PLA2G16-related to Lipodystrophy, familial partial, type 9, MIM# 620683
Intellectual disability syndromic and non-syndromic v0.5679 PLA2G16 Zornitza Stark Phenotypes for gene: PLA2G16 were changed from Lipodystrophy (MONDO:0006573), PLA2G16-related to Lipodystrophy, familial partial, type 9, MIM# 620683
Mendeliome v1.1496 PLA2G16 Zornitza Stark Phenotypes for gene: PLA2G16 were changed from Lipodystrophy (MONDO:0006573), PLA2G16-related to Lipodystrophy, familial partial, type 9, MIM# 620683
Lipodystrophy_Lipoatrophy v1.14 PLA2G16 Zornitza Stark Phenotypes for gene: PLA2G16 were changed from Lipodystrophy (MONDO:0006573), PLA2G16-related to Lipodystrophy, familial partial, type 9, MIM# 620683
Lipodystrophy_Lipoatrophy v1.13 PLA2G16 Zornitza Stark edited their review of gene: PLA2G16: Changed rating: GREEN; Changed phenotypes: Lipodystrophy, familial partial, type 9, MIM# 620683; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2186 KDM6A Elena Savva Marked gene: KDM6A as ready
Genetic Epilepsy v0.2186 KDM6A Elena Savva Gene: kdm6a has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2186 KDM6A Elena Savva gene: KDM6A was added
gene: KDM6A was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: KDM6A was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: KDM6A were set to PMID: 28442529
Phenotypes for gene: KDM6A were set to Kabuki syndrome 2 MIM#300867
Review for gene: KDM6A was set to RED
Added comment: PMID: 28442529 - describes generalized epilepsy with febrile seizures plus in a family with a co-segregating SCN1A variant. Proband had GEFS+, dysmorphic facial features, short stature, developmental delay, and intellectual disability.

Gene was on the Oliver list
Sources: Literature
Genetic Epilepsy v0.2185 KDM5A Elena Savva Marked gene: KDM5A as ready
Genetic Epilepsy v0.2185 KDM5A Elena Savva Gene: kdm5a has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2185 KDM5A Elena Savva gene: KDM5A was added
gene: KDM5A was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: KDM5A was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: KDM5A were set to PMID: 34210021
Phenotypes for gene: KDM5A were set to Neurodevelopmental disorder MONDO:0700092, KDM5A-related
Review for gene: KDM5A was set to RED
Added comment: PMID: 34210021 - large multigene deletion in a family with ID, epilepsy and schizophrenia. This gene and CACNA1C were considered the best candidates.

No evidence of SNVs in this gene causing epilepsy. This gene was on the Oliver list
Sources: Literature
Mendeliome v1.1495 KDM5A Elena Savva Phenotypes for gene: KDM5A were changed from autism spectrum disorder, MONDO:0005258; intellectual disability, MONDO:0001071 to autism spectrum disorder, MONDO:0005258; Neurodevelopmental disorder MONDO:0700092, KDM5A-related
Genetic Epilepsy v0.2184 KATNB1 Elena Savva gene: KATNB1 was added
gene: KATNB1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: KATNB1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KATNB1 were set to PMID: 26640080
Phenotypes for gene: KATNB1 were set to Lissencephaly 6, with microcephaly MIM#616212
Review for gene: KATNB1 was set to RED
Added comment: PMID: 26640080 - Proband with congenital microcephaly, lissencephaly, short stature, polysyndactyly, and dental abnormalities. Seizures developed by 6mo, had a homozygous canonical splice deletion

PMID: 31484711 - describes patients with seizures (epilepsy was documented in 69%) from a cohort with subcortical heterotopic gray matter malformations, but unclear which were specific for this gene
Sources: Literature
Genetic Epilepsy v0.2183 KAT6A Elena Savva Marked gene: KAT6A as ready
Genetic Epilepsy v0.2183 KAT6A Elena Savva Gene: kat6a has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2183 KAT6A Elena Savva Classified gene: KAT6A as Green List (high evidence)
Genetic Epilepsy v0.2183 KAT6A Elena Savva Gene: kat6a has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2182 KAT6A Elena Savva gene: KAT6A was added
gene: KAT6A was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: KAT6A was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: KAT6A were set to PMID: 34748993
Phenotypes for gene: KAT6A were set to Arboleda-Tham syndrome MIM#616268
Review for gene: KAT6A was set to GREEN
Added comment: PMID: 34748993 - 2 new probands with KAT6A syndrome and epilepsy.
Proband 1 - Epilepsy onset was at 3 months of age when daily right hemiclonic seizures appeared in sleep. Had a de novo missense, previously reported as pathogenic.
Proband 2 - Seizures onset was at 5 months with daily clusters of symmetric spasms characterized by flexion of the arms, extension of the legs and eyes’ rolling. Had a de novo PTC

Paper then reviews literature, notes 17/90 probands had epilepsy
Sources: Literature
Genetic Epilepsy v0.2181 KANSL1 Elena Savva Classified gene: KANSL1 as Green List (high evidence)
Genetic Epilepsy v0.2181 KANSL1 Elena Savva Gene: kansl1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2180 KANSL1 Elena Savva Marked gene: KANSL1 as ready
Genetic Epilepsy v0.2180 KANSL1 Elena Savva Gene: kansl1 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2180 KANSL1 Elena Savva gene: KANSL1 was added
gene: KANSL1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: KANSL1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: KANSL1 were set to PMID: 28440867
Phenotypes for gene: KANSL1 were set to Koolen-De Vries syndrome MIM#610443
Review for gene: KANSL1 was set to GREEN
Added comment: GeneReviews: describes seizures/epilepsy as a less common trait, where OMIM notes its in 50% of cases.

PMID: 28440867 - Median age at seizure onset was 3.5 years, and 9 of 22 had refractory seizures 2 years after onset. Focal impaired awareness seizures were the most frequent seizure type occurring in 20 of 31, usually with prominent autonomic features.
Sources: Literature
Genetic Epilepsy v0.2179 JMJD1C Elena Savva Classified gene: JMJD1C as Amber List (moderate evidence)
Genetic Epilepsy v0.2179 JMJD1C Elena Savva Gene: jmjd1c has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2178 JMJD1C Elena Savva Classified gene: JMJD1C as Amber List (moderate evidence)
Genetic Epilepsy v0.2178 JMJD1C Elena Savva Gene: jmjd1c has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2177 JMJD1C Elena Savva Marked gene: JMJD1C as ready
Genetic Epilepsy v0.2177 JMJD1C Elena Savva Gene: jmjd1c has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2177 JMJD1C Elena Savva gene: JMJD1C was added
gene: JMJD1C was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: JMJD1C was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: JMJD1C were set to PMID: 32996679; 26181491; 31954878
Phenotypes for gene: JMJD1C were set to Intellectual disability (MONDO#0001071), JMJD1C-related
Review for gene: JMJD1C was set to AMBER
Added comment: PMID: 32996679 - de novo synonymous variant resulting in a 21bp deletion, who had learning disability and myoclonic epilepsy (onset 10yo).
Paper reviews prev reports, notes only 1/19 other patients with seizures (p.P163L)

PMID: 26181491 - de novo p.P163L (same as above), in a proband with gait dyspraxia, hand-washing stereotype, learning impairment, teeth grinding, air swallowing, kyphoscoliosis, and tonic epilepsy. Functional studies support missense pathogenicity.

PMID: 31954878 - 2/7 patients with de novo variants with ASD, ID and seizures. One proband had a de novo missense (p.V117I), another a PTC (p.P109Lfs*3) of unknown inheritance
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5678 JMJD1C Elena Savva Phenotypes for gene: JMJD1C were changed from Intellectual disability to Intellectual disability (MONDO#0001071), JMJD1C-related
Mendeliome v1.1494 JMJD1C Elena Savva Phenotypes for gene: JMJD1C were changed from Intellectual disability to Intellectual disability (MONDO#0001071), JMJD1C-related
Genetic Epilepsy v0.2176 JARID2 Elena Savva gene: JARID2 was added
gene: JARID2 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: JARID2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: JARID2 were set to PMID: 22480366
Phenotypes for gene: JARID2 were set to Developmental delay with variable intellectual disability and dysmorphic facies MIM#620098
Review for gene: JARID2 was set to RED
Added comment: PMID: 22480366 - part of a larger multigene deletion, where a patient had seizures.

No patients with seizures reported with SNVs, but on the Oliver list as a gene to be considered.
Sources: Literature
Genetic Epilepsy v0.2175 ITGB4 Elena Savva Marked gene: ITGB4 as ready
Genetic Epilepsy v0.2175 ITGB4 Elena Savva Gene: itgb4 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2175 ITGB4 Elena Savva gene: ITGB4 was added
gene: ITGB4 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: ITGB4 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ITGB4 were set to Epidermolysis bullosa, junctional 5A, intermediate MIM#619816; Epidermolysis bullosa, junctional 5B, with pyloric atresia MIM#226730
Review for gene: ITGB4 was set to RED
Added comment: No reports of seizures/epilepsy in probands with biallelic variants in this gene
Sources: Literature
Genetic Epilepsy v0.2174 INTS8 Elena Savva Marked gene: INTS8 as ready
Genetic Epilepsy v0.2174 INTS8 Elena Savva Gene: ints8 has been classified as Red List (Low Evidence).
Red cell disorders v1.24 PKLR Zornitza Stark Mode of inheritance for gene: PKLR was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Red cell disorders v1.23 PKLR Zornitza Stark edited their review of gene: PKLR: Added comment: Only single family for the mono-allelic condition.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5677 CRELD1 Zornitza Stark Marked gene: CRELD1 as ready
Intellectual disability syndromic and non-syndromic v0.5677 CRELD1 Zornitza Stark Gene: creld1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5677 CRELD1 Zornitza Stark Classified gene: CRELD1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5677 CRELD1 Zornitza Stark Gene: creld1 has been classified as Green List (High Evidence).
Mendeliome v1.1493 MEIOB Zornitza Stark Phenotypes for gene: MEIOB were changed from Spermatogenic failure 22 MIM#617706; primary ovarian insufficiency to Spermatogenic failure 22 MIM#617706; Premature ovarian failure 23, MIM# 620686
Mendeliome v1.1492 MEIOB Zornitza Stark Publications for gene: MEIOB were set to 34794894; 24068956; 31000419; 28206990
Mendeliome v1.1491 MEIOB Zornitza Stark reviewed gene: MEIOB: Rating: GREEN; Mode of pathogenicity: None; Publications: 35991565, 34392356, 31000419; Phenotypes: Premature ovarian failure 23, MIM# 620686; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2174 INTS8 Elena Savva gene: INTS8 was added
gene: INTS8 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: INTS8 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: INTS8 were set to ?Neurodevelopmental disorder with cerebellar hypoplasia and spasticity MIM#618572
Review for gene: INTS8 was set to RED
Added comment: No published evidence associating this gene and epilepsy
Sources: Literature
Genetic Epilepsy v0.2173 IBA57 Elena Savva Marked gene: IBA57 as ready
Genetic Epilepsy v0.2173 IBA57 Elena Savva Gene: iba57 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2173 IBA57 Elena Savva gene: IBA57 was added
gene: IBA57 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: IBA57 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IBA57 were set to PMID: 30258207
Phenotypes for gene: IBA57 were set to Multiple mitochondrial dysfunctions syndrome 3 MIM#615330
Review for gene: IBA57 was set to RED
Added comment: PMID: 30258207 - girl with developmental regression and spastic quadriplegia. Brain MRI at 8 months showed cerebral white matter involvement, periventricular rarefaction, and corpus callosum involvement. She developed febrile seizures at the age of 18 months.
Chet missense pair found, no functional studies to support pathogenicity
Sources: Literature
Genetic Epilepsy v0.2172 IARS2 Elena Savva Marked gene: IARS2 as ready
Genetic Epilepsy v0.2172 IARS2 Elena Savva Gene: iars2 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2172 IARS2 Elena Savva gene: IARS2 was added
gene: IARS2 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: IARS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IARS2 were set to PMID: 30041933
Phenotypes for gene: IARS2 were set to Cataracts, growth hormone deficiency, sensory neuropathy, sensorineural hearing loss, and skeletal dysplasia MIM#616007
Review for gene: IARS2 was set to RED
Added comment: PMID: 30041933 - Japanese sibling pair presented with Leigh syndrome and infantile spasms. The siblings were identified with compound heterozygous missense mutations p.[(Phe227Ser)];[(Arg817His)]. No functional studies to support the pathogenicity of the missense variants
Sources: Literature
Gastrointestinal neuromuscular disease v1.24 OPA3 Bryony Thompson Marked gene: OPA3 as ready
Gastrointestinal neuromuscular disease v1.24 OPA3 Bryony Thompson Gene: opa3 has been classified as Green List (High Evidence).
Gastrointestinal neuromuscular disease v1.24 OPA3 Bryony Thompson Classified gene: OPA3 as Green List (high evidence)
Gastrointestinal neuromuscular disease v1.24 OPA3 Bryony Thompson Gene: opa3 has been classified as Green List (High Evidence).
Gastrointestinal neuromuscular disease v1.23 OPA3 Bryony Thompson gene: OPA3 was added
gene: OPA3 was added to Gastrointestinal neuromuscular disease. Sources: Literature
Mode of inheritance for gene: OPA3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: OPA3 were set to 31119193
Phenotypes for gene: OPA3 were set to Optic atrophy 3 MONDO:0008133
Mode of pathogenicity for gene: OPA3 was set to Other
Review for gene: OPA3 was set to GREEN
gene: OPA3 was marked as current diagnostic
Added comment: 11 of the 12 affected individuals from 3 families with OPA3 missense (p.Met8Thr, & p.Gln105Glu) had possible or confirmed gastrointestinal dysmotility symptoms as a feature of the condition. Haploinsufficiency is not expected to be the mechanism of disease. Gain of function or dominant negative effect have been suggested mechanisms of disease.
Sources: Literature
Mitochondrial disease v0.915 OPA3 Bryony Thompson Marked gene: OPA3 as ready
Mitochondrial disease v0.915 OPA3 Bryony Thompson Gene: opa3 has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v1.9 OPA3 Bryony Thompson Marked gene: OPA3 as ready
Hereditary Neuropathy - complex v1.9 OPA3 Bryony Thompson Gene: opa3 has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v1.9 OPA3 Bryony Thompson Classified gene: OPA3 as Green List (high evidence)
Hereditary Neuropathy - complex v1.9 OPA3 Bryony Thompson Gene: opa3 has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v1.8 OPA3 Bryony Thompson gene: OPA3 was added
gene: OPA3 was added to Hereditary Neuropathy - complex. Sources: Literature
Mode of inheritance for gene: OPA3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: OPA3 were set to 31119193; 28050599
Phenotypes for gene: OPA3 were set to Optic atrophy 3 MONDO:0008133
Mode of pathogenicity for gene: OPA3 was set to Other
Review for gene: OPA3 was set to GREEN
gene: OPA3 was marked as current diagnostic
Added comment: Peripheral neuropathy has been reported in multiple individuals with ADOA associated with OPA3. Haploinsufficiency is not expected to be the mechanism of disease. Gain of function or dominant negative effect have been suggested mechanisms of disease.
PMID: 31119193 - 9 of the 12 affected individuals from 3 families with OPA3 missense (p.Met8Thr, & p.Gln105Glu) had a possible or confirmed peripheral neuropathy. Was presenting feature in a single case.
PMID: 28050599 - de novo c.235C>G p.(Leu79Val) identified in a woman who presented with cataracts, optic atrophy, lipodystrophy/lipoatrophy, and peripheral neuropathy.
Sources: Literature
Mitochondrial disease v0.915 OPA3 Bryony Thompson Phenotypes for gene: OPA3 were changed from to 3-methylglutaconic aciduria, type III (MGA3) (MIM#258501), AR; Optic atrophy 3 with cataract (MIM#165300), AD
Mitochondrial disease v0.914 OPA3 Bryony Thompson Publications for gene: OPA3 were set to
Mitochondrial disease v0.913 OPA3 Bryony Thompson Mode of inheritance for gene: OPA3 was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Early-onset Parkinson disease v0.265 OPA3 Bryony Thompson Marked gene: OPA3 as ready
Early-onset Parkinson disease v0.265 OPA3 Bryony Thompson Gene: opa3 has been classified as Red List (Low Evidence).
Early-onset Parkinson disease v0.265 OPA3 Bryony Thompson Classified gene: OPA3 as Red List (low evidence)
Early-onset Parkinson disease v0.265 OPA3 Bryony Thompson Gene: opa3 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2171 DHX16 Zornitza Stark Marked gene: DHX16 as ready
Genetic Epilepsy v0.2171 DHX16 Zornitza Stark Gene: dhx16 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2171 DHX16 Zornitza Stark Classified gene: DHX16 as Green List (high evidence)
Genetic Epilepsy v0.2171 DHX16 Zornitza Stark Gene: dhx16 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2170 DOHH Zornitza Stark Marked gene: DOHH as ready
Genetic Epilepsy v0.2170 DOHH Zornitza Stark Gene: dohh has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2170 DOHH Zornitza Stark Classified gene: DOHH as Green List (high evidence)
Genetic Epilepsy v0.2170 DOHH Zornitza Stark Gene: dohh has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2169 ECHS1 Zornitza Stark Marked gene: ECHS1 as ready
Genetic Epilepsy v0.2169 ECHS1 Zornitza Stark Gene: echs1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2169 ECHS1 Zornitza Stark Phenotypes for gene: ECHS1 were changed from Mitochondrial short-chain enoyl-CoA hydratase 1 deficiency, MIM# 616277; Leigh syndrome MONDO:0009723; cerebral palsy MONDO:0006497; paroxysmal dystonia MONDO:0016058 to Mitochondrial short-chain enoyl-CoA hydratase 1 deficiency, MIM# 616277
Genetic Epilepsy v0.2168 ECHS1 Zornitza Stark Classified gene: ECHS1 as Green List (high evidence)
Genetic Epilepsy v0.2168 ECHS1 Zornitza Stark Gene: echs1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2167 EED Zornitza Stark Marked gene: EED as ready
Genetic Epilepsy v0.2167 EED Zornitza Stark Gene: eed has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2167 EED Zornitza Stark Classified gene: EED as Red List (low evidence)
Genetic Epilepsy v0.2167 EED Zornitza Stark Gene: eed has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2166 ECM1 Zornitza Stark Phenotypes for gene: ECM1 were changed from Urbach-Wiethe disease, MIM# 247100 to Urbach-Wiethe disease, MIM# 247100
Genetic Epilepsy v0.2166 ECM1 Zornitza Stark Marked gene: ECM1 as ready
Genetic Epilepsy v0.2166 ECM1 Zornitza Stark Gene: ecm1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2166 ECM1 Zornitza Stark Phenotypes for gene: ECM1 were changed from to Urbach-Wiethe disease, MIM# 247100
Genetic Epilepsy v0.2165 ECM1 Zornitza Stark Classified gene: ECM1 as Green List (high evidence)
Genetic Epilepsy v0.2165 ECM1 Zornitza Stark Gene: ecm1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2164 ECM1 Zornitza Stark reviewed gene: ECM1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Urbach-Wiethe disease, MIM# 247100; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2164 KARS Zornitza Stark Marked gene: KARS as ready
Genetic Epilepsy v0.2164 KARS Zornitza Stark Gene: kars has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2164 KARS Zornitza Stark Phenotypes for gene: KARS were changed from to Leukoencephalopathy, progressive, infantile-onset, with or without deafness MIM#619147
Genetic Epilepsy v0.2163 KARS Zornitza Stark Publications for gene: KARS were set to
Genetic Epilepsy v0.2162 KARS Zornitza Stark Mode of inheritance for gene: KARS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1491 NEPRO Zornitza Stark Publications for gene: NEPRO were set to 26633546; 29620724; 31250547
Mendeliome v1.1490 NEPRO Zornitza Stark Classified gene: NEPRO as Green List (high evidence)
Mendeliome v1.1490 NEPRO Zornitza Stark Gene: nepro has been classified as Green List (High Evidence).
Mendeliome v1.1489 NEPRO Zornitza Stark reviewed gene: NEPRO: Rating: GREEN; Mode of pathogenicity: None; Publications: 37294112; Phenotypes: Anauxetic dysplasia 3, MIM618853; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v0.262 NEPRO Zornitza Stark Marked gene: NEPRO as ready
Skeletal dysplasia v0.262 NEPRO Zornitza Stark Gene: nepro has been classified as Green List (High Evidence).
Skeletal dysplasia v0.262 NEPRO Zornitza Stark Publications for gene: NEPRO were set to 26633546; 29620724; 31250547
Skeletal dysplasia v0.261 NEPRO Zornitza Stark Classified gene: NEPRO as Green List (high evidence)
Skeletal dysplasia v0.261 NEPRO Zornitza Stark Gene: nepro has been classified as Green List (High Evidence).
Stroke v1.14 JAM3 Zornitza Stark Marked gene: JAM3 as ready
Stroke v1.14 JAM3 Zornitza Stark Gene: jam3 has been classified as Green List (High Evidence).
Stroke v1.14 JAM3 Zornitza Stark Classified gene: JAM3 as Green List (high evidence)
Stroke v1.14 JAM3 Zornitza Stark Gene: jam3 has been classified as Green List (High Evidence).
Stroke v1.13 JAM3 Zornitza Stark gene: JAM3 was added
gene: JAM3 was added to Stroke. Sources: Expert Review
Mode of inheritance for gene: JAM3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: JAM3 were set to 23255084; 21109224
Phenotypes for gene: JAM3 were set to Hemorrhagic destruction of the brain, subependymal calcification, and cataracts, MIM# 613730
Review for gene: JAM3 was set to GREEN
Added comment: Autosomal recessive disorder with a distinctive phenotype comprising haemorrhagic destruction of the brain, subependymal calcification, and congenital cataracts. Affected individuals have a catastrophic neurologic clinical course resulting in death in infancy.

Four unrelated families reported.
Sources: Expert Review
Aortopathy_Connective Tissue Disorders v1.80 COL12A1 Elena Savva Publications for gene: COL12A1 were set to 28306229; 31273343; 24334604
Aortopathy_Connective Tissue Disorders v1.79 COL12A1 Elena Savva reviewed gene: COL12A1: Rating: ; Mode of pathogenicity: None; Publications: 37458870, 37353357; Phenotypes: ; Mode of inheritance: None
Cerebral vascular malformations v0.37 RNF213 Zornitza Stark Marked gene: RNF213 as ready
Cerebral vascular malformations v0.37 RNF213 Zornitza Stark Gene: rnf213 has been classified as Green List (High Evidence).
Cerebral vascular malformations v0.37 RNF213 Zornitza Stark Phenotypes for gene: RNF213 were changed from {Moyamoya disease 2, susceptibility to} to susceptibility to Moyamoya disease 2, (MIM# 607151)
Cerebral vascular malformations v0.36 RNF213 Zornitza Stark Publications for gene: RNF213 were set to 21048783
Cerebral vascular malformations v0.35 RNF213 Zornitza Stark Mode of inheritance for gene: RNF213 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.1489 RNF213 Zornitza Stark Publications for gene: RNF213 were set to
Mendeliome v1.1488 RNF213 Zornitza Stark Mode of inheritance for gene: RNF213 was changed from BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital Heart Defect v0.410 MYOCD Zornitza Stark Classified gene: MYOCD as Amber List (moderate evidence)
Congenital Heart Defect v0.410 MYOCD Zornitza Stark Gene: myocd has been classified as Amber List (Moderate Evidence).
Congenital Heart Defect v0.409 MYOCD Zornitza Stark edited their review of gene: MYOCD: Added comment: Single family with bi-allelic disease reported, which seems to be more severe expression of the mono-allelic disease, hence the Amber (rather than Red) rating.; Changed rating: AMBER
Intellectual disability syndromic and non-syndromic v0.5676 POLR1A Zornitza Stark Phenotypes for gene: POLR1A were changed from Acrofacial dysostosis, Cincinnati type MIM#616462 to Acrofacial dysostosis, Cincinnati type MIM#616462; Leukodystrophy, hypomyelinating, 27, MIM# 620675
Leukodystrophy - paediatric v0.304 POLR1A Zornitza Stark changed review comment from: Further two unrelated patients reported.; to: Further two unrelated patients reported but overall two homozygous missense variants only.
Leukodystrophy - paediatric v0.304 POLR1A Zornitza Stark edited their review of gene: POLR1A: Changed rating: AMBER
Leukodystrophy - paediatric v0.304 POLR1A Zornitza Stark Classified gene: POLR1A as Amber List (moderate evidence)
Leukodystrophy - paediatric v0.304 POLR1A Zornitza Stark Gene: polr1a has been classified as Amber List (Moderate Evidence).
Leukodystrophy - paediatric v0.303 POLR1A Zornitza Stark Classified gene: POLR1A as Green List (high evidence)
Leukodystrophy - paediatric v0.303 POLR1A Zornitza Stark Gene: polr1a has been classified as Green List (High Evidence).
Leukodystrophy - paediatric v0.302 POLR1A Zornitza Stark edited their review of gene: POLR1A: Added comment: Further two unrelated patients reported.; Changed rating: GREEN; Changed publications: 36917474
Intellectual disability syndromic and non-syndromic v0.5675 POLR1A Zornitza Stark Mode of inheritance for gene: POLR1A was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5674 POLR1A Zornitza Stark reviewed gene: POLR1A: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Leukodystrophy, hypomyelinating, 27, MIM# 620675; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Leukodystrophy - paediatric v0.302 POLR1A Zornitza Stark Phenotypes for gene: POLR1A were changed from Leukodystrophy MONDO:0019046, POLR1A related to Leukodystrophy, hypomyelinating, 27, MIM# 620675
Leukodystrophy - paediatric v0.301 POLR1A Zornitza Stark reviewed gene: POLR1A: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Leukodystrophy, hypomyelinating, 27, MIM# 620675; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1487 POLR1A Zornitza Stark Phenotypes for gene: POLR1A were changed from Acrofacial dysostosis, Cincinnati type, (MIM#616462); Leukodystrophy MONDO:0019046, POLR1A-related to Leukodystrophy, hypomyelinating, 27, MIM# 620675; Acrofacial dysostosis, Cincinnati type, (MIM#616462)
Mendeliome v1.1486 POLR1A Zornitza Stark edited their review of gene: POLR1A: Changed phenotypes: Leukodystrophy, hypomyelinating, 27, MIM# 620675, Acrofacial dysostosis, Cincinnati type, (MIM#616462)
Mendeliome v1.1486 PCYT1A Zornitza Stark Phenotypes for gene: PCYT1A were changed from Spondylometaphyseal dysplasia with cone-rod dystrophy, MIM# 608940; Congenital lipodystrophy to Spondylometaphyseal dysplasia with cone-rod dystrophy, MIM# 608940; Lipodystrophy, congenital generalized, type 5, MIM# 620680
Mendeliome v1.1485 PCYT1A Zornitza Stark edited their review of gene: PCYT1A: Changed phenotypes: Spondylometaphyseal dysplasia with cone-rod dystrophy, MIM# 608940, Lipodystrophy, congenital generalized, type 5, MIM# 620680
Lipodystrophy_Lipoatrophy v1.13 PCYT1A Zornitza Stark Phenotypes for gene: PCYT1A were changed from Congenital lipodystrophy; fatty liver disease to Lipodystrophy, congenital generalized, type 5, MIM# 620680
Lipodystrophy_Lipoatrophy v1.12 PCYT1A Zornitza Stark edited their review of gene: PCYT1A: Changed phenotypes: Lipodystrophy, congenital generalized, type 5, MIM# 620680
Optic Atrophy v1.27 SPG7 Elena Savva commented on gene: SPG7: PMID: 32548275 - fs reported in AD optic atrophy where in NMD-predicted regions of the protein, were either isolated cases (1 proband) or segregated in a single family (2 affected).
**Several families with missense variants had more extensive segregation within families, and one was de novo - this is in ANOTHER gene, NOT SPG7
Intellectual disability syndromic and non-syndromic v0.5674 ATP6V0A1 Elena Savva Phenotypes for gene: ATP6V0A1 were changed from Developmental and epileptic encephalopathy 104 MIM#619970; Neurodevelopmental disorder with epilepsy and brain atrophy MIM#619971 to Developmental and epileptic encephalopathy 104 MIM#619970; Neurodevelopmental disorder with epilepsy and brain atrophy MIM#619971
Intellectual disability syndromic and non-syndromic v0.5673 ATP6V0A1 Elena Savva Phenotypes for gene: ATP6V0A1 were changed from Developmental and epileptic encephalopathy 104 MIM#619970; Neurodevelopmental disorder with epilepsy and brain atrophy MIM#619971 to Developmental and epileptic encephalopathy 104 MIM#619970; Neurodevelopmental disorder with epilepsy and brain atrophy MIM#619971
Genetic Epilepsy v0.2161 ATP6V0A1 Elena Savva Phenotypes for gene: ATP6V0A1 were changed from Developmental and epileptic encephalopathy 104 MIM#619970; Neurodevelopmental disorder with epilepsy and brain atrophy MIM#619971 to Developmental and epileptic encephalopathy 104 MIM#619970; Neurodevelopmental disorder with epilepsy and brain atrophy MIM#619971
Intellectual disability syndromic and non-syndromic v0.5673 ATP6V0A1 Elena Savva Phenotypes for gene: ATP6V0A1 were changed from Neurodevelopmental disorder, MONDO:0700092, ATP6V0A1-related to Developmental and epileptic encephalopathy 104 MIM#619970; Neurodevelopmental disorder with epilepsy and brain atrophy MIM#619971
Genetic Epilepsy v0.2161 ATP6V0A1 Elena Savva Phenotypes for gene: ATP6V0A1 were changed from Neurodevelopmental disorder, MONDO:0700092, ATP6V0A1-associated to Developmental and epileptic encephalopathy 104 MIM#619970; Neurodevelopmental disorder with epilepsy and brain atrophy MIM#619971
Mendeliome v1.1485 ATP6V0A1 Elena Savva Phenotypes for gene: ATP6V0A1 were changed from Neurodevelopmental disorder MONDO:0700092, ATP6V0A1-associated to Developmental and epileptic encephalopathy 104 MIM#619970; Neurodevelopmental disorder with epilepsy and brain atrophy MIM#619971
Ataxia - paediatric v1.18 ATP6V0A1 Elena Savva Phenotypes for gene: ATP6V0A1 were changed from Neurodevelopmental disorder, MONDO:0700092, ATP6V0A1-associated to Developmental and epileptic encephalopathy 104 MIM#619970; Neurodevelopmental disorder with epilepsy and brain atrophy MIM#619971
Skeletal dysplasia v0.260 NEPRO Achchuthan Shanmugasundram reviewed gene: NEPRO: Rating: GREEN; Mode of pathogenicity: None; Publications: 37294112; Phenotypes: Anauxetic dysplasia 3, OMIM:618853; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1484 TREX1 Zornitza Stark Mode of inheritance for gene: TREX1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genetic Epilepsy v0.2160 EIF2AK2 Zornitza Stark Marked gene: EIF2AK2 as ready
Genetic Epilepsy v0.2160 EIF2AK2 Zornitza Stark Gene: eif2ak2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2160 EIF2AK2 Zornitza Stark Classified gene: EIF2AK2 as Green List (high evidence)
Genetic Epilepsy v0.2160 EIF2AK2 Zornitza Stark Gene: eif2ak2 has been classified as Green List (High Evidence).
Neurodegeneration with brain iron accumulation v0.31 FTH1 Zornitza Stark Phenotypes for gene: FTH1 were changed from Neuroferritinopathy (MONDO:0011638) to Neurodegeneration with brain iron accumulation 9, MIM# 620669
Neurodegeneration with brain iron accumulation v0.30 FTH1 Zornitza Stark reviewed gene: FTH1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodegeneration with brain iron accumulation 9, MIM# 620669; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Regression v0.542 FTH1 Zornitza Stark Phenotypes for gene: FTH1 were changed from Neuroferritinopathy (MONDO:0011638) to Neurodegeneration with brain iron accumulation 9, MIM# 620669
Regression v0.541 FTH1 Zornitza Stark reviewed gene: FTH1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodegeneration with brain iron accumulation 9, MIM# 620669; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.1483 FTH1 Zornitza Stark Phenotypes for gene: FTH1 were changed from Hemochromatosis, type 5, MIM# 615517; Neuroferritinopathy (MONDO:0011638) to Hemochromatosis, type 5, MIM# 615517; Neurodegeneration with brain iron accumulation 9, MIM# 620669
Cerebellar and Pontocerebellar Hypoplasia v1.64 FTH1 Zornitza Stark Phenotypes for gene: FTH1 were changed from Neuroferritinopathy (MONDO:0011638) to Neurodegeneration with brain iron accumulation 9, MIM# 620669
Cerebellar and Pontocerebellar Hypoplasia v1.63 FTH1 Zornitza Stark reviewed gene: FTH1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodegeneration with brain iron accumulation 9, MIM# 620669; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendelian susceptibility to Immune Disorders v0.48 TBX21 Zornitza Stark Phenotypes for gene: TBX21 were changed from Inherited susceptibility to mycobacterial disease, MONDO:0019146, TBX21-related to Immunodeficiency 88, MIM# 619630
Mendelian susceptibility to Immune Disorders v0.47 TBX21 Zornitza Stark Phenotypes for gene: TBX21 were changed from Susceptibility to mycobacterial disease to Inherited susceptibility to mycobacterial disease, MONDO:0019146, TBX21-related
Mendelian susceptibility to Immune Disorders v0.46 TBX21 Zornitza Stark Marked gene: TBX21 as ready
Mendelian susceptibility to Immune Disorders v0.46 TBX21 Zornitza Stark Gene: tbx21 has been classified as Amber List (Moderate Evidence).
Mendelian susceptibility to Immune Disorders v0.46 TBX21 Zornitza Stark Phenotypes for gene: TBX21 were changed from Susceptibility to mycobacterial disease to Susceptibility to mycobacterial disease
Mendelian susceptibility to Immune Disorders v0.45 TBX21 Zornitza Stark Classified gene: TBX21 as Amber List (moderate evidence)
Mendelian susceptibility to Immune Disorders v0.45 TBX21 Zornitza Stark Gene: tbx21 has been classified as Amber List (Moderate Evidence).
Mendelian susceptibility to Immune Disorders v0.44 SPPL2A Zornitza Stark Marked gene: SPPL2A as ready
Mendelian susceptibility to Immune Disorders v0.44 SPPL2A Zornitza Stark Gene: sppl2a has been classified as Amber List (Moderate Evidence).
Mendelian susceptibility to Immune Disorders v0.44 SPPL2A Zornitza Stark Phenotypes for gene: SPPL2A were changed from Susceptibility to mycobacterial disease to Immunodeficiency 86, MIM#619549
Mendelian susceptibility to Immune Disorders v0.43 SPPL2A Zornitza Stark Classified gene: SPPL2A as Amber List (moderate evidence)
Mendelian susceptibility to Immune Disorders v0.43 SPPL2A Zornitza Stark Gene: sppl2a has been classified as Amber List (Moderate Evidence).
Mendelian susceptibility to Immune Disorders v0.42 SPPL2A Zornitza Stark reviewed gene: SPPL2A: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Immunodeficiency 86, MIM#619549; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendelian susceptibility to Immune Disorders v0.42 IRF1 Zornitza Stark Phenotypes for gene: IRF1 were changed from Inherited susceptibility to mycobacterial disease, MONDO:0019146, IRF1-related to Immunodeficiency 117, mycobacteriosis, autosomal recessive, MIM# 620668
Mendelian susceptibility to Immune Disorders v0.41 IRF1 Zornitza Stark edited their review of gene: IRF1: Changed phenotypes: Immunodeficiency 117, mycobacteriosis, autosomal recessive, MIM# 620668
Mendeliome v1.1482 IRF1 Zornitza Stark Phenotypes for gene: IRF1 were changed from Inherited susceptibility to mycobacterial disease, MONDO:0019146, IRF1-related to Immunodeficiency 117, mycobacteriosis, autosomal recessive, MIM# 620668
Mendeliome v1.1481 IRF1 Zornitza Stark edited their review of gene: IRF1: Changed phenotypes: Immunodeficiency 117, mycobacteriosis, autosomal recessive, MIM# 620668
Ataxia - adult onset v1.6 COQ4 Zornitza Stark Marked gene: COQ4 as ready
Ataxia - adult onset v1.6 COQ4 Zornitza Stark Gene: coq4 has been classified as Green List (High Evidence).
Ataxia - adult onset v1.6 COQ4 Zornitza Stark Classified gene: COQ4 as Green List (high evidence)
Ataxia - adult onset v1.6 COQ4 Zornitza Stark Gene: coq4 has been classified as Green List (High Evidence).
Ataxia - adult onset v1.5 COQ4 Zornitza Stark gene: COQ4 was added
gene: COQ4 was added to Ataxia - adult onset. Sources: Expert Review
Mode of inheritance for gene: COQ4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COQ4 were set to 36047608; 38014483; 38013626
Phenotypes for gene: COQ4 were set to Spastic ataxia 10, autosomal recessive, MIM# 620666
Review for gene: COQ4 was set to GREEN
Added comment: PMIDs 36047608;38014483;38013626: more than 10 families reported with more limited spastic ataxia phenotype, onset from infancy to adulthood.
Sources: Expert Review
Ataxia - paediatric v1.17 COQ4 Zornitza Stark edited their review of gene: COQ4: Added comment: PMIDs 36047608;38014483;38013626: more than 10 families reported with more limited spastic ataxia phenotype, onset from infancy to adulthood.; Changed publications: 30225196, 33704555, 30847826, 36047608, 38014483, 38013626; Changed phenotypes: Coenzyme Q10 deficiency, primary, 7, MIM# 616276, Spastic ataxia 10, autosomal recessive, MIM# 620666
Mitochondrial disease v0.912 COQ4 Zornitza Stark Phenotypes for gene: COQ4 were changed from Coenzyme Q10 deficiency, primary, 7, MIM# 616276 to Coenzyme Q10 deficiency, primary, 7, MIM# 616276; Spastic ataxia 10, autosomal recessive, MIM# 620666
Mitochondrial disease v0.911 COQ4 Zornitza Stark Publications for gene: COQ4 were set to 25658047; 26185144; 33704555
Mitochondrial disease v0.910 COQ4 Zornitza Stark edited their review of gene: COQ4: Added comment: PMIDs 36047608;38014483;38013626: more than 10 families reported with more limited spastic ataxia phenotype, onset from infancy to adulthood.; Changed publications: 25658047, 26185144, 33704555, 36047608, 38014483, 38013626; Changed phenotypes: Coenzyme Q10 deficiency, primary, 7, MIM# 616276, Spastic ataxia 10, autosomal recessive, MIM# 620666
Mendeliome v1.1481 COQ4 Zornitza Stark Phenotypes for gene: COQ4 were changed from Coenzyme Q10 deficiency, primary, 7, MIM# 616276 to Coenzyme Q10 deficiency, primary, 7, MIM# 616276; Spastic ataxia 10, autosomal recessive, MIM# 620666
Mendeliome v1.1480 COQ4 Zornitza Stark Publications for gene: COQ4 were set to 25658047; 26185144; 33704555
Mendeliome v1.1479 COQ4 Zornitza Stark edited their review of gene: COQ4: Added comment: PMIDs 36047608;38014483;38013626: more than 10 families reported with more limited spastic ataxia phenotype, onset from infancy to adulthood.; Changed publications: 25658047, 26185144, 33704555, 36047608, 38014483, 38013626; Changed phenotypes: Coenzyme Q10 deficiency, primary, 7, MIM# 616276, Spastic ataxia 10, autosomal recessive, MIM# 620666
Mendeliome v1.1479 SEC61A1 Zornitza Stark Phenotypes for gene: SEC61A1 were changed from Hyperuricemic nephropathy, familial juvenile, 4, MIM# 617056; Hypogammaglobulinaemia; Neutropaenia to Hyperuricemic nephropathy, familial juvenile, 4, MIM# 617056; Immunodeficiency, common variable, 15, MIM# 620670; Neutropenia, severe congenital, 11, autosomal dominant, MIM# 620674
Mendeliome v1.1478 SEC61A1 Zornitza Stark Publications for gene: SEC61A1 were set to 27392076; 32325141; 28782633
Mendeliome v1.1477 SEC61A1 Zornitza Stark edited their review of gene: SEC61A1: Added comment: PMID 32325141: single individual with de novo missense and phenotype primarily characterised by severe neutropenia.; Changed publications: 27392076, 32325141, 28782633, 32325141
Mendeliome v1.1477 SEC61A1 Zornitza Stark edited their review of gene: SEC61A1: Changed phenotypes: Hyperuricemic nephropathy, familial juvenile, 4, MIM# 617056, Immunodeficiency, common variable, 15, MIM# 620670, Neutropenia, severe congenital, 11, autosomal dominant, MIM# 620674
Phagocyte Defects v1.25 SEC61A1 Zornitza Stark Phenotypes for gene: SEC61A1 were changed from Hyperuricemic nephropathy, familial juvenile, 4, MIM# 617056; Hypogammaglobulinaemia; Neutropaenia to Hyperuricemic nephropathy, familial juvenile, 4, MIM# 617056; Neutropenia, severe congenital, 11, autosomal dominant, MIM# 620674; Immunodeficiency, common variable, 15, MIM# 620670
Phagocyte Defects v1.24 SEC61A1 Zornitza Stark Classified gene: SEC61A1 as Green List (high evidence)
Phagocyte Defects v1.24 SEC61A1 Zornitza Stark Gene: sec61a1 has been classified as Green List (High Evidence).
Phagocyte Defects v1.23 SEC61A1 Zornitza Stark edited their review of gene: SEC61A1: Changed rating: GREEN
Phagocyte Defects v1.23 SEC61A1 Zornitza Stark edited their review of gene: SEC61A1: Added comment: PMID 32325141: single individual with de novo missense and phenotype primarily characterised by severe neutropenia.

PMID 28782633: 11 individuals with primarily CVID phenotype, including neutropenia.; Changed publications: 27392076, 32325141, 28782633, 32325141; Changed phenotypes: Hyperuricemic nephropathy, familial juvenile, 4, MIM# 617056, Neutropenia, severe congenital, 11, autosomal dominant, MIM# 620674, Immunodeficiency, common variable, 15, MIM# 620670
Mendeliome v1.1477 SEC61A1 Zornitza Stark edited their review of gene: SEC61A1: Changed phenotypes: Hyperuricemic nephropathy, familial juvenile, 4, MIM# 617056, Immunodeficiency, common variable, 15, MIM# 620670
Common Variable Immunodeficiency v1.12 SEC61A1 Zornitza Stark Phenotypes for gene: SEC61A1 were changed from hypogammaglobulinemia; common variable immunodeficiency to Immunodeficiency, common variable, 15, MIM# 620670
Common Variable Immunodeficiency v1.11 SEC61A1 Zornitza Stark Classified gene: SEC61A1 as Green List (high evidence)
Common Variable Immunodeficiency v1.11 SEC61A1 Zornitza Stark Gene: sec61a1 has been classified as Green List (High Evidence).
Common Variable Immunodeficiency v1.10 SEC61A1 Zornitza Stark edited their review of gene: SEC61A1: Added comment: Further 11 individuals from two families reported in PMID: 28782633 with immunological phenotype.; Changed publications: 28782633
Common Variable Immunodeficiency v1.10 SEC61A1 Zornitza Stark reviewed gene: SEC61A1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Immunodeficiency, common variable, 15, MIM# 620670; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Predominantly Antibody Deficiency v0.132 SEC61A1 Zornitza Stark Phenotypes for gene: SEC61A1 were changed from Hyperuricemic nephropathy, familial juvenile, 4, MIM# 617056; Hypogammaglobulinaemia; Severe recurrent respiratory tract infections to Hyperuricemic nephropathy, familial juvenile, 4, MIM# 617056; Immunodeficiency, common variable, 15, MIM# 620670
Predominantly Antibody Deficiency v0.131 SEC61A1 Zornitza Stark edited their review of gene: SEC61A1: Changed phenotypes: Hyperuricemic nephropathy, familial juvenile, 4, MIM# 617056, Immunodeficiency, common variable, 15, MIM# 620670
Genetic Epilepsy v0.2159 KPNA7 Elena Savva Phenotypes for gene: KPNA7 were changed from severe neurodevelopmental defects; epilepsy to Neurodevelopmental disorder (MONDO#0700092), KPNA7-related
Mendeliome v1.1477 KPNA7 Elena Savva Phenotypes for gene: KPNA7 were changed from Oocyte/zygote/embryo maturation arrest 17, MIM# 620319; Neurodevelopmental disorder to Oocyte/zygote/embryo maturation arrest 17, MIM# 620319; Neurodevelopmental disorder (MONDO#0700092), KPNA7-related
Genetic Epilepsy v0.2158 KIF4A Elena Savva Publications for gene: KIF4A were set to 24812067; 34346154
Genetic Epilepsy v0.2158 KIF4A Elena Savva Classified gene: KIF4A as Amber List (moderate evidence)
Genetic Epilepsy v0.2158 KIF4A Elena Savva Gene: kif4a has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2157 KIF4A Elena Savva reviewed gene: KIF4A: Rating: ; Mode of pathogenicity: None; Publications: PMID: 36482480, 24812067, 34346154; Phenotypes: ; Mode of inheritance: None
Intellectual disability syndromic and non-syndromic v0.5672 KIF4A Elena Savva Phenotypes for gene: KIF4A were changed from Mental retardation, X-linked 100, MIM# 300923 to Intellectual developmental disorder, X-linked 100 MIM#300923
Mendeliome v1.1476 KIF4A Elena Savva Phenotypes for gene: KIF4A were changed from Mental retardation, X-linked 100, MIM# 300923; Taurodontism, microdontia, and dens invaginatus (MIM#313490) to Intellectual developmental disorder, X-linked 100 MIM#300923; Taurodontism, microdontia, and dens invaginatus MIM#313490
Hydrocephalus_Ventriculomegaly v0.121 KIF4A Elena Savva Phenotypes for gene: KIF4A were changed from Mental retardation, X-linked 100, MIM# 300923 to Intellectual developmental disorder, X-linked 100 MIM#300923
Genetic Epilepsy v0.2157 KIF4A Elena Savva Phenotypes for gene: KIF4A were changed from Mental retardation, X-linked 100, MIM# 300923 to Intellectual developmental disorder, X-linked 100 MIM#300923
Genetic Epilepsy v0.2156 KIF1BP Elena Savva Classified gene: KIF1BP as Red List (low evidence)
Genetic Epilepsy v0.2156 KIF1BP Elena Savva Gene: kif1bp has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2155 KIF1BP Elena Savva reviewed gene: KIF1BP: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 28277559; Phenotypes: Goldberg-Shprintzen megacolon syndrome, MIM#609460; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5671 KCTD13 Elena Savva Mode of inheritance for gene: KCTD13 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Genetic Epilepsy v0.2155 KCTD13 Elena Savva Mode of inheritance for gene: KCTD13 was changed from BIALLELIC, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v1.1475 KCTD13 Elena Savva Mode of inheritance for gene: KCTD13 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Intellectual disability syndromic and non-syndromic v0.5670 KCTD13 Elena Savva Phenotypes for gene: KCTD13 were changed from Intellectual disability to Neurodevelopmental disorder (MONDO#0700092), KCTD13-related
Genetic Epilepsy v0.2154 KCTD13 Elena Savva Phenotypes for gene: KCTD13 were changed from Neurodevelopmental disorder (MONDO#0700092), KCTD13-related to Neurodevelopmental disorder (MONDO#0700092), KCTD13-related
Genetic Epilepsy v0.2154 KCTD13 Elena Savva Phenotypes for gene: KCTD13 were changed from to Neurodevelopmental disorder (MONDO#0700092), KCTD13-related
Mendeliome v1.1474 KCTD13 Elena Savva Phenotypes for gene: KCTD13 were changed from Intellectual disability; seizures to Neurodevelopmental disorder (MONDO#0700092), KCTD13-related
Hypertrichosis syndromes v0.46 KCNN3 Elena Savva Classified gene: KCNN3 as Amber List (moderate evidence)
Hypertrichosis syndromes v0.46 KCNN3 Elena Savva Gene: kcnn3 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5669 KCNN3 Elena Savva Phenotypes for gene: KCNN3 were changed from Zimmermann-Laband syndrome 3; OMIM# 618658 to Zimmermann-Laband syndrome 3 MIM#618658
Hypertrichosis syndromes v0.45 KCNN3 Elena Savva Marked gene: KCNN3 as ready
Hypertrichosis syndromes v0.45 KCNN3 Elena Savva Gene: kcnn3 has been classified as Red List (Low Evidence).
Hypertrichosis syndromes v0.45 KCNN3 Elena Savva gene: KCNN3 was added
gene: KCNN3 was added to Hypertrichosis syndromes. Sources: Literature
Mode of inheritance for gene: KCNN3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: KCNN3 were set to 34907639
Phenotypes for gene: KCNN3 were set to Zimmermann-Laband syndrome 3 MIM#618658
Review for gene: KCNN3 was set to AMBER
Added comment: PMID: 34907639 - literature review of previous ZLS patients, describes hypertrichosis as mild/moderate on trunk and limbs (3/7), or synophrys (4/7) in all patients
Sources: Literature
Mendeliome v1.1473 KCNN3 Elena Savva Phenotypes for gene: KCNN3 were changed from Zimmermann-Laband syndrome 3; OMIM# 618658 to Zimmermann-Laband syndrome 3; MIM#618658
Genetic Epilepsy v0.2153 KCNN3 Elena Savva Phenotypes for gene: KCNN3 were changed from Zimmermann-Laband syndrome to Zimmermann-Laband syndrome 3 MIM#618658
Genetic Epilepsy v0.2153 KCNN3 Elena Savva Publications for gene: KCNN3 were set to PMID: 33594261
Genetic Epilepsy v0.2152 KCNN3 Elena Savva reviewed gene: KCNN3: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 34907639; Phenotypes: Zimmermann-Laband syndrome 3 MIM#618658; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Genetic Epilepsy v0.2152 KCNAB3 Elena Savva Publications for gene: KCNAB3 were set to PMID: 32990398
Mendeliome v1.1472 KCNAB3 Elena Savva Publications for gene: KCNAB3 were set to PMID: 32990398
Genetic Epilepsy v0.2151 KCNAB3 Elena Savva reviewed gene: KCNAB3: Rating: RED; Mode of pathogenicity: None; Publications: 37396552, 32990398, 36345448; Phenotypes: Neurodevelopmental disorder (MONDO#0700092), KCNAB3-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v1.1471 KCNAB3 Elena Savva reviewed gene: KCNAB3: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 37396552, 32990398, 36345448; Phenotypes: Neurodevelopmental disorder (MONDO#0700092), KCNAB3-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Genetic Epilepsy v0.2151 KCNAB3 Elena Savva Phenotypes for gene: KCNAB3 were changed from febrile seizures; afebrile seizure; genetic epilepsy with febrile seizures plus to Neurodevelopmental disorder (MONDO#0700092), KCNAB3-related
Mendeliome v1.1471 KCNAB3 Elena Savva Phenotypes for gene: KCNAB3 were changed from febrile seizures; afebrile seizure; genetic epilepsy with febrile seizures plus to Neurodevelopmental disorder (MONDO#0700092), KCNAB3-related
Genetic Epilepsy v0.2150 KARS Elena Savva reviewed gene: KARS: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 33942428; Phenotypes: Leukoencephalopathy, progressive, infantile-onset, with or without deafness MIM#619147; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5668 JAKMIP1 Elena Savva Phenotypes for gene: JAKMIP1 were changed from Intellectual disability; Seizures to Neurodevelopmental disorder (MONDO#0700092), JAKMIP1-related
Genetic Epilepsy v0.2150 JAKMIP1 Elena Savva Phenotypes for gene: JAKMIP1 were changed from Intellectual disability; Seizures to Neurodevelopmental disorder (MONDO#0700092), JAKMIP1-related
Mendeliome v1.1470 JAKMIP1 Elena Savva Phenotypes for gene: JAKMIP1 were changed from Intellectual disability; Seizures to Neurodevelopmental disorder (MONDO#0700092), JAKMIP1-related
Genetic Epilepsy v0.2149 ECM1 Andrew Fennell changed review comment from: PMID: 28434238 - 4 individuals with seizures from a cohort of 16. Note, that the authors focused on long-term progress of patients with seizures and/or brain calcification and excluded from the description those without those features. This means the quoted 57% prevalence of seizures was actually 25%. Seizure types included focal & absence.

PMID: 11929856 - references to previous studies predating the molecular understanding of the disorder with seizures being a common feature.
Sources: Literature; to: PMID: 28434238 - 4 individuals with seizures from a cohort of 16. Note, that the authors focused on long-term progress of patients with seizures and/or brain calcification and excluded from the description those without those features. This means the quoted 57% prevalence of seizures was actually 25%. Seizure types included focal & absence.

PMID: 11929856 - references to previous studies predating the molecular understanding of the disorder with seizures being a common feature.
Sources: Literature
Genetic Epilepsy v0.2149 EIF2AK2 Andrew Fennell gene: EIF2AK2 was added
gene: EIF2AK2 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: EIF2AK2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: EIF2AK2 were set to PMID: 32197074
Phenotypes for gene: EIF2AK2 were set to Leukoencephalopathy, developmental delay, and episodic neurologic regression syndrome, MIM# 618877
Review for gene: EIF2AK2 was set to GREEN
Added comment: PMID: 32197074 - Four individuals (50%) with seizures including GTCS, focal tonic, and focal complex types.

PMID: 33236446 - a single individual with neonatal generalised tonic seizures, dystonia, significant ID and later spasticity.
Sources: Literature
Genetic Epilepsy v0.2149 EED Andrew Fennell gene: EED was added
gene: EED was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: EED was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: EED were set to PMID: 34533271
Phenotypes for gene: EED were set to Cohen-Gibson syndrome, MIM# 617561
Review for gene: EED was set to RED
Added comment: PMID: 34533271 - single case report of child with absence epilepsy aged 5yrs and subsequent GTC seizures throughout childhood.

Note, Griffiths et al (2019) reported 1 patient with seizures but later attributed this to hyperinsulinaemic hypoglycaemia.
Sources: Literature
Genetic Epilepsy v0.2149 ECM1 Andrew Fennell gene: ECM1 was added
gene: ECM1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: ECM1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ECM1 were set to PMID: 11929856; 28434238
Review for gene: ECM1 was set to GREEN
Added comment: PMID: 28434238 - 4 individuals with seizures from a cohort of 16. Note, that the authors focused on long-term progress of patients with seizures and/or brain calcification and excluded from the description those without those features. This means the quoted 57% prevalence of seizures was actually 25%. Seizure types included focal & absence.

PMID: 11929856 - references to previous studies predating the molecular understanding of the disorder with seizures being a common feature.
Sources: Literature
Genetic Epilepsy v0.2149 ECHS1 Andrew Fennell gene: ECHS1 was added
gene: ECHS1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: ECHS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ECHS1 were set to PMID: 29575569; 35098523
Phenotypes for gene: ECHS1 were set to Mitochondrial short-chain enoyl-CoA hydratase 1 deficiency, MIM# 616277; Leigh syndrome MONDO:0009723; cerebral palsy MONDO:0006497; paroxysmal dystonia MONDO:0016058
Review for gene: ECHS1 was set to GREEN
Added comment: PMID: 29575569 - 4 of 4 patients with Mitochondrial short-chain enoyl-CoA hydratase 1 deficiency (ECHS1) had seizures onset in infancy.

PMID: 35098523 - single case report of an infant with Mitochondrial short-chain enoyl-CoA hydratase 1 deficiency with status epilepticus after propofol administration.
Sources: Literature
Genetic Epilepsy v0.2149 DOHH Andrew Fennell gene: DOHH was added
gene: DOHH was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: DOHH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DOHH were set to PMID: 30661771; 35858628
Phenotypes for gene: DOHH were set to Neurodevelopmental disorder, DOHH-related (MONDO#0700092)
Review for gene: DOHH was set to GREEN
Added comment: PMID: 35858628 - three of the five reported individuals with this neurodevelopmental disorder identified to have seizures. Two individuals had febrile seizures in mid-childhood with one going on to have generalised epilepsy. A third individual had generalised epilepsy.

PMID: 30661771 - Of note, DOHH is a key part of the same two-step enzymatic pathway as DHPS which is also associated with a neurodevelopmental disorder that prominently features seizures.
Sources: Literature
Genetic Epilepsy v0.2149 DHX16 Andrew Fennell gene: DHX16 was added
gene: DHX16 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: DHX16 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DHX16 were set to PMID: 31256877; 36211162
Phenotypes for gene: DHX16 were set to Neuromuscular disease and ocular or auditory anomalies with or without seizures, MIM# 618733
Review for gene: DHX16 was set to GREEN
Added comment: PMID: 31256877 - two of the four reported individuals had seizures (infantile spasms in one & GTC in one)

PMID: 36211162 - single case report of an 18-month old child with infantile spasms, likely for several months prior to presentation.
Sources: Literature
Motor Neurone Disease v1.8 DNAJC7 Sarah Leigh reviewed gene: DNAJC7: Rating: GREEN; Mode of pathogenicity: None; Publications: 31768050, 35039179, 34233860, 32897108, 37870677, 35456894; Phenotypes: amyotrophic lateral sclerosis; Mode of inheritance: None
Ciliary Dyskinesia v1.38 Bryony Thompson Panel types changed to Victorian Clinical Genetics Services; Royal Melbourne Hospital; Rare Disease
Congenital nystagmus v1.19 Bryony Thompson Panel types changed to Victorian Clinical Genetics Services; Royal Melbourne Hospital; Rare Disease
Overgrowth v1.11 SPIN4 Zornitza Stark Marked gene: SPIN4 as ready
Overgrowth v1.11 SPIN4 Zornitza Stark Gene: spin4 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2149 PRIMA1 Chris Ciotta gene: PRIMA1 was added
gene: PRIMA1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: PRIMA1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PRIMA1 were set to PMID: 26339676
Phenotypes for gene: PRIMA1 were set to Frontal Lobe Epilepsy MONDO:0002612
Review for gene: PRIMA1 was set to RED
Added comment: - 2/3 siblings from unaffected parents in PMID: 26339676 were diagnosed with nocturnal frontal lobe epilepsy, which was confirmed by EEG. The affected siblings were homozygous for the c.93+2T>C variant canonical splice site variant. This variant was demonstrated by mini-gene assay to skip exon 2 of PRIMA1.

Overall 1 family, 2 individuals with epilepsy and high impact variants in PRIMA1.
Sources: Literature
Genetic Epilepsy v0.2149 POMGNT2 Chris Ciotta gene: POMGNT2 was added
gene: POMGNT2 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: POMGNT2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POMGNT2 were set to PMID: 36808730
Phenotypes for gene: POMGNT2 were set to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 8 MIM#614830
Review for gene: POMGNT2 was set to RED
Added comment: This gene was included in the Genes4Epilepsy (PMID: 36808730) Gene resource and was said to be associated with developmental and epileptic encephalopathies and malformations of cortical development. In a review of the literature an association with individuals presenting with epilepsy was not found.
Sources: Literature
Genetic Epilepsy v0.2149 PLXNC1 Chris Ciotta gene: PLXNC1 was added
gene: PLXNC1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: PLXNC1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PLXNC1 were set to PMID: 36808730
Phenotypes for gene: PLXNC1 were set to Malformations of cortical development
Review for gene: PLXNC1 was set to RED
Added comment: This gene was included in the genes4epilepsy resource (PMID:36808730) and was reported as being associated with the clinical phenotype "malformations of cortical development".

There are no current PubMed articles linking this gene with epilepsy however
Sources: Literature
Genetic Epilepsy v0.2149 PRDM8 Chris Ciotta gene: PRDM8 was added
gene: PRDM8 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: PRDM8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PRDM8 were set to PMID: 2296154; 35034233
Phenotypes for gene: PRDM8 were set to ?Epilepsy, progressive myoclonic, 10 MIM#616640
Review for gene: PRDM8 was set to RED
Added comment: - PMID:22961547, 3 individuals from one family, all with myoclonic epilepsy, all had the Phe261Leu variant. This variant is absent from gnomAD V4.

- PMID: 35034233, Two individuals from one family, no clinical seizures but presented with myoclonus and abnormal EEG (generalised epileptiform charges), these individuals had the Ala230Gly missense change, which has currently been reported as a VUS.
Sources: Literature
Genetic Epilepsy v0.2149 PPP2R5D Chris Ciotta reviewed gene: PPP2R5D: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 26168268, 29296277, 26576547; Phenotypes: Houge-Janssens syndrome 1 MIM#616355; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2149 PPP2R5D Chris Ciotta Deleted their review
Genetic Epilepsy v0.2149 PPP2R5D Chris Ciotta gene: PPP2R5D was added
gene: PPP2R5D was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: PPP2R5D was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: PPP2R5D were set to Houge-Janssens syndrome 1 MIM#616355
Review for gene: PPP2R5D was set to GREEN
Added comment: - PMID:26168268, 3/11 individuals with intellectual disability also presented with epilepsy, In these three individuals two had the commonly reported pathogenic Glu198Lys variant while the third had another very well reported Glu200Lys variant.

- PMID:29296277, 2/2 individuals in this study with variants in PPP2R5D with epilepsy. Both individuals had the Glu198Lys variant.

- PMID: 26576547, 1/7 individuals with variants in this gene presented with complex partial seizures, this individual also had the Glu198Lys well reported variant.
Sources: Literature
Genetic Epilepsy v0.2149 POMK Chris Ciotta gene: POMK was added
gene: POMK was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: POMK was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POMK were set to PMID: 24925318
Phenotypes for gene: POMK were set to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 12 MIM#615249
Review for gene: POMK was set to RED
Added comment: - PMID:24925318, 1/3 unrelated individuals with bi-allelic POMK variants presented with seizures along with Cobblestone lissencephaly and hydrocephalus. This individual was compound heterozgyous for a high impact frameshift variant (c.286delT, p.F96fs) and a missense variant (c.905T>A , p.V302D).
Sources: Literature
Genetic Epilepsy v0.2149 POGZ Chris Ciotta gene: POGZ was added
gene: POGZ was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: POGZ was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: POGZ were set to PMIS: 34645992; 31136090; 28490548; 26739615; 27824329
Phenotypes for gene: POGZ were set to White-Sutton syndrome MIM#616364
Review for gene: POGZ was set to GREEN
Added comment: - 2/12 Individuals in this in PMID:34645992 with POGZ PTVs were reported as having a history of at least 1 seizure. This information is mentioned in the article but seems to be left out in the clinical characteristics table on page 97 so we are unsure which individuals had a history of seizures.

- PMID:31136090, a de novo POGZ truncating variant (c.2711T>G; p.Leu904*) in an individual with dysmorphic features and poor tolerance to oral feeding. No family history of seizures or ID. First epileptic seizure occurred at age 2 and persisted despite clobazam. MRI at age 3 showed cortical and sub cortical atrophy and individual presented with dev delay and epileptic encephalopathy.

- PMID: 28480548, 15 year old female with healthy parents, MRI revealed global cerebellar atrophy, individual presented with dev delay and no verbal capacity, was being treated for epilepsy with medication. p.Asn941fs*3 variant was identified in this individual.

- PMID:26739615, 5 individuals with POGZ p.Ser278* variant, only 1/5 with complex, partial seizures.

- PMID:27824329, One chinese individual with autism, POGZ variant p.Gln127* who presented with seizures.

All the above variants are high impact and absent from gnomAD V4. 6 unique cases of individuals with high impact POGZ variants presenting with seizures/epilepsy.
Sources: Literature
Genetic Epilepsy v0.2149 POLG2 Zornitza Stark Marked gene: POLG2 as ready
Genetic Epilepsy v0.2149 POLG2 Zornitza Stark Gene: polg2 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2149 POLG2 Zornitza Stark Classified gene: POLG2 as Amber List (moderate evidence)
Genetic Epilepsy v0.2149 POLG2 Zornitza Stark Gene: polg2 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2148 POLG2 Zornitza Stark reviewed gene: POLG2: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 4 MIM#610131; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2148 PLP1 Zornitza Stark Marked gene: PLP1 as ready
Genetic Epilepsy v0.2148 PLP1 Zornitza Stark Gene: plp1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2148 PLP1 Zornitza Stark Classified gene: PLP1 as Green List (high evidence)
Genetic Epilepsy v0.2148 PLP1 Zornitza Stark Gene: plp1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2147 PLP1 Zornitza Stark Classified gene: PLP1 as Green List (high evidence)
Genetic Epilepsy v0.2147 PLP1 Zornitza Stark Gene: plp1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2146 POLG2 Chris Ciotta gene: POLG2 was added
gene: POLG2 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: POLG2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: POLG2 were set to PMID: 21555342
Phenotypes for gene: POLG2 were set to Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 4 MIM#610131
Review for gene: POLG2 was set to AMBER
Added comment: PMID:21555342 reports 4/11 unrelated individuals with mitochondrial disease as presenting with seizures and heterozygous variants in POLG2, 3/4 of these individuals had missense variants. Of these variants, 2 have been reported in Clinvar as benign and have high homozygote counts in gnomAD V4. The p.P205R variant was seen in an individual with seizures and is absent from gnomAD V4 and has been reported as pathogenic once in ClinVar for MIM#610131.

The last individual with seizures had a high impact variant (p.L475DfsX2) with 3 heterozygotes in the population (V4) which has been classified as pathogenic in ClinVar.

Overall, 2/11 unrelated individuals with plausible pathogenic variants presenting with seizures.
Sources: Literature
Genetic Epilepsy v0.2146 PPFIA3 Zornitza Stark Marked gene: PPFIA3 as ready
Genetic Epilepsy v0.2146 PPFIA3 Zornitza Stark Gene: ppfia3 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2146 PPFIA3 Zornitza Stark Classified gene: PPFIA3 as Green List (high evidence)
Genetic Epilepsy v0.2146 PPFIA3 Zornitza Stark Gene: ppfia3 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2145 PPFIA3 Zornitza Stark gene: PPFIA3 was added
gene: PPFIA3 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: PPFIA3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PPFIA3 were set to 37034625
Phenotypes for gene: PPFIA3 were set to Neurodevelopmental disorder, MONDO:0700092, PPFIA3-related
Review for gene: PPFIA3 was set to GREEN
Added comment: 19 individuals with mono-allelic variants presenting with features including developmental delay, intellectual disability, hypotonia, micro/macrocephaly, autism, and epilepsy. One individual with compound het variants: insufficient evidence for bi-allelic variants causing disease.
Sources: Literature
Mendeliome v1.1469 PPFIA3 Zornitza Stark Marked gene: PPFIA3 as ready
Mendeliome v1.1469 PPFIA3 Zornitza Stark Gene: ppfia3 has been classified as Green List (High Evidence).
Mendeliome v1.1469 PPFIA3 Zornitza Stark Classified gene: PPFIA3 as Green List (high evidence)
Mendeliome v1.1469 PPFIA3 Zornitza Stark Gene: ppfia3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5667 PPFIA3 Zornitza Stark Marked gene: PPFIA3 as ready
Intellectual disability syndromic and non-syndromic v0.5667 PPFIA3 Zornitza Stark Gene: ppfia3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5667 PPFIA3 Zornitza Stark Classified gene: PPFIA3 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5667 PPFIA3 Zornitza Stark Gene: ppfia3 has been classified as Green List (High Evidence).
Mendeliome v1.1468 PPFIA3 Zornitza Stark gene: PPFIA3 was added
gene: PPFIA3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PPFIA3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PPFIA3 were set to 37034625
Phenotypes for gene: PPFIA3 were set to Neurodevelopmental disorder, MONDO:0700092, PPFIA3-related
Review for gene: PPFIA3 was set to GREEN
Added comment: 19 individuals with mono-allelic variants presenting with features including developmental delay, intellectual disability, hypotonia, micro/macrocephaly, autism, and epilepsy.

One individual with compound het variants: insufficient evidence for bi-allelic variants causing disease.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5666 PPFIA3 Zornitza Stark gene: PPFIA3 was added
gene: PPFIA3 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: PPFIA3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PPFIA3 were set to 37034625
Phenotypes for gene: PPFIA3 were set to Neurodevelopmental disorder, MONDO:0700092, PPFIA3-related
Review for gene: PPFIA3 was set to GREEN
Added comment: 19 individuals with mono-allelic variants presenting with features including developmental delay, intellectual disability, hypotonia, micro/macrocephaly, autism, and epilepsy.

One individual with compound het variants: insufficient evidence for bi-allelic variants causing disease.
Sources: Literature
Genetic Epilepsy v0.2144 PLP1 Lisa Norbart gene: PLP1 was added
gene: PLP1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: PLP1 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: PLP1 were set to 7512350; 11071483; 21679407; 28133555; 29486744; 35346287; 37637647
Phenotypes for gene: PLP1 were set to Pelizaeus-Merzbacher Disease, MIM#312080
Review for gene: PLP1 was set to GREEN
Added comment: PMID: 7512350 (1994) - Mouse study demonstrating that seizures and convulsions are a result of a 2-fold increased PLP gene dosage. (Cited in OMIM)

PMID: 11071483 (2000) - One family with 2x brothers affected with PMD, both developing seizures in late teens. Other symptoms in both brothers include hypotonia at birth, nystagmus, and slowly progressive spastic paraplegia. (Cited in OMIM)

PMID: 21679407 (2011) - Male cohort, 43 individuals from 38 unrelated families with a PLP1-related disorder diagnosis. Seizures present in 2/43 males (both PLP1 duplication mutations). Additional symptoms include 3/43 stridor, 4/43 developmental delay, and 18/43 muscular hypotonia.

PMID: 28133555 (2017) - Case report on 9 year old male affected with classic PMD. Presented with a history of seizures since age 4. Also presents with developmental delay, nystagmus, microcephaly, spastic quadriplegia. Maternally inherited gain of 436Kb on Xq22.2 encompassing TCEAL1,MORF4L2, PLP1, and RAB9B, of which only PLP1 is associated with a disease.

PMID: 29486744 (2018) - Case report on family diagnosed with connatal PMD (previously diagnosed as X-linked epileptic seizures). The PLP1 missense mutation p.Ala84Asp was found to segregate in the family. 1x proband presenting with daily generalised seizures, onset at 8 months and no treatment response. 2x cousins and 2x maternal uncles also presented with epilepsy, all onset around 6 months and all died in childhood. Additional symptoms include 5/5 hypotonia and 5/5 psycho-motor delay. Consanguinity reported in the family.

PMID: 35346287 (2022) - Chinese cohort of 141 patients, 111 whom were followed up with. Seizures present in 4/28 individuals with connatal PMD, including 1 patient who died due to epileptic seizures at age 7, and 4/56 individuals with transitional PMD. Additional symptoms include 111/111 development delay, 110/111 nystagmus, 93/111 hypotonia, 35/111 stridor, and 4/111 respiratory difficulty.

PMID: 37637647 (2023) - Case report on 1x newborn individual diagnosed with failure to thrive and later PMD. Presented with episodes of rapid eye and side-to-side head movement episodes of 5-10 seconds, onset one month after birth. Diagnosis of seizure disorder considered before further testing. Individual hemizygous for PLP1: c.67G>A (p.Gly23Arg), maternally inherited.

GeneReviews: Seizures may develop in infants affected by 'severe connatal PMD'.
Sources: Literature
Leukodystrophy - paediatric v0.301 SLC13A3 Zornitza Stark Marked gene: SLC13A3 as ready
Leukodystrophy - paediatric v0.301 SLC13A3 Zornitza Stark Gene: slc13a3 has been classified as Green List (High Evidence).
Leukodystrophy - paediatric v0.301 SLC13A3 Zornitza Stark Publications for gene: SLC13A3 were set to https://www.neurology.org/doi/full/10.1212/NXG.0000000000200101 (No PMID)
Leukodystrophy - paediatric v0.300 SLC13A3 Zornitza Stark Classified gene: SLC13A3 as Green List (high evidence)
Leukodystrophy - paediatric v0.300 SLC13A3 Zornitza Stark Gene: slc13a3 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2144 SLC13A3 Zornitza Stark Marked gene: SLC13A3 as ready
Genetic Epilepsy v0.2144 SLC13A3 Zornitza Stark Gene: slc13a3 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2144 SLC13A3 Zornitza Stark Publications for gene: SLC13A3 were set to 30635937 35527102; https://www.neurology.org/doi/full/10.1212/NXG.0000000000200101 (No PMID)
Genetic Epilepsy v0.2143 SLC13A3 Zornitza Stark Publications for gene: SLC13A3 were set to 30635937 35527102; https://www.neurology.org/doi/full/10.1212/NXG.0000000000200101 (No PMID)
Genetic Epilepsy v0.2142 SLC13A3 Zornitza Stark Publications for gene: SLC13A3 were set to https://www.neurology.org/doi/full/10.1212/NXG.0000000000200101 (No PMID)
Genetic Epilepsy v0.2141 SLC13A3 Zornitza Stark Classified gene: SLC13A3 as Green List (high evidence)
Genetic Epilepsy v0.2141 SLC13A3 Zornitza Stark Gene: slc13a3 has been classified as Green List (High Evidence).
Mendeliome v1.1467 SLC13A3 Zornitza Stark Marked gene: SLC13A3 as ready
Mendeliome v1.1467 SLC13A3 Zornitza Stark Gene: slc13a3 has been classified as Green List (High Evidence).
Mendeliome v1.1467 SLC13A3 Zornitza Stark Publications for gene: SLC13A3 were set to https://www.neurology.org/doi/full/10.1212/NXG.0000000000200101 (No PMID)
Mendeliome v1.1466 SLC13A3 Zornitza Stark Classified gene: SLC13A3 as Green List (high evidence)
Mendeliome v1.1466 SLC13A3 Zornitza Stark Gene: slc13a3 has been classified as Green List (High Evidence).
Ataxia - paediatric v1.17 SLC13A3 Zornitza Stark Marked gene: SLC13A3 as ready
Ataxia - paediatric v1.17 SLC13A3 Zornitza Stark Gene: slc13a3 has been classified as Green List (High Evidence).
Ataxia - paediatric v1.17 SLC13A3 Zornitza Stark Classified gene: SLC13A3 as Green List (high evidence)
Ataxia - paediatric v1.17 SLC13A3 Zornitza Stark Gene: slc13a3 has been classified as Green List (High Evidence).
Fetal anomalies v1.182 MAX Zornitza Stark Marked gene: MAX as ready
Fetal anomalies v1.182 MAX Zornitza Stark Gene: max has been classified as Green List (High Evidence).
Fetal anomalies v1.182 MAX Zornitza Stark Classified gene: MAX as Green List (high evidence)
Fetal anomalies v1.182 MAX Zornitza Stark Gene: max has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5665 MAX Zornitza Stark Marked gene: MAX as ready
Intellectual disability syndromic and non-syndromic v0.5665 MAX Zornitza Stark Gene: max has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5665 MAX Zornitza Stark Classified gene: MAX as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5665 MAX Zornitza Stark Gene: max has been classified as Green List (High Evidence).
Polydactyly v0.270 MAX Zornitza Stark Marked gene: MAX as ready
Polydactyly v0.270 MAX Zornitza Stark Gene: max has been classified as Green List (High Evidence).
Polydactyly v0.270 MAX Zornitza Stark Classified gene: MAX as Green List (high evidence)
Polydactyly v0.270 MAX Zornitza Stark Gene: max has been classified as Green List (High Evidence).
Mendeliome v1.1465 MAX Zornitza Stark Phenotypes for gene: MAX were changed from {Pheochromocytoma, susceptibility to}, MIM# 171300 to {Pheochromocytoma, susceptibility to}, MIM# 171300; Syndromic disease (MONDO:0002254), MAX-related
Mendeliome v1.1464 MAX Zornitza Stark Publications for gene: MAX were set to 21685915
Macrocephaly_Megalencephaly v0.138 MAX Zornitza Stark Marked gene: MAX as ready
Macrocephaly_Megalencephaly v0.138 MAX Zornitza Stark Gene: max has been classified as Amber List (Moderate Evidence).
Macrocephaly_Megalencephaly v0.138 MAX Zornitza Stark Classified gene: MAX as Amber List (moderate evidence)
Macrocephaly_Megalencephaly v0.138 MAX Zornitza Stark Gene: max has been classified as Amber List (Moderate Evidence).
Alternating Hemiplegia and Hemiplegic Migraine v0.55 SCN2A Zornitza Stark Marked gene: SCN2A as ready
Alternating Hemiplegia and Hemiplegic Migraine v0.55 SCN2A Zornitza Stark Gene: scn2a has been classified as Green List (High Evidence).
Alternating Hemiplegia and Hemiplegic Migraine v0.55 SCN2A Zornitza Stark Classified gene: SCN2A as Green List (high evidence)
Alternating Hemiplegia and Hemiplegic Migraine v0.55 SCN2A Zornitza Stark Gene: scn2a has been classified as Green List (High Evidence).
Fetal anomalies v1.181 ZRSR2 Zornitza Stark Marked gene: ZRSR2 as ready
Fetal anomalies v1.181 ZRSR2 Zornitza Stark Gene: zrsr2 has been classified as Green List (High Evidence).
Fetal anomalies v1.181 ZRSR2 Zornitza Stark Classified gene: ZRSR2 as Green List (high evidence)
Fetal anomalies v1.181 ZRSR2 Zornitza Stark Gene: zrsr2 has been classified as Green List (High Evidence).
Clefting disorders v0.246 ZRSR2 Zornitza Stark Marked gene: ZRSR2 as ready
Clefting disorders v0.246 ZRSR2 Zornitza Stark Gene: zrsr2 has been classified as Green List (High Evidence).
Clefting disorders v0.246 ZRSR2 Zornitza Stark Classified gene: ZRSR2 as Green List (high evidence)
Clefting disorders v0.246 ZRSR2 Zornitza Stark Gene: zrsr2 has been classified as Green List (High Evidence).
Pituitary hormone deficiency v0.34 ZRSR2 Zornitza Stark Marked gene: ZRSR2 as ready
Pituitary hormone deficiency v0.34 ZRSR2 Zornitza Stark Gene: zrsr2 has been classified as Green List (High Evidence).
Pituitary hormone deficiency v0.34 ZRSR2 Zornitza Stark Classified gene: ZRSR2 as Green List (high evidence)
Pituitary hormone deficiency v0.34 ZRSR2 Zornitza Stark Gene: zrsr2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5664 ZRSR2 Zornitza Stark Marked gene: ZRSR2 as ready
Intellectual disability syndromic and non-syndromic v0.5664 ZRSR2 Zornitza Stark Gene: zrsr2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5664 ZRSR2 Zornitza Stark Classified gene: ZRSR2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5664 ZRSR2 Zornitza Stark Gene: zrsr2 has been classified as Green List (High Evidence).
Holoprosencephaly and septo-optic dysplasia v1.10 ZRSR2 Zornitza Stark Marked gene: ZRSR2 as ready
Holoprosencephaly and septo-optic dysplasia v1.10 ZRSR2 Zornitza Stark Gene: zrsr2 has been classified as Green List (High Evidence).
Holoprosencephaly and septo-optic dysplasia v1.10 ZRSR2 Zornitza Stark Classified gene: ZRSR2 as Green List (high evidence)
Holoprosencephaly and septo-optic dysplasia v1.10 ZRSR2 Zornitza Stark Gene: zrsr2 has been classified as Green List (High Evidence).
Anophthalmia_Microphthalmia_Coloboma v1.38 ZRSR2 Zornitza Stark Marked gene: ZRSR2 as ready
Anophthalmia_Microphthalmia_Coloboma v1.38 ZRSR2 Zornitza Stark Gene: zrsr2 has been classified as Amber List (Moderate Evidence).
Anophthalmia_Microphthalmia_Coloboma v1.38 ZRSR2 Zornitza Stark Classified gene: ZRSR2 as Amber List (moderate evidence)
Anophthalmia_Microphthalmia_Coloboma v1.38 ZRSR2 Zornitza Stark Gene: zrsr2 has been classified as Amber List (Moderate Evidence).
Polydactyly v0.269 ZRSR2 Zornitza Stark Marked gene: ZRSR2 as ready
Polydactyly v0.269 ZRSR2 Zornitza Stark Gene: zrsr2 has been classified as Green List (High Evidence).
Polydactyly v0.269 ZRSR2 Zornitza Stark Classified gene: ZRSR2 as Green List (high evidence)
Polydactyly v0.269 ZRSR2 Zornitza Stark Gene: zrsr2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2140 TSPYL1 Zornitza Stark Publications for gene: TSPYL1 were set to 32885560; 15273283; 33075815
Overgrowth v1.11 SPIN4 Zornitza Stark Mode of inheritance for gene: SPIN4 was changed from X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v1.1463 SPIN4 Zornitza Stark Marked gene: SPIN4 as ready
Mendeliome v1.1463 SPIN4 Zornitza Stark Gene: spin4 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1463 SPIN4 Zornitza Stark Mode of inheritance for gene: SPIN4 was changed from X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v1.1462 SPIN4 Zornitza Stark Classified gene: SPIN4 as Amber List (moderate evidence)
Mendeliome v1.1462 SPIN4 Zornitza Stark Gene: spin4 has been classified as Amber List (Moderate Evidence).
Overgrowth v1.10 SPIN4 Zornitza Stark Marked gene: SPIN4 as ready
Overgrowth v1.10 SPIN4 Zornitza Stark Gene: spin4 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v0.260 SOX8 Zornitza Stark Marked gene: SOX8 as ready
Skeletal dysplasia v0.260 SOX8 Zornitza Stark Gene: sox8 has been classified as Red List (Low Evidence).
Skeletal dysplasia v0.260 SOX8 Zornitza Stark Classified gene: SOX8 as Red List (low evidence)
Skeletal dysplasia v0.260 SOX8 Zornitza Stark Gene: sox8 has been classified as Red List (Low Evidence).
Muscular dystrophy and myopathy_Paediatric v1.8 SOX8 Zornitza Stark Marked gene: SOX8 as ready
Muscular dystrophy and myopathy_Paediatric v1.8 SOX8 Zornitza Stark Gene: sox8 has been classified as Red List (Low Evidence).
Muscular dystrophy and myopathy_Paediatric v1.8 SOX8 Zornitza Stark Classified gene: SOX8 as Red List (low evidence)
Muscular dystrophy and myopathy_Paediatric v1.8 SOX8 Zornitza Stark Gene: sox8 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2139 CP Zornitza Stark Marked gene: CP as ready
Genetic Epilepsy v0.2139 CP Zornitza Stark Gene: cp has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2139 CP Zornitza Stark Classified gene: CP as Amber List (moderate evidence)
Genetic Epilepsy v0.2139 CP Zornitza Stark Gene: cp has been classified as Amber List (Moderate Evidence).
Leukodystrophy - paediatric v0.299 BORCS8 Zornitza Stark Marked gene: BORCS8 as ready
Leukodystrophy - paediatric v0.299 BORCS8 Zornitza Stark Gene: borcs8 has been classified as Green List (High Evidence).
Leukodystrophy - paediatric v0.299 BORCS8 Zornitza Stark Classified gene: BORCS8 as Green List (high evidence)
Leukodystrophy - paediatric v0.299 BORCS8 Zornitza Stark Gene: borcs8 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5663 BORCS8 Zornitza Stark Marked gene: BORCS8 as ready
Intellectual disability syndromic and non-syndromic v0.5663 BORCS8 Zornitza Stark Gene: borcs8 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5663 BORCS8 Zornitza Stark Classified gene: BORCS8 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5663 BORCS8 Zornitza Stark Gene: borcs8 has been classified as Green List (High Evidence).
Microcephaly v1.248 GTPBP1 Zornitza Stark Marked gene: GTPBP1 as ready
Microcephaly v1.248 GTPBP1 Zornitza Stark Gene: gtpbp1 has been classified as Green List (High Evidence).
Microcephaly v1.248 GTPBP1 Zornitza Stark Classified gene: GTPBP1 as Green List (high evidence)
Microcephaly v1.248 GTPBP1 Zornitza Stark Gene: gtpbp1 has been classified as Green List (High Evidence).
Mendeliome v1.1461 GTPBP1 Zornitza Stark Marked gene: GTPBP1 as ready
Mendeliome v1.1461 GTPBP1 Zornitza Stark Gene: gtpbp1 has been classified as Green List (High Evidence).
Mendeliome v1.1461 GTPBP1 Zornitza Stark Classified gene: GTPBP1 as Green List (high evidence)
Mendeliome v1.1461 GTPBP1 Zornitza Stark Gene: gtpbp1 has been classified as Green List (High Evidence).
Fetal anomalies v1.180 CACHD1 Zornitza Stark Marked gene: CACHD1 as ready
Fetal anomalies v1.180 CACHD1 Zornitza Stark Gene: cachd1 has been classified as Green List (High Evidence).
Fetal anomalies v1.180 CACHD1 Zornitza Stark Classified gene: CACHD1 as Green List (high evidence)
Fetal anomalies v1.180 CACHD1 Zornitza Stark Gene: cachd1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5662 CACHD1 Zornitza Stark Marked gene: CACHD1 as ready
Intellectual disability syndromic and non-syndromic v0.5662 CACHD1 Zornitza Stark Gene: cachd1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5662 CACHD1 Zornitza Stark Classified gene: CACHD1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5662 CACHD1 Zornitza Stark Gene: cachd1 has been classified as Green List (High Evidence).
Mendeliome v1.1460 CACHD1 Zornitza Stark Marked gene: CACHD1 as ready
Mendeliome v1.1460 CACHD1 Zornitza Stark Gene: cachd1 has been classified as Green List (High Evidence).
Mendeliome v1.1460 CACHD1 Zornitza Stark Classified gene: CACHD1 as Green List (high evidence)
Mendeliome v1.1460 CACHD1 Zornitza Stark Gene: cachd1 has been classified as Green List (High Evidence).
Mendeliome v1.1459 CACHD1 Zornitza Stark reviewed gene: CACHD1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: syndromic complex neurodevelopmental disorder MONDO:0800439; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1459 SLC13A3 Daniel Flanagan gene: SLC13A3 was added
gene: SLC13A3 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: SLC13A3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC13A3 were set to https://www.neurology.org/doi/full/10.1212/NXG.0000000000200101 (No PMID)
Phenotypes for gene: SLC13A3 were set to Leukoencephalopathy, acute reversible, with increased urinary alpha-ketoglutarate (MIM# 618384)
Review for gene: SLC13A3 was set to GREEN
Added comment: Seven patients reported with biallelic SLC13A3 variants, causing acute reversible leukoencephalopathy and α-ketoglutarate accumulation. Patients presented with acute neurological deterioration after a febrile illness. 5/7 with ataxia, 4/7 had seizures, 1/7 developmental delay.
Sources: Expert list
Leukodystrophy - paediatric v0.298 SLC13A3 Daniel Flanagan gene: SLC13A3 was added
gene: SLC13A3 was added to Leukodystrophy - paediatric. Sources: Expert list
Mode of inheritance for gene: SLC13A3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC13A3 were set to https://www.neurology.org/doi/full/10.1212/NXG.0000000000200101 (No PMID)
Phenotypes for gene: SLC13A3 were set to Leukoencephalopathy, acute reversible, with increased urinary alpha-ketoglutarate (MIM# 618384)
Review for gene: SLC13A3 was set to GREEN
Added comment: Seven patients reported with biallelic SLC13A3 variants, causing acute reversible leukoencephalopathy and α-ketoglutarate accumulation. Patients presented with acute neurological deterioration after a febrile illness. 5/7 with ataxia, 4/7 had seizures, 1/7 developmental delay.
Sources: Expert list
Genetic Epilepsy v0.2138 SLC13A3 Daniel Flanagan gene: SLC13A3 was added
gene: SLC13A3 was added to Genetic Epilepsy. Sources: Expert list
Mode of inheritance for gene: SLC13A3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC13A3 were set to https://www.neurology.org/doi/full/10.1212/NXG.0000000000200101 (No PMID)
Phenotypes for gene: SLC13A3 were set to Leukoencephalopathy, acute reversible, with increased urinary alpha-ketoglutarate (MIM# 618384)
Review for gene: SLC13A3 was set to GREEN
Added comment: Seven patients reported with biallelic SLC13A3 variants, causing acute reversible leukoencephalopathy and α-ketoglutarate accumulation. Patients presented with acute neurological deterioration after a febrile illness. 5/7 with ataxia, 4/7 had seizures, 1/7 developmental delay.
Sources: Expert list
Ataxia - paediatric v1.16 SLC13A3 Daniel Flanagan gene: SLC13A3 was added
gene: SLC13A3 was added to Ataxia - paediatric. Sources: Expert list
Mode of inheritance for gene: SLC13A3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC13A3 were set to https://www.neurology.org/doi/full/10.1212/NXG.0000000000200101 (No PMID)
Phenotypes for gene: SLC13A3 were set to Leukoencephalopathy, acute reversible, with increased urinary alpha-ketoglutarate (MIM# 618384)
Review for gene: SLC13A3 was set to GREEN
Added comment: Seven patients reported with biallelic SLC13A3 variants, causing acute reversible leukoencephalopathy and α-ketoglutarate accumulation. Patients presented with acute neurological deterioration after a febrile illness. 5/7 with ataxia, 4/7 had seizures, 1/7 developmental delay.
Sources: Expert list
Fetal anomalies v1.179 MAX Rylee Peters gene: MAX was added
gene: MAX was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: MAX was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAX were set to 38141607
Phenotypes for gene: MAX were set to Syndromic disease (MONDO:0002254), MAX-related
Review for gene: MAX was set to GREEN
Added comment: Three individuals who each share a recurrent de novo germline variant in the MAX gene, resulting in a p.Arg60Gln substitution in the loop of the b-HLH-LZ domain.

Affected individuals have a complex disorder consisting primarily of macrocephaly, polydactyly, and delayed ophthalmic development. Other phenotypes reported include intellectual disability, perianal abscesses, pectus carinatum, hypospadias, renal agenesis, single umbilical artery, flattened thoracic vertebrae.

Functional analysis of the p.Arg60Gln variant shows a significant increase in CCND2 protein and a more efficient heterodimerization with c-Myc resulting in an increase in transcriptional activity of c-Myc.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5661 MAX Rylee Peters gene: MAX was added
gene: MAX was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: MAX was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAX were set to 38141607
Phenotypes for gene: MAX were set to Syndromic disease (MONDO:0002254), MAX-related
Review for gene: MAX was set to GREEN
Added comment: Three individuals who each share a recurrent de novo germline variant in the MAX gene, resulting in a p.Arg60Gln substitution in the loop of the b-HLH-LZ domain.

Affected individuals have a complex disorder consisting primarily of macrocephaly, polydactyly, and delayed ophthalmic development. Other phenotypes reported include intellectual disability, perianal abscesses, pectus carinatum, hypospadias, renal agenesis, single umbilical artery, flattened thoracic vertebrae.

Functional analysis of the p.Arg60Gln variant shows a significant increase in CCND2 protein and a more efficient heterodimerization with c-Myc resulting in an increase in transcriptional activity of c-Myc.
Sources: Literature
Polydactyly v0.268 MAX Rylee Peters gene: MAX was added
gene: MAX was added to Polydactyly. Sources: Literature
Mode of inheritance for gene: MAX was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAX were set to 38141607
Phenotypes for gene: MAX were set to Syndromic disease (MONDO:0002254), MAX-related
Review for gene: MAX was set to GREEN
Added comment: Three individuals who each share a recurrent de novo germline variant in the MAX gene, resulting in a p.Arg60Gln substitution in the loop of the b-HLH-LZ domain.

Affected individuals have a complex disorder consisting primarily of macrocephaly, polydactyly, and delayed ophthalmic development. Other phenotypes reported include intellectual disability, perianal abscesses, pectus carinatum, hypospadias, renal agenesis, single umbilical artery, flattened thoracic vertebrae.

Functional analysis of the p.Arg60Gln variant shows a significant increase in CCND2 protein and a more efficient heterodimerization with c-Myc resulting in an increase in transcriptional activity of c-Myc.
Sources: Literature
Macrocephaly_Megalencephaly v0.137 MAX Rylee Peters gene: MAX was added
gene: MAX was added to Macrocephaly_Megalencephaly. Sources: Literature
Mode of inheritance for gene: MAX was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAX were set to 38141607
Phenotypes for gene: MAX were set to Syndromic disease (MONDO:0002254), MAX-related
Review for gene: MAX was set to AMBER
Added comment: Three individuals who each share a recurrent de novo germline variant in the MAX gene, resulting in a p.Arg60Gln substitution in the loop of the b-HLH-LZ domain.

Affected individuals have a complex disorder consisting primarily of macrocephaly, polydactyly, and delayed ophthalmic development. Other phenotypes reported include intellectual disability, perianal abscesses, pectus carinatum, hypospadias, renal agenesis, single umbilical artery, flattened thoracic vertebrae.

Functional analysis of the p.Arg60Gln variant shows a significant increase in CCND2 protein and a more efficient heterodimerization with c-Myc resulting in an increase in transcriptional activity of c-Myc.
Sources: Literature
Mendeliome v1.1459 MAX Rylee Peters reviewed gene: MAX: Rating: GREEN; Mode of pathogenicity: None; Publications: 38141607; Phenotypes: Syndromic disease (MONDO:0002254), MAX-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Overgrowth v1.10 SPIN4 Zornitza Stark Classified gene: SPIN4 as Amber List (moderate evidence)
Overgrowth v1.10 SPIN4 Zornitza Stark Gene: spin4 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1459 SOX8 Zornitza Stark Marked gene: SOX8 as ready
Mendeliome v1.1459 SOX8 Zornitza Stark Gene: sox8 has been classified as Red List (Low Evidence).
Mendeliome v1.1459 SOX8 Zornitza Stark Classified gene: SOX8 as Red List (low evidence)
Mendeliome v1.1459 SOX8 Zornitza Stark Gene: sox8 has been classified as Red List (Low Evidence).
Anophthalmia_Microphthalmia_Coloboma v1.37 ZRSR2 Michelle Torres gene: ZRSR2 was added
gene: ZRSR2 was added to Anophthalmia_Microphthalmia_Coloboma. Sources: Literature
Mode of inheritance for gene: ZRSR2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: ZRSR2 were set to 38158857
Phenotypes for gene: ZRSR2 were set to Orofacialdigital syndrome MONDO:0015375, ZRSR2-related
Review for gene: ZRSR2 was set to AMBER
Added comment: Oral-facial-digital (OFD) syndrome with brain anomalies ranging from alobar holoprosencephaly to pituitary anomalies.

Six unrelated families with two truncating variants and functional studies:
- p.(Gly404GlufsTer23): detected in one family with 2x affected males
- p.(Arg403GlyfsTer24): 5 unrelated families, both de novo and inherited

Only 2x probands with microphthalmia and/or optic disc coloboma.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5661 SOX8 Zornitza Stark Marked gene: SOX8 as ready
Intellectual disability syndromic and non-syndromic v0.5661 SOX8 Zornitza Stark Gene: sox8 has been classified as Red List (Low Evidence).
Optic Atrophy v1.27 BORCS8 Zornitza Stark Marked gene: BORCS8 as ready
Optic Atrophy v1.27 BORCS8 Zornitza Stark Gene: borcs8 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5661 SOX8 Zornitza Stark Classified gene: SOX8 as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.5661 SOX8 Zornitza Stark Gene: sox8 has been classified as Red List (Low Evidence).
Optic Atrophy v1.27 BORCS8 Zornitza Stark Classified gene: BORCS8 as Green List (high evidence)
Optic Atrophy v1.27 BORCS8 Zornitza Stark Gene: borcs8 has been classified as Green List (High Evidence).
Skeletal dysplasia v0.259 SOX8 Paul De Fazio gene: SOX8 was added
gene: SOX8 was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: SOX8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SOX8 were set to https://www.neurology.org/doi/full/10.1212/NXG.0000000000200088
Phenotypes for gene: SOX8 were set to Neurodevelopmental disorder (MONDO:0700092), SOX8-related
Review for gene: SOX8 was set to RED
gene: SOX8 was marked as current diagnostic
Added comment: Proband presented to genetics clinic at 27 years of age with BMI -3.4SD, height -2.7SD, head circumference -1.8SD. She had mild intellectual delay and clinical features of a congenital, nonprogressive myopathy with moderate proximal and distal weakness. X-rays showed skeletal dysplasia, including cervical thoracic scoliosis and lumbar scoliosis. She was reported as having had weakness at birth with poor suck, micrognathia, hypotonia, and talipes. She was documented to have significant motor delay as a child. MRI of the brain demonstrated large posterior fossa CSF spaces.

Biallelic SOX8 variants biallelic (NM_014587.3:c.422+5G>C; c.583dup p.(His195ProfsTer11)) were identified by WGS. The +5 variant was shown to affect splicing, while the frameshift variant resulted in production of low-level truncated protein (not NMD predicted). Functional studies on patient fibroblasts showed misregulation of downstream SOX8 targets.
Sources: Literature
Mendeliome v1.1458 BORCS8 Zornitza Stark Marked gene: BORCS8 as ready
Mendeliome v1.1458 BORCS8 Zornitza Stark Gene: borcs8 has been classified as Green List (High Evidence).
Clefting disorders v0.245 ZRSR2 Chris Ciotta gene: ZRSR2 was added
gene: ZRSR2 was added to Clefting disorders. Sources: Literature
Mode of inheritance for gene: ZRSR2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: ZRSR2 were set to PMID: 38158857
Phenotypes for gene: ZRSR2 were set to Orofacialdigital syndrome MONDO:0015375, ZRSR2-related
Review for gene: ZRSR2 was set to GREEN
Added comment: Oral-facial-digital (OFD) syndrome with brain anomalies ranging from alobar holoprosencephaly to pituitary anomalies.
Six unrelated families with two truncating variants and functional studies:
- p.(Gly404GlufsTer23): detected in one family with 2x affected males
- p.(Arg403GlyfsTer24): 5 unrelated families, both de novo and inherited
Sources: Literature
Pituitary hormone deficiency v0.33 ZRSR2 Michelle Torres gene: ZRSR2 was added
gene: ZRSR2 was added to Pituitary hormone deficiency. Sources: Literature
Mode of inheritance for gene: ZRSR2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: ZRSR2 were set to 38158857
Phenotypes for gene: ZRSR2 were set to Orofacialdigital syndrome MONDO:0015375, ZRSR2-related
Review for gene: ZRSR2 was set to GREEN
gene: ZRSR2 was marked as current diagnostic
Added comment: Oral-facial-digital (OFD) syndrome with brain anomalies ranging from alobar holoprosencephaly to pituitary anomalies.

Six unrelated families with two truncating variants and functional studies:
- p.(Gly404GlufsTer23): detected in one family with 2x affected males
- p.(Arg403GlyfsTer24): 5 unrelated families, both de novo and inherited
Sources: Literature
Mendeliome v1.1458 BORCS8 Zornitza Stark Classified gene: BORCS8 as Green List (high evidence)
Mendeliome v1.1458 BORCS8 Zornitza Stark Gene: borcs8 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v1.7 SOX8 Paul De Fazio gene: SOX8 was added
gene: SOX8 was added to Muscular dystrophy and myopathy_Paediatric. Sources: Literature
Mode of inheritance for gene: SOX8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SOX8 were set to https://www.neurology.org/doi/full/10.1212/NXG.0000000000200088
Phenotypes for gene: SOX8 were set to Neurodevelopmental disorder (MONDO:0700092), SOX8-related
Review for gene: SOX8 was set to RED
gene: SOX8 was marked as current diagnostic
Added comment: Proband presented to genetics clinic at 27 years of age with BMI -3.4SD, height -2.7SD, head circumference -1.8SD. She had mild intellectual delay and clinical features of a congenital, nonprogressive myopathy with moderate proximal and distal weakness. X-rays showed skeletal dysplasia, including cervical thoracic scoliosis and lumbar scoliosis. She was reported as having had weakness at birth with poor suck, micrognathia, hypotonia, and talipes. She was documented to have significant motor delay as a child. MRI of the brain demonstrated large posterior fossa CSF spaces.

Muscle biopsy of the right medial gastrocnemius at age 1 demonstrated mild variation in fiber size with scattered, moderately small, rounded polyhedral fibers of both types. There were no significant dystrophic features.

Biallelic SOX8 variants biallelic (NM_014587.3:c.422+5G>C; c.583dup p.(His195ProfsTer11)) were identified by WGS. The +5 variant was shown to affect splicing, while the frameshift variant resulted in production of low-level truncated protein (not NMD predicted). Functional studies on patient fibroblasts showed misregulation of downstream SOX8 targets.
Sources: Literature
Regression v0.541 BORCS8 Zornitza Stark Marked gene: BORCS8 as ready
Regression v0.541 BORCS8 Zornitza Stark Gene: borcs8 has been classified as Green List (High Evidence).
Fetal anomalies v1.179 ZRSR2 Chris Ciotta gene: ZRSR2 was added
gene: ZRSR2 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: ZRSR2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: ZRSR2 were set to PMID: 38158857
Phenotypes for gene: ZRSR2 were set to Orofacialdigital syndrome MONDO:0015375, ZRSR2-related
Review for gene: ZRSR2 was set to GREEN
Added comment: Oral-facial-digital (OFD) syndrome with brain anomalies ranging from alobar holoprosencephaly to pituitary anomalies.
Six unrelated families with two truncating variants and functional studies:
- p.(Gly404GlufsTer23): detected in one family with 2x affected males
- p.(Arg403GlyfsTer24): 5 unrelated families, both de novo and inherited
Sources: Literature
Mendeliome v1.1457 CACHD1 Suliman Khan gene: CACHD1 was added
gene: CACHD1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CACHD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CACHD1 were set to PMID: 38158856
Phenotypes for gene: CACHD1 were set to syndromic complex neurodevelopmental disorder MONDO:0800439
Penetrance for gene: CACHD1 were set to unknown
Review for gene: CACHD1 was set to GREEN
Added comment: Sources: Literature
Alternating Hemiplegia and Hemiplegic Migraine v0.54 SCN2A Ee Ming Wong gene: SCN2A was added
gene: SCN2A was added to Alternating Hemiplegia and Hemiplegic Migraine. Sources: Literature
Mode of inheritance for gene: SCN2A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SCN2A were set to 38097767
Phenotypes for gene: SCN2A were set to Alternating hemiplegia of childhood MONDO:0016241, SCN2A-related
Review for gene: SCN2A was set to GREEN
gene: SCN2A was marked as current diagnostic
Added comment: - 1x in-frame del and 2x missense variants identified in three individuals with typical alternating
hemiplegia of childhood (2x confirmed de novo, 1x unknown inheritance)
- Loss of function demonstrated by functional studies of all three variants (mutant transcripts transfected into HEK293T cells showed either complete loss of function or altered electrophysiological properties)
Sources: Literature
Holoprosencephaly and septo-optic dysplasia v1.9 ZRSR2 Michelle Torres gene: ZRSR2 was added
gene: ZRSR2 was added to Holoprosencephaly and septo-optic dysplasia. Sources: Literature
Mode of inheritance for gene: ZRSR2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: ZRSR2 were set to 38158857
Phenotypes for gene: ZRSR2 were set to Orofacialdigital syndrome MONDO:0015375, ZRSR2-related
Review for gene: ZRSR2 was set to GREEN
gene: ZRSR2 was marked as current diagnostic
Added comment: Oral-facial-digital (OFD) syndrome with brain anomalies ranging from alobar holoprosencephaly to pituitary anomalies.

Six unrelated families with two truncating variants and functional studies:
- p.(Gly404GlufsTer23): detected in one family with 2x affected males
- p.(Arg403GlyfsTer24): 5 unrelated families, both de novo and inherited
Sources: Literature
Regression v0.541 BORCS8 Zornitza Stark Classified gene: BORCS8 as Green List (high evidence)
Regression v0.541 BORCS8 Zornitza Stark Gene: borcs8 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5660 ZRSR2 Chris Ciotta gene: ZRSR2 was added
gene: ZRSR2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: ZRSR2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: ZRSR2 were set to PMID: 38158857
Phenotypes for gene: ZRSR2 were set to Orofacialdigital syndrome MONDO:0015375, ZRSR2-related
Review for gene: ZRSR2 was set to GREEN
Added comment: Oral-facial-digital (OFD) syndrome with brain anomalies ranging from alobar holoprosencephaly to pituitary anomalies.
Six unrelated families with two truncating variants and functional studies:
- p.(Gly404GlufsTer23): detected in one family with 2x affected males
- p.(Arg403GlyfsTer24): 5 unrelated families, both de novo and inherited
Sources: Literature
Fetal anomalies v1.179 CACHD1 Suliman Khan gene: CACHD1 was added
gene: CACHD1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: CACHD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CACHD1 were set to PMID: 38158856
Phenotypes for gene: CACHD1 were set to syndromic complex neurodevelopmental disorder MONDO:0800439
Penetrance for gene: CACHD1 were set to unknown
Review for gene: CACHD1 was set to GREEN
Added comment: PMID: 38158856 - Six affected individuals from four unrelated families with homozygous CACHD1 variants (3 splice, 2 frameshift and 1 nonsense variant). Excluding the two fatal cases, all other were affected by syndromic neurodevelopmental abnormalities, multiple organ systems featuring global impairment of psychomotor development, dysmorphic facial features, genitourinary abnormalities, oculo-auricular and congenital malformation. Seizure was reported in one case. Whole exome sequencing identified bi-allelic loss of function variants in the CACHD1 gene. In vitro human neural models of CACHD1 depletion displayed dysregulated of Wnt signaling in the developing brain.
Sources: Literature
Polydactyly v0.268 ZRSR2 Michelle Torres gene: ZRSR2 was added
gene: ZRSR2 was added to Polydactyly. Sources: Literature
Mode of inheritance for gene: ZRSR2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: ZRSR2 were set to 38158857
Phenotypes for gene: ZRSR2 were set to Orofacialdigital syndrome MONDO:0015375, ZRSR2-related
Review for gene: ZRSR2 was set to GREEN
gene: ZRSR2 was marked as current diagnostic
Added comment: Oral-facial-digital (OFD) syndrome with brain anomalies ranging from alobar holoprosencephaly to pituitary anomalies.

Six unrelated families with two truncating variants and functional studies:
- p.(Gly404GlufsTer23): detected in one family with 2x affected males
- p.(Arg403GlyfsTer24): 5 unrelated families, both de novo and inherited
Sources: Literature
Leukodystrophy - paediatric v0.298 BORCS8 Lauren Rogers changed review comment from: 3 unrelated families with five affected children with homozygous or compound heterozygous loss of function missense and PTC variants. 5/5 hypotonia, failure to thrive, global developmental delay, profound intellectual disability, muscle weakness and atrophy, dysmorphic features. 3/5 with microcephaly, 3/5 with seizures, 4/5 with spasticity, 3/5 with scoliosis, 4/4 with optic atrophy.

HEK293T cells show the missense variants are expressed at normal levels but exhibit reduced assembly with other BORC subunits and reduced ability to drive lysosome distribution. The BORCS8 PTC frameshift variant is expressed at lower levels and is completely incapable of assembling with other BORC subunits and promoting lysosome distribution. Zebrafish KO of the orthologous brocs8 causes decreased brain and eye size, neuromuscular anomalies and impaired locomotion, recapitulating some of the key traits of the human disease.
Sources: Literature; to: 3 unrelated families with five affected children with homozygous or compound heterozygous loss of function missense and PTC variants. 5/5 hypotonia, failure to thrive, global developmental delay, profound intellectual disability, muscle weakness and atrophy, dysmorphic features. 3/5 with microcephaly, 3/5 with seizures, 4/5 with spasticity, 3/5 with scoliosis, 4/4 with optic atrophy.

HEK293T cells show the missense variants are expressed at normal levels but exhibit reduced assembly with other BORC subunits and reduced ability to drive lysosome distribution. The BORCS8 PTC frameshift variant is expressed at lower levels and is completely incapable of assembling with other BORC subunits and promoting lysosome distribution. Zebrafish KO of the orthologous brocs8 causes decreased brain and eye size, neuromuscular anomalies and impaired locomotion, recapitulating some of the key traits of the human disease.
Sources: Literature
Mendeliome v1.1457 SPIN4 Belinda Chong gene: SPIN4 was added
gene: SPIN4 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SPIN4 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: SPIN4 were set to 36927955
Phenotypes for gene: SPIN4 were set to Lui-Jee-Baron syndrome MIM#301114
Review for gene: SPIN4 was set to AMBER
Added comment: PMID 36927955
* Single family, hemizygous frameshift variant (NM_001012968.3, c.312_313AGdel) identified in a male individual with generalized overgrowth of prenatal onset, variant also present in the mother and grandmother (both had adult heights 2 SDS greater than their midparental heights).
* In vitro shows loss of function and mice studies recapitulated the human phenotype with
generalized overgrowth, including increased longitudinal bone growth.
Sources: Literature
Sources: Literature
Leukodystrophy - paediatric v0.298 BORCS8 Lauren Rogers changed review comment from: 3 unrelated families with five affected children with homozygous or compound heterozygous loss of function missense and PTC variants.

HEK293T cells show the missense variants are expressed at normal levels but exhibit reduced assembly with other BORC subunits and reduced ability to drive lysosome distribution. The BORCS8 PTC frameshift variant is expressed at lower levels and is completely incapable of assembling with other BORC subunits and promoting lysosome distribution. Zebrafish KO of the orthologous brocs8 causes decreased brain and eye size, neuromuscular anomalies and impaired locomotion, recapitulating some of the key traits of the human disease.
Sources: Literature; to: 3 unrelated families with five affected children with homozygous or compound heterozygous loss of function missense and PTC variants. 5/5 hypotonia, failure to thrive, global developmental delay, profound intellectual disability, muscle weakness and atrophy, dysmorphic features. 3/5 with microcephaly, 3/5 with seizures, 4/5 with spasticity, 3/5 with scoliosis, 4/4 with optic atrophy.

HEK293T cells show the missense variants are expressed at normal levels but exhibit reduced assembly with other BORC subunits and reduced ability to drive lysosome distribution. The BORCS8 PTC frameshift variant is expressed at lower levels and is completely incapable of assembling with other BORC subunits and promoting lysosome distribution. Zebrafish KO of the orthologous brocs8 causes decreased brain and eye size, neuromuscular anomalies and impaired locomotion, recapitulating some of the key traits of the human disease.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5660 BORCS8 Lauren Rogers changed review comment from: 3 unrelated families with five affected children with homozygous or compound heterozygous loss of function missense and PTC variants.

HEK293T cells show the missense variants are expressed at normal levels but exhibit reduced assembly with other BORC subunits and reduced ability to drive lysosome distribution. The BORCS8 PTC frameshift variant is expressed at lower levels and is completely incapable of assembling with other BORC subunits and promoting lysosome distribution. Zebrafish KO of the orthologous brocs8 causes decreased brain and eye size, neuromuscular anomalies and impaired locomotion, recapitulating some of the key traits of the human disease.
Sources: Literature; to: 3 unrelated families with five affected children with homozygous or compound heterozygous loss of function missense and PTC variants. 5/5 hypotonia, failure to thrive, global developmental delay, profound intellectual disability, muscle weakness and atrophy, dysmorphic features. 3/5 with microcephaly, 3/5 with seizures, 4/5 with spasticity, 3/5 with scoliosis, 4/4 with optic atrophy.

HEK293T cells show the missense variants are expressed at normal levels but exhibit reduced assembly with other BORC subunits and reduced ability to drive lysosome distribution. The BORCS8 PTC frameshift variant is expressed at lower levels and is completely incapable of assembling with other BORC subunits and promoting lysosome distribution. Zebrafish KO of the orthologous brocs8 causes decreased brain and eye size, neuromuscular anomalies and impaired locomotion, recapitulating some of the key traits of the human disease.
Sources: Literature
Regression v0.540 BORCS8 Lauren Rogers changed review comment from: 3 unrelated families with five affected children with homozygous or compound heterozygous loss of function missense and PTC variants.

HEK293T cells show the missense variants are expressed at normal levels but exhibit reduced assembly with other BORC subunits and reduced ability to drive lysosome distribution. The BORCS8 PTC frameshift variant is expressed at lower levels and is completely incapable of assembling with other BORC subunits and promoting lysosome distribution. Zebrafish KO of the orthologous brocs8 causes decreased brain and eye size, neuromuscular anomalies and impaired locomotion, recapitulating some of the key traits of the human disease.
Sources: Literature; to: 3 unrelated families with five affected children with homozygous or compound heterozygous loss of function missense and PTC variants. 5/5 hypotonia, failure to thrive, global developmental delay, profound intellectual disability, muscle weakness and atrophy, dysmorphic features. 3/5 with microcephaly, 3/5 with seizures, 4/5 with spasticity, 3/5 with scoliosis, 4/4 with optic atrophy.

HEK293T cells show the missense variants are expressed at normal levels but exhibit reduced assembly with other BORC subunits and reduced ability to drive lysosome distribution. The BORCS8 PTC frameshift variant is expressed at lower levels and is completely incapable of assembling with other BORC subunits and promoting lysosome distribution. Zebrafish KO of the orthologous brocs8 causes decreased brain and eye size, neuromuscular anomalies and impaired locomotion, recapitulating some of the key traits of the human disease.
Sources: Literature
Genetic Epilepsy v0.2138 TSPYL1 Lilian Downie reviewed gene: TSPYL1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 36082874; Phenotypes: Sudden infant death with dysgenesis of the testes syndrome MIM#608800; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5660 SOX8 Paul De Fazio changed review comment from: Proband presented to genetics clinic at 27 years of age with BMI -3.4SD, height -2.7SD, head circumference -1.8SD. She had mild intellectual delay and clinical features of a congenital, nonprogressive myopathy with moderate proximal and distal weakness. X-rays showed skeletal dysplasia, including cervical thoracic scoliosis and lumbar scoliosis. She was reported as having had weakness at birth with poor suck, micrognathia, hypotonia, and talipes. She was documented to have significant motor delay as a child. MRI of the brain demonstrated large posterior fossa CSF spaces.

Biallelic SOX8 variants biallelic (NM_014587.3:c.422+5G>C; c.583dup p.(His195ProfsTer11)) were identified by WGS. The +5 variant was shown to affect splicing, while the frameshift variant resulted in production of low-level truncated protein (not NMD predicted).
Sources: Literature; to: Proband presented to genetics clinic at 27 years of age with BMI -3.4SD, height -2.7SD, head circumference -1.8SD. She had mild intellectual delay and clinical features of a congenital, nonprogressive myopathy with moderate proximal and distal weakness. X-rays showed skeletal dysplasia, including cervical thoracic scoliosis and lumbar scoliosis. She was reported as having had weakness at birth with poor suck, micrognathia, hypotonia, and talipes. She was documented to have significant motor delay as a child. MRI of the brain demonstrated large posterior fossa CSF spaces.

Biallelic SOX8 variants biallelic (NM_014587.3:c.422+5G>C; c.583dup p.(His195ProfsTer11)) were identified by WGS. The +5 variant was shown to affect splicing, while the frameshift variant resulted in production of low-level truncated protein (not NMD predicted). Functional studies on patient fibroblasts showed misregulation of downstream SOX8 targets.
Sources: Literature
Optic Atrophy v1.26 BORCS8 Lauren Rogers changed review comment from: 3 unrelated families with five affected children with homozygous or compound heterozygous loss of function missense and PTC variants.

HEK293T cells show the missense variants are expressed at normal levels but exhibit reduced assembly with other BORC subunits and reduced ability to drive lysosome distribution. The BORCS8 PTC frameshift variant is expressed at lower levels and is completely incapable of assembling with other BORC subunits and promoting lysosome distribution. Zebrafish KO of the orthologous brocs8 causes decreased brain and eye size, neuromuscular anomalies and impaired locomotion, recapitulating some of the key traits of the human disease.
Sources: Literature; to: 3 unrelated families with five affected children with homozygous or compound heterozygous loss of function missense and PTC variants. 5/5 hypotonia, failure to thrive, global developmental delay, profound intellectual disability, muscle weakness and atrophy, dysmorphic features. 3/5 with microcephaly, 3/5 with seizures, 4/5 with spasticity, 3/5 with scoliosis, 4/4 with optic atrophy.

HEK293T cells show the missense variants are expressed at normal levels but exhibit reduced assembly with other BORC subunits and reduced ability to drive lysosome distribution. The BORCS8 PTC frameshift variant is expressed at lower levels and is completely incapable of assembling with other BORC subunits and promoting lysosome distribution. Zebrafish KO of the orthologous brocs8 causes decreased brain and eye size, neuromuscular anomalies and impaired locomotion, recapitulating some of the key traits of the human disease.
Sources: Literature
Mendeliome v1.1457 SOX8 Paul De Fazio gene: SOX8 was added
gene: SOX8 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SOX8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SOX8 were set to https://www.neurology.org/doi/full/10.1212/NXG.0000000000200088
Phenotypes for gene: SOX8 were set to Neurodevelopmental disorder (MONDO:0700092), SOX8-related
Review for gene: SOX8 was set to RED
gene: SOX8 was marked as current diagnostic
Added comment: Proband presented to genetics clinic at 27 years of age with BMI -3.4SD, height -2.7SD, head circumference -1.8SD. She had mild intellectual delay and clinical features of a congenital, nonprogressive myopathy with moderate proximal and distal weakness. X-rays showed skeletal dysplasia, including cervical thoracic scoliosis and lumbar scoliosis. She was reported as having had weakness at birth with poor suck, micrognathia, hypotonia, and talipes. She was documented to have significant motor delay as a child. MRI of the brain demonstrated large posterior fossa CSF spaces.

Biallelic SOX8 variants biallelic (NM_014587.3:c.422+5G>C; c.583dup p.(His195ProfsTer11)) were identified by WGS. The +5 variant was shown to affect splicing, while the frameshift variant resulted in production of low-level truncated protein (not NMD predicted). Functional studies on patient fibroblasts showed misregulation of downstream SOX8 targets.
Sources: Literature
Mendeliome v1.1457 BORCS8 Lauren Rogers changed review comment from: 3 unrelated families with five affected children with homozygous or compound heterozygous loss of function missense and PTC variants.

HEK293T cells show the missense variants are expressed at normal levels but exhibit reduced assembly with other BORC subunits and reduced ability to drive lysosome distribution. The BORCS8 PTC frameshift variant is expressed at lower levels and is completely incapable of assembling with other BORC subunits and promoting lysosome distribution. Zebrafish KO of the orthologous brocs8 causes decreased brain and eye size, neuromuscular anomalies and impaired locomotion, recapitulating some of the key traits of the human disease.
Sources: Literature; to: 3 unrelated families with five affected children with homozygous or compound heterozygous loss of function missense and PTC variants. 5/5 hypotonia, failure to thrive, global developmental delay, profound intellectual disability, muscle weakness and atrophy, dysmorphic features. 3/5 with microcephaly, 3/5 with seizures, 4/5 with spasticity, 3/5 with scoliosis, 4/4 with optic atrophy.

HEK293T cells show the missense variants are expressed at normal levels but exhibit reduced assembly with other BORC subunits and reduced ability to drive lysosome distribution. The BORCS8 PTC frameshift variant is expressed at lower levels and is completely incapable of assembling with other BORC subunits and promoting lysosome distribution. Zebrafish KO of the orthologous brocs8 causes decreased brain and eye size, neuromuscular anomalies and impaired locomotion, recapitulating some of the key traits of the human disease.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5660 CACHD1 Suliman Khan gene: CACHD1 was added
gene: CACHD1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: CACHD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CACHD1 were set to PMID: 38158856
Phenotypes for gene: CACHD1 were set to syndromic complex neurodevelopmental disorder MONDO:0800439
Penetrance for gene: CACHD1 were set to unknown
Review for gene: CACHD1 was set to GREEN
Added comment: PMID: 38158856 - Six affected individuals from four unrelated families with homozygous CACHD1 variants (3 splice, 2 frameshift and 1 nonsense variant). Excluding the two fatal cases, all other were affected by syndromic neurodevelopmental abnormalities, multiple organ systems featuring global impairment of psychomotor development, dysmorphic facial features, genitourinary abnormalities, oculo-auricular and congenital malformation. Seizure was reported in one case. Whole exome sequencing identified bi-allelic loss of function variants in the CACHD1 gene. In vitro human neural models of CACHD1 depletion displayed dysregulated of Wnt signaling in the developing brain.
Sources: Literature
Overgrowth v1.9 SPIN4 Belinda Chong gene: SPIN4 was added
gene: SPIN4 was added to Overgrowth. Sources: Literature
Mode of inheritance for gene: SPIN4 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: SPIN4 were set to 36927955
Phenotypes for gene: SPIN4 were set to Lui-Jee-Baron syndrome MIM#301114
Review for gene: SPIN4 was set to AMBER
gene: SPIN4 was marked as current diagnostic
Added comment: PMID 36927955
* Single family, hemizygous frameshift variant (NM_001012968.3, c.312_313AGdel) identified in a male individual with generalized overgrowth of prenatal onset, variant also present in the mother and grandmother (both had adult heights 2 SDS greater than their midparental heights).
* In vitro shows loss of function and mice studies recapitulated the human phenotype with
generalized overgrowth, including increased longitudinal bone growth.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5660 SOX8 Paul De Fazio gene: SOX8 was added
gene: SOX8 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: SOX8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SOX8 were set to https://www.neurology.org/doi/full/10.1212/NXG.0000000000200088
Phenotypes for gene: SOX8 were set to Neurodevelopmental disorder (MONDO:0700092), SOX8-related
Review for gene: SOX8 was set to RED
gene: SOX8 was marked as current diagnostic
Added comment: Proband presented to genetics clinic at 27 years of age with BMI -3.4SD, height -2.7SD, head circumference -1.8SD. She had mild intellectual delay and clinical features of a congenital, nonprogressive myopathy with moderate proximal and distal weakness. X-rays showed skeletal dysplasia, including cervical thoracic scoliosis and lumbar scoliosis. She was reported as having had weakness at birth with poor suck, micrognathia, hypotonia, and talipes. She was documented to have significant motor delay as a child. MRI of the brain demonstrated large posterior fossa CSF spaces.

Biallelic SOX8 variants biallelic (NM_014587.3:c.422+5G>C; c.583dup p.(His195ProfsTer11)) were identified by WGS. The +5 variant was shown to affect splicing, while the frameshift variant resulted in production of low-level truncated protein (not NMD predicted).
Sources: Literature
Mendeliome v1.1457 BORCS8 Lauren Rogers gene: BORCS8 was added
gene: BORCS8 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: BORCS8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BORCS8 were set to 38128568
Phenotypes for gene: BORCS8 were set to Neurodevelopmental disorder (MONDO#0700092), BORCS8-related
Review for gene: BORCS8 was set to GREEN
Added comment: 3 unrelated families with five affected children with homozygous or compound heterozygous loss of function missense and PTC variants.

HEK293T cells show the missense variants are expressed at normal levels but exhibit reduced assembly with other BORC subunits and reduced ability to drive lysosome distribution. The BORCS8 PTC frameshift variant is expressed at lower levels and is completely incapable of assembling with other BORC subunits and promoting lysosome distribution. Zebrafish KO of the orthologous brocs8 causes decreased brain and eye size, neuromuscular anomalies and impaired locomotion, recapitulating some of the key traits of the human disease.
Sources: Literature
Optic Atrophy v1.26 BORCS8 Lauren Rogers gene: BORCS8 was added
gene: BORCS8 was added to Optic Atrophy. Sources: Literature
Mode of inheritance for gene: BORCS8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BORCS8 were set to 38128568
Phenotypes for gene: BORCS8 were set to Neurodevelopmental disorder (MONDO#0700092), BORCS8-related
Review for gene: BORCS8 was set to GREEN
Added comment: 3 unrelated families with five affected children with homozygous or compound heterozygous loss of function missense and PTC variants.

HEK293T cells show the missense variants are expressed at normal levels but exhibit reduced assembly with other BORC subunits and reduced ability to drive lysosome distribution. The BORCS8 PTC frameshift variant is expressed at lower levels and is completely incapable of assembling with other BORC subunits and promoting lysosome distribution. Zebrafish KO of the orthologous brocs8 causes decreased brain and eye size, neuromuscular anomalies and impaired locomotion, recapitulating some of the key traits of the human disease.
Sources: Literature
Leukodystrophy - paediatric v0.298 BORCS8 Lauren Rogers gene: BORCS8 was added
gene: BORCS8 was added to Leukodystrophy - paediatric. Sources: Literature
Mode of inheritance for gene: BORCS8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BORCS8 were set to 38128568
Phenotypes for gene: BORCS8 were set to Neurodevelopmental disorder (MONDO#0700092), BORCS8-related
Review for gene: BORCS8 was set to GREEN
Added comment: 3 unrelated families with five affected children with homozygous or compound heterozygous loss of function missense and PTC variants.

HEK293T cells show the missense variants are expressed at normal levels but exhibit reduced assembly with other BORC subunits and reduced ability to drive lysosome distribution. The BORCS8 PTC frameshift variant is expressed at lower levels and is completely incapable of assembling with other BORC subunits and promoting lysosome distribution. Zebrafish KO of the orthologous brocs8 causes decreased brain and eye size, neuromuscular anomalies and impaired locomotion, recapitulating some of the key traits of the human disease.
Sources: Literature
Genetic Epilepsy v0.2138 CP Lilian Downie gene: CP was added
gene: CP was added to Genetic Epilepsy. Sources: Expert list
Mode of inheritance for gene: CP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CP were set to PMID: 32741407, PMID: 18200628
Phenotypes for gene: CP were set to Hemosiderosis, systemic, due to aceruloplasminemia MIM#604290
Review for gene: CP was set to AMBER
Added comment: Reports of patients x3 with seizures as part of this phenotype.
***This is an adult onset brain iron accumulation neurodegenerative disorder***
Sources: Expert list
Regression v0.540 BORCS8 Lauren Rogers gene: BORCS8 was added
gene: BORCS8 was added to Regression. Sources: Literature
Mode of inheritance for gene: BORCS8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BORCS8 were set to 38128568
Phenotypes for gene: BORCS8 were set to Neurodevelopmental disorder (MONDO#0700092), BORCS8-related
Review for gene: BORCS8 was set to GREEN
Added comment: 3 unrelated families with five affected children with homozygous or compound heterozygous loss of function missense and PTC variants.

HEK293T cells show the missense variants are expressed at normal levels but exhibit reduced assembly with other BORC subunits and reduced ability to drive lysosome distribution. The BORCS8 PTC frameshift variant is expressed at lower levels and is completely incapable of assembling with other BORC subunits and promoting lysosome distribution. Zebrafish KO of the orthologous brocs8 causes decreased brain and eye size, neuromuscular anomalies and impaired locomotion, recapitulating some of the key traits of the human disease.
Sources: Literature
Genetic Epilepsy v0.2138 COQ8A Zornitza Stark Marked gene: COQ8A as ready
Genetic Epilepsy v0.2138 COQ8A Zornitza Stark Gene: coq8a has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5660 BORCS8 Lauren Rogers gene: BORCS8 was added
gene: BORCS8 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: BORCS8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BORCS8 were set to 38128568
Phenotypes for gene: BORCS8 were set to Neurodevelopmental disorder (MONDO#0700092), BORCS8-related
Review for gene: BORCS8 was set to GREEN
Added comment: 3 unrelated families with five affected children with homozygous or compound heterozygous loss of function missense and PTC variants.

HEK293T cells show the missense variants are expressed at normal levels but exhibit reduced assembly with other BORC subunits and reduced ability to drive lysosome distribution. The BORCS8 PTC frameshift variant is expressed at lower levels and is completely incapable of assembling with other BORC subunits and promoting lysosome distribution. Zebrafish KO of the orthologous brocs8 causes decreased brain and eye size, neuromuscular anomalies and impaired locomotion, recapitulating some of the key traits of the human disease.
Sources: Literature
Genetic Epilepsy v0.2138 COQ8A Zornitza Stark Classified gene: COQ8A as Green List (high evidence)
Genetic Epilepsy v0.2138 COQ8A Zornitza Stark Gene: coq8a has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2137 COQ8A Zornitza Stark Classified gene: COQ8A as Green List (high evidence)
Genetic Epilepsy v0.2137 COQ8A Zornitza Stark Gene: coq8a has been classified as Green List (High Evidence).
Mendeliome v1.1457 GTPBP1 Lucy Spencer gene: GTPBP1 was added
gene: GTPBP1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GTPBP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GTPBP1 were set to 38118446
Phenotypes for gene: GTPBP1 were set to Neurodevelopmental disorder (MONDO#0700092), GTPBP1-related
Review for gene: GTPBP1 was set to GREEN
Added comment: PMID: 38118446- Cohort of individuals with variants in GTPBP2 (which has been previously described) and GTPBP1 (new) who have an identical neurodevelopmental syndrome. 4 homozygous individuals from 3 consanguineous families. 2 families have different NMD-predicted nonsense variants and the third has a missense, all are absent from gnomad v4.

The shared cardinal features of GTPBP1 and 2 related disease are microcephaly, profound neurodevelopmental impairment, and distinctive craniofacial features. Epilepsy was present in 10 of 20 individuals but its not clear if those individuals had GTPBP1 or 2 variants.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5660 GTPBP1 Zornitza Stark Marked gene: GTPBP1 as ready
Intellectual disability syndromic and non-syndromic v0.5660 GTPBP1 Zornitza Stark Gene: gtpbp1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5660 GTPBP1 Zornitza Stark Marked gene: GTPBP1 as ready
Intellectual disability syndromic and non-syndromic v0.5660 GTPBP1 Zornitza Stark Gene: gtpbp1 has been classified as Green List (High Evidence).
Microcephaly v1.247 GTPBP1 Lucy Spencer gene: GTPBP1 was added
gene: GTPBP1 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: GTPBP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GTPBP1 were set to 38118446
Phenotypes for gene: GTPBP1 were set to Neurodevelopmental disorder (MONDO#0700092), GTPBP1-related
Review for gene: GTPBP1 was set to GREEN
Added comment: PMID: 38118446- Cohort of individuals with variants in GTPBP2 (which has been previously described) and GTPBP1 (new) who have an identical neurodevelopmental syndrome. 4 homozygous individuals from 3 consanguineous families. 2 families have different NMD-predicted nonsense variants and the third has a missense, all are absent from gnomad v4.

The shared cardinal features of GTPBP1 and 2 related disease are microcephaly, profound neurodevelopmental impairment, and distinctive craniofacial features. Epilepsy was present in 10 of 20 individuals but its not clear if those individuals had GTPBP1 or 2 variants.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5660 GTPBP1 Zornitza Stark Classified gene: GTPBP1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5660 GTPBP1 Zornitza Stark Gene: gtpbp1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5659 GTPBP1 Lucy Spencer gene: GTPBP1 was added
gene: GTPBP1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: GTPBP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GTPBP1 were set to 38118446
Phenotypes for gene: GTPBP1 were set to Neurodevelopmental disorder (MONDO#0700092), GTPBP1-related
Review for gene: GTPBP1 was set to GREEN
Added comment: PMID: 38118446- Cohort of individuals with variants in GTPBP2 (which has been previously described) and GTPBP1 (new) who have an identical neurodevelopmental syndrome. 4 homozygous individuals from 3 consanguineous families. 2 families have different NMD-predicted nonsense variants and the third has a missense, all are absent from gnomad v4.

The shared cardinal features of GTPBP1 and 2 related disease are microcephaly, profound neurodevelopmental impairment, and distinctive craniofacial features. Epilepsy was present in 10 of 20 individuals but its not clear if those individuals had GTPBP1 or 2 variants.
Sources: Literature
Genetic Epilepsy v0.2136 COQ8A Lilian Downie gene: COQ8A was added
gene: COQ8A was added to Genetic Epilepsy. Sources: Expert list
Mode of inheritance for gene: COQ8A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COQ8A were set to PMID 32337771
Phenotypes for gene: COQ8A were set to Coenzyme Q10 deficiency, primary, 4 MIM#612016
Review for gene: COQ8A was set to GREEN
Added comment: PMID 32337771: cohort of 59 individuals. COQ8A-ataxia presented as variable multisystemic, early-onset cerebellar ataxia, with complicating features ranging from epilepsy (32%) and cognitive impairment (49%) to exercise intolerance (25%) and hyperkinetic movement disorders (41%), including dystonia and myoclonus as presenting symptoms.
Sources: Expert list
Fetal anomalies v1.179 NUDT2 Zornitza Stark Marked gene: NUDT2 as ready
Fetal anomalies v1.179 NUDT2 Zornitza Stark Gene: nudt2 has been classified as Green List (High Evidence).
Fetal anomalies v1.179 NUDT2 Zornitza Stark Classified gene: NUDT2 as Green List (high evidence)
Fetal anomalies v1.179 NUDT2 Zornitza Stark Gene: nudt2 has been classified as Green List (High Evidence).
Callosome v0.515 NUDT2 Zornitza Stark Marked gene: NUDT2 as ready
Callosome v0.515 NUDT2 Zornitza Stark Gene: nudt2 has been classified as Green List (High Evidence).
Callosome v0.515 NUDT2 Zornitza Stark Classified gene: NUDT2 as Green List (high evidence)
Callosome v0.515 NUDT2 Zornitza Stark Gene: nudt2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2136 CENPF Zornitza Stark Marked gene: CENPF as ready
Genetic Epilepsy v0.2136 CENPF Zornitza Stark Gene: cenpf has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2136 CENPF Zornitza Stark Publications for gene: CENPF were set to
Fetal anomalies v1.178 NUDT2 Lilian Downie gene: NUDT2 was added
gene: NUDT2 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: NUDT2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NUDT2 were set to PMID: 38141063
Phenotypes for gene: NUDT2 were set to Intellectual developmental disorder with or without peripheral neuropathy MIM#619844
Review for gene: NUDT2 was set to GREEN
Added comment: 9 individuals with partial agenesis or hypoplasia of the corpus callosum
Sources: Literature
Genetic Epilepsy v0.2135 CENPF Zornitza Stark Classified gene: CENPF as Red List (low evidence)
Genetic Epilepsy v0.2135 CENPF Zornitza Stark Gene: cenpf has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2134 CDK5 Zornitza Stark Marked gene: CDK5 as ready
Genetic Epilepsy v0.2134 CDK5 Zornitza Stark Gene: cdk5 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2134 CDK5 Zornitza Stark Classified gene: CDK5 as Amber List (moderate evidence)
Genetic Epilepsy v0.2134 CDK5 Zornitza Stark Gene: cdk5 has been classified as Amber List (Moderate Evidence).
Callosome v0.514 NUDT2 Lilian Downie edited their review of gene: NUDT2: Changed rating: GREEN
Callosome v0.514 NUDT2 Lilian Downie gene: NUDT2 was added
gene: NUDT2 was added to Callosome. Sources: Literature
Mode of inheritance for gene: NUDT2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NUDT2 were set to PMID: 38141063
Phenotypes for gene: NUDT2 were set to Intellectual developmental disorder with or without peripheral neuropathy MIM#619844
Added comment: 9 individuals with partial agenesis or hypoplasia of the corpus callosum
Sources: Literature
Genetic Epilepsy v0.2133 CDK13 Zornitza Stark Marked gene: CDK13 as ready
Genetic Epilepsy v0.2133 CDK13 Zornitza Stark Gene: cdk13 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2133 CDK13 Zornitza Stark Classified gene: CDK13 as Green List (high evidence)
Genetic Epilepsy v0.2133 CDK13 Zornitza Stark Gene: cdk13 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2132 CCND2 Zornitza Stark Classified gene: CCND2 as Red List (low evidence)
Genetic Epilepsy v0.2132 CCND2 Zornitza Stark Gene: ccnd2 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2131 CCND2 Zornitza Stark Marked gene: CCND2 as ready
Genetic Epilepsy v0.2131 CCND2 Zornitza Stark Gene: ccnd2 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2131 CCND2 Zornitza Stark Classified gene: CCND2 as Red List (low evidence)
Genetic Epilepsy v0.2131 CCND2 Zornitza Stark Gene: ccnd2 has been classified as Red List (Low Evidence).
Fetal anomalies v1.178 CNOT2 Zornitza Stark Marked gene: CNOT2 as ready
Fetal anomalies v1.178 CNOT2 Zornitza Stark Gene: cnot2 has been classified as Green List (High Evidence).
Fetal anomalies v1.178 CNOT2 Zornitza Stark Classified gene: CNOT2 as Green List (high evidence)
Fetal anomalies v1.178 CNOT2 Zornitza Stark Gene: cnot2 has been classified as Green List (High Evidence).
Fetal anomalies v1.177 CNOT2 Zornitza Stark gene: CNOT2 was added
gene: CNOT2 was added to Fetal anomalies. Sources: Expert Review
Mode of inheritance for gene: CNOT2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CNOT2 were set to 31512373; 31145527; 28135719
Phenotypes for gene: CNOT2 were set to Intellectual developmental disorder with nasal speech, dysmorphic facies, and variable skeletal anomalies 618608
Review for gene: CNOT2 was set to GREEN
Added comment: Congenital heart disease and poor growth may be detectable prenatally.
Sources: Expert Review
Genetic Epilepsy v0.2130 COL3A1 Lilian Downie gene: COL3A1 was added
gene: COL3A1 was added to Genetic Epilepsy. Sources: Expert list
Mode of inheritance for gene: COL3A1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COL3A1 were set to PMID: 28258187, PMID: 37393059, PMID: 28742248, PMID: 22235340
Phenotypes for gene: COL3A1 were set to Polymicrogyria with or without vascular-type ehlers-danlos syndrome, MIM # 618343
Review for gene: COL3A1 was set to GREEN
Added comment: PMID: 37393059: 1 family with 2 sibs with epilepsy homozygous VUS variants in COL3A1
PMID: 28742248 1 family 2 sibs with seizures ID and biallelic variants in COL3A1
PMID: 22235340 mouse model with seizures
Sources: Expert list
Genetic Epilepsy v0.2130 CHD1 Lilian Downie gene: CHD1 was added
gene: CHD1 was added to Genetic Epilepsy. Sources: Expert list
Mode of inheritance for gene: CHD1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CHD1 were set to 28866611
Phenotypes for gene: CHD1 were set to Pilarowski-Bjornsson syndrome, MIM#617682
Review for gene: CHD1 was set to GREEN
Added comment: 3/6 seizures
Sources: Expert list
Genetic Epilepsy v0.2130 CENPF Lilian Downie edited their review of gene: CENPF: Changed publications: PMID: 35488810; Changed phenotypes: Stromme syndrome MIM#243605
Genetic Epilepsy v0.2130 CENPF Lilian Downie changed review comment from: No reports of seizures in this phenotype
Sources: Expert list; to: No reports of seizures in this phenotype or in the microcephaly phenotype described
Sources: Expert list
Genetic Epilepsy v0.2130 CENPF Lilian Downie gene: CENPF was added
gene: CENPF was added to Genetic Epilepsy. Sources: Expert list
Mode of inheritance for gene: CENPF was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CENPF were set to Stromme syndrome MIM#243605
Review for gene: CENPF was set to RED
Added comment: No reports of seizures in this phenotype
Sources: Expert list
Genetic Epilepsy v0.2130 CDK5 Lilian Downie gene: CDK5 was added
gene: CDK5 was added to Genetic Epilepsy. Sources: Expert list
Mode of inheritance for gene: CDK5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CDK5 were set to 25560765
Phenotypes for gene: CDK5 were set to Lissencephaly 7 with cerebellar hypoplasia MIM#616342
Review for gene: CDK5 was set to AMBER
Added comment: Single family multiple affected individuals, early onset seizures with burst supression pattern on EEG part of the phenotype
Sources: Expert list
Genetic Epilepsy v0.2130 CDK13 Lilian Downie gene: CDK13 was added
gene: CDK13 was added to Genetic Epilepsy. Sources: Expert list
Mode of inheritance for gene: CDK13 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CDK13 were set to PMID: 29021403, PMID: 35063350
Phenotypes for gene: CDK13 were set to Congenital heart defects, dysmorphic facial features, and intellectual developmental disorder MIM#617360
Review for gene: CDK13 was set to GREEN
Added comment: PMID: 29021403 4/16 had seizures
PMID: 35063350 1 with seizures
Sources: Expert list
Genetic Epilepsy v0.2130 CCND2 Lilian Downie gene: CCND2 was added
gene: CCND2 was added to Genetic Epilepsy. Sources: Expert list
Mode of inheritance for gene: CCND2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CCND2 were set to PMID: 24705253
Phenotypes for gene: CCND2 were set to Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 3 MIM#615938
Review for gene: CCND2 was set to RED
Added comment: seizures not reported in MPPH due to this gene to date
Sources: Expert list
Genetic Epilepsy v0.2130 PIGF Zornitza Stark Marked gene: PIGF as ready
Genetic Epilepsy v0.2130 PIGF Zornitza Stark Gene: pigf has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2130 PIGF Zornitza Stark Classified gene: PIGF as Red List (low evidence)
Genetic Epilepsy v0.2130 PIGF Zornitza Stark Gene: pigf has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2129 PEX26 Zornitza Stark Marked gene: PEX26 as ready
Genetic Epilepsy v0.2129 PEX26 Zornitza Stark Gene: pex26 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2129 PEX26 Zornitza Stark Classified gene: PEX26 as Green List (high evidence)
Genetic Epilepsy v0.2129 PEX26 Zornitza Stark Gene: pex26 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2128 PEX26 Zornitza Stark reviewed gene: PEX26: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Peroxisome biogenesis disorder 7A (Zellweger), MIM#614872; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2128 PEX2 Zornitza Stark Marked gene: PEX2 as ready
Genetic Epilepsy v0.2128 PEX2 Zornitza Stark Gene: pex2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2128 PEX2 Zornitza Stark Classified gene: PEX2 as Green List (high evidence)
Genetic Epilepsy v0.2128 PEX2 Zornitza Stark Gene: pex2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2127 PEX2 Zornitza Stark Classified gene: PEX2 as Green List (high evidence)
Genetic Epilepsy v0.2127 PEX2 Zornitza Stark Gene: pex2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2126 PEX2 Zornitza Stark reviewed gene: PEX2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Peroxisome biogenesis disorder 5A (Zellweger), MIM#614866; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2126 NAA10 Zornitza Stark Phenotypes for gene: NAA10 were changed from Microphthalmia, syndromic 1, MIM# 309800; NAA10-related syndrome; Seizures to NAA10-related syndrome MONDO:0100124
Genetic Epilepsy v0.2125 NAA10 Zornitza Stark Publications for gene: NAA10 were set to 11426460
Genetic Epilepsy v0.2124 NAA10 Zornitza Stark Classified gene: NAA10 as Green List (high evidence)
Genetic Epilepsy v0.2124 NAA10 Zornitza Stark Gene: naa10 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2123 LSS Zornitza Stark Marked gene: LSS as ready
Genetic Epilepsy v0.2123 LSS Zornitza Stark Gene: lss has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2123 LSS Zornitza Stark Classified gene: LSS as Green List (high evidence)
Genetic Epilepsy v0.2123 LSS Zornitza Stark Gene: lss has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2122 RPS6KA3 Zornitza Stark Marked gene: RPS6KA3 as ready
Genetic Epilepsy v0.2122 RPS6KA3 Zornitza Stark Gene: rps6ka3 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2122 RPS6KA3 Zornitza Stark Classified gene: RPS6KA3 as Green List (high evidence)
Genetic Epilepsy v0.2122 RPS6KA3 Zornitza Stark Gene: rps6ka3 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2121 RERE Zornitza Stark Marked gene: RERE as ready
Genetic Epilepsy v0.2121 RERE Zornitza Stark Gene: rere has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2121 RERE Zornitza Stark Classified gene: RERE as Green List (high evidence)
Genetic Epilepsy v0.2121 RERE Zornitza Stark Gene: rere has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2120 RAPGEF2 Zornitza Stark Tag STR tag was added to gene: RAPGEF2.
Mendeliome v1.1457 RAPGEF2 Zornitza Stark Tag STR tag was added to gene: RAPGEF2.
Genetic Epilepsy v0.2120 RANBP2 Zornitza Stark Marked gene: RANBP2 as ready
Genetic Epilepsy v0.2120 RANBP2 Zornitza Stark Gene: ranbp2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2120 RANBP2 Zornitza Stark Classified gene: RANBP2 as Green List (high evidence)
Genetic Epilepsy v0.2120 RANBP2 Zornitza Stark Gene: ranbp2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2119 PTBP1 Zornitza Stark Marked gene: PTBP1 as ready
Genetic Epilepsy v0.2119 PTBP1 Zornitza Stark Gene: ptbp1 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2119 PTBP1 Zornitza Stark Classified gene: PTBP1 as Red List (low evidence)
Genetic Epilepsy v0.2119 PTBP1 Zornitza Stark Gene: ptbp1 has been classified as Red List (Low Evidence).
Mendeliome v1.1457 PTBP1 Zornitza Stark Marked gene: PTBP1 as ready
Mendeliome v1.1457 PTBP1 Zornitza Stark Gene: ptbp1 has been classified as Red List (Low Evidence).
Mendeliome v1.1457 PTBP1 Zornitza Stark Classified gene: PTBP1 as Red List (low evidence)
Mendeliome v1.1457 PTBP1 Zornitza Stark Gene: ptbp1 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2118 RAI1 Zornitza Stark Marked gene: RAI1 as ready
Genetic Epilepsy v0.2118 RAI1 Zornitza Stark Gene: rai1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2118 RAI1 Zornitza Stark Classified gene: RAI1 as Green List (high evidence)
Genetic Epilepsy v0.2118 RAI1 Zornitza Stark Gene: rai1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2117 RAB39B Zornitza Stark Marked gene: RAB39B as ready
Genetic Epilepsy v0.2117 RAB39B Zornitza Stark Gene: rab39b has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2117 RAB39B Zornitza Stark Classified gene: RAB39B as Green List (high evidence)
Genetic Epilepsy v0.2117 RAB39B Zornitza Stark Gene: rab39b has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2116 CCDC88C Zornitza Stark Marked gene: CCDC88C as ready
Genetic Epilepsy v0.2116 CCDC88C Zornitza Stark Gene: ccdc88c has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2116 CCDC88C Zornitza Stark Classified gene: CCDC88C as Green List (high evidence)
Genetic Epilepsy v0.2116 CCDC88C Zornitza Stark Gene: ccdc88c has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2115 CCDC22 Zornitza Stark Marked gene: CCDC22 as ready
Genetic Epilepsy v0.2115 CCDC22 Zornitza Stark Gene: ccdc22 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2115 CCDC22 Zornitza Stark Classified gene: CCDC22 as Red List (low evidence)
Genetic Epilepsy v0.2115 CCDC22 Zornitza Stark Gene: ccdc22 has been classified as Red List (Low Evidence).
Microcephaly v1.247 COPB2 Zornitza Stark Publications for gene: COPB2 were set to 29036432
BabyScreen+ newborn screening v1.110 TSHR Zornitza Stark Phenotypes for gene: TSHR were changed from Hypothyroidism, congenital, nongoitrous, 1 - MIM#275200; HYPERTHYROIDISM, FAMILIAL GESTATIONAL HYPERTHYROIDISM to Hypothyroidism, congenital, nongoitrous, 1 - MIM#275200
BabyScreen+ newborn screening v1.109 TSHR Zornitza Stark Mode of inheritance for gene: TSHR was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v1.108 TSHR Zornitza Stark edited their review of gene: TSHR: Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2114 PIGF Lisa Norbart gene: PIGF was added
gene: PIGF was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: PIGF was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PIGF were set to 33386993
Phenotypes for gene: PIGF were set to Onychodystrophy, osteodystrophy, impaired intellectual development, and seizures syndrome, MIM#619356
Review for gene: PIGF was set to RED
Added comment: PMID: 33386993 (2021) - The same homozygous missense mutation (p.Pro172Arg) in 2x unrelated individuals affected with DOORS syndrome (without deafness). 1/2 presented with generalised tonic-clonic seizues and 1/2 with tonic posturing.
Sources: Literature
Genetic Epilepsy v0.2114 PEX26 Lisa Norbart gene: PEX26 was added
gene: PEX26 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: PEX26 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PEX26 were set to 34430430; 28823628
Phenotypes for gene: PEX26 were set to Peroxisome biogenesis disorder 7A (Zellweger), MIM#614872
Review for gene: PEX26 was set to AMBER
Added comment: PMID: 34430430 (2021) - Case report on 1 infant with a homozygous frameshift variant and Zellweger Syndrome diagnosis. Presented with an epileptic seizure at 8 months old and focal seizures during sleep, died at 9 months old. Also described a literature review resulting in 1/4 previously reported infants with Zellweger Syndrome presenting with seizures, described below.

PMID: 28823628 (2017) - Case report on 1 infant with a homozygous missense variant and Zellweger Syndrome diagnosis. Developed tonic-clonic jerking of extremities.

GeneReviews: Seizures can be a symptom of Zellweger Syndrome in newborns (caused by underlying neuronal migration defects).
Sources: Literature
Genetic Epilepsy v0.2114 PEX2 Lisa Norbart gene: PEX2 was added
gene: PEX2 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: PEX2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PEX2 were set to 14630978; 23430938; 17041890
Phenotypes for gene: PEX2 were set to Peroxisome biogenesis disorder 5A (Zellweger), MIM#614866
Review for gene: PEX2 was set to AMBER
Added comment: PMID: 14630978 (2004) - 3 individuals with homozygous missense mutations and diagnosed with Zellweger syndrome. 1/3 presented with generalised seizures for which treatment was not effective. 2/3 had no seizures.

PMID: 23430938 (2012) - 1 individual with compound heterozygous nonsense mutations affected with mild Zellweger Syndrome, did not present with seizures.

PMID: 17041890 (2006) - 3/3 individuals with homozygous PEX2 nonsense/frameshift variants affected with Zellweger Syndrome. 2/3 presented with seizures, died at <6 months old.

GeneReviews: Seizures can be a symptom of Zellweger Syndrome in newborns (caused by underlying neuronal migration defects).
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5659 PUS3 Zornitza Stark Phenotypes for gene: PUS3 were changed from Mental retardation, autosomal recessive 55, MIM# 617051 to Neurodevelopmental disorder with microcephaly and gray sclerae, MIM# 617051
Intellectual disability syndromic and non-syndromic v0.5658 PUS3 Zornitza Stark edited their review of gene: PUS3: Changed phenotypes: Neurodevelopmental disorder with microcephaly and gray sclerae, MIM# 617051
Mendeliome v1.1456 PUS3 Zornitza Stark Phenotypes for gene: PUS3 were changed from Mental retardation, autosomal recessive 55, MIM# 617051 to Neurodevelopmental disorder with microcephaly and gray sclerae, MIM# 617051
Mendeliome v1.1455 PUS3 Zornitza Stark edited their review of gene: PUS3: Changed phenotypes: Neurodevelopmental disorder with microcephaly and gray sclerae, MIM# 617051
Genetic Epilepsy v0.2114 PUS3 Zornitza Stark Marked gene: PUS3 as ready
Genetic Epilepsy v0.2114 PUS3 Zornitza Stark Gene: pus3 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2114 PUS3 Zornitza Stark Phenotypes for gene: PUS3 were changed from Mental retardation, autosomal recessive 55, MIM# 617051 to Neurodevelopmental disorder with microcephaly and gray sclerae, MIM# 617051
Genetic Epilepsy v0.2113 PUS3 Zornitza Stark Classified gene: PUS3 as Green List (high evidence)
Genetic Epilepsy v0.2113 PUS3 Zornitza Stark Gene: pus3 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2112 NAA10 Rylee Peters reviewed gene: NAA10: Rating: GREEN; Mode of pathogenicity: None; Publications: 37130971; Phenotypes: NAA10-related syndrome MONDO:0100124; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Genetic Epilepsy v0.2112 LSS Rylee Peters changed review comment from: PMID: 30723320 - Cohort of 11 individuals from 7 unrelated families; all affected with alopecia, scaly skin, other ectodermal abnormalities, variable MRI abnormalities and neurological symptoms. All affected individuals (except 1x individual with a single missense variant and an allelic imbalance) were hom/compound het, whilst heterozygous carriers, for all the families, were asymptomatic. Epilepsy was reported in 7/11 individuals (Table 1).

PMID: 37157980 - Four-year-old male with global developmental delay, epilepsy and striking alopecia; identified novel compound heterozygous LSS splice site (c.14+2T>C) and missense (c.1357 G>A; p.V453L) variants. Presented with myoclonic epilepsy at 14 months.

Note: PanelApp UK has this gene rating as amber based on advice from Genomics England Clinical Team and West Midlands, Oxford and Wessex GLH for GMS Neurology specialist test group.
Sources: Literature; to: PMID: 30723320 - Cohort of 11 individuals from 7 unrelated families; all affected with alopecia, scaly skin, other ectodermal abnormalities, variable MRI abnormalities and neurological symptoms. All affected individuals (except 1x individual with a single missense variant and an allelic imbalance) were hom/compound het, whilst heterozygous carriers, for all the families, were asymptomatic. Epilepsy was reported in 7/11 individuals (Table 1).

PMID: 37157980 - Four-year-old male with global developmental delay, epilepsy and striking alopecia; identified novel compound heterozygous LSS splice site (c.14+2T>C) and missense (c.1357 G>A; p.V453L) variants. Presented with myoclonic epilepsy at 14 months.

Note: PanelApp UK has this gene rating as amber based on advice from Genomics England Clinical Team and West Midlands, Oxford and Wessex GLH for GMS Neurology specialist test group.
Sources: Literature
Genetic Epilepsy v0.2112 LSS Rylee Peters gene: LSS was added
gene: LSS was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: LSS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LSS were set to PMID: 30723320; 37157980
Phenotypes for gene: LSS were set to Alopecia-intellectual disability syndrome 4, MIM#618840
Review for gene: LSS was set to GREEN
Added comment: PMID: 30723320 - Cohort of 11 individuals from 7 unrelated families; all affected with alopecia, scaly skin, other ectodermal abnormalities, variable MRI abnormalities and neurological symptoms. All affected individuals (except 1x individual with a single missense variant and an allelic imbalance) were hom/compound het, whilst heterozygous carriers, for all the families, were asymptomatic. Epilepsy was reported in 7/11 individuals (Table 1).

PMID: 37157980 - Four-year-old male with global developmental delay, epilepsy and striking alopecia; identified novel compound heterozygous LSS splice site (c.14+2T>C) and missense (c.1357 G>A; p.V453L) variants. Presented with myoclonic epilepsy at 14 months.

Note: PanelApp UK has this gene rating as amber based on advice from Genomics England Clinical Team and West Midlands, Oxford and Wessex GLH for GMS Neurology specialist test group.
Sources: Literature
Genetic Epilepsy v0.2112 RPS6KA3 Belinda Chong gene: RPS6KA3 was added
gene: RPS6KA3 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: RPS6KA3 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: RPS6KA3 were set to 12210291; 6879200
Phenotypes for gene: RPS6KA3 were set to Coffin-Lowry syndrome MIM# 303600; Intellectual disability; short stature; delayed bone age; hearing deficit; hypotonia; tapering fingers; abnormal facies (hypertelorism, anteverted nares, prominent frontal region)
Review for gene: RPS6KA3 was set to GREEN
gene: RPS6KA3 was marked as current diagnostic
Added comment: Seizures is a feature in Coffin-Lowry syndrome individuals.
Sources: Literature
Genetic Epilepsy v0.2112 RERE Belinda Chong gene: RERE was added
gene: RERE was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: RERE was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RERE were set to 30896913; 27087320; 23451234; 30558068
Phenotypes for gene: RERE were set to Neurodevelopmental disorder with or without anomalies of the brain, eye, or heart, MIM# 616975
Review for gene: RERE was set to GREEN
gene: RERE was marked as current diagnostic
Added comment: Seizure is a feature
Sources: Literature
Genetic Epilepsy v0.2112 RAPGEF2 Belinda Chong gene: RAPGEF2 was added
gene: RAPGEF2 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: RAPGEF2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RAPGEF2 were set to 37021642; 30351492; 29507423
Phenotypes for gene: RAPGEF2 were set to ?Epilepsy, familial adult myoclonic, 7 MIM# 618075
Review for gene: RAPGEF2 was set to RED
Added comment: Heterozygous 5-bp repeat expansion (TTTCA(n)) in intron 14 of RAPGEF2 gene. Two individuals previously reported (PMID: 30351492 and 29507423) with seizures
Sources: Literature
Mendeliome v1.1455 RAPGEF2 Belinda Chong gene: RAPGEF2 was added
gene: RAPGEF2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RAPGEF2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RAPGEF2 were set to 37021642; 30351492; 29507423
Phenotypes for gene: RAPGEF2 were set to ?Epilepsy, familial adult myoclonic, 7 MIM# 618075
Review for gene: RAPGEF2 was set to RED
Added comment: Heterozygous 5-bp repeat expansion (TTTCA(n)) in intron 14 of RAPGEF2 gene. Two individuals previously reported (PMID: 30351492 and 29507423) with seizures
Sources: Literature
Genetic Epilepsy v0.2112 RANBP2 Belinda Chong gene: RANBP2 was added
gene: RANBP2 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: RANBP2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RANBP2 were set to 32426208; 35485383; 33777149; 19118815; 25128471; 25522933; 32048120
Phenotypes for gene: RANBP2 were set to {Encephalopathy, acute, infection-induced, 3, susceptibility to} MIM#608033
Review for gene: RANBP2 was set to GREEN
gene: RANBP2 was marked as current diagnostic
Added comment: Individuals have seizures
Sources: Literature
Genetic Epilepsy v0.2112 PTBP1 Belinda Chong gene: PTBP1 was added
gene: PTBP1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: PTBP1 was set to Unknown
Review for gene: PTBP1 was set to RED
Added comment: No evidence for Mendelian disease association. In Oliver's Gene list.
Sources: Literature
Mendeliome v1.1455 PTBP1 Belinda Chong gene: PTBP1 was added
gene: PTBP1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PTBP1 was set to Unknown
Review for gene: PTBP1 was set to RED
Added comment: No evidence for Mendelian disease association.
Sources: Literature
Genetic Epilepsy v0.2112 RAI1 Belinda Chong gene: RAI1 was added
gene: RAI1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: RAI1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RAI1 were set to 36256819; 11404004; 12652298; 15788730
Phenotypes for gene: RAI1 were set to Smith-Magenis syndrome MIM#182290
Review for gene: RAI1 was set to GREEN
gene: RAI1 was marked as current diagnostic
Added comment: PMID 36256819: Spontaneous seizures have been detected in 30% of Rai1−/− mice and SMS patients

PMID: 16566870: Considering that close to one third of individuals with Smith-Magenis syndrome with epileptiform abnormalities also had a history of clinical seizures, cortical hyperexcitability and epilepsy should be considered an important component of the Smith-Magenis syndrome clinical phenotype.
Sources: Literature
Genetic Epilepsy v0.2112 RAB39B Belinda Chong gene: RAB39B was added
gene: RAB39B was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: RAB39B was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: RAB39B were set to 4025396; 11050621; 20159109
Phenotypes for gene: RAB39B were set to Intellectual developmental disorder, X-linked 72 MIM#300271; Waisman syndrome MIM#311510
Review for gene: RAB39B was set to GREEN
Added comment: Seizures observed in most individuals.
Sources: Literature
Genetic Epilepsy v0.2112 CCDC88C Lilian Downie gene: CCDC88C was added
gene: CCDC88C was added to Genetic Epilepsy. Sources: Expert list
Mode of inheritance for gene: CCDC88C was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CCDC88C were set to PMID: 29341397, PMID: 23042809, PMID: 21031079
Phenotypes for gene: CCDC88C were set to Hydrocephalus, congenital, 1 MIM#236600
Review for gene: CCDC88C was set to GREEN
Added comment: 3 independant families with seizures reported as a feature, onset between birth and 2 years. Focal and tonic clonic. Summary table in PMID: 29341397.
Sources: Expert list
Genetic Epilepsy v0.2112 CCDC22 Lilian Downie gene: CCDC22 was added
gene: CCDC22 was added to Genetic Epilepsy. Sources: Expert list
Mode of inheritance for gene: CCDC22 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: CCDC22 were set to PMID: 34020006
Phenotypes for gene: CCDC22 were set to Ritscher-Schinzel syndrome 2 MIM#300963
Review for gene: CCDC22 was set to RED
Added comment: X-linked recessive syndromic form of intellectual disability associated with posterior fossa defects, cardiac malformations, and minor abnormalities of the face and distal extremities

Reviewed as on a research epilepsy gene list

PMID: 34020006 patient with epileptic encephalopathy but they had a missense variant VUS - segregated only in healthy mother and grandmother, no healthy males tested, maternal uncle deceased but wasn't tested. Didn't have the typical features of the condition (no posterior fossa anomalies or cardiac malformations).
Sources: Expert list
Microcephaly v1.246 COPB2 Rylee Peters changed review comment from: This paper reports an unrelated individual with the same homozygous variant (NM_004766.3:c.760C>T, p.Arg254Cys) identified in 2xsiblings in PMID: 29036432 (the same two siblings are also described in PMID: 34450031).

The proband is an 8.5yo Iranian female born to consanguineous parents. This individual has symptoms consistent with autosomal recessive microcephaly 19 (MIM#617800) including, global developmental delay, intellectual disability, microcephaly, seizures, spasticity, strabismus, and failure to thrive symptoms; she is unable to stand, walk, or speak.; to: PMID: 37734708 - This paper reports an unrelated individual with the same homozygous variant (NM_004766.3:c.760C>T, p.Arg254Cys) identified in 2xsiblings in PMID: 29036432 (the same two siblings are also described in PMID: 34450031).

The proband is an 8.5yo Iranian female born to consanguineous parents. This individual has symptoms consistent with autosomal recessive microcephaly 19 (MIM#617800) including, global developmental delay, intellectual disability, microcephaly, seizures, spasticity, strabismus, and failure to thrive symptoms; she is unable to stand, walk, or speak.
Microcephaly v1.246 COPB2 Rylee Peters reviewed gene: COPB2: Rating: AMBER; Mode of pathogenicity: None; Publications: 37734708, 29036432, 34450031; Phenotypes: Microcephaly 19, primary, autosomal recessive, MIM# 617800; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2112 PUS3 Belinda Chong gene: PUS3 was added
gene: PUS3 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: PUS3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PUS3 were set to 36125428; 30308082; 28454995; 27055666; 30697592; 31444731
Phenotypes for gene: PUS3 were set to Mental retardation, autosomal recessive 55, MIM# 617051
Review for gene: PUS3 was set to GREEN
gene: PUS3 was marked as current diagnostic
Added comment: Most affected individuals have seizures; some may have brain imaging abnormalities
Sources: Literature
Mendeliome v1.1455 ALG8 Zornitza Stark Publications for gene: ALG8 were set to 26066342; 28375157; 15235028
Intellectual disability syndromic and non-syndromic v0.5658 ALG8 Zornitza Stark Publications for gene: ALG8 were set to 26066342
Genetic Epilepsy v0.2112 ALG8 Zornitza Stark Publications for gene: ALG8 were set to 26066342
Genetic Epilepsy v0.2111 OCRL Zornitza Stark Marked gene: OCRL as ready
Genetic Epilepsy v0.2111 OCRL Zornitza Stark Gene: ocrl has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2111 OCRL Zornitza Stark Classified gene: OCRL as Red List (low evidence)
Genetic Epilepsy v0.2111 OCRL Zornitza Stark Gene: ocrl has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2110 CAMTA1 Zornitza Stark Marked gene: CAMTA1 as ready
Genetic Epilepsy v0.2110 CAMTA1 Zornitza Stark Gene: camta1 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2110 CAMTA1 Zornitza Stark Classified gene: CAMTA1 as Red List (low evidence)
Genetic Epilepsy v0.2110 CAMTA1 Zornitza Stark Gene: camta1 has been classified as Red List (Low Evidence).
Microcephaly v1.246 SOX5 Zornitza Stark Marked gene: SOX5 as ready
Microcephaly v1.246 SOX5 Zornitza Stark Gene: sox5 has been classified as Amber List (Moderate Evidence).
Microcephaly v1.246 SOX5 Zornitza Stark Classified gene: SOX5 as Amber List (moderate evidence)
Microcephaly v1.246 SOX5 Zornitza Stark Gene: sox5 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2109 C19orf12 Zornitza Stark Marked gene: C19orf12 as ready
Genetic Epilepsy v0.2109 C19orf12 Zornitza Stark Gene: c19orf12 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2109 C19orf12 Zornitza Stark Classified gene: C19orf12 as Red List (low evidence)
Genetic Epilepsy v0.2109 C19orf12 Zornitza Stark Gene: c19orf12 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2108 PDE2A Zornitza Stark Marked gene: PDE2A as ready
Genetic Epilepsy v0.2108 PDE2A Zornitza Stark Gene: pde2a has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2108 PDE2A Zornitza Stark Classified gene: PDE2A as Green List (high evidence)
Genetic Epilepsy v0.2108 PDE2A Zornitza Stark Gene: pde2a has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2107 PDE2A Zornitza Stark reviewed gene: PDE2A: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Intellectual developmental disorder with paroxysmal dyskinesia or seizures MIM#619150; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2107 PDCD10 Zornitza Stark Marked gene: PDCD10 as ready
Genetic Epilepsy v0.2107 PDCD10 Zornitza Stark Gene: pdcd10 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2107 PDCD10 Zornitza Stark Classified gene: PDCD10 as Green List (high evidence)
Genetic Epilepsy v0.2107 PDCD10 Zornitza Stark Gene: pdcd10 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2106 PDCD10 Zornitza Stark reviewed gene: PDCD10: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cerebral cavernous malformations-3 MIM#603285; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2106 OGT Zornitza Stark edited their review of gene: OGT: Changed rating: GREEN
Genetic Epilepsy v0.2106 OGT Zornitza Stark edited their review of gene: OGT: Changed rating: RED
Genetic Epilepsy v0.2106 ODC1 Zornitza Stark Publications for gene: ODC1 were set to PMID:30475435; 30239107
Genetic Epilepsy v0.2105 ODC1 Zornitza Stark edited their review of gene: ODC1: Changed rating: RED
Genetic Epilepsy v0.2105 PAK2 Zornitza Stark Marked gene: PAK2 as ready
Genetic Epilepsy v0.2105 PAK2 Zornitza Stark Gene: pak2 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2105 PAK2 Zornitza Stark Classified gene: PAK2 as Red List (low evidence)
Genetic Epilepsy v0.2105 PAK2 Zornitza Stark Gene: pak2 has been classified as Red List (Low Evidence).
Mendeliome v1.1454 PRICKLE2 Zornitza Stark changed review comment from: LIMITED by ClinGen.; to: LIMITED by ClinGen; however, experimental evidence appears not to have been considered.
Intellectual disability syndromic and non-syndromic v0.5657 PRICKLE2 Zornitza Stark changed review comment from: LIMITED by ClinGen.; to: LIMITED by ClinGen; however, experimental evidence appears not to have been considered.
Genetic Epilepsy v0.2104 PRICKLE2 Zornitza Stark changed review comment from: LIMITED by ClinGen.; to: LIMITED by ClinGen, however experimental evidence appears not to have been considered.
Intellectual disability syndromic and non-syndromic v0.5657 PRICKLE2 Zornitza Stark Phenotypes for gene: PRICKLE2 were changed from Neurodevelopmental disorder; global developmental delay; behavioural difficulties ± epilepsy; autistic features; attention deficit hyperactive disorder; psychiatric symptoms to Neurodevelopmental disorder MONDO:0700092, PRICKLE2-related
Intellectual disability syndromic and non-syndromic v0.5656 PRICKLE2 Zornitza Stark Publications for gene: PRICKLE2 were set to PMID: 34092786
Intellectual disability syndromic and non-syndromic v0.5655 PRICKLE2 Zornitza Stark Classified gene: PRICKLE2 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.5655 PRICKLE2 Zornitza Stark Gene: prickle2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5654 PRICKLE2 Zornitza Stark reviewed gene: PRICKLE2: Rating: AMBER; Mode of pathogenicity: None; Publications: 34092786, 21276947, 26942291, 26942292; Phenotypes: Neurodevelopmental disorder MONDO:0700092, PRICKLE2-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.1454 PRICKLE2 Zornitza Stark Phenotypes for gene: PRICKLE2 were changed from Neurodevelopmental disorder, MONDO:0700092; global developmental delay, behavioural difficulties ± epilepsy, autistic features, and attention deficit hyperactive disorder. to Neurodevelopmental disorder MONDO:0700092, PRICKLE2-related
Mendeliome v1.1453 PRICKLE2 Zornitza Stark Publications for gene: PRICKLE2 were set to 34092786
Mendeliome v1.1452 PRICKLE2 Zornitza Stark Classified gene: PRICKLE2 as Amber List (moderate evidence)
Mendeliome v1.1452 PRICKLE2 Zornitza Stark Gene: prickle2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1451 PRICKLE2 Zornitza Stark reviewed gene: PRICKLE2: Rating: AMBER; Mode of pathogenicity: None; Publications: 34092786, 21276947, 26942291, 26942292; Phenotypes: Neurodevelopmental disorder MONDO:0700092, PRICKLE2-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2104 PRICKLE2 Zornitza Stark Phenotypes for gene: PRICKLE2 were changed from Neurodevelopmental disorder; global developmental delay; behavioural difficulties ± epilepsy; autistic features; attention deficit hyperactive disorder; psychiatric symptoms to Neurodevelopmental disorder MONDO:0700092, PRICKLE2-related
Genetic Epilepsy v0.2103 PRICKLE2 Zornitza Stark Publications for gene: PRICKLE2 were set to 34092786
Genetic Epilepsy v0.2102 PRICKLE2 Zornitza Stark Classified gene: PRICKLE2 as Amber List (moderate evidence)
Genetic Epilepsy v0.2102 PRICKLE2 Zornitza Stark Gene: prickle2 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2101 PRICKLE2 Zornitza Stark edited their review of gene: PRICKLE2: Added comment: LIMITED by ClinGen.; Changed rating: AMBER
Prepair 1000+ v1.4 PRICKLE1 Zornitza Stark Tag for review tag was added to gene: PRICKLE1.
Prepair 1000+ v1.4 PRICKLE1 Zornitza Stark reviewed gene: PRICKLE1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Epilepsy, progressive myoclonic 1B, MIM# 612437; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia - paediatric v1.16 PRICKLE1 Zornitza Stark Classified gene: PRICKLE1 as Red List (low evidence)
Ataxia - paediatric v1.16 PRICKLE1 Zornitza Stark Gene: prickle1 has been classified as Red List (Low Evidence).
Ataxia - paediatric v1.15 PRICKLE1 Zornitza Stark edited their review of gene: PRICKLE1: Added comment: LIMITED by ClinGen for AR PME.; Changed rating: RED
Regression v0.540 PRICKLE1 Zornitza Stark Classified gene: PRICKLE1 as Red List (low evidence)
Regression v0.540 PRICKLE1 Zornitza Stark Gene: prickle1 has been classified as Red List (Low Evidence).
Regression v0.539 PRICKLE1 Zornitza Stark edited their review of gene: PRICKLE1: Added comment: LIMITED by ClinGen for AR PME, DISPUTED for AD epilepsy.; Changed rating: RED
Mendeliome v1.1451 PRICKLE1 Zornitza Stark Classified gene: PRICKLE1 as Red List (low evidence)
Mendeliome v1.1451 PRICKLE1 Zornitza Stark Gene: prickle1 has been classified as Red List (Low Evidence).
Mendeliome v1.1450 PRICKLE1 Zornitza Stark edited their review of gene: PRICKLE1: Added comment: LIMITED by ClinGen for AR PME and DISPUTED for AD epilepsy.; Changed rating: RED
Progressive Myoclonic Epilepsy v0.19 PRICKLE1 Zornitza Stark Classified gene: PRICKLE1 as Red List (low evidence)
Progressive Myoclonic Epilepsy v0.19 PRICKLE1 Zornitza Stark Gene: prickle1 has been classified as Red List (Low Evidence).
Progressive Myoclonic Epilepsy v0.18 PRICKLE1 Zornitza Stark changed review comment from: LIMITED by ClinGen.; to: LIMITED by ClinGen for AR PME, and DISPUTED for AD epilepsy.
Progressive Myoclonic Epilepsy v0.18 PRICKLE1 Zornitza Stark edited their review of gene: PRICKLE1: Added comment: LIMITED by ClinGen.; Changed rating: RED
Genetic Epilepsy v0.2101 PRICKLE1 Zornitza Stark Classified gene: PRICKLE1 as Red List (low evidence)
Genetic Epilepsy v0.2101 PRICKLE1 Zornitza Stark Gene: prickle1 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2100 PRICKLE1 Zornitza Stark edited their review of gene: PRICKLE1: Changed rating: RED
Genetic Epilepsy v0.2100 PRICKLE1 Zornitza Stark changed review comment from: LIMITED by ClinGen for PME, and DISPUTED for epilepsy.; to: LIMITED by ClinGen for AR PME, and DISPUTED for AD epilepsy.
Genetic Epilepsy v0.2100 PRICKLE1 Zornitza Stark commented on gene: PRICKLE1: LIMITED by ClinGen for PME, and DISPUTED for epilepsy.
Progressive Myoclonic Epilepsy v0.18 PRICKLE1 Zornitza Stark Marked gene: PRICKLE1 as ready
Progressive Myoclonic Epilepsy v0.18 PRICKLE1 Zornitza Stark Gene: prickle1 has been classified as Amber List (Moderate Evidence).
Progressive Myoclonic Epilepsy v0.18 PRICKLE1 Zornitza Stark Publications for gene: PRICKLE1 were set to
Progressive Myoclonic Epilepsy v0.17 PRICKLE1 Zornitza Stark Classified gene: PRICKLE1 as Amber List (moderate evidence)
Progressive Myoclonic Epilepsy v0.17 PRICKLE1 Zornitza Stark Gene: prickle1 has been classified as Amber List (Moderate Evidence).
Progressive Myoclonic Epilepsy v0.16 PRICKLE1 Zornitza Stark reviewed gene: PRICKLE1: Rating: AMBER; Mode of pathogenicity: None; Publications: 18976727, 30564977; Phenotypes: Epilepsy, progressive myoclonic 1B, MIM# 612437; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia - paediatric v1.15 PRICKLE1 Zornitza Stark Classified gene: PRICKLE1 as Amber List (moderate evidence)
Ataxia - paediatric v1.15 PRICKLE1 Zornitza Stark Gene: prickle1 has been classified as Amber List (Moderate Evidence).
Ataxia - paediatric v1.14 PRICKLE1 Zornitza Stark edited their review of gene: PRICKLE1: Added comment: Note most reported variants are missense with little further supportive evidence and ClinVar variants in this gene are all VOUS/LB/B.; Changed rating: AMBER
Regression v0.539 PRICKLE1 Zornitza Stark Marked gene: PRICKLE1 as ready
Regression v0.539 PRICKLE1 Zornitza Stark Gene: prickle1 has been classified as Amber List (Moderate Evidence).
Regression v0.539 PRICKLE1 Zornitza Stark Phenotypes for gene: PRICKLE1 were changed from to Epilepsy, progressive myoclonic 1B, MIM# 612437
Regression v0.538 PRICKLE1 Zornitza Stark Publications for gene: PRICKLE1 were set to
Regression v0.537 PRICKLE1 Zornitza Stark Mode of inheritance for gene: PRICKLE1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Regression v0.536 PRICKLE1 Zornitza Stark Classified gene: PRICKLE1 as Amber List (moderate evidence)
Regression v0.536 PRICKLE1 Zornitza Stark Gene: prickle1 has been classified as Amber List (Moderate Evidence).
Regression v0.535 PRICKLE1 Zornitza Stark reviewed gene: PRICKLE1: Rating: AMBER; Mode of pathogenicity: None; Publications: 34597683, 30564977, 30345727, 29790814, 26727662, 31035234; Phenotypes: Epilepsy, progressive myoclonic 1B, MIM# 612437; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Callosome v0.514 PRICKLE1 Zornitza Stark Marked gene: PRICKLE1 as ready
Callosome v0.514 PRICKLE1 Zornitza Stark Gene: prickle1 has been classified as Red List (Low Evidence).
Callosome v0.514 PRICKLE1 Zornitza Stark Phenotypes for gene: PRICKLE1 were changed from to Neurodevelopmental disorder, MONDO:0700092, PRICKLE1-related
Callosome v0.513 PRICKLE1 Zornitza Stark Publications for gene: PRICKLE1 were set to
Callosome v0.512 PRICKLE1 Zornitza Stark Mode of inheritance for gene: PRICKLE1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Callosome v0.511 PRICKLE1 Zornitza Stark Classified gene: PRICKLE1 as Red List (low evidence)
Callosome v0.511 PRICKLE1 Zornitza Stark Gene: prickle1 has been classified as Red List (Low Evidence).
Callosome v0.510 PRICKLE1 Zornitza Stark reviewed gene: PRICKLE1: Rating: RED; Mode of pathogenicity: None; Publications: 26727662; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, PRICKLE1-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.1450 PRICKLE1 Zornitza Stark Classified gene: PRICKLE1 as Amber List (moderate evidence)
Mendeliome v1.1450 PRICKLE1 Zornitza Stark Gene: prickle1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1449 PRICKLE1 Zornitza Stark edited their review of gene: PRICKLE1: Added comment: Note all ClinVar entries for this gene are VOUS/LB/B. The variants reported in bi-allelic cases are almost all missense without further supportive data.; Changed rating: AMBER
Genetic Epilepsy v0.2100 PRICKLE1 Zornitza Stark edited their review of gene: PRICKLE1: Added comment: Note ClinVar submissions for this gene are all VOUS/LB/B.; Changed rating: AMBER
Genetic Epilepsy v0.2100 PGM3 Zornitza Stark Phenotypes for gene: PGM3 were changed from Idiopathic focal epilepsy to Idiopathic focal epilepsy; Immunodeficiency 23, MIM# 615816
Genetic Epilepsy v0.2099 PGM3 Zornitza Stark Mode of inheritance for gene: PGM3 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v1.176 ERI1 Zornitza Stark Phenotypes for gene: ERI1 were changed from Spondyloepimetaphyseal dysplasia (MONDO#0100510) to Spondyloepimetaphyseal dysplasia, Guo-Salian type, MIM# 620663
Fetal anomalies v1.175 ERI1 Zornitza Stark Mode of inheritance for gene: ERI1 was changed from BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.174 ERI1 Zornitza Stark edited their review of gene: ERI1: Changed phenotypes: Spondyloepimetaphyseal dysplasia, Guo-Salian type, MIM# 620663; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Multiple epiphyseal dysplasia and pseudoachondroplasia v0.11 ERI1 Zornitza Stark Phenotypes for gene: ERI1 were changed from to Spondyloepimetaphyseal dysplasia, Guo-Salian type, MIM# 620663
Multiple epiphyseal dysplasia and pseudoachondroplasia v0.10 ERI1 Zornitza Stark reviewed gene: ERI1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Spondyloepimetaphyseal dysplasia, Guo-Salian type, MIM# 620663; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v0.259 ERI1 Zornitza Stark Phenotypes for gene: ERI1 were changed from Spondyloepimetaphyseal dysplasia (MONDO#0100510), ERI1-related to Spondyloepimetaphyseal dysplasia, Guo-Salian type, MIM# 620663
Skeletal dysplasia v0.258 ERI1 Zornitza Stark reviewed gene: ERI1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Spondyloepimetaphyseal dysplasia, Guo-Salian type, MIM# 620663; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal Dysplasia_Fetal v0.211 ERI1 Zornitza Stark Phenotypes for gene: ERI1 were changed from Spondyloepimetaphyseal dysplasia (MONDO#0100510), ERI1-related to Spondyloepimetaphyseal dysplasia, Guo-Salian type, MIM# 620663
Skeletal Dysplasia_Fetal v0.210 ERI1 Zornitza Stark reviewed gene: ERI1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Spondyloepimetaphyseal dysplasia, Guo-Salian type, MIM# 620663; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1449 ERI1 Zornitza Stark Phenotypes for gene: ERI1 were changed from Spondyloepimetaphyseal dysplasia (MONDO#0100510), ERI1-related, Intellectual disability (MONDO#0001071), ERI1-related to Hoxha-Aliu syndrome, MIM# 620662; Spondyloepimetaphyseal dysplasia, Guo-Salian type, MIM# 620663
Mendeliome v1.1448 ERI1 Zornitza Stark reviewed gene: ERI1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Hoxha-Aliu syndrome, MIM# 620662, Spondyloepimetaphyseal dysplasia, Guo-Salian type, MIM# 620663; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5654 ERI1 Zornitza Stark Phenotypes for gene: ERI1 were changed from Intellectual disability (MONDO#0001071), ERI1-related to Hoxha-Aliu syndrome, MIM# 620662
Intellectual disability syndromic and non-syndromic v0.5653 ERI1 Zornitza Stark reviewed gene: ERI1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Hoxha-Aliu syndrome, MIM# 620662; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1448 ALG8 Rylee Peters reviewed gene: ALG8: Rating: GREEN; Mode of pathogenicity: None; Publications: 35716054; Phenotypes: Congenital disorder of glycosylation, type Ih, MIM# 608104; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5653 ALG8 Rylee Peters reviewed gene: ALG8: Rating: GREEN; Mode of pathogenicity: None; Publications: 35716054; Phenotypes: Congenital disorder of glycosylation, type Ih, MIM# 608104; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2098 ALG8 Rylee Peters reviewed gene: ALG8: Rating: GREEN; Mode of pathogenicity: None; Publications: 35716054; Phenotypes: Congenital disorder of glycosylation, type Ih, MIM# 608104; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2098 OCRL Lauren Rogers gene: OCRL was added
gene: OCRL was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: OCRL was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: OCRL were set to 35919034
Phenotypes for gene: OCRL were set to Lowe syndrome MIM#309000
Review for gene: OCRL was set to RED
Added comment: PMID: 35919034: In a cohort of 83 Chinese individuals with Lowes syndrome or Dent-2 disease, 1/48 individuals with Lowes syndrome had epilepsy, developmental delay and intellectual disability with a maternally inherited p.R678X variant.
Sources: Literature
Genetic Epilepsy v0.2098 PANK2 Elena Savva Classified gene: PANK2 as Red List (low evidence)
Genetic Epilepsy v0.2098 PANK2 Elena Savva Gene: pank2 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2098 PANK2 Elena Savva Classified gene: PANK2 as Red List (low evidence)
Genetic Epilepsy v0.2098 PANK2 Elena Savva Gene: pank2 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2097 PANK2 Elena Savva Classified gene: PANK2 as Red List (low evidence)
Genetic Epilepsy v0.2097 PANK2 Elena Savva Gene: pank2 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2097 PANK2 Elena Savva Marked gene: PANK2 as ready
Genetic Epilepsy v0.2097 PANK2 Elena Savva Gene: pank2 has been removed from the panel.
Genetic Epilepsy v0.2097 OGT Elena Savva Publications for gene: OGT were set to PMID: 28302723; 28584052; 31296563; 31627256; 29769320; 29606577
Genetic Epilepsy v0.2096 CAMTA1 Lilian Downie gene: CAMTA1 was added
gene: CAMTA1 was added to Genetic Epilepsy. Sources: Expert list
Mode of inheritance for gene: CAMTA1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CAMTA1 were set to PMID: 31957018
Phenotypes for gene: CAMTA1 were set to Cerebellar dysfunction with variable cognitive and behavioral abnormalities MIM#614756
Review for gene: CAMTA1 was set to RED
Added comment: PMID: 31957018 sequencing in an epilepsy cohort - if negative looked at 'candidate epilepy genes', variant identified in CAMTA1 in patient with infantile spasms, refractory epilepsy, dev delay and corticovisual impairment.
Sources: Expert list
Microcephaly v1.245 SOX5 Rylee Peters gene: SOX5 was added
gene: SOX5 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: SOX5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SOX5 were set to PMID: 36861937
Phenotypes for gene: SOX5 were set to Lamb-Shaffer syndrome, MIM#616803
Review for gene: SOX5 was set to AMBER
Added comment: Cohort of 16 patients with heterozygous variants in SOX5. Paper also describes 71 previously reported cases of individuals with variants in SOX5 associated with Lamb–Shaffer Syndrome.

Microcephaly is reported in 14% of individuals with variants in SOX5 (calculated from both the current and previously reported cohorts).
Sources: Literature
Genetic Epilepsy v0.2096 C19orf12 Lilian Downie gene: C19orf12 was added
gene: C19orf12 was added to Genetic Epilepsy. Sources: Expert list
Mode of inheritance for gene: C19orf12 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: C19orf12 were set to Neurodegeneration with brain iron accumulation 4 MIM#614298
Review for gene: C19orf12 was set to RED
Added comment: Review of literature, no evidence of seizures as part of the phenotype with this gene
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.5653 PDE2A Lauren Rogers reviewed gene: PDE2A: Rating: GREEN; Mode of pathogenicity: None; Publications: 32467598, 29392776, 37317634; Phenotypes: Intellectual developmental disorder with paroxysmal dyskinesia or seizures MIM#619150; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2096 PDE2A Lauren Rogers gene: PDE2A was added
gene: PDE2A was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: PDE2A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PDE2A were set to 32467598; 32196122; 37317634
Phenotypes for gene: PDE2A were set to Intellectual developmental disorder with paroxysmal dyskinesia or seizures MIM#619150
Review for gene: PDE2A was set to AMBER
Added comment: PMID: 32467598: In a case report of 2 unrelated families with childhood-onset refractory paroxysmal dyskinesia with cognitive impairment, one family had two affected siblings who had a homozygous p.(Gln394*) variant. The younger sibling having epilepsy (unclear in the other sibling).

PMID: 32196122: A case report of 2 affected individuals from a consanguineous Iraqi family presenting with the atypical Rett phenotype with a homozygous c.323 + 1G > A variant. Both had epilepsy.

PMID: 37317634: 6 Pakistani individuals from 3 families with paroxysmal dyskinesia, developmental delay, cognitive abnormalities, speech impairment, and seizures with variable disease onset. Seizures included tonic clonic/generalised, upper limb only or myoclonic pattern/focal seizures. All individuals had the same homozygous missense variant p.(Phe505Ser), called a founder variant.
Sources: Literature
Genetic Epilepsy v0.2096 PDCD10 Lauren Rogers gene: PDCD10 was added
gene: PDCD10 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: PDCD10 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PDCD10 were set to 25354366; 26246098
Phenotypes for gene: PDCD10 were set to Cerebral cavernous malformations-3 MIM#603285
Review for gene: PDCD10 was set to AMBER
Added comment: PMID: 25354366: in a cohort of 11 Italian individuals with multiple/familial cerebral cavernous malformations, and PDCD10 variants, 4 individuals had seizures, including left-sided focal sensory-motor seizures. The associated variants were a de novo p.(R35X) variant, c.376_380del; 392_393ins, p.(E54X) and a whole gene deletion. The father with the whole gene deletion had a child with the variant who does not have seizures.

PMID: 26246098: A case report of an Italian family with three individuals (2x sisters and daughter) with cerebral cavernous malformations associated with meningioma. They had a a p.(Gln112PhefsX13) variant. The daughter had a severe form of epilepsy and both sisters had seizures.
Sources: Literature
Genetic Epilepsy v0.2096 PANK2 Lauren Rogers gene: PANK2 was added
gene: PANK2 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: PANK2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PANK2 were set to 27303611; 18462962
Phenotypes for gene: PANK2 were set to Neurodegeneration with brain iron accumulation 1 MIM#234200
Review for gene: PANK2 was set to RED
Added comment: PMID: 27303611: A case report of 1x child with neurodegeneration with brain iron accumulation 1, with seizure onset age 4 with frequent falls, not gaining milestones, progressive muscle dystonia, neuro-regression, and multiple injury marks of different stages. They had 2nd degree consanguineous parents. They were compound heterozygous for p.(Leu385CysfsX13) and p.(Arg440Pro).

PMID: 18462962: A case report of 1x child neurodegeneration with brain iron accumulation 1, with refractory severe dystonia resulting in essentially complete loss of motor control, and an episode of a reported single generalized tonic clonic seizure. They were homozygous for a p.(Ala382Val)
Sources: Literature
Fetal anomalies v1.174 RAP1B Zornitza Stark Phenotypes for gene: RAP1B were changed from Syndromic disease, MONDO:0002254, RAP1B-related to Thrombocytopenia 1 with multiple congenital anomalies and dysmorphic facies, MIM# 620654
Fetal anomalies v1.173 RAP1B Zornitza Stark reviewed gene: RAP1B: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Thrombocytopenia 1 with multiple congenital anomalies and dysmorphic facies, MIM# 620654; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Growth failure v1.73 RAP1B Zornitza Stark Phenotypes for gene: RAP1B were changed from Syndromic disease, MONDO:0002254, RAP1B-related to Thrombocytopenia 1 with multiple congenital anomalies and dysmorphic facies, MIM# 620654
Growth failure v1.72 RAP1B Zornitza Stark edited their review of gene: RAP1B: Changed phenotypes: Thrombocytopenia 1 with multiple congenital anomalies and dysmorphic facies, MIM# 620654
Kabuki syndrome v0.15 RAP1B Zornitza Stark Phenotypes for gene: RAP1B were changed from Syndromic disease, MONDO:0002254, RAP1B-related; Kabuki-like syndrome to Thrombocytopenia 1 with multiple congenital anomalies and dysmorphic facies, MIM# 620654; Kabuki-like syndrome
Kabuki syndrome v0.14 RAP1B Zornitza Stark edited their review of gene: RAP1B: Changed phenotypes: Thrombocytopenia 1 with multiple congenital anomalies and dysmorphic facies, MIM# 620654, Kabuki-like syndrome
Bone Marrow Failure v1.80 RAP1B Zornitza Stark Phenotypes for gene: RAP1B were changed from Syndromic disease, MONDO:0002254, RAP1B-related to Thrombocytopenia 1 with multiple congenital anomalies and dysmorphic facies, MIM# 620654
Bone Marrow Failure v1.79 RAP1B Zornitza Stark edited their review of gene: RAP1B: Changed phenotypes: Thrombocytopenia 1 with multiple congenital anomalies and dysmorphic facies, MIM# 620654
Intellectual disability syndromic and non-syndromic v0.5653 RAP1B Zornitza Stark Phenotypes for gene: RAP1B were changed from Syndromic disease, MONDO:0002254, RAP1B-related to Thrombocytopenia 1 with multiple congenital anomalies and dysmorphic facies, MIM# 620654
Intellectual disability syndromic and non-syndromic v0.5652 RAP1B Zornitza Stark edited their review of gene: RAP1B: Changed phenotypes: Thrombocytopenia 1 with multiple congenital anomalies and dysmorphic facies, MIM# 620654
Mendeliome v1.1448 RAP1B Zornitza Stark Phenotypes for gene: RAP1B were changed from Syndromic disease, MONDO:0002254, RAP1B-related; intellectual disability; microcephaly; thrombocytopaenia to Thrombocytopenia 1 with multiple congenital anomalies and dysmorphic facies, MIM# 620654
Mendeliome v1.1447 RAP1B Zornitza Stark edited their review of gene: RAP1B: Changed phenotypes: Thrombocytopenia 1 with multiple congenital anomalies and dysmorphic facies, MIM# 620654
Genetic Epilepsy v0.2096 OGT Lauren Rogers reviewed gene: OGT: Rating: RED; Mode of pathogenicity: None; Publications: 29769320, 37334838; Phenotypes: Intellectual developmental disorder, X-linked 106 MIM#300997; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Genetic Epilepsy v0.2096 PRICKLE1 Elena Savva Publications for gene: PRICKLE1 were set to 34597683; 30564977; 30345727; 29790814; 26727662; 31035234
Genetic Epilepsy v0.2096 PRICKLE1 Elena Savva Classified gene: PRICKLE1 as Amber List (moderate evidence)
Genetic Epilepsy v0.2096 PRICKLE1 Elena Savva Gene: prickle1 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2095 PGM3 Elena Savva Publications for gene: PGM3 were set to 33193641
Genetic Epilepsy v0.2094 ODC1 Lauren Rogers reviewed gene: ODC1: Rating: RED; Mode of pathogenicity: None; Publications: 34477286; Phenotypes: Bachmann-Bupp syndrome MIM#619075; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2094 PAK2 Lauren Rogers gene: PAK2 was added
gene: PAK2 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: PAK2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PAK2 were set to 33693784
Phenotypes for gene: PAK2 were set to Knobloch 2 syndrome MIM#618458
Review for gene: PAK2 was set to RED
Added comment: Antonarakis et al., 2021 (PMID: 33693784) reported two affected siblings from a non-consanguineous New Zealand family. Both had retinal detachment and interstitial parenchymal pulmonary changes on chest X-rays, but only one child had additional significant features such as cataract, posterior encephalocele, severe DD/ID with ASD, and epilepsy. WES revealed a heterozygous PAK2 variant (c.1303 G>A, p.Glu435Lys) in both individuals that apparently occurred de novo indicating parental germ-line mosaicism; however, mosaicism could not be detected by deep sequencing of blood parental DNA. Functional studies showed that the variant, located in the kinase domain, results in a partial loss of the kinase activity.
Sources: Literature
Genetic Epilepsy v0.2094 RALGAPB Lisa Norbart reviewed gene: RALGAPB: Rating: AMBER; Mode of pathogenicity: None; Publications: 32853829; Phenotypes: Epilepsy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Genetic Epilepsy v0.2094 RBL2 Lisa Norbart reviewed gene: RBL2: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Epilepsy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2094 PRICKLE2 Lisa Norbart reviewed gene: PRICKLE2: Rating: AMBER; Mode of pathogenicity: None; Publications: 34092786, 21276947, 26942291, 26942292; Phenotypes: Epilepsy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Genetic Epilepsy v0.2094 PRICKLE1 Lisa Norbart reviewed gene: PRICKLE1: Rating: AMBER; Mode of pathogenicity: None; Publications: 18976727, 30564977; Phenotypes: Epilepsy, progressive myoclonic 1B, MIM# 612437; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2094 PPP1CB Lisa Norbart reviewed gene: PPP1CB: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Noonan syndrome-like disorder with loose anagen hair 2 MIM#617506; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Genetic Epilepsy v0.2094 PGM3 Lisa Norbart reviewed gene: PGM3: Rating: AMBER; Mode of pathogenicity: None; Publications: 24589341; Phenotypes: Epilepsy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2094 OTUD7A Lisa Norbart reviewed gene: OTUD7A: Rating: AMBER; Mode of pathogenicity: None; Publications: 31997314, 29395075, 29395074, 33381903; Phenotypes: Epilepsy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2094 PRRT2 Zornitza Stark Marked gene: PRRT2 as ready
Genetic Epilepsy v0.2094 PRRT2 Zornitza Stark Gene: prrt2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2094 PRRT2 Zornitza Stark Phenotypes for gene: PRRT2 were changed from to Convulsions, familial infantile, with paroxysmal choreoathetosis 602066; Episodic kinesigenic dyskinesia 1 128200; Seizures, benign familial infantile, 2 605751
Genetic Epilepsy v0.2093 PRRT2 Zornitza Stark Publications for gene: PRRT2 were set to
Genetic Epilepsy v0.2092 PRRT2 Zornitza Stark Mode of inheritance for gene: PRRT2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genetic Epilepsy v0.2091 PTS Zornitza Stark Marked gene: PTS as ready
Genetic Epilepsy v0.2091 PTS Zornitza Stark Gene: pts has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2091 PTS Zornitza Stark Phenotypes for gene: PTS were changed from to Hyperphenylalaninemia, BH4-deficient, A, MIM# 261640
Genetic Epilepsy v0.2090 PTS Zornitza Stark Mode of inheritance for gene: PTS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2089 PTS Zornitza Stark changed review comment from: Well established gene-disease association.; to: Well established gene-disease association. Seizures are part of the phenotype.
Genetic Epilepsy v0.2089 PTPN23 Zornitza Stark Marked gene: PTPN23 as ready
Genetic Epilepsy v0.2089 PTPN23 Zornitza Stark Gene: ptpn23 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2089 PTPN23 Zornitza Stark Phenotypes for gene: PTPN23 were changed from to Neurodevelopmental disorder and structural brain anomalies with or without seizures and spasticity, MIM# 618890
Genetic Epilepsy v0.2088 PTPN23 Zornitza Stark Publications for gene: PTPN23 were set to
Genetic Epilepsy v0.2087 PTPN23 Zornitza Stark Mode of inheritance for gene: PTPN23 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2086 PSAP Zornitza Stark Marked gene: PSAP as ready
Genetic Epilepsy v0.2086 PSAP Zornitza Stark Gene: psap has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2086 PSAP Zornitza Stark Phenotypes for gene: PSAP were changed from to Combined SAP deficiency, MIM# 611721; Encephalopathy due to prosaposin deficiency, MONDO:0012719; Krabbe disease, atypical, MIM# 611722; MONDO:0012720; Metachromatic leukodystrophy due to SAP-b deficiency, MIM# 249900; MONDO:0009590; Gaucher disease, atypical, MIM# 610539; MONDO:0012517
Genetic Epilepsy v0.2085 PSAP Zornitza Stark Publications for gene: PSAP were set to
Genetic Epilepsy v0.2084 PSAP Zornitza Stark Mode of inheritance for gene: PSAP was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genetic Epilepsy v0.2083 PRODH Zornitza Stark Marked gene: PRODH as ready
Genetic Epilepsy v0.2083 PRODH Zornitza Stark Gene: prodh has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2083 PRODH Zornitza Stark Phenotypes for gene: PRODH were changed from to Hyperprolinemia, type I, MIM# 239500; Proline oxidase deficiency
Genetic Epilepsy v0.2082 PRODH Zornitza Stark Publications for gene: PRODH were set to
Genetic Epilepsy v0.2081 PRODH Zornitza Stark Mode of inheritance for gene: PRODH was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2080 PRODH Zornitza Stark changed review comment from: At least 5 unrelated families reported.
Sources: Expert list; to: At least 5 unrelated families reported. Epilepsy is part of the phenotype.
Sources: Expert list
Genetic Epilepsy v0.2080 PRICKLE1 Zornitza Stark Marked gene: PRICKLE1 as ready
Genetic Epilepsy v0.2080 PRICKLE1 Zornitza Stark Gene: prickle1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2080 PRICKLE1 Zornitza Stark Phenotypes for gene: PRICKLE1 were changed from to Epilepsy, progressive myoclonic 1B, MIM# 612437
Genetic Epilepsy v0.2079 PRICKLE1 Zornitza Stark Publications for gene: PRICKLE1 were set to
Genetic Epilepsy v0.2078 PRICKLE1 Zornitza Stark Mode of inheritance for gene: PRICKLE1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genetic Epilepsy v0.2077 PPP3CA Zornitza Stark Marked gene: PPP3CA as ready
Genetic Epilepsy v0.2077 PPP3CA Zornitza Stark Gene: ppp3ca has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2077 PPP3CA Zornitza Stark Publications for gene: PPP3CA were set to
Genetic Epilepsy v0.2076 PPP3CA Zornitza Stark Phenotypes for gene: PPP3CA were changed from Developmental and epileptic encephalopathy 91, MIM#617711 to Developmental and epileptic encephalopathy 91, MIM#617711
Genetic Epilepsy v0.2075 PPP3CA Zornitza Stark Phenotypes for gene: PPP3CA were changed from to Developmental and epileptic encephalopathy 91, MIM#617711
Genetic Epilepsy v0.2075 PPP3CA Zornitza Stark Mode of inheritance for gene: PPP3CA was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2074 PPT1 Zornitza Stark Marked gene: PPT1 as ready
Genetic Epilepsy v0.2074 PPT1 Zornitza Stark Gene: ppt1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2074 PPT1 Zornitza Stark Phenotypes for gene: PPT1 were changed from to Ceroid lipofuscinosis, neuronal, 1, MIM# 256730; MONDO:0009744
Genetic Epilepsy v0.2073 PPT1 Zornitza Stark Publications for gene: PPT1 were set to
Genetic Epilepsy v0.2072 PPT1 Zornitza Stark Mode of inheritance for gene: PPT1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2071 PPT1 Zornitza Stark changed review comment from: Well established gene-disease association. Variable age of onset and severity.; to: Well established gene-disease association. Variable age of onset and severity Seizures are part of the phenotype.
Genetic Epilepsy v0.2071 FAM50A Zornitza Stark changed review comment from: Lee et al (2020 - PMID: 32703943) provide evidence that Armfield X-Linked intellectual disability syndrome is caused by monoallelic FAM50A pathogenic variants. The current review is based only on this reference. The authors provide clinical details on 6 affected individuals from 5 families. Features included postnatal growth delay, DD and ID (6/6 - also evident for those without formal IQ assesment), seizures (3/6 from 2 families), prominent forehead with presence of other facial features and variable head circumference (5th to >97th %le), ocular anomalies (5/6 - strabismus/nystagmus/Axenfeld-Rieger), cardiac (3/6 - ASD/Fallot) and genitourinary anomalies (3/6). In the first of these families (Armfield et al 1999 - PMID: 10398235), linkage analysis followed by additional studies (Sanger, NGS of 718 genes on chrX, X-exome NGS - several refs provided) allowed the identification of a FAM50A variant. Variants in other families were identified by singleton (1 fam) or trio-ES (3 fam). In affected individuals from 3 families, the variant had occurred de novo. Carrier females in the other families were unaffected (based on pedigrees and/or the original publication). XCI was rather biased in most obligate carrier females from the 1st family (although this ranged from 95:5 to 60:40). Missense variants were reported in all affected subjects incl. Trp206Gly, Asp255Gly, Asp255Asn (dn), Glu254Gly (dn), Arg273Trp (dn) (NM_004699.3). Previous studies have demonstrated that FAM50A has ubiquitous expression in human fetal and adult tissues (incl. brain in fetal ones). Immunostaining suggests a nuclear localization for the protein (NIH/3T3 cells). Comparison of protein levels in LCLs from affected males and controls did not demonstrate significant differences. Protein localization for 3 variants (transfection of COS-7 cells) was shown to be similar to wt. Complementation studies in zebrafish provided evidence that the identified variants confer partial loss of function (rescue of the morpholino phenotype with co-injection of wt but not mt mRNA). The zebrafish ko model seemed to recapitulate the abnormal development of cephalic structures and was indicative of diminished/defective neurogenesis. Transcriptional dysregulation was demonstrated in zebrafish (altered levels and mis-splicing). Upregulation of spliceosome effectors was demonstrated in ko zebrafish. Similarly, mRNA expression and splicing defects were demonstrated in LCLs from affected individuals. FAM50A pulldown followed by mass spectrometry in transfected HEK293T cells demonstrated enrichment of binding proteins involved in RNA processing and co-immunoprecipitation assays (transfected U-87 cells) suggested that FAM50A interacts with spliceosome U5 and C-complex proteins. Overall aberrant spliceosome C-complex function is suggested as the underlying pathogenetic mechanism. Several other neurodevelopmental syndromes are caused by variants in genes encoding C-complex affiliated proteins (incl. EFTUD2, EIF4A3, THOC2, etc.).
Sources: Literature; to: Lee et al (2020 - PMID: 32703943) 6 affected individuals from 5 families.

Seizures in 3/6 from 2 families.
Genetic Epilepsy v0.2071 FAM50A Zornitza Stark edited their review of gene: FAM50A: Changed rating: AMBER
Genetic Epilepsy v0.2071 HNRNPK Zornitza Stark Marked gene: HNRNPK as ready
Genetic Epilepsy v0.2071 HNRNPK Zornitza Stark Gene: hnrnpk has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2071 HNRNPK Zornitza Stark Classified gene: HNRNPK as Amber List (moderate evidence)
Genetic Epilepsy v0.2071 HNRNPK Zornitza Stark Gene: hnrnpk has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2070 HNRNPK Zornitza Stark gene: HNRNPK was added
gene: HNRNPK was added to Genetic Epilepsy. Sources: Expert list
Mode of inheritance for gene: HNRNPK was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HNRNPK were set to 30998304; 26173930; 29904177; 26954065; 28771707
Phenotypes for gene: HNRNPK were set to Au-Kline syndrome MIM#616580
Review for gene: HNRNPK was set to AMBER
Added comment: Seizures are reported in a minority of individuals affected by Au-Kline syndrome.
Sources: Expert list
Genetic Epilepsy v0.2069 HIVEP2 Zornitza Stark Marked gene: HIVEP2 as ready
Genetic Epilepsy v0.2069 HIVEP2 Zornitza Stark Gene: hivep2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2069 HIVEP2 Zornitza Stark Classified gene: HIVEP2 as Green List (high evidence)
Genetic Epilepsy v0.2069 HIVEP2 Zornitza Stark Gene: hivep2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2068 HIVEP2 Zornitza Stark gene: HIVEP2 was added
gene: HIVEP2 was added to Genetic Epilepsy. Sources: Expert list
Mode of inheritance for gene: HIVEP2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HIVEP2 were set to 27003583
Phenotypes for gene: HIVEP2 were set to Intellectual developmental disorder, autosomal dominant 43, MIM# 616977
Review for gene: HIVEP2 was set to GREEN
Added comment: Seizures reported in at least 3 affected individuals.
Sources: Expert list
Genetic Epilepsy v0.2067 HDAC8 Zornitza Stark Marked gene: HDAC8 as ready
Genetic Epilepsy v0.2067 HDAC8 Zornitza Stark Gene: hdac8 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2067 HDAC8 Zornitza Stark Classified gene: HDAC8 as Amber List (moderate evidence)
Genetic Epilepsy v0.2067 HDAC8 Zornitza Stark Gene: hdac8 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2066 HDAC8 Zornitza Stark gene: HDAC8 was added
gene: HDAC8 was added to Genetic Epilepsy. Sources: Expert list
Mode of inheritance for gene: HDAC8 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Phenotypes for gene: HDAC8 were set to Cornelia de Lange syndrome 5, MIM# 300882
Review for gene: HDAC8 was set to AMBER
Added comment: Seizures reported in 25% of individuals with CdL though what proportion of individuals with HDAC8-related disease have seizures is uncertain.
Sources: Expert list
Mitochondrial disease v0.910 AFG3L2 Zornitza Stark Marked gene: AFG3L2 as ready
Mitochondrial disease v0.910 AFG3L2 Zornitza Stark Gene: afg3l2 has been classified as Green List (High Evidence).
Mitochondrial disease v0.910 AFG3L2 Zornitza Stark Phenotypes for gene: AFG3L2 were changed from Spastic ataxia 5, autosomal recessive (MIM#614487); Spinocerebellar ataxia 28 (MIM#610246); Optic atrophy 12, MIM# 618977 to Spastic ataxia 5, autosomal recessive (MIM#614487); Spinocerebellar ataxia 28 (MIM#610246); Optic atrophy 12, MIM# 618977
Mitochondrial disease v0.909 AFG3L2 Zornitza Stark Phenotypes for gene: AFG3L2 were changed from to Spastic ataxia 5, autosomal recessive (MIM#614487); Spinocerebellar ataxia 28 (MIM#610246); Optic atrophy 12, MIM# 618977
Mitochondrial disease v0.908 AFG3L2 Zornitza Stark Publications for gene: AFG3L2 were set to
Mitochondrial disease v0.907 AFG3L2 Zornitza Stark Mode of inheritance for gene: AFG3L2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genetic Epilepsy v0.2065 GRIA1 Zornitza Stark Marked gene: GRIA1 as ready
Genetic Epilepsy v0.2065 GRIA1 Zornitza Stark Gene: gria1 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2065 GRIA1 Zornitza Stark gene: GRIA1 was added
gene: GRIA1 was added to Genetic Epilepsy. Sources: Expert list
Mode of inheritance for gene: GRIA1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: GRIA1 were set to 35675825
Phenotypes for gene: GRIA1 were set to Intellectual developmental disorder, autosomal dominant 67, MIM# 619927; Intellectual developmental disorder, autosomal recessive 76, MIM# 619931
Review for gene: GRIA1 was set to RED
Added comment: RED/AMBER for the bi-allelic association: single family reported.

Recurrent missense for the mono-allelic association. However phenotype was predominantly ID. Seizures in one individual only.
Sources: Expert list
Prepair 1000+ v1.4 GPT2 Zornitza Stark Phenotypes for gene: GPT2 were changed from Mental retardation, autosomal recessive 49, 616281 (3) to Neurodevelopmental disorder with microcephaly and spastic paraplegia, MIM# 616281
Hereditary Spastic Paraplegia - paediatric v1.72 GPT2 Zornitza Stark Phenotypes for gene: GPT2 were changed from Mental retardation, autosomal recessive 49 MIM#616281 to Neurodevelopmental disorder with microcephaly and spastic paraplegia, MIM# 616281
Intellectual disability syndromic and non-syndromic v0.5652 GPT2 Zornitza Stark Phenotypes for gene: GPT2 were changed from Mental retardation, autosomal recessive 49, MIM#616281 to Neurodevelopmental disorder with microcephaly and spastic paraplegia, MIM# 616281
Microcephaly v1.245 GPT2 Zornitza Stark Phenotypes for gene: GPT2 were changed from Mental retardation, autosomal recessive 49, MIM#616281 to Neurodevelopmental disorder with microcephaly and spastic paraplegia, MIM# 616281
Microcephaly v1.244 GPT2 Zornitza Stark edited their review of gene: GPT2: Changed phenotypes: Neurodevelopmental disorder with microcephaly and spastic paraplegia, MIM# 616281
Mendeliome v1.1447 GPT2 Zornitza Stark Phenotypes for gene: GPT2 were changed from Mental retardation, autosomal recessive 49, MIM#616281 to Neurodevelopmental disorder with microcephaly and spastic paraplegia, MIM# 616281
Genetic Epilepsy v0.2064 GPT2 Zornitza Stark Marked gene: GPT2 as ready
Genetic Epilepsy v0.2064 GPT2 Zornitza Stark Gene: gpt2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2064 GPT2 Zornitza Stark Classified gene: GPT2 as Green List (high evidence)
Genetic Epilepsy v0.2064 GPT2 Zornitza Stark Gene: gpt2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2063 GPT2 Zornitza Stark gene: GPT2 was added
gene: GPT2 was added to Genetic Epilepsy. Sources: Expert list
Mode of inheritance for gene: GPT2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GPT2 were set to 27601654; 25758935; 31471722
Phenotypes for gene: GPT2 were set to Neurodevelopmental disorder with microcephaly and spastic paraplegia, MIM# 616281
Review for gene: GPT2 was set to GREEN
Added comment: 10 families reported. Typically presents with ID, HSP and microcephaly but seizures reported in some.
Sources: Expert list
Mendeliome v1.1446 GPT2 Zornitza Stark edited their review of gene: GPT2: Added comment: 10 families reported.; Changed publications: 27601654, 25758935, 31471722
Mendeliome v1.1446 GPT2 Zornitza Stark edited their review of gene: GPT2: Changed phenotypes: Neurodevelopmental disorder with microcephaly and spastic paraplegia, MIM# 616281
Genetic Epilepsy v0.2062 GPSM2 Zornitza Stark Marked gene: GPSM2 as ready
Genetic Epilepsy v0.2062 GPSM2 Zornitza Stark Gene: gpsm2 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2062 GPSM2 Zornitza Stark Classified gene: GPSM2 as Amber List (moderate evidence)
Genetic Epilepsy v0.2062 GPSM2 Zornitza Stark Gene: gpsm2 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2061 GPSM2 Zornitza Stark gene: GPSM2 was added
gene: GPSM2 was added to Genetic Epilepsy. Sources: Expert list
Mode of inheritance for gene: GPSM2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GPSM2 were set to 20602914; 22578326; 28387217; 27180139; 27064331
Phenotypes for gene: GPSM2 were set to Chudley-McCullough syndrome, MIM# 604213
Review for gene: GPSM2 was set to AMBER
Added comment: Chudley-McCullough syndrome is an autosomal recessive neurologic disorder characterized by early-onset sensorineural deafness and specific brain anomalies on MRI, including hypoplasia of the corpus callosum, enlarged cysterna magna with mild focal cerebellar dysplasia, and nodular heterotopia/PMG. Some individuals have hydrocephalus. Development is generally normal. Over 10 families reported, supportive functional data.

Seizures reported but rare.
Sources: Expert list
Genetic Epilepsy v0.2060 NAGA Rylee Peters reviewed gene: NAGA: Rating: RED; Mode of pathogenicity: None; Publications: 8782044, 31468281, 15619430, 31890708, 11313741; Phenotypes: Kanzaki disease, MIM# 609242, Schindler disease, type I and type II 609241; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2060 NR2F1 Rylee Peters gene: NR2F1 was added
gene: NR2F1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: NR2F1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NR2F1 were set to 32275123
Phenotypes for gene: NR2F1 were set to Bosch-Boonstra-Schaaf optic atrophy syndrome, MIM# 615722
Review for gene: NR2F1 was set to GREEN
Added comment: PMID: 32275123
- Cohort of 54 individuals with a deletion of or likely pathogenic variant in NR2F1, including previously published individuals with Bosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS).
-24/46 (52%) individuals described with seizures, some of which include infantile spasms.
- Rech et al. (2020) also described that mutations in the DBD were associated with a higher prevalence of motor delay, the inability to walk unassisted, the absence of speech, seizures, and sensitivity to touch compared to other types of mutations.
Sources: Literature
Genetic Epilepsy v0.2060 NF1 Rylee Peters changed review comment from: Seizures occur in about 5% of individuals with NF1, with a slightly higher prevalence in adults than in children (PMIDs: 32613422, 34944956).

PMID: 34944956 - Cohort of NF1 patients; Epilepsy was reported in 37/784 cases. 24/37 individuals with NF1 and epilepsy had an NF1 mutation, 1 individual was negative (NGS+MLPA), remaining 12 individuals were not tested.
Sources: Literature; to: Seizures occur in about 5% of individuals with NF1, with a slightly higher prevalence in adults than in children (PMIDs: 32613422, 34944956, GeneReviews).

PMID: 34944956 - Cohort of NF1 patients; Epilepsy was reported in 37/784 cases. 24/37 individuals with NF1 and epilepsy had an NF1 mutation, 1 individual was negative (NGS+MLPA), remaining 12 individuals were not tested.
Sources: Literature
Genetic Epilepsy v0.2060 NF1 Rylee Peters gene: NF1 was added
gene: NF1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: NF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NF1 were set to 34944956
Phenotypes for gene: NF1 were set to Neurofibromatosis, type 1 (MIM#162200)
Review for gene: NF1 was set to RED
Added comment: Seizures occur in about 5% of individuals with NF1, with a slightly higher prevalence in adults than in children (PMIDs: 32613422, 34944956).

PMID: 34944956 - Cohort of NF1 patients; Epilepsy was reported in 37/784 cases. 24/37 individuals with NF1 and epilepsy had an NF1 mutation, 1 individual was negative (NGS+MLPA), remaining 12 individuals were not tested.
Sources: Literature
Genetic Epilepsy v0.2060 NALCN Rylee Peters gene: NALCN was added
gene: NALCN was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: NALCN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NALCN were set to 30167850
Phenotypes for gene: NALCN were set to Hypotonia, infantile, with psychomotor retardation and characteristic facies 1 (MIM#615419)
Review for gene: NALCN was set to GREEN
Added comment: PMID: 30167850
– Cohort of individuals with novel NALCN or UNC80 variants; includes 16 individuals with biallelic NALCN variants and 1 individual with a de novo NALCN variant.
- All individuals (16/16) with biallelic NALCN variants presented with neonatal hypotonia, failure to thrive, ID, and muscular hypotonia. Other clinical features include severe ID (14/16), nonverbal (14/16), non-walking (13/16), chronic constipation (14/16), extrapyramidal/abnormal movements (12/16), strabismus (12/16), sleeping difficulties (10/16), increased tendency to infections (9/16), and some individuals presented with seizures (7/16).
- Table 1 describes clinical features of individuals with biallelic NALCN variants, showing 13/19 previously published individuals also had seizures.
Sources: Literature
Genetic Epilepsy v0.2060 MCM3AP Rylee Peters gene: MCM3AP was added
gene: MCM3AP was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: MCM3AP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MCM3AP were set to 32202298
Phenotypes for gene: MCM3AP were set to Peripheral neuropathy, autosomal recessive, with or without impaired intellectual development (MIM#618124)
Review for gene: MCM3AP was set to RED
Added comment: - 2 families with probands compound heterozygous for variants in MCM3AP and a phenotype consistent with peripheral neuropathy with or without impaired intellectual development (MIM#618124).
- Two siblings from one family have severe generalised epilepsy and mild spastic diplegia.
- Functional studies using skin fibroblasts from these and other affected patients showed that disease variants result in depletion of GANP (encoded by MCM3AP) except when they alter critical residues in the Sac3 mRNA binding domain. GANP depletion was associated with more severe phenotypes compared with the Sac3 variants.
Sources: Literature
Genetic Epilepsy v0.2060 LRPPRC Rylee Peters gene: LRPPRC was added
gene: LRPPRC was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: LRPPRC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LRPPRC were set to 21266382; 26510951; 38046674; 29152527
Phenotypes for gene: LRPPRC were set to Mitochondrial complex IV deficiency, nuclear type 5, (French-Canadian) (MIM#220111)
Review for gene: LRPPRC was set to AMBER
Added comment: PMID: 21266382
- Cohort of patients with French-Canadian Leigh disease (MIM#220111). 55 of 56 patients were homozygous for the A354V mutation in LRPPRC.
- Condition is distinct for metabolic crises. 6/44 affected patients experienced seizures.
- During presentation of metabolic crises, 5 patients presented seizures. During neurological crises, 9 patients presented seizures.
- 10 patients were living at the time of the study and have had a stable clinical course (since puberty), with mild ID and seizures (3/6 patients).

PMID: 26510951
- 10 individuals (7 unrelated families) with recessive LRPPRC variants (identified via WES and candidate gene sequencing) with phenotypes resembling French-Canadian Leigh syndrome patients.
- 1/10 patients compound heterozygous for premature termination variants, experienced several brief generalised seizures and developed a severe encephalopathy and persistent metabolic acidosis.
- Functional characterisation of patients' fibroblasts and skeletal muscle homogenates (homozygous p.Arg1276_Lys1300del and compound heterozygous p.Glu497*; p.Gly1050Argfs*4 individuals) showed decreased levels of mutant LRPPRC protein and impaired Complex IV enzyme activity, associated with abnormal COX assembly and reduced steady-state levels of numerous oxidative phosphorylation subunits.

PMID: 38046674
- Case report; 1 individual with novel homozygous splice donor variant (c.469+2T>A) in LRPPRC causing Leigh syndrome with epilepsy. Parents are consanguineous and are unaffected carriers. The affected child had intrauterine developmental delays, absence of the corpus callosum and was suspected of exhibiting neurodevelopmental disorder, specifically experiencing seizures.

PMID: 29152527
- 1 individual with novel compound heterozygous missense variants with mild French-Canadian Type Leigh Syndrome. Developed refractory multifocal epilepsy at 3 years of age requiring multiple antiepileptics and ketogenic diet to control his seizures.
Sources: Literature
Genetic Epilepsy v0.2060 LMNB1 Rylee Peters reviewed gene: LMNB1: Rating: AMBER; Mode of pathogenicity: None; Publications: 32910914, 33033404; Phenotypes: Microcephaly 26, primary, autosomal dominant (MIM#619179); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2060 LETM1 Rylee Peters reviewed gene: LETM1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 36055214; Phenotypes: Mitochondrial disease MONDO#0044970, LETM1-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2060 PEX10 Lauren Rogers gene: PEX10 was added
gene: PEX10 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: PEX10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PEX10 were set to 32069232
Phenotypes for gene: PEX10 were set to Peroxisome biogenesis disorder 6A (Zellweger), MIM#614870
Review for gene: PEX10 was set to RED
Added comment: PMID: 32069232: A case report of a 4 month old boy with Zellweger syndrome, with myoclonic seizures, hypotonia and hepatosplenomegaly, who was homozygous for a p.(C296F) variant.
Sources: Literature
Genetic Epilepsy v0.2060 PCLO Lauren Rogers gene: PCLO was added
gene: PCLO was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: PCLO was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PCLO were set to 25832664; 32122952
Phenotypes for gene: PCLO were set to Pontocerebellar hypoplasia, type 3, MIM#608027
Review for gene: PCLO was set to RED
Added comment: PMID: 25832664: Seizures are part of the phenotype, but a single consanguineous family reported with bi-allelic variant in this gene.

PMID: 32122952: Knockout PCLO rats had a smaller cerebral cortex, a reduced volume of the cerebellum and pons, as well as impaired motor control and the presence of seizures BUT they don’t talk about seizures in the results, only introduction and discussion
Sources: Literature
Genetic Epilepsy v0.2060 PEX13 Lauren Rogers gene: PEX13 was added
gene: PEX13 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: PEX13 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PEX13 were set to 19449432; 37962062; 34055681; 37962062; 30919572; 33547378; 35854306
Phenotypes for gene: PEX13 were set to Peroxisome biogenesis disorder 11A (Zellweger)
Review for gene: PEX13 was set to GREEN
Added comment: PMID: 19449432: 2x unrelated Saudi children of consanguineous parents with Zellweger syndrome. Both children had seizures alongside other features of Zellweger and died young. One patient had a homozygous deletion (147,308 bp) encompassing the entire PEX3 gene and the other had a homozygous p.(G36DfsX61) variant.

PMID: 37962062: A consanguineous patient had severe hypotonia, seizures, hepatic dysfunction, failure to thrive, and dysmorphic features. They had a homozygous p.(Ala165Pro) variant and died at 14 months.

PMID: 34055681: An individual with global developmental delay, focal seizures, peritrigonal white matter disease and thinning corpus callosum with a homozygous p.(Met1Val) variant.

PMID: 37962062: 1x individual with hypotonia, seizures, developmental delay and suspicious abnormal signal in the bilateral basal ganglia with a homozygous p.(A165P) variant.

PMID: 30919572: 1x individual with developmental delay and seizures, cerebral atrophy and white matter volume loss. Homozygous for a p.(G23R) variant.

PMID: 33547378: 1x individual with a homozygous p.(K177del) variant with motor regression, seizure at 2 months, digestive problems, hypotonia, hypodontia, abnormal white matter and demyelination.

PMID: 35854306: 1x individual with a homozygous p.(W313*) variant with phycomotor delay, motor impairments, intellectual disability, language impairment and seizures, cortical malformations.
Sources: Literature
Genetic Epilepsy v0.2060 PAX6 Lauren Rogers gene: PAX6 was added
gene: PAX6 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: PAX6 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PAX6 were set to 34200146; 17417613; 12731001
Phenotypes for gene: PAX6 were set to Aniridia (MIM#106210)
Review for gene: PAX6 was set to AMBER
Added comment: PMID: 34200146: A case report of 1x male born with anophthalmia, who underwent hypoglycemic seizures starting at 5 months old, and showed a prediabetic condition at 60 months. They were heterozygous for a p.(S63C) variant.

PMID: 17417613: in a cohort of 78 individuals affected by aniridia; those with diverse ocular manifestations; and those with Peters' anomaly, and unaffected relatives. 1 large family with congenital ocular abnormalities, 14/36 had a PAX6 p.(S74G) variant. Most affected patients of this family had minor or major bilateral foveal hypoplasia. At least four individuals of this family had epilepsy, while others displayed variable neurological deficits along with severe cognitive deficiencies.

PMID: 12731001: In a cohort of 24 individuals with ocular abnormalities and defined PAX6 variants, 4x individuals with a single or recurrent unprovoked seizures. 1x individual had isolated unilateral polymicrogyria with a C-terminal extension, gave a history of frequent complex partial seizures compatible with temporal lobe epilepsy. Variant was inherited from mother who had a subtle gyral abnormality of the left temporal lobe, most probably polymicrogyria but she did not give a history of seizure. For the other patients it is not clear which are associated with the epilepsy patients.
Sources: Literature
Genetic Epilepsy v0.2060 PAK3 Lauren Rogers gene: PAK3 was added
gene: PAK3 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: PAK3 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: PAK3 were set to 17853471; 12884430; 29246092; 25666757
Phenotypes for gene: PAK3 were set to Intellectual developmental disorder, X-linked 30 (MIM#300558)
Review for gene: PAK3 was set to AMBER
Added comment: PMID: 17853471: Report of 1 family with intellectual disability (5 affected males and 4 carrier females), EEG was reported for 4 affected males and 1 carrier female; only one had epilepsy, another individual had one seizure but no epileptic discharges on EEG. The familial variant in affected males and carrier females was p.(W446S).

PMID: 12884430: In an Australian multigenerational family with mild to borderline non-syndromic X-linked intellectual disability, 1/13 affected males had myoclonic epilepsy. The familial variant in affected males and carrier females was p.(A365E) determined via linkage analysis.

PMID: 29246092: A case report of one individual with intellectual disability, severe auto-mutilation and epilepsy had a p.(Ser527Gly) variant.

PMID: 25666757: In a cohort of 183 individuals with cerebral palsy, 1 male individual had hemiplegic cerebral palsy and epilepsy and showed cognitive abilities in the upper limit of the low average range. They had a PAK3 p.(R493C) variant.
Sources: Literature
Genetic Epilepsy v0.2060 OFD1 Lauren Rogers gene: OFD1 was added
gene: OFD1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: OFD1 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: OFD1 were set to 23033313; 31373179
Phenotypes for gene: OFD1 were set to Orofaciodigital syndrome I (MIM#311200)
Review for gene: OFD1 was set to AMBER
Added comment: PMID: 23033313: Cohort of 25 with OFD1 variants with orofaciodigital syndrome I. 4/25 had epilepsy. One female individual had a p.(His50Alafs*2) variant, the other variants it is not clear which were associated with the epilepsy patients.

PMID: 31373179: In a cohort of 3 males with primary ciliary dyskinesia, 1 individual had seizures, dysmorphic features, intellectual disability, minimally verbal and minimally able to ambulate, chronic cerebral atrophy, hypotonia, and apnea. He had a de novo hemizygous p.(Glu995*) variant.
Sources: Literature
Mendeliome v1.1446 POLD1 Zornitza Stark Phenotypes for gene: POLD1 were changed from Mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome, MIM# 615381; MONDO:0014157 to Mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome, MIM# 615381; MONDO:0014157; Combined immunodeficiency, MONDO:0015131, POLD1-related
Combined Immunodeficiency v1.59 POLD1 Zornitza Stark Publications for gene: POLD1 were set to 31629014
Mendeliome v1.1445 POLD1 Zornitza Stark Publications for gene: POLD1 were set to 23770608; 33618333; 33369179; 32826474; 30023403; 29199204; 28791128
Mendeliome v1.1444 POLD1 Zornitza Stark Mode of inheritance for gene: POLD1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.1443 POLD1 Zornitza Stark edited their review of gene: POLD1: Added comment: Association with combined immunodeficiency: Three individuals from two generations of a consanguineous family reported, some functional data. Another unrelated individual reported in PMID 31449058, more functional data. Third family identified in Melbourne, two affected sibs, compound het variants and combined immunodeficiency.; Changed phenotypes: Mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome, MIM# 615381, MONDO:0014157, Combined immunodeficiency, MONDO:0015131, POLD1-related; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Combined Immunodeficiency v1.58 POLD1 Zornitza Stark Phenotypes for gene: POLD1 were changed from Low CD4 T cells; Low B cells, normal maturation; recurrent respiratory tract infections, skin infections, warts and molluscum; short stature; intellectual disability to Combined immunodeficiency, MONDO:0015131, POLD1-related; Low CD4 T cells; Low B cells, normal maturation; recurrent respiratory tract infections, skin infections, warts and molluscum; short stature; intellectual disability
Combined Immunodeficiency v1.57 POLD1 Zornitza Stark Classified gene: POLD1 as Green List (high evidence)
Combined Immunodeficiency v1.57 POLD1 Zornitza Stark Gene: pold1 has been classified as Green List (High Evidence).
Combined Immunodeficiency v1.56 POLD1 Zornitza Stark edited their review of gene: POLD1: Added comment: Another family identified in Melbourne: two affected siblings with compound heterozygous variants and combined immunodeficiency.; Changed rating: GREEN
Genetic Epilepsy v0.2060 PTCH1 Elena Savva Marked gene: PTCH1 as ready
Genetic Epilepsy v0.2060 PTCH1 Elena Savva Gene: ptch1 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2060 PTCH1 Elena Savva Classified gene: PTCH1 as Red List (low evidence)
Genetic Epilepsy v0.2060 PTCH1 Elena Savva Gene: ptch1 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2059 PTCH1 Belinda Chong gene: PTCH1 was added
gene: PTCH1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: PTCH1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PTCH1 were set to 11941477; 17001668; 29575684; 36171624
Phenotypes for gene: PTCH1 were set to Holoprosencephaly 7, MIM# 610828
Review for gene: PTCH1 was set to RED
Added comment: Currently red for this panel.

PMID: 11941477 - In a female with holoprosencephaly, seizures, and bilateral cleft lip, a heterozygous c.2467A>G variant was identified in the PTCH gene. However, this variant is classified as benign in ClinVar.

PMID: 36171624 - A 10-month-old Chinese female patient with mobility disorders on the right limbs and recurrent seizures. Epidermal nevus syndrome was diagnosed, the patient also has a de novo mutation (c.109G > T) in PTCH1 gene and cerebral infarction.
Sources: Literature
Genetic Epilepsy v0.2059 CTU2 Zornitza Stark Marked gene: CTU2 as ready
Genetic Epilepsy v0.2059 CTU2 Zornitza Stark Gene: ctu2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2059 CTU2 Zornitza Stark Classified gene: CTU2 as Green List (high evidence)
Genetic Epilepsy v0.2059 CTU2 Zornitza Stark Gene: ctu2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2058 CYP27A1 Zornitza Stark Marked gene: CYP27A1 as ready
Genetic Epilepsy v0.2058 CYP27A1 Zornitza Stark Gene: cyp27a1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2058 CYP27A1 Zornitza Stark Classified gene: CYP27A1 as Green List (high evidence)
Genetic Epilepsy v0.2058 CYP27A1 Zornitza Stark Gene: cyp27a1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2057 DAG1 Zornitza Stark Marked gene: DAG1 as ready
Genetic Epilepsy v0.2057 DAG1 Zornitza Stark Gene: dag1 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2057 DAG1 Zornitza Stark Classified gene: DAG1 as Red List (low evidence)
Genetic Epilepsy v0.2057 DAG1 Zornitza Stark Gene: dag1 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2057 DAG1 Zornitza Stark Classified gene: DAG1 as Red List (low evidence)
Genetic Epilepsy v0.2057 DAG1 Zornitza Stark Gene: dag1 has been classified as Red List (Low Evidence).
Mendeliome v1.1443 LCK Zornitza Stark Classified gene: LCK as Green List (high evidence)
Mendeliome v1.1443 LCK Zornitza Stark Gene: lck has been classified as Green List (High Evidence).
Mendeliome v1.1442 LCK Zornitza Stark edited their review of gene: LCK: Added comment: Additional cases:
PMID 38100037: Description of a second unrelated patient with novel biallelic missense LCK c.1393T>C, p.C465R variant in a patient from a consanguineous Syrian family with profound T-cell immune deficiency characterized by complete LCK protein expression deficiency and ensuing proximal TCR signaling-and CD4 and CD8-co-receptor-mediated functional and phenotypical defects.

PMID: 27087313 reported 3 siblings of a consanguineous family presenting with recurrent pneumonia and severe viral skin disease leading to malignant transformation. The patients had an intronic LCK c.188-2A>G splice site variant resulting in skipping of exon 3 and mRNA decay. Clinical data alongside with CD4+ T-cell lymphocytopenia suggested a hypomorphic LCK deficiency.; Changed rating: GREEN; Changed publications: 22985903, 1579166, 11021796, 27087313, 38100037
Combined Immunodeficiency v1.56 LCK Zornitza Stark Publications for gene: LCK were set to 22985903; 1579166; 11021796
Combined Immunodeficiency v1.55 LCK Zornitza Stark Classified gene: LCK as Green List (high evidence)
Combined Immunodeficiency v1.55 LCK Zornitza Stark Gene: lck has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5651 RAP1GDS1 Zornitza Stark Phenotypes for gene: RAP1GDS1 were changed from Intellectual disability; dysmorphic features to Alfadhel syndrome, MIM# 620655
Intellectual disability syndromic and non-syndromic v0.5650 RAP1GDS1 Zornitza Stark edited their review of gene: RAP1GDS1: Changed phenotypes: Alfadhel syndrome, MIM# 620655
Mendeliome v1.1442 RAP1GDS1 Zornitza Stark Phenotypes for gene: RAP1GDS1 were changed from Intellectual disability; dysmorphic features to Alfadhel syndrome, MIM# 620655
Mendeliome v1.1441 RAP1GDS1 Zornitza Stark edited their review of gene: RAP1GDS1: Changed phenotypes: Alfadhel syndrome, MIM# 620655
Fetal anomalies v1.173 CASP2 Zornitza Stark Phenotypes for gene: CASP2 were changed from neurodevelopmental disorder MONDO:0700092, CASP2-related to Intellectual developmental disorder, autosomal recessive 80, with variant lissencephaly, MIM# 620653
Fetal anomalies v1.172 CASP2 Zornitza Stark edited their review of gene: CASP2: Changed phenotypes: Intellectual developmental disorder, autosomal recessive 80, with variant lissencephaly, MIM# 620653
Intellectual disability syndromic and non-syndromic v0.5650 CASP2 Zornitza Stark Phenotypes for gene: CASP2 were changed from neurodevelopmental disorder MONDO:0700092, CASP2-related to Intellectual developmental disorder, autosomal recessive 80, with variant lissencephaly, MIM# 620653
Intellectual disability syndromic and non-syndromic v0.5649 CASP2 Zornitza Stark reviewed gene: CASP2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Intellectual developmental disorder, autosomal recessive 80, with variant lissencephaly, MIM# 620653; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1441 CASP2 Zornitza Stark Phenotypes for gene: CASP2 were changed from neurodevelopmental disorder MONDO:0700092, CASP2-related to Intellectual developmental disorder, autosomal recessive 80, with variant lissencephaly, MIM# 620653
Mendeliome v1.1440 CASP2 Zornitza Stark reviewed gene: CASP2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Intellectual developmental disorder, autosomal recessive 80, with variant lissencephaly, MIM# 620653; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Lissencephaly and Band Heterotopia v1.19 CASP2 Zornitza Stark Phenotypes for gene: CASP2 were changed from neurodevelopmental disorder MONDO:0700092, CASP2-related to Intellectual developmental disorder, autosomal recessive 80, with variant lissencephaly, MIM# 620653
Lissencephaly and Band Heterotopia v1.18 CASP2 Zornitza Stark reviewed gene: CASP2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Intellectual developmental disorder, autosomal recessive 80, with variant lissencephaly, MIM# 620653; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Combined Immunodeficiency v1.54 LCK Peter McNaughton reviewed gene: LCK: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38100037, PMID: 27087313; Phenotypes: Combined Immune deficiency; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1440 RBFOX1 Zornitza Stark Phenotypes for gene: RBFOX1 were changed from Intellectual disability; autism to Neurodevelopmental disorder (MONDO:0700092), RBFOX1-related
Mendeliome v1.1439 RBFOX1 Zornitza Stark Publications for gene: RBFOX1 were set to 24664471
Mendeliome v1.1438 RBFOX1 Zornitza Stark Classified gene: RBFOX1 as Green List (high evidence)
Mendeliome v1.1438 RBFOX1 Zornitza Stark Gene: rbfox1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2056 RBFOX1 Zornitza Stark Marked gene: RBFOX1 as ready
Genetic Epilepsy v0.2056 RBFOX1 Zornitza Stark Gene: rbfox1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2056 RBFOX1 Zornitza Stark Classified gene: RBFOX1 as Green List (high evidence)
Genetic Epilepsy v0.2056 RBFOX1 Zornitza Stark Gene: rbfox1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2055 DAG1 Andrew Fennell gene: DAG1 was added
gene: DAG1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: DAG1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DAG1 were set to PMID: 24052401; 25934851; 30450679
Phenotypes for gene: DAG1 were set to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 9; Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 9, 613818; Walker-Warburg syndrome and tectocerebellar dysgraphia
Review for gene: DAG1 was set to RED
Added comment: Only 7 individuals reported with MDDGA9 and none had seizures. MDDGC9 phenotype is related to limb-girdle dystrophy and also has no association with seizures.
Sources: Literature
Genetic Epilepsy v0.2055 CYP27A1 Andrew Fennell gene: CYP27A1 was added
gene: CYP27A1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: CYP27A1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CYP27A1 were set to PMID: 16816916; 20301583; 22658436
Phenotypes for gene: CYP27A1 were set to Cerebrotendinous xanthomatosis MIM#213700; Disorders of bile acid biosynthesis
Review for gene: CYP27A1 was set to GREEN
Added comment: PMID: 16816916 - Approximately 50% of CTX patients reported to have seizures in older literature.

PMID: 20301583 - GeneReviews quotes seizures are present in 33% of cases.

PMID 22336472, 22658436, 33414089 - Multiple single case reports of individuals with seizures onset earlier in the disease process ranging from 2.5yo to 12yo.
Sources: Literature
Genetic Epilepsy v0.2055 CTU2 Andrew Fennell gene: CTU2 was added
gene: CTU2 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: CTU2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CTU2 were set to PMID: 27480277; 33559988
Phenotypes for gene: CTU2 were set to Microcephaly, facial dysmorphism, renal agenesis, and ambiguous genitalia syndrome, MIM#618142
Review for gene: CTU2 was set to GREEN
Added comment: PMID: 33559988 - 6 individuals from 5 different families (2 individuals previously reported in PMID 27480277) with DREAM-PL reported to have seizures. The age of onset ranges from birth to 9yo.
Sources: Literature
Genetic Epilepsy v0.2055 GMPPB Zornitza Stark Marked gene: GMPPB as ready
Genetic Epilepsy v0.2055 GMPPB Zornitza Stark Gene: gmppb has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2055 GMPPB Zornitza Stark Classified gene: GMPPB as Green List (high evidence)
Genetic Epilepsy v0.2055 GMPPB Zornitza Stark Gene: gmppb has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2054 GMPPB Zornitza Stark gene: GMPPB was added
gene: GMPPB was added to Genetic Epilepsy. Sources: Expert list
Mode of inheritance for gene: GMPPB was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GMPPB were set to 30257713
Phenotypes for gene: GMPPB were set to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 14 615350
Review for gene: GMPPB was set to GREEN
Added comment: Established gene-disease association, spectrum of severity. Seizures reported as part of the severe end of the spectrum.
Sources: Expert list
Genetic Epilepsy v0.2053 GMPPA Zornitza Stark Marked gene: GMPPA as ready
Genetic Epilepsy v0.2053 GMPPA Zornitza Stark Gene: gmppa has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2053 GMPPA Zornitza Stark Classified gene: GMPPA as Amber List (moderate evidence)
Genetic Epilepsy v0.2053 GMPPA Zornitza Stark Gene: gmppa has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2053 GMPPA Zornitza Stark Classified gene: GMPPA as Amber List (moderate evidence)
Genetic Epilepsy v0.2053 GMPPA Zornitza Stark Gene: gmppa has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2052 GMPPA Zornitza Stark gene: GMPPA was added
gene: GMPPA was added to Genetic Epilepsy. Sources: Expert list
Mode of inheritance for gene: GMPPA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GMPPA were set to 24035193; 28574218
Phenotypes for gene: GMPPA were set to Alacrima, achalasia, and mental retardation syndrome (MIM# 615510)
Review for gene: GMPPA was set to AMBER
Added comment: 10 families reported, of which one had seizures.
Sources: Expert list
Genetic Epilepsy v0.2051 GABRA4 Zornitza Stark Publications for gene: GABRA4 were set to 35152403
Genetic Epilepsy v0.2050 GABRA4 Zornitza Stark edited their review of gene: GABRA4: Changed publications: 35152403, 35781801
Genetic Epilepsy v0.2050 DARS2 Zornitza Stark Publications for gene: DARS2 were set to 17384640; 15002045; 16788019; 30352563
Genetic Epilepsy v0.2049 DARS2 Zornitza Stark Classified gene: DARS2 as Amber List (moderate evidence)
Genetic Epilepsy v0.2049 DARS2 Zornitza Stark Gene: dars2 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2048 CRADD Zornitza Stark Classified gene: CRADD as Green List (high evidence)
Genetic Epilepsy v0.2048 CRADD Zornitza Stark Gene: cradd has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2047 CRADD Zornitza Stark reviewed gene: CRADD: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Intellectual developmental disorder, autosomal recessive 34, with variant lissencephaly, MIM# 614499; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2047 ISPD Zornitza Stark Publications for gene: ISPD were set to
Genetic Epilepsy v0.2046 ISPD Zornitza Stark Classified gene: ISPD as Green List (high evidence)
Genetic Epilepsy v0.2046 ISPD Zornitza Stark Gene: ispd has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2045 CTSF Zornitza Stark Marked gene: CTSF as ready
Genetic Epilepsy v0.2045 CTSF Zornitza Stark Gene: ctsf has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2045 CTSF Elena Savva Phenotypes for gene: CTSF were changed from Ceroid lipofuscinosis, neuronal, 13 (Kufs type) MIM#615362 to Ceroid lipofuscinosis, neuronal, 13 (Kufs type) MIM#615362
Genetic Epilepsy v0.2044 CTSF Elena Savva Phenotypes for gene: CTSF were changed from to Ceroid lipofuscinosis, neuronal, 13 (Kufs type) MIM#615362
Genetic Epilepsy v0.2044 CTSF Elena Savva Classified gene: CTSF as Green List (high evidence)
Genetic Epilepsy v0.2044 CTSF Elena Savva Gene: ctsf has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2043 CRADD Elena Savva Classified gene: CRADD as Amber List (moderate evidence)
Genetic Epilepsy v0.2043 CRADD Elena Savva Gene: cradd has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2043 CSNK2A1 Elena Savva Classified gene: CSNK2A1 as Green List (high evidence)
Genetic Epilepsy v0.2043 CSNK2A1 Elena Savva Gene: csnk2a1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2042 CSNK2A1 Elena Savva Classified gene: CSNK2A1 as Green List (high evidence)
Genetic Epilepsy v0.2042 CSNK2A1 Elena Savva Gene: csnk2a1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2041 CSNK2A1 Elena Savva Marked gene: CSNK2A1 as ready
Genetic Epilepsy v0.2041 CSNK2A1 Elena Savva Gene: csnk2a1 has been removed from the panel.
Genetic Epilepsy v0.2041 CRADD Elena Savva Classified gene: CRADD as Amber List (moderate evidence)
Genetic Epilepsy v0.2041 CRADD Elena Savva Gene: cradd has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2040 CRADD Elena Savva Marked gene: CRADD as ready
Genetic Epilepsy v0.2040 CRADD Elena Savva Gene: cradd has been removed from the panel.
Genetic Epilepsy v0.2040 CPT2 Elena Savva Marked gene: CPT2 as ready
Genetic Epilepsy v0.2040 CPT2 Elena Savva Gene: cpt2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2040 CPT2 Elena Savva Classified gene: CPT2 as Green List (high evidence)
Genetic Epilepsy v0.2040 CPT2 Elena Savva Gene: cpt2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2040 CSF1R Elena Savva Classified gene: CSF1R as Green List (high evidence)
Genetic Epilepsy v0.2040 CSF1R Elena Savva Gene: csf1r has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2039 CSF1R Elena Savva Mode of pathogenicity for gene: CSF1R was changed from None to None
Genetic Epilepsy v0.2039 CSF1R Elena Savva Classified gene: CSF1R as Green List (high evidence)
Genetic Epilepsy v0.2039 CSF1R Elena Savva Gene: csf1r has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2038 CSF1R Elena Savva Marked gene: CSF1R as ready
Genetic Epilepsy v0.2038 CSF1R Elena Savva Gene: csf1r has been removed from the panel.
Genetic Epilepsy v0.2038 CTSF Andrew Fennell gene: CTSF was added
gene: CTSF was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: CTSF was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CTSF were set to PMID: 23297359; 25274848; 27668283; 27524508; 35139754
Review for gene: CTSF was set to GREEN
Added comment: PMID: 23297359 - Four affected individuals from three different families all with seizures of varying types and frequency (two in family Ku4, one in family Ku10, one in family Ku16).

PMID: 25274848 - 5/6 affected individuals from a single family presented with tonic-clonic seizures as a first manifestation of their disease aged 21-66 years. All progressed to dementia. All were homozygous for c.213+1G>C.

PMID: 27668283 - 1/4 affected siblings, presented with myoclonic seizures at 35yo.

PMID: 27524508 - single report of 39yo female with chronic psychosis and new seizures.
Sources: Literature
Genetic Epilepsy v0.2038 CSNK2A1 Andrew Fennell gene: CSNK2A1 was added
gene: CSNK2A1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: CSNK2A1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CSNK2A1 were set to PMID: 35679446; 36588763
Phenotypes for gene: CSNK2A1 were set to Okur-Chung neurodevelopmental syndrome, MIM# 617062
Review for gene: CSNK2A1 was set to GREEN
Added comment: PMID 36588763 - Review of previously reported cases noted 9/31 (29%) individuals with Okur-Chung neurodevelopmental syndrome reported to have seizures.

PMID: 35679446 - GeneReviews article includes seizures among the more common features of the disorder, present in 11/36 cases reported to date. No specific type of seizure has been noted. Intractable seizures are reported in some individuals while only one case status has been reported.
Sources: Literature
Anophthalmia_Microphthalmia_Coloboma v1.37 FZD5 Elena Savva Phenotypes for gene: FZD5 were changed from Coloboma to Coloboma (MONDO:0001476), FZD5-related
Genetic Epilepsy v0.2038 CSF1R Andrew Fennell gene: CSF1R was added
gene: CSF1R was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: CSF1R was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: CSF1R were set to PMID: 22197934; 24336230; 30982608; 30982609
Phenotypes for gene: CSF1R were set to Brain abnormalities, neurodegeneration, and dysosteosclerosis, (MIM#618476)
Review for gene: CSF1R was set to GREEN
Added comment: Monoallelic disease is onset in 3rd or 4th decades whereas biallelic disease is associated with early-onset disease in infancy or childhood.

Monoallelic association:
PMID: 22197934 - 13/23 individuals from 9 different families reported to have seizures.
PMID: 24336230 - 2/7 individuals with seizures reported from a Japanese cohort.

Biallelic association:
PMID: 30982608 - Two individuals with a seizure history. First was an infant who presented with prenatal structural brain abnormalities, including ACC, ventriculomegaly, and pontocerebellar hypoplasia, and died at 10 months had intractable epilepsy. Second individuals presented with generalized tonic-clonic seizures aged 12 years old associated with regression and loss of all skills.

PMID: 30982609 - Two individuals with seizures were reported from a cohort of 7 individuals. A-III-1 was a male infant who developed seizures in early infancy (after 3 months of age). Individual C-III-4 was a male who developed focal seizures in early infancy.
Sources: Literature
Genetic Epilepsy v0.2038 ISPD Andrew Fennell reviewed gene: ISPD: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 24120487, 35863218; Phenotypes: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7 614643, Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 7 616052; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2038 CRADD Andrew Fennell gene: CRADD was added
gene: CRADD was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: CRADD was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CRADD were set to PMID: 27773430; 30914828
Phenotypes for gene: CRADD were set to Intellectual developmental disorder, autosomal recessive 34, with variant lissencephaly, MIM# 614499
Review for gene: CRADD was set to AMBER
Added comment: PMID: 27773430 - 3/13 individuals with IDD34 were reported to have seizures.

PMID: 30914828 - 2/22 individuals with a Finnish founder mutation were reported to have seizures
Sources: Literature
Genetic Epilepsy v0.2038 CPT2 Andrew Fennell gene: CPT2 was added
gene: CPT2 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: CPT2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CPT2 were set to PMID: 20301431; 35028265; 36478999
Phenotypes for gene: CPT2 were set to CPT II deficiency, infantile 600649; CPT II deficiency, lethal neonatal 608836; CPT II deficiency, myopathic, stress-induced 255110
Review for gene: CPT2 was set to GREEN
Added comment: GeneReviews quotes seizures as a core component of the phenotype in lethal neonatal and severe infantile forms of the disorder.

PMID: 36478999 - single report of a 10yo male with CPT2 who developed focal seizures during an acute episode.

PMID: 35028265 - single report of a male who presented at 5 months of age with infantile‐onset carnitine palmitoyltransferase 2 (CPT2) deficiency. He also had X‐linked nephrogenic diabetes insipidus. He developed focal seizures at 17yo.
Sources: Literature
Genetic Epilepsy v0.2038 DARS2 Andrew Fennell reviewed gene: DARS2: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 34104671; Phenotypes: Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation, MIM# 611105; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v1.244 BRD4 Zornitza Stark Phenotypes for gene: BRD4 were changed from Cornelia de Lange-like syndrome, MONDO:0016033 to Cornelia de Lange syndrome 6, MIM# 620568
Microcephaly v1.243 BRD4 Zornitza Stark edited their review of gene: BRD4: Changed phenotypes: Cornelia de Lange syndrome 6, MIM# 620568
Mendeliome v1.1437 BRD4 Zornitza Stark Phenotypes for gene: BRD4 were changed from Cornelia de Lange syndrome, MONDO:0016033 to Cornelia de Lange syndrome 6, MIM# 620568
Mendeliome v1.1436 BRD4 Zornitza Stark edited their review of gene: BRD4: Changed phenotypes: Cornelia de Lange syndrome 6, MIM# 620568
Hypertrichosis syndromes v0.44 BRD4 Zornitza Stark Phenotypes for gene: BRD4 were changed from Cornelia de Lange syndrome, MONDO:0016033 to Cornelia de Lange syndrome 6, MIM# 620568
Hypertrichosis syndromes v0.43 BRD4 Zornitza Stark edited their review of gene: BRD4: Changed phenotypes: Cornelia de Lange syndrome 6, MIM# 620568
Genetic Epilepsy v0.2038 ALG12 Zornitza Stark Marked gene: ALG12 as ready
Genetic Epilepsy v0.2038 ALG12 Zornitza Stark Gene: alg12 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2038 ALG12 Zornitza Stark Classified gene: ALG12 as Red List (low evidence)
Genetic Epilepsy v0.2038 ALG12 Zornitza Stark Gene: alg12 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2037 ASXL3 Zornitza Stark Classified gene: ASXL3 as Green List (high evidence)
Genetic Epilepsy v0.2037 ASXL3 Zornitza Stark Gene: asxl3 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2037 ASXL3 Zornitza Stark Marked gene: ASXL3 as ready
Genetic Epilepsy v0.2037 ASXL3 Zornitza Stark Gene: asxl3 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2037 ASXL3 Zornitza Stark Classified gene: ASXL3 as Green List (high evidence)
Genetic Epilepsy v0.2037 ASXL3 Zornitza Stark Gene: asxl3 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2036 ABCA2 John Coleman reviewed gene: ABCA2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 37777370, 30237576, 29302074, 31047799; Phenotypes: Intellectual developmental disorder with poor growth and with or without seizures or ataxia, OMIM 618808; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2036 TRAPPC2L Zornitza Stark Publications for gene: TRAPPC2L were set to 30120216; 32843486
Genetic Epilepsy v0.2035 TMEM163 Zornitza Stark Publications for gene: TMEM163 were set to PMID: 35953447
Genetic Epilepsy v0.2034 BICD2 Zornitza Stark Marked gene: BICD2 as ready
Genetic Epilepsy v0.2034 BICD2 Zornitza Stark Gene: bicd2 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2034 BICD2 Zornitza Stark Phenotypes for gene: BICD2 were changed from spinal muscular atrophy MONDO:0001516 to Neurodevelopmental disorder, BICD2-related (MONDO#0700092)
Genetic Epilepsy v0.2033 BICD2 Zornitza Stark Classified gene: BICD2 as Amber List (moderate evidence)
Genetic Epilepsy v0.2033 BICD2 Zornitza Stark Gene: bicd2 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2032 BCKDK Zornitza Stark Marked gene: BCKDK as ready
Genetic Epilepsy v0.2032 BCKDK Zornitza Stark Gene: bckdk has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2032 BCKDK Zornitza Stark Classified gene: BCKDK as Green List (high evidence)
Genetic Epilepsy v0.2032 BCKDK Zornitza Stark Gene: bckdk has been classified as Green List (High Evidence).
Inflammatory bowel disease v0.112 DUOX2 Zornitza Stark Mode of inheritance for gene: DUOX2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Inflammatory bowel disease v0.111 DUOX2 Zornitza Stark Classified gene: DUOX2 as Green List (high evidence)
Inflammatory bowel disease v0.111 DUOX2 Zornitza Stark Gene: duox2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2031 B4GAT1 Zornitza Stark Marked gene: B4GAT1 as ready
Genetic Epilepsy v0.2031 B4GAT1 Zornitza Stark Gene: b4gat1 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2031 B4GAT1 Zornitza Stark Classified gene: B4GAT1 as Amber List (moderate evidence)
Genetic Epilepsy v0.2031 B4GAT1 Zornitza Stark Gene: b4gat1 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2030 B3GALNT2 Zornitza Stark Marked gene: B3GALNT2 as ready
Genetic Epilepsy v0.2030 B3GALNT2 Zornitza Stark Gene: b3galnt2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2030 B3GALNT2 Zornitza Stark Classified gene: B3GALNT2 as Green List (high evidence)
Genetic Epilepsy v0.2030 B3GALNT2 Zornitza Stark Gene: b3galnt2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2029 PRUNE1 Zornitza Stark Marked gene: PRUNE1 as ready
Genetic Epilepsy v0.2029 PRUNE1 Zornitza Stark Gene: prune1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2029 PRUNE1 Zornitza Stark Classified gene: PRUNE1 as Green List (high evidence)
Genetic Epilepsy v0.2029 PRUNE1 Zornitza Stark Gene: prune1 has been classified as Green List (High Evidence).
Bone Marrow Failure v1.79 RPS15A Zornitza Stark Marked gene: RPS15A as ready
Bone Marrow Failure v1.79 RPS15A Zornitza Stark Gene: rps15a has been classified as Red List (Low Evidence).
Bone Marrow Failure v1.79 RPL35 Zornitza Stark Marked gene: RPL35 as ready
Bone Marrow Failure v1.79 RPL35 Zornitza Stark Gene: rpl35 has been classified as Red List (Low Evidence).
Bone Marrow Failure v1.79 RPS28 Zornitza Stark Marked gene: RPS28 as ready
Bone Marrow Failure v1.79 RPS28 Zornitza Stark Gene: rps28 has been classified as Amber List (Moderate Evidence).
Bone Marrow Failure v1.79 RPL8 Zornitza Stark Marked gene: RPL8 as ready
Bone Marrow Failure v1.79 RPL8 Zornitza Stark Gene: rpl8 has been classified as Amber List (Moderate Evidence).
Bone Marrow Failure v1.79 RPL18 Zornitza Stark Marked gene: RPL18 as ready
Bone Marrow Failure v1.79 RPL18 Zornitza Stark Gene: rpl18 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1436 MAP1LC3B2 Zornitza Stark Marked gene: MAP1LC3B2 as ready
Mendeliome v1.1436 MAP1LC3B2 Zornitza Stark Gene: map1lc3b2 has been classified as Red List (Low Evidence).
Mendeliome v1.1436 MAP1LC3B2 Zornitza Stark gene: MAP1LC3B2 was added
gene: MAP1LC3B2 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: MAP1LC3B2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAP1LC3B2 were set to 35748970; 33310865
Phenotypes for gene: MAP1LC3B2 were set to Hereditary susceptibility to infection, MONDO:0015979, MAP1LC3B2 -related; Mollaret’s meningitis (recurrent lymphocytic meningitis) due to HSV2
Review for gene: MAP1LC3B2 was set to RED
Added comment: PMID: 35748970 Affects CNS (resident cells and fibroblasts) Impaired autophagy induction after HSV2 infection - increased viral replication and apoptosis of patient fibroblasts.

PMID: 33310865 one affected individual with heterozygous variant in MAP1LC3B2 (p.L109M)
Sources: Expert Review
Defects of innate immunity v0.134 MAP1LC3B2 Zornitza Stark Marked gene: MAP1LC3B2 as ready
Defects of innate immunity v0.134 MAP1LC3B2 Zornitza Stark Gene: map1lc3b2 has been classified as Red List (Low Evidence).
Defects of innate immunity v0.134 MAP1LC3B2 Zornitza Stark Phenotypes for gene: MAP1LC3B2 were changed from Mollaret’s meningitis (recurrent lymphocytic meningitis) due to HSV2 to Hereditary susceptibility to infection, MONDO:0015979, MAP1LC3B2 -related; Mollaret’s meningitis (recurrent lymphocytic meningitis) due to HSV2
Defects of innate immunity v0.133 MAP1LC3B2 Zornitza Stark Classified gene: MAP1LC3B2 as Red List (low evidence)
Defects of innate immunity v0.133 MAP1LC3B2 Zornitza Stark Gene: map1lc3b2 has been classified as Red List (Low Evidence).
Bone Marrow Failure v1.79 TBXAS1 Zornitza Stark Marked gene: TBXAS1 as ready
Bone Marrow Failure v1.79 TBXAS1 Zornitza Stark Gene: tbxas1 has been classified as Green List (High Evidence).
Bone Marrow Failure v1.79 DNASE2 Zornitza Stark Marked gene: DNASE2 as ready
Bone Marrow Failure v1.79 DNASE2 Zornitza Stark Gene: dnase2 has been classified as Green List (High Evidence).
Bone Marrow Failure v1.79 MPIG6B Zornitza Stark Marked gene: MPIG6B as ready
Bone Marrow Failure v1.79 MPIG6B Zornitza Stark Gene: mpig6b has been classified as Green List (High Evidence).
Bone Marrow Failure v1.79 ACTB Zornitza Stark Marked gene: ACTB as ready
Bone Marrow Failure v1.79 ACTB Zornitza Stark Gene: actb has been classified as Green List (High Evidence).
Disorders of immune dysregulation v0.185 ELF4 Zornitza Stark Marked gene: ELF4 as ready
Disorders of immune dysregulation v0.185 ELF4 Zornitza Stark Gene: elf4 has been classified as Green List (High Evidence).
Disorders of immune dysregulation v0.185 ELF4 Zornitza Stark Classified gene: ELF4 as Green List (high evidence)
Disorders of immune dysregulation v0.185 ELF4 Zornitza Stark Gene: elf4 has been classified as Green List (High Evidence).
Bone Marrow Failure v1.79 TCN2 Zornitza Stark Marked gene: TCN2 as ready
Bone Marrow Failure v1.79 TCN2 Zornitza Stark Gene: tcn2 has been classified as Green List (High Evidence).
Bone Marrow Failure v1.79 NBN Zornitza Stark Marked gene: NBN as ready
Bone Marrow Failure v1.79 NBN Zornitza Stark Gene: nbn has been classified as Green List (High Evidence).
Systemic Autoinflammatory Disease_Periodic Fever v1.31 RNU7-1 Zornitza Stark Marked gene: RNU7-1 as ready
Systemic Autoinflammatory Disease_Periodic Fever v1.31 RNU7-1 Zornitza Stark Gene: rnu7-1 has been classified as Green List (High Evidence).
Systemic Autoinflammatory Disease_Periodic Fever v1.31 RNU7-1 Zornitza Stark Classified gene: RNU7-1 as Green List (high evidence)
Systemic Autoinflammatory Disease_Periodic Fever v1.31 RNU7-1 Zornitza Stark Gene: rnu7-1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2028 ALG12 John Coleman gene: ALG12 was added
gene: ALG12 was added to Genetic Epilepsy. Sources: NHS GMS,Literature
Mode of inheritance for gene: ALG12 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ALG12 were set to (PMID: 33618527)
Phenotypes for gene: ALG12 were set to CONGENITAL DISORDER OF GLYCOSYLATION, TYPE Ig; OMIM: 607144
Review for gene: ALG12 was set to RED
Added comment: Causes AR congenital disorder of gylcosolation type Ig. Listed as red list on panel app UK for Genetic Epilepsy. Epilepsy/ seizures not reported on OMIM phenotype. Seizure listed on Gene-reviews under CDG Ig however citations for this are linked to papers about CDG overall/ biochemical evidence rather than ALG12 variants. Pubmed search for "ALG12" and "epilepsy" shows no results. Search for "ALG12" and "seizure" linked to one paper only (PMID: 33618527), again only mention of seizure in this paper is related to CDGs in general and not a specific patient with ALG12/ CDG Type Ig. No established evidence of seizures or epilepsy in ALG12/ CDG type Ig phenotype.
Sources: NHS GMS, Literature
Genetic Epilepsy v0.2028 ASXL3 John Coleman gene: ASXL3 was added
gene: ASXL3 was added to Genetic Epilepsy. Sources: NHS GMS,ClinGen,Literature
Mode of inheritance for gene: ASXL3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ASXL3 were set to PMID:33151654; 34436830; 29367179
Phenotypes for gene: ASXL3 were set to Bainbridge-Ropers syndrome, OMIM:615115
Review for gene: ASXL3 was set to GREEN
Added comment: Listed as Green entity on panel app uk. De novo loss of function variants and dominant negative variants reported. 1/3rd of patients with epilepsy according to Clingen and Genereviews. 11/39 phenotyped patients in a large cohort (PMID: 34436830) had seizures. Various types - absence, GTC, onset in pediatric age group or adult. Generally treatment responsive. Some adults with intractable difficult to treat seizures. Smaller cohort of 3 unrelated individuals (29367179) with seizures, 2 had PTC variants and 1 patient had a splice variant.
Sources: NHS GMS, ClinGen, Literature
Genetic Epilepsy v0.2028 TRAPPC2L Belinda Chong reviewed gene: TRAPPC2L: Rating: RED; Mode of pathogenicity: None; Publications: 36849228, 30120216, 32843486; Phenotypes: Encephalopathy, progressive, early-onset, with episodic rhabdomyolysis, MIM#618331; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2028 TRA2B Belinda Chong reviewed gene: TRA2B: Rating: GREEN; Mode of pathogenicity: None; Publications: 36549593; Phenotypes: Neurodevelopmental disorder, TRA2B-related (MONDO#0700092); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Genetic Epilepsy v0.2028 TMEM163 Belinda Chong reviewed gene: TMEM163: Rating: GREEN; Mode of pathogenicity: None; Publications: 35455965, 35953447; Phenotypes: Leukodystrophy, hypomyelinating, 25 MIM#620243; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Genetic Epilepsy v0.2028 BICD2 Lilian Downie gene: BICD2 was added
gene: BICD2 was added to Genetic Epilepsy. Sources: Expert list
Mode of inheritance for gene: BICD2 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: BICD2 were set to PMID: 35896821, PMID: 28635954, PMID: 32057122, PMID: 25497877, PMID: 35338243
Phenotypes for gene: BICD2 were set to spinal muscular atrophy MONDO:0001516
Review for gene: BICD2 was set to AMBER
Added comment: mostly AD cases reported, new more severe presentation reported x2 with biallelic variants: seizures part of the AR phenotype in both cases

From the literature of AD SMA cases:
PMID: PMID: 32057122 2x patients from same family with seizures as part of the phenotype
PMID: 28635954 patient suspected clinically as having seizures but not proven
PMID: 25497877 large cohort (N=32 patients from 9 families) no seizures
Sources: Expert list
Genetic Epilepsy v0.2028 BCKDK Lilian Downie gene: BCKDK was added
gene: BCKDK was added to Genetic Epilepsy. Sources: Expert list
Mode of inheritance for gene: BCKDK was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BCKDK were set to PMID: 22956686, PMID: 35216372, PMID: 36729635
Phenotypes for gene: BCKDK were set to Branched-chain keto acid dehydrogenase kinase deficiency MIM#614923
Review for gene: BCKDK was set to GREEN
Added comment: Epilepsy well reported part of this phenotype
Sources: Expert list
Inflammatory bowel disease v0.110 DUOX2 Peter McNaughton edited their review of gene: DUOX2: Added comment: 1mo girl with IBD and colonic polyps with compound het variants c.2524C>T and c.3175C>T with functional studies showing decreased H2O2 generation.
This case along with previous case reports - PMID: 28683258 & PMID: 35429653 suggest that biallelic DUOX2 variants should be part of evaluation for VEO-IBD.; Changed rating: GREEN; Changed publications: PMID: 38075699; Changed phenotypes: neonatal onset IBD
Genetic Epilepsy v0.2028 B4GAT1 Lilian Downie gene: B4GAT1 was added
gene: B4GAT1 was added to Genetic Epilepsy. Sources: Expert list
Mode of inheritance for gene: B4GAT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: B4GAT1 were set to PMID 23877401, PMID: 23359570
Phenotypes for gene: B4GAT1 were set to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 13 MIM#615287
Review for gene: B4GAT1 was set to AMBER
Added comment: PMID 23877401 multiple family members affected, 1 with seizures
PMID: 23359570 affected 2yo with seizures
Sources: Expert list
Genetic Epilepsy v0.2028 B3GALNT2 Lilian Downie gene: B3GALNT2 was added
gene: B3GALNT2 was added to Genetic Epilepsy. Sources: Expert list
Mode of inheritance for gene: B3GALNT2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: B3GALNT2 were set to PMID: 29791932, PMID: 29273094, PMID: 35127920
Phenotypes for gene: B3GALNT2 were set to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 11 MIM#615181
Review for gene: B3GALNT2 was set to GREEN
Added comment: Severe congenital muscular dystrophy and ID phenotype. Seizures not consistent feature with early phenotypic reports
PMID: 29791932 epileptic encephalopathy
PMID: 29273094 5 individuals with ID and seizures from single large consanguineous family but they had no or mild muscle symptoms so quite different from previously reported phenotype
PMID: 35127920 not a great article but does have a table summarising the previous cases and 9/21 had seizures.
Sources: Expert list
Genetic Epilepsy v0.2028 PRUNE1 Chris Ciotta gene: PRUNE1 was added
gene: PRUNE1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: PRUNE1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PRUNE1 were set to PMID: 28334956; 26539891; 30556349; 29940663; 29797509
Phenotypes for gene: PRUNE1 were set to Neurodevelopmental disorder with microcephaly, hypotonia, and variable brain anomalies MIM#617481
Review for gene: PRUNE1 was set to GREEN
Added comment: PRUNE1 is associated with neurodevelopmental disorder with microcephaly, hypotonia and variable brain anomalies (MIM#617481). Seizures are a listed phenotype in OMIM in some patients.
- Seizures were seen in 6/13 individuals (PMID:28334956) from Oman, Iran, India and Italy, the variants identified in individuals with seizures were absent from gnomAD besides the commonly reported Asp109Asn variant (41 hets, 0 Homs in V4) which has also been extensively reported in ClinVar (10x pathogenic reports).
- Seizures were also reported in 7/9 Cree children from the Canadian province of Manitoba (PMID:30556349), they all shared a likely founder homozygous c.521-2A>G splicing variant. The normally spliced product was absent in RNA prepared from two individuals with exon 5 skipping or multiple exon skipping leading to a frameshift and premature termination observed as outcomes of this variant.
- Epilepsy was reported in 11/12 unrelated individuals (paediatric patients with neurological symptoms from Munich) with bi-allelic variants in PRUNE1 (PMID:29940663).
Sources: Literature
Bone Marrow Failure v1.79 RPS15A Chirag Patel gene: RPS15A was added
gene: RPS15A was added to Bone Marrow Failure. Sources: Expert list
Mode of inheritance for gene: RPS15A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RPS15A were set to PMID: 27909223
Phenotypes for gene: RPS15A were set to Diamond-Blackfan anemia 20, MIM# 618313
Review for gene: RPS15A was set to RED
Added comment: Single family reported.
Sources: Expert list
Bone Marrow Failure v1.78 RPL35 Chirag Patel gene: RPL35 was added
gene: RPL35 was added to Bone Marrow Failure. Sources: Expert list
Mode of inheritance for gene: RPL35 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RPL35 were set to PMID: 28280134
Phenotypes for gene: RPL35 were set to Diamond-Blackfan anemia 19, MIM# 618312
Review for gene: RPL35 was set to RED
Added comment: Single family reported.
Sources: Expert list
Bone Marrow Failure v1.77 RPS28 Chirag Patel Classified gene: RPS28 as Amber List (moderate evidence)
Bone Marrow Failure v1.77 RPS28 Chirag Patel Gene: rps28 has been classified as Amber List (Moderate Evidence).
Bone Marrow Failure v1.76 RPS28 Chirag Patel gene: RPS28 was added
gene: RPS28 was added to Bone Marrow Failure. Sources: Expert list
Mode of inheritance for gene: RPS28 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RPS28 were set to PMID: 24942156
Phenotypes for gene: RPS28 were set to Diamond Blackfan anemia 15 with mandibulofacial dysostosis, MIM# 606164
Review for gene: RPS28 was set to AMBER
Added comment: Two individuals reported in 2014, none since.
Sources: Expert list
Bone Marrow Failure v1.75 RPL8 Chirag Patel Classified gene: RPL8 as Amber List (moderate evidence)
Bone Marrow Failure v1.75 RPL8 Chirag Patel Gene: rpl8 has been classified as Amber List (Moderate Evidence).
Bone Marrow Failure v1.74 RPL8 Chirag Patel gene: RPL8 was added
gene: RPL8 was added to Bone Marrow Failure. Sources: Literature
Mode of inheritance for gene: RPL8 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RPL8 were set to PMID: 25424902, 34961992
Phenotypes for gene: RPL8 were set to Diamond-Blackfan anemia MONDO:0015253
Review for gene: RPL8 was set to AMBER
Added comment: 2 unrelated DBA cases with de novo missense variants, and functional studies in lymphoblastoid cells and yeast models demonstrate the 2 missense variants are functionally deficient proteins that affect ribosome production.
Sources: Literature
Bone Marrow Failure v1.73 RPL18 Chirag Patel Classified gene: RPL18 as Amber List (moderate evidence)
Bone Marrow Failure v1.73 RPL18 Chirag Patel Gene: rpl18 has been classified as Amber List (Moderate Evidence).
Bone Marrow Failure v1.72 RPL18 Chirag Patel gene: RPL18 was added
gene: RPL18 was added to Bone Marrow Failure. Sources: Expert list
Mode of inheritance for gene: RPL18 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RPL18 were set to PMID: 28280134, 32075953
Phenotypes for gene: RPL18 were set to Diamond-Blackfan anemia 18, MIM# 618310
Review for gene: RPL18 was set to AMBER
Added comment: One family and a zebrafish model.
Sources: Expert list
Defects of innate immunity v0.132 MAP1LC3B2 Sangavi Sivagnanasundram gene: MAP1LC3B2 was added
gene: MAP1LC3B2 was added to Defects of innate immunity. Sources: Other
Mode of inheritance for gene: MAP1LC3B2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAP1LC3B2 were set to 35748970; 33310865
Phenotypes for gene: MAP1LC3B2 were set to Mollaret’s meningitis (recurrent lymphocytic meningitis) due to HSV2
Review for gene: MAP1LC3B2 was set to RED
Added comment: Reviewed from PMID: 35748970

No published gene-disease association as of yet.

Affects CNS (resident cells and fibroblasts)
Impaired autophagy induction after HSV2 infection - increased viral replication and apoptosis of patient fibroblasts.

PMID: 33310865
one affected individual with heterozygous mutation in MAP1LC3B2 (p.L109M)
Sources: Other
Bone Marrow Failure v1.71 TBXAS1 Chirag Patel Classified gene: TBXAS1 as Green List (high evidence)
Bone Marrow Failure v1.71 TBXAS1 Chirag Patel Gene: tbxas1 has been classified as Green List (High Evidence).
Bone Marrow Failure v1.70 TBXAS1 Chirag Patel gene: TBXAS1 was added
gene: TBXAS1 was added to Bone Marrow Failure. Sources: Expert list
Mode of inheritance for gene: TBXAS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TBXAS1 were set to PMID: 18264100
Phenotypes for gene: TBXAS1 were set to Ghosal hematodiaphyseal syndrome, MIM#231095
Review for gene: TBXAS1 was set to GREEN
gene: TBXAS1 was marked as current diagnostic
Added comment: Ghosal hematodiaphyseal dysplasia (GHDD) is an autosomal recessive disorder characterized by increased bone density with predominant diaphyseal involvement and aregenerative corticosteroid-sensitive anemia. Cases with severe anemia, leukopenia, thrombocytopenia, and hypocellular bone marrow.
Sources: Expert list
Bone Marrow Failure v1.69 DNASE2 Chirag Patel Classified gene: DNASE2 as Green List (high evidence)
Bone Marrow Failure v1.69 DNASE2 Chirag Patel Gene: dnase2 has been classified as Green List (High Evidence).
Bone Marrow Failure v1.68 DNASE2 Chirag Patel gene: DNASE2 was added
gene: DNASE2 was added to Bone Marrow Failure. Sources: Expert list
Mode of inheritance for gene: DNASE2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DNASE2 were set to PMID: 29259162, 31775019
Phenotypes for gene: DNASE2 were set to Autoinflammatory-pancytopenia syndrome, MIM#619858
Review for gene: DNASE2 was set to GREEN
gene: DNASE2 was marked as current diagnostic
Added comment: Autoinflammatory-pancytopenia syndrome (AIPCS) is an autosomal recessive disorder characterized by severe anemia and thrombocytopenia apparent from early infancy, hepatosplenomegaly, and recurrent fevers associated with a hyperinflammatory state. Additional systemic features may include chronic diarrhea, proteinuria with renal disease, liver fibrosis with elevated liver enzymes, deforming arthropathy, and vasculitic skin lesions. Some patients may have motor delay or learning difficulties associated with subcortical white matter lesions on brain imaging.
Sources: Expert list
Bone Marrow Failure v1.67 MPIG6B Chirag Patel Classified gene: MPIG6B as Green List (high evidence)
Bone Marrow Failure v1.67 MPIG6B Chirag Patel Gene: mpig6b has been classified as Green List (High Evidence).
Bone Marrow Failure v1.66 MPIG6B Chirag Patel gene: MPIG6B was added
gene: MPIG6B was added to Bone Marrow Failure. Sources: Expert list
Mode of inheritance for gene: MPIG6B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MPIG6B were set to PMID: 31276734, 29898956, 27743390
Phenotypes for gene: MPIG6B were set to Thrombocytopenia, anemia, and myelofibrosis, MIM# 617441
Review for gene: MPIG6B was set to GREEN
gene: MPIG6B was marked as current diagnostic
Added comment: Six families reported.
Sources: Expert list
Bone Marrow Failure v1.65 ACTB Chirag Patel Classified gene: ACTB as Green List (high evidence)
Bone Marrow Failure v1.65 ACTB Chirag Patel Gene: actb has been classified as Green List (High Evidence).
Bone Marrow Failure v1.64 ACTB Chirag Patel gene: ACTB was added
gene: ACTB was added to Bone Marrow Failure. Sources: Expert list
Mode of inheritance for gene: ACTB was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ACTB were set to PMID: 30315159
Phenotypes for gene: ACTB were set to Thrombocytopenia 8, with dysmorphic features and developmental delay, MIM# 620475
Review for gene: ACTB was set to GREEN
gene: ACTB was marked as current diagnostic
Added comment: Six unrelated individuals reported with heterozygous variants clustered in the 3'-coding region of ACTB (exons 5 and 6) and clinical features distinct from BWCFF, including mild developmental disability, microcephaly, and thrombocytopenia with platelet anisotropy.
Sources: Expert list
Disorders of immune dysregulation v0.184 ELF4 Sangavi Sivagnanasundram gene: ELF4 was added
gene: ELF4 was added to Disorders of immune dysregulation. Sources: Other
Mode of inheritance for gene: ELF4 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: ELF4 were set to 34326534, 35266071; 35748970
Phenotypes for gene: ELF4 were set to Autoinflammatory syndrome, familial, X-linked, Behcet-like 2 (MIM#301074)
Review for gene: ELF4 was set to GREEN
Added comment: Reviewed according to PMID: 35748970

AIFBL2 is characterised by the onset of inflammatory symptoms in the first decade of life in males. Typically present with oral mucosal ulceration and skin inflammation however can present with decreased NK cells and low memory B cells.
Individuals typical have normal levels of serum IgM, G, A but reduced responses to live viral vaccines

Hemizygous mutations reported in at least 3 unrelated affected males with an autoinflammatory condition
Sources: Other
Bone Marrow Failure v1.63 TCN2 Chirag Patel Classified gene: TCN2 as Green List (high evidence)
Bone Marrow Failure v1.63 TCN2 Chirag Patel Gene: tcn2 has been classified as Green List (High Evidence).
Bone Marrow Failure v1.63 TCN2 Chirag Patel Classified gene: TCN2 as Green List (high evidence)
Bone Marrow Failure v1.63 TCN2 Chirag Patel Gene: tcn2 has been classified as Green List (High Evidence).
Bone Marrow Failure v1.62 TCN2 Chirag Patel gene: TCN2 was added
gene: TCN2 was added to Bone Marrow Failure. Sources: Expert list
Mode of inheritance for gene: TCN2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TCN2 were set to PMID: 24305960, 7980584, 7849710, 20352340, 18956254, 32841161, 33023511, 30124850
Phenotypes for gene: TCN2 were set to Transcobalamin II deficiency, MIM#275350
Review for gene: TCN2 was set to GREEN
gene: TCN2 was marked as current diagnostic
Added comment: 26 pathogenic TCN2 variants have been reported in over 40 individuals; Bi-allelic (deletions, insertions, nonsense, mutations) variants have been reported; multiple mouse models

Transcobalamin II deficiency is characterised by early onset (infancy) failure to thrive, megaloblastic anaemia, immunodeficiency and pancytopaenia. Other features include methylmalonic aciduria, recurrent infections, hypogammaglobulinaemia, pallor, hypotonia and vomiting and diarrhoea. Treatment with cobalamin (B12) may be of clinical benefit, but left untreated may result in intellectual disability and neurologic abnormalities.
Sources: Expert list
Bone Marrow Failure v1.61 NBN Chirag Patel Classified gene: NBN as Green List (high evidence)
Bone Marrow Failure v1.61 NBN Chirag Patel Gene: nbn has been classified as Green List (High Evidence).
Bone Marrow Failure v1.60 NBN Chirag Patel gene: NBN was added
gene: NBN was added to Bone Marrow Failure. Sources: Expert list
Mode of inheritance for gene: NBN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NBN were set to PMID: 11325820, 15338273, 33488600, 33082212
Phenotypes for gene: NBN were set to Nijmegen breakage syndrome, MIM#251260; Aplastic anemia, MIM#609135; Leukemia, acute lymphoblastic, MIM#613065
Review for gene: NBN was set to GREEN
gene: NBN was marked as current diagnostic
Added comment: The Nijmegen breakage syndrome and the phenotypically indistinguishable Berlin breakage syndrome are autosomal recessive chromosomal instability syndromes characterized by microcephaly, growth retardation, immunodeficiency, and predisposition to cancer. >100 patients reported.
Sources: Expert list
Systemic Autoinflammatory Disease_Periodic Fever v1.30 RNU7-1 Sangavi Sivagnanasundram gene: RNU7-1 was added
gene: RNU7-1 was added to Systemic Autoinflammatory Disease_Periodic Fever. Sources: Other
Mode of inheritance for gene: RNU7-1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RNU7-1 were set to 33230297; 35748970
Phenotypes for gene: RNU7-1 were set to Aicardi-Goutieres syndrome 9 (MIM#619487)
Review for gene: RNU7-1 was set to GREEN
Added comment: Reviewed from PMID: 35748970

Aicardi-Goutieres syndrome 9 (AGS9) is a type I interferonopathy typically caused by compound heterozygous mutations in RNU7-1

PubMed: 33230297
16 individuals from 11 families with AGS - all affected individuals had typical clinical features of AGS (elevated interferon score).
RT-PCR functional assay on patient and control fibroblasts were conducted that showed a loss of function mechanism of disease.
Sources: Other
Genetic Epilepsy v0.2028 NDUFV2 Lauren Rogers reviewed gene: NDUFV2: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Mitochondrial complex I deficiency, nuclear type 7 - MIM#618229; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2028 NDUFA8 Lauren Rogers reviewed gene: NDUFA8: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Mitochondrial complex I deficiency, nuclear type 37 - 619272, Epilepsy, Microcephaly, Developmental Delay; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2028 NAT8L Lauren Rogers reviewed gene: NAT8L: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: N-acetylaspartate deficiency - MIM#614063; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2028 OSTC Lauren Rogers reviewed gene: OSTC: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Oligosaccharyltransferase complex-congenital disorders of glycosylation; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2028 STX1A Zornitza Stark Publications for gene: STX1A were set to
Genetic Epilepsy v0.2027 ATP5E Zornitza Stark Marked gene: ATP5E as ready
Genetic Epilepsy v0.2027 ATP5E Zornitza Stark Gene: atp5e has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2027 ATP5E Zornitza Stark Classified gene: ATP5E as Amber List (moderate evidence)
Genetic Epilepsy v0.2027 ATP5E Zornitza Stark Gene: atp5e has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2026 ATP5G3 Zornitza Stark Marked gene: ATP5G3 as ready
Genetic Epilepsy v0.2026 ATP5G3 Zornitza Stark Gene: atp5g3 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2026 ATP5G3 Zornitza Stark Classified gene: ATP5G3 as Red List (low evidence)
Genetic Epilepsy v0.2026 ATP5G3 Zornitza Stark Gene: atp5g3 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2025 ATP5G3 Zornitza Stark edited their review of gene: ATP5G3: Changed publications: 34954817
Genetic Epilepsy v0.2025 ATP5G3 Zornitza Stark reviewed gene: ATP5G3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Dystonia, early-onset, and/or spastic paraplegia MIM#619681; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2025 ATP5O Zornitza Stark Tag new gene name tag was added to gene: ATP5O.
Genetic Epilepsy v0.2025 AUTS2 Zornitza Stark Marked gene: AUTS2 as ready
Genetic Epilepsy v0.2025 AUTS2 Zornitza Stark Gene: auts2 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2025 AUTS2 Zornitza Stark Classified gene: AUTS2 as Red List (low evidence)
Genetic Epilepsy v0.2025 AUTS2 Zornitza Stark Gene: auts2 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2024 SYNCRIP Zornitza Stark Phenotypes for gene: SYNCRIP were changed from Global developmental delay; Intellectual disability; Autism; Myoclonic atonic seizures; Abnormality of nervous system morphology to Neurodevelopmental disorder, MONDO:0700092, SYNCRIP-related; Global developmental delay; Intellectual disability; Autism; Myoclonic atonic seizures; Abnormality of nervous system morphology
Genetic Epilepsy v0.2023 CPT1A Zornitza Stark Publications for gene: CPT1A were set to 12189492; 33565078
Genetic Epilepsy v0.2022 CPT1A Zornitza Stark Classified gene: CPT1A as Green List (high evidence)
Genetic Epilepsy v0.2022 CPT1A Zornitza Stark Gene: cpt1a has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2021 CWF19L1 Zornitza Stark Publications for gene: CWF19L1 were set to 33012273
Genetic Epilepsy v0.2020 CWF19L1 Zornitza Stark Classified gene: CWF19L1 as Green List (high evidence)
Genetic Epilepsy v0.2020 CWF19L1 Zornitza Stark Gene: cwf19l1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2019 CWF19L1 Andrew Fennell reviewed gene: CWF19L1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 36453471, 37752213; Phenotypes: Spinocerebellar ataxia, autosomal recessive 17, MIM# 616127; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2019 CPT1A Andrew Fennell reviewed gene: CPT1A: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 34869124, 20696606; Phenotypes: CPT deficiency, hepatic, type IA, MIM# 255120; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2019 TCEAL1 Belinda Chong reviewed gene: TCEAL1: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 36368327; Phenotypes: Neurodevelopmental disorder with gait disturbance, dysmorphic facies and behavioral abnormalities, X-linked, MIM# 301094; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Genetic Epilepsy v0.2019 SYNCRIP Belinda Chong reviewed gene: SYNCRIP: Rating: AMBER; Mode of pathogenicity: None; Publications: 34157790, 30504930, 27479843, 23020937; Phenotypes: Global developmental delay, Intellectual disability, Autism, Myoclonic atonic seizures, Abnormality of nervous system morphology; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Genetic Epilepsy v0.2019 SV2B Belinda Chong reviewed gene: SV2B: Rating: RED; Mode of pathogenicity: None; Publications: 23617838, 23937191; Phenotypes: seizures; Mode of inheritance: Unknown
Genetic Epilepsy v0.2019 AUTS2 Lilian Downie gene: AUTS2 was added
gene: AUTS2 was added to Genetic Epilepsy. Sources: Expert list
Mode of inheritance for gene: AUTS2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: AUTS2 were set to PMID: 34573342, PMID: 33346930, PMID: 27075013, PMID: 23332918, PMID: 12160723
Phenotypes for gene: AUTS2 were set to Intellectual developmental disorder, autosomal dominant 26 MIM#615834
Review for gene: AUTS2 was set to RED
Added comment: PMID: 33346930 1 patient with epilepsy
PMID: 12160723 gene discovery paper with twins epilepsy was a feature as per description in PMID: 23332918 but the actual paper doesn't describe seizures.
Seizures are not part of the phenotype in the other reported cases.
Sources: Expert list
Genetic Epilepsy v0.2019 ATP5O Lilian Downie reviewed gene: ATP5O: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 35621276, 34954817; Phenotypes: Mitochondrial complex V (ATP synthase) deficiency, nuclear type 7, MIM# 620359; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2019 ATP5G3 Lilian Downie gene: ATP5G3 was added
gene: ATP5G3 was added to Genetic Epilepsy. Sources: Expert list
Mode of inheritance for gene: ATP5G3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ATP5G3 were set to PMIDS: 34636445, 34954817
Phenotypes for gene: ATP5G3 were set to Dystonia, early-onset, and/or spastic paraplegia MIM#619681
Review for gene: ATP5G3 was set to RED
Added comment: Reviewed for epilepsy gene list review - no new evidence for seizures as part of this dystonia phenotype
Sources: Expert list
Genetic Epilepsy v0.2019 ATP5E Lilian Downie gene: ATP5E was added
gene: ATP5E was added to Genetic Epilepsy. Sources: Expert list
Mode of inheritance for gene: ATP5E was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATP5E were set to PMID: 34954817, PMID: 22231385
Phenotypes for gene: ATP5E were set to Mitochondrial complex V (ATP synthase) deficiency, nuclear type 3 MIM#614053
Review for gene: ATP5E was set to AMBER
Added comment: Reviewed as included on the review list for genetic epilepsy
2/3 patients had seizures in the paper PMID 34954817
1 type not specified, the 2nd GTCS
1 patient in PMID: 22231385, no seizures
no new evidence
Sources: Expert list
Genetic Epilepsy v0.2019 ATP5A1 Lilian Downie reviewed gene: ATP5A1: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 34954817; Phenotypes: Mitochondrial complex V (ATP synthase) deficiency, nuclear type 4A MIM#620358; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2019 STX1A Belinda Chong reviewed gene: STX1A: Rating: GREEN; Mode of pathogenicity: None; Publications: 37029317, 36564538; Phenotypes: Neurodevelopmental disorder MONDO#0700092, STX1A-related; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genetic Epilepsy v0.2019 SPEN Belinda Chong reviewed gene: SPEN: Rating: AMBER; Mode of pathogenicity: None; Publications: 33596411; Phenotypes: Radio-Tartaglia syndrome MIM#619312; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Intellectual disability syndromic and non-syndromic v0.5649 CAPRIN1 Zornitza Stark Phenotypes for gene: CAPRIN1 were changed from Neurodevelopmental disorder, CAPRIN1-related MONDO:0700092; Neurodegeneration, childhood-onset, with cerebellar ataxia and cognitive decline, MIM# 620636 to Neurodevelopmental disorder, CAPRIN1-related MONDO:0700092; Neurodegeneration, childhood-onset, with cerebellar ataxia and cognitive decline, MIM# 620636
Intellectual disability syndromic and non-syndromic v0.5648 CAPRIN1 Zornitza Stark Phenotypes for gene: CAPRIN1 were changed from Neurodevelopmental disorder, CAPRIN1-related MONDO:0700092 to Neurodevelopmental disorder, CAPRIN1-related MONDO:0700092; Neurodegeneration, childhood-onset, with cerebellar ataxia and cognitive decline, MIM# 620636
Intellectual disability syndromic and non-syndromic v0.5648 CAPRIN1 Zornitza Stark Publications for gene: CAPRIN1 were set to 35979925; 35977029; 28135719; 31398340
Intellectual disability syndromic and non-syndromic v0.5647 CAPRIN1 Zornitza Stark reviewed gene: CAPRIN1: Rating: AMBER; Mode of pathogenicity: None; Publications: 36136249; Phenotypes: Neurodegeneration, childhood-onset, with cerebellar ataxia and cognitive decline, MIM# 620636; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.1435 CAPRIN1 Zornitza Stark Phenotypes for gene: CAPRIN1 were changed from Neurodegeneration, childhood-onset, with cerebellar ataxia and cognitive decline, MIM# 620636 to Neurodevelopmental disorder, CAPRIN1-related MONDO:0700092; Neurodegeneration, childhood-onset, with cerebellar ataxia and cognitive decline, MIM# 620636
Mendeliome v1.1434 CAPRIN1 Zornitza Stark Publications for gene: CAPRIN1 were set to 35979925
Mendeliome v1.1433 CAPRIN1 Zornitza Stark edited their review of gene: CAPRIN1: Added comment: Two individuals reported with the same de novo c.1535C > T (p.Pro512Leu) variant and a progressive course.; Changed rating: AMBER; Changed publications: 36136249
Regression v0.535 CAPRIN1 Zornitza Stark Marked gene: CAPRIN1 as ready
Regression v0.535 CAPRIN1 Zornitza Stark Gene: caprin1 has been classified as Amber List (Moderate Evidence).
Regression v0.535 CAPRIN1 Zornitza Stark Classified gene: CAPRIN1 as Amber List (moderate evidence)
Regression v0.535 CAPRIN1 Zornitza Stark Gene: caprin1 has been classified as Amber List (Moderate Evidence).
Regression v0.534 CAPRIN1 Zornitza Stark edited their review of gene: CAPRIN1: Changed rating: AMBER
Regression v0.534 CAPRIN1 Zornitza Stark gene: CAPRIN1 was added
gene: CAPRIN1 was added to Regression. Sources: Expert Review
Mode of inheritance for gene: CAPRIN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CAPRIN1 were set to 36136249
Phenotypes for gene: CAPRIN1 were set to Neurodegeneration, childhood-onset, with cerebellar ataxia and cognitive decline, MIM# 620636
Review for gene: CAPRIN1 was set to GREEN
Added comment: Two individuals reported with the same de novo c.1535C > T (p.Pro512Leu) variant and a progressive course with onset in childhood.

Another 12 individuals reported in previous publications with ID/SZ.
Sources: Expert Review
Genetic Epilepsy v0.2019 CAPRIN1 Zornitza Stark Phenotypes for gene: CAPRIN1 were changed from Neurodegeneration, childhood-onset, with cerebellar ataxia and cognitive decline, MIM# 620636 to Neurodevelopmental disorder, CAPRIN1-related MONDO:0700092; Neurodegeneration, childhood-onset, with cerebellar ataxia and cognitive decline, MIM# 620636
Genetic Epilepsy v0.2018 CAPRIN1 Zornitza Stark edited their review of gene: CAPRIN1: Added comment: Two individuals reported with the same de novo c.1535C > T (p.Pro512Leu) variant and a progressive course.; Changed publications: 36136249
Genetic Epilepsy v0.2018 CAPRIN1 Zornitza Stark Phenotypes for gene: CAPRIN1 were changed from Neurodegeneration, childhood-onset, with cerebellar ataxia and cognitive decline, MIM# 620636 to Neurodegeneration, childhood-onset, with cerebellar ataxia and cognitive decline, MIM# 620636
Genetic Epilepsy v0.2018 CAPRIN1 Zornitza Stark Phenotypes for gene: CAPRIN1 were changed from Neurodevelopmental disorder, CAPRIN1-related MONDO:0700092 to Neurodegeneration, childhood-onset, with cerebellar ataxia and cognitive decline, MIM# 620636
Genetic Epilepsy v0.2017 CAPRIN1 Zornitza Stark reviewed gene: CAPRIN1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodegeneration, childhood-onset, with cerebellar ataxia and cognitive decline, MIM# 620636; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.1433 CAPRIN1 Zornitza Stark Phenotypes for gene: CAPRIN1 were changed from Neurodevelopmental disorder, CAPRIN1-related MONDO:0700092 to Neurodegeneration, childhood-onset, with cerebellar ataxia and cognitive decline, MIM# 620636
Mendeliome v1.1432 CAPRIN1 Zornitza Stark reviewed gene: CAPRIN1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodegeneration, childhood-onset, with cerebellar ataxia and cognitive decline, MIM# 620636; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Ciliary Dyskinesia v1.37 NME5 Achchuthan Shanmugasundram reviewed gene: NME5: Rating: GREEN; Mode of pathogenicity: None; Publications: 37957793; Phenotypes: Ciliary dyskinesia, primary, 48, without situs inversus, OMIM:620032; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5647 MANF Zornitza Stark Marked gene: MANF as ready
Intellectual disability syndromic and non-syndromic v0.5647 MANF Zornitza Stark Gene: manf has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5647 MANF Zornitza Stark Classified gene: MANF as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.5647 MANF Zornitza Stark Gene: manf has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5646 MANF Zornitza Stark gene: MANF was added
gene: MANF was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review
Mode of inheritance for gene: MANF was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MANF were set to 26077850; 33500254; 34815294
Phenotypes for gene: MANF were set to Diabetes, deafness, developmental delay, and short stature syndrome, MIM# 620651
Review for gene: MANF was set to AMBER
Added comment: Two individuals reported with homozygous variants. Mouse model recapitulates deafness phenotype.
Sources: Expert Review
Monogenic Diabetes v0.43 MANF Zornitza Stark Marked gene: MANF as ready
Monogenic Diabetes v0.43 MANF Zornitza Stark Gene: manf has been classified as Amber List (Moderate Evidence).
Monogenic Diabetes v0.43 MANF Zornitza Stark Classified gene: MANF as Amber List (moderate evidence)
Monogenic Diabetes v0.43 MANF Zornitza Stark Gene: manf has been classified as Amber List (Moderate Evidence).
Monogenic Diabetes v0.42 MANF Zornitza Stark gene: MANF was added
gene: MANF was added to Monogenic Diabetes. Sources: Expert Review
Mode of inheritance for gene: MANF was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MANF were set to 26077850; 33500254; 34815294
Phenotypes for gene: MANF were set to Diabetes, deafness, developmental delay, and short stature syndrome, MIM# 620651
Review for gene: MANF was set to AMBER
Added comment: Two individuals reported with homozygous variants. Mouse model recapitulates deafness phenotype.
Sources: Expert Review
Deafness_IsolatedAndComplex v1.168 MANF Zornitza Stark Marked gene: MANF as ready
Deafness_IsolatedAndComplex v1.168 MANF Zornitza Stark Gene: manf has been classified as Amber List (Moderate Evidence).
Deafness_IsolatedAndComplex v1.168 MANF Zornitza Stark Classified gene: MANF as Amber List (moderate evidence)
Deafness_IsolatedAndComplex v1.168 MANF Zornitza Stark Gene: manf has been classified as Amber List (Moderate Evidence).
Deafness_IsolatedAndComplex v1.167 MANF Zornitza Stark gene: MANF was added
gene: MANF was added to Deafness_IsolatedAndComplex. Sources: Expert Review
Mode of inheritance for gene: MANF was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MANF were set to 26077850; 33500254; 34815294
Phenotypes for gene: MANF were set to Diabetes, deafness, developmental delay, and short stature syndrome, MIM# 620651
Review for gene: MANF was set to AMBER
Added comment: Two individuals reported with homozygous variants. Mouse model recapitulates deafness phenotype.
Sources: Expert Review
Mendeliome v1.1432 MANF Zornitza Stark Marked gene: MANF as ready
Mendeliome v1.1432 MANF Zornitza Stark Gene: manf has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1432 MANF Zornitza Stark Classified gene: MANF as Amber List (moderate evidence)
Mendeliome v1.1432 MANF Zornitza Stark Gene: manf has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1431 MANF Zornitza Stark gene: MANF was added
gene: MANF was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: MANF was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MANF were set to 26077850; 33500254; 34815294
Phenotypes for gene: MANF were set to Diabetes, deafness, developmental delay, and short stature syndrome, MIM# 620651
Review for gene: MANF was set to AMBER
Added comment: Two individuals reported with homozygous variants. Mouse model recapitulates deafness phenotype.
Sources: Expert Review
Mendeliome v1.1430 RRM1 Zornitza Stark Phenotypes for gene: RRM1 were changed from Multiple mitochondrial DNA deletion syndrome (MONDO:0016797) to Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 6, MIM# 620647
Mitochondrial disease v0.906 RRM1 Zornitza Stark Phenotypes for gene: RRM1 were changed from Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 6, MIM# 620647 to Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 6, MIM# 620647
Mitochondrial disease v0.905 RRM1 Zornitza Stark Phenotypes for gene: RRM1 were changed from Multiple mitochondrial DNA deletion syndrome (MONDO:0016797) to Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 6, MIM# 620647
Fetal anomalies v1.172 DRG1 Zornitza Stark Phenotypes for gene: DRG1 were changed from Neurodevelopmental disorder (MONDO:0700092), DRG1-related to Tan-Almurshedi syndrome, MIM# 620641
Growth failure v1.72 DRG1 Zornitza Stark Phenotypes for gene: DRG1 were changed from Neurodevelopmental disorder (MONDO:0700092), DRG1-related to Tan-Almurshedi syndrome, MIM# 620641
Intellectual disability syndromic and non-syndromic v0.5645 DRG1 Zornitza Stark Phenotypes for gene: DRG1 were changed from Neurodevelopmental disorder (MONDO:0700092), DRG1-related to Tan-Almurshedi syndrome, MIM# 620641
Microcephaly v1.243 DRG1 Zornitza Stark Phenotypes for gene: DRG1 were changed from Neurodevelopmental disorder (MONDO:0700092), DRG1-related to Tan-Almurshedi syndrome, MIM# 620641
Mendeliome v1.1429 DRG1 Zornitza Stark Phenotypes for gene: DRG1 were changed from Neurodevelopmental disorder (MONDO:0700092), DRG1-related to Tan-Almurshedi syndrome, MIM# 620641
Mitochondrial disease v0.904 AMACR Zornitza Stark Marked gene: AMACR as ready
Mitochondrial disease v0.904 AMACR Zornitza Stark Gene: amacr has been classified as Green List (High Evidence).
Mitochondrial disease v0.904 AMACR Zornitza Stark Classified gene: AMACR as Green List (high evidence)
Mitochondrial disease v0.904 AMACR Zornitza Stark Gene: amacr has been classified as Green List (High Evidence).
Mitochondrial disease v0.903 AMACR Zornitza Stark Classified gene: AMACR as Green List (high evidence)
Mitochondrial disease v0.903 AMACR Zornitza Stark Gene: amacr has been classified as Green List (High Evidence).
Mitochondrial disease v0.902 AMACR Zornitza Stark gene: AMACR was added
gene: AMACR was added to Mitochondrial disease. Sources: Expert Review
Mode of inheritance for gene: AMACR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AMACR were set to 35641312; 35428665
Phenotypes for gene: AMACR were set to Bile acid synthesis defect, congenital, 4, MIM# 214950; Alpha-methylacyl-CoA racemase deficiency, MIM# 614307
Review for gene: AMACR was set to GREEN
Added comment: Mito disease mimic, repeatedly identified in cohorts of patients undergoing testing for suspected mitochondrial disease.
Sources: Expert Review
Fetal anomalies v1.171 MMP13 Zornitza Stark Classified gene: MMP13 as Red List (low evidence)
Fetal anomalies v1.171 MMP13 Zornitza Stark Gene: mmp13 has been classified as Red List (Low Evidence).
Fetal anomalies v1.170 MMP13 Zornitza Stark reviewed gene: MMP13: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Metaphyseal anadysplasia 1 (MIM#602111), Metaphyseal dysplasia, Spahr type (MIM#250400); Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genetic Epilepsy v0.2017 GLI3 Zornitza Stark Marked gene: GLI3 as ready
Genetic Epilepsy v0.2017 GLI3 Zornitza Stark Gene: gli3 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2017 GLI3 Zornitza Stark Classified gene: GLI3 as Green List (high evidence)
Genetic Epilepsy v0.2017 GLI3 Zornitza Stark Gene: gli3 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2016 GLI3 Zornitza Stark gene: GLI3 was added
gene: GLI3 was added to Genetic Epilepsy. Sources: Expert Review
Mode of inheritance for gene: GLI3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: GLI3 were set to Pallister-Hall syndrome, MIM# 146510
Review for gene: GLI3 was set to GREEN
Added comment: Seizures in the setting of hypothalamic hamartomas associated with the Pallister-Hall syndrome (PHS) phenotype which is caused by truncating mutations in the middle third of the gene that produce a truncated functional repressor protein.
Sources: Expert Review
Intellectual disability syndromic and non-syndromic v0.5644 GCDH Zornitza Stark Marked gene: GCDH as ready
Intellectual disability syndromic and non-syndromic v0.5644 GCDH Zornitza Stark Gene: gcdh has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2015 GCDH Zornitza Stark Marked gene: GCDH as ready
Genetic Epilepsy v0.2015 GCDH Zornitza Stark Gene: gcdh has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5644 GCDH Zornitza Stark Phenotypes for gene: GCDH were changed from to Glutaric aciduria, type I MIM#231670
Intellectual disability syndromic and non-syndromic v0.5643 GCDH Zornitza Stark Mode of inheritance for gene: GCDH was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2015 GCDH Zornitza Stark Classified gene: GCDH as Green List (high evidence)
Genetic Epilepsy v0.2015 GCDH Zornitza Stark Gene: gcdh has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2014 GCDH Zornitza Stark gene: GCDH was added
gene: GCDH was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: GCDH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GCDH were set to 25875215
Phenotypes for gene: GCDH were set to Glutaric aciduria, type I MIM#231670
Review for gene: GCDH was set to GREEN
Added comment: Well established gene-disease association. Seizures present in around 7% of affected individuals.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5642 GCDH Zornitza Stark reviewed gene: GCDH: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Glutaric aciduria, type I MIM#231670; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2013 GATM Zornitza Stark Marked gene: GATM as ready
Genetic Epilepsy v0.2013 GATM Zornitza Stark Gene: gatm has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2013 GATM Zornitza Stark Classified gene: GATM as Amber List (moderate evidence)
Genetic Epilepsy v0.2013 GATM Zornitza Stark Gene: gatm has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2012 GATM Zornitza Stark gene: GATM was added
gene: GATM was added to Genetic Epilepsy. Sources: Expert Review
Mode of inheritance for gene: GATM was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GATM were set to 36856349; 12468279; 20682460; 22386973
Phenotypes for gene: GATM were set to Cerebral creatine deficiency syndrome 3, MIM# 612718
Review for gene: GATM was set to AMBER
Added comment: Seizures described in cerebral creatine disorders in general.
Sources: Expert Review
Mendeliome v1.1428 GABRA4 Zornitza Stark Marked gene: GABRA4 as ready
Mendeliome v1.1428 GABRA4 Zornitza Stark Gene: gabra4 has been classified as Red List (Low Evidence).
Mendeliome v1.1428 GABRA4 Zornitza Stark gene: GABRA4 was added
gene: GABRA4 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GABRA4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GABRA4 were set to 35152403
Phenotypes for gene: GABRA4 were set to Developmental and epileptic encephalopathy MONDO:0100062, GABRA4-related
Review for gene: GABRA4 was set to RED
Added comment: Single individual with de novo missense variant reported, supportive functional data.
Sources: Literature
Genetic Epilepsy v0.2011 GABRA4 Zornitza Stark Marked gene: GABRA4 as ready
Genetic Epilepsy v0.2011 GABRA4 Zornitza Stark Gene: gabra4 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2011 GABRA4 Zornitza Stark gene: GABRA4 was added
gene: GABRA4 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: GABRA4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GABRA4 were set to 35152403
Phenotypes for gene: GABRA4 were set to Developmental and epileptic encephalopathy MONDO:0100062, GABRA4-related
Review for gene: GABRA4 was set to RED
Added comment: Single individual with de novo missense variant reported, supportive functional data.
Sources: Literature
Genetic Epilepsy v0.2010 FRA10AC1 Zornitza Stark Classified gene: FRA10AC1 as Amber List (moderate evidence)
Genetic Epilepsy v0.2010 FRA10AC1 Zornitza Stark Gene: fra10ac1 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2009 FRA10AC1 Zornitza Stark Marked gene: FRA10AC1 as ready
Genetic Epilepsy v0.2009 FRA10AC1 Zornitza Stark Gene: fra10ac1 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2009 FRA10AC1 Zornitza Stark Classified gene: FRA10AC1 as Amber List (moderate evidence)
Genetic Epilepsy v0.2009 FRA10AC1 Zornitza Stark Gene: fra10ac1 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2008 FRA10AC1 Zornitza Stark gene: FRA10AC1 was added
gene: FRA10AC1 was added to Genetic Epilepsy. Sources: Expert Review
Mode of inheritance for gene: FRA10AC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FRA10AC1 were set to 34694367; 35871492; 35821753
Phenotypes for gene: FRA10AC1 were set to Neurodevelopmental disorder with growth retardation, dysmorphic facies, and corpus callosum abnormalities, MIM# 620113
Review for gene: FRA10AC1 was set to AMBER
Added comment: 6 families reported, 10 individuals with neurodevelopmental phenotype. 2 had seizures.
Sources: Expert Review
Hereditary Neuropathy - complex v1.7 PLA2G16 Zornitza Stark Marked gene: PLA2G16 as ready
Hereditary Neuropathy - complex v1.7 PLA2G16 Zornitza Stark Added comment: Comment when marking as ready: HGNC name is PLAAT3
Hereditary Neuropathy - complex v1.7 PLA2G16 Zornitza Stark Gene: pla2g16 has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v1.7 PLA2G16 Zornitza Stark Tag new gene name tag was added to gene: PLA2G16.
Intellectual disability syndromic and non-syndromic v0.5642 PLA2G16 Zornitza Stark Marked gene: PLA2G16 as ready
Intellectual disability syndromic and non-syndromic v0.5642 PLA2G16 Zornitza Stark Added comment: Comment when marking as ready: HGNC name is PLAAT3
Intellectual disability syndromic and non-syndromic v0.5642 PLA2G16 Zornitza Stark Gene: pla2g16 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5642 PLA2G16 Zornitza Stark Tag new gene name tag was added to gene: PLA2G16.
Mendeliome v1.1427 PLA2G16 Zornitza Stark Marked gene: PLA2G16 as ready
Mendeliome v1.1427 PLA2G16 Zornitza Stark Added comment: Comment when marking as ready: HGNC name is PLAAT3
Mendeliome v1.1427 PLA2G16 Zornitza Stark Gene: pla2g16 has been classified as Green List (High Evidence).
Mendeliome v1.1427 PLA2G16 Zornitza Stark Tag new gene name tag was added to gene: PLA2G16.
Lipodystrophy_Lipoatrophy v1.12 PLA2G16 Zornitza Stark Marked gene: PLA2G16 as ready
Lipodystrophy_Lipoatrophy v1.12 PLA2G16 Zornitza Stark Added comment: Comment when marking as ready: HGNC approved name is PLAAT3
Lipodystrophy_Lipoatrophy v1.12 PLA2G16 Zornitza Stark Gene: pla2g16 has been classified as Green List (High Evidence).
Lipodystrophy_Lipoatrophy v1.12 PLA2G16 Zornitza Stark Tag new gene name tag was added to gene: PLA2G16.
Deafness_IsolatedAndComplex v1.166 FOXL1 Zornitza Stark Marked gene: FOXL1 as ready
Deafness_IsolatedAndComplex v1.166 FOXL1 Zornitza Stark Gene: foxl1 has been classified as Red List (Low Evidence).
Deafness_IsolatedAndComplex v1.166 FOXL1 Zornitza Stark Classified gene: FOXL1 as Red List (low evidence)
Deafness_IsolatedAndComplex v1.166 FOXL1 Zornitza Stark Gene: foxl1 has been classified as Red List (Low Evidence).
Mendeliome v1.1427 FOXL1 Zornitza Stark Marked gene: FOXL1 as ready
Mendeliome v1.1427 FOXL1 Zornitza Stark Gene: foxl1 has been classified as Red List (Low Evidence).
Mendeliome v1.1427 FOXL1 Zornitza Stark Classified gene: FOXL1 as Red List (low evidence)
Mendeliome v1.1427 FOXL1 Zornitza Stark Gene: foxl1 has been classified as Red List (Low Evidence).
Mitochondrial disease v0.901 RANBP2 Zornitza Stark Marked gene: RANBP2 as ready
Mitochondrial disease v0.901 RANBP2 Zornitza Stark Gene: ranbp2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2007 RBFOX1 Dean Phelan gene: RBFOX1 was added
gene: RBFOX1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: RBFOX1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RBFOX1 were set to PMID: 37962958
Phenotypes for gene: RBFOX1 were set to Neurodevelopmental disorder (MONDO:0700092), RBFOX1-related
Review for gene: RBFOX1 was set to GREEN
Added comment: PMID: 37962958
De novo missense variants identified in six unrelated patients with neurodevelopmental disorder and severe seizures.
Sources: Literature
Mendeliome v1.1426 RBFOX1 Dean Phelan reviewed gene: RBFOX1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 37962958; Phenotypes: Neurodevelopmental disorder (MONDO:0700092), RBFOX1-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mitochondrial disease v0.901 RANBP2 Zornitza Stark Classified gene: RANBP2 as Green List (high evidence)
Mitochondrial disease v0.901 RANBP2 Zornitza Stark Gene: ranbp2 has been classified as Green List (High Evidence).
Mitochondrial disease v0.900 RANBP2 Zornitza Stark gene: RANBP2 was added
gene: RANBP2 was added to Mitochondrial disease. Sources: Expert Review
Mode of inheritance for gene: RANBP2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: RANBP2 were set to {Encephalopathy, acute, infection-induced, 3, susceptibility to} MIM#608033
Review for gene: RANBP2 was set to GREEN
Added comment: Not a mitochondrial condition, but significant overlap in clinical presentation, described as Leigh-like previously.
Sources: Expert Review
Mendeliome v1.1426 MGP Zornitza Stark Phenotypes for gene: MGP were changed from Keutel syndrome, MIM #245150 to Keutel syndrome, MIM #245150; Skeletal dysplasia MONDO:0018230, MGP-related
Mendeliome v1.1425 MGP Zornitza Stark Publications for gene: MGP were set to 9916809; 15810001; 33996798
Mendeliome v1.1424 MGP Zornitza Stark Mode of inheritance for gene: MGP was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.1423 KIF5B Zornitza Stark Phenotypes for gene: KIF5B were changed from Skeletal dysplasia, MONDO:0018230, KIF5B-related; Kyphomelic dysplasia to osteogenesis imperfecta, MONDO:0019019; Skeletal dysplasia, MONDO:0018230, KIF5B-related; Kyphomelic dysplasia
Mendeliome v1.1422 KIF5B Zornitza Stark Publications for gene: KIF5B were set to PMID: 35342932; 36018820
Mendeliome v1.1421 KIF5B Zornitza Stark edited their review of gene: KIF5B: Added comment: Four additional patients with three distinct de-novo missense variants and features consistent with osteogenesis imperfecta. All variants are in the Kinesin motor domain (~50% of the protein). Functional data in C. Elegans and cell lines shows impaired protein function. Not clear what distinguishes OI causing variants from other phenotypes for this gene at this stage. Dominant negative effect proposed but not conclusively proven.; Changed publications: 37934770; Changed phenotypes: Skeletal dysplasia, MONDO:0018230, osteogenesis imperfecta, MONDO:0019019
Intellectual disability syndromic and non-syndromic v0.5642 PRPF19 Zornitza Stark Marked gene: PRPF19 as ready
Intellectual disability syndromic and non-syndromic v0.5642 PRPF19 Zornitza Stark Gene: prpf19 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5642 PRPF19 Zornitza Stark Classified gene: PRPF19 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5642 PRPF19 Zornitza Stark Gene: prpf19 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5641 PRPF19 Zornitza Stark gene: PRPF19 was added
gene: PRPF19 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: PRPF19 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PRPF19 were set to 37962958
Phenotypes for gene: PRPF19 were set to Neurodevelopmental disorder (MONDO:0700092), PRPF19-related
Review for gene: PRPF19 was set to GREEN
Added comment: PMID: 37962958 Six unrelated individuals with de novo variants. Five had speech language motor delay, four had formal diagnosis of autism, three hypotonia and one fetus with multiple congenital abnormalities.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5641 PRPF19 Zornitza Stark gene: PRPF19 was added
gene: PRPF19 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: PRPF19 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PRPF19 were set to 37962958
Phenotypes for gene: PRPF19 were set to Neurodevelopmental disorder (MONDO:0700092), PRPF19-related
Review for gene: PRPF19 was set to GREEN
Added comment: PMID: 37962958 Six unrelated individuals with de novo variants. Five had speech language motor delay, four had formal diagnosis of autism, three hypotonia and one fetus with multiple congenital abnormalities.
Sources: Literature
Mendeliome v1.1421 PRPF19 Zornitza Stark Marked gene: PRPF19 as ready
Mendeliome v1.1421 PRPF19 Zornitza Stark Gene: prpf19 has been classified as Green List (High Evidence).
Mendeliome v1.1421 PRPF19 Zornitza Stark Classified gene: PRPF19 as Green List (high evidence)
Mendeliome v1.1421 PRPF19 Zornitza Stark Gene: prpf19 has been classified as Green List (High Evidence).
Fetal anomalies v1.170 WBP4 Zornitza Stark Marked gene: WBP4 as ready
Fetal anomalies v1.170 WBP4 Zornitza Stark Gene: wbp4 has been classified as Green List (High Evidence).
Fetal anomalies v1.170 WBP4 Zornitza Stark Classified gene: WBP4 as Green List (high evidence)
Fetal anomalies v1.170 WBP4 Zornitza Stark Gene: wbp4 has been classified as Green List (High Evidence).
Callosome v0.510 WBP4 Zornitza Stark Marked gene: WBP4 as ready
Callosome v0.510 WBP4 Zornitza Stark Gene: wbp4 has been classified as Green List (High Evidence).
Callosome v0.510 WBP4 Zornitza Stark Classified gene: WBP4 as Green List (high evidence)
Callosome v0.510 WBP4 Zornitza Stark Gene: wbp4 has been classified as Green List (High Evidence).
Growth failure v1.71 WBP4 Zornitza Stark Marked gene: WBP4 as ready
Growth failure v1.71 WBP4 Zornitza Stark Gene: wbp4 has been classified as Green List (High Evidence).
Growth failure v1.71 WBP4 Zornitza Stark Classified gene: WBP4 as Green List (high evidence)
Growth failure v1.71 WBP4 Zornitza Stark Gene: wbp4 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5640 PLA2G16 Zornitza Stark Marked gene: PLA2G16 as ready
Intellectual disability syndromic and non-syndromic v0.5640 PLA2G16 Zornitza Stark Gene: pla2g16 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5640 PLA2G16 Zornitza Stark Phenotypes for gene: PLA2G16 were changed from Lipodystrophy (MONDO:0006573) to Lipodystrophy (MONDO:0006573), PLA2G16-related
Intellectual disability syndromic and non-syndromic v0.5639 PLA2G16 Zornitza Stark Mode of inheritance for gene: PLA2G16 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v0.176 PKP2 Suliman Khan edited their review of gene: PKP2: Changed phenotypes: Cardiomyopathy, MONDO:0004994, PKP2-related
Intellectual disability syndromic and non-syndromic v0.5638 PLA2G16 Zornitza Stark Classified gene: PLA2G16 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5638 PLA2G16 Zornitza Stark Gene: pla2g16 has been classified as Green List (High Evidence).
Mendeliome v1.1420 PLA2G16 Zornitza Stark Marked gene: PLA2G16 as ready
Mendeliome v1.1420 PLA2G16 Zornitza Stark Gene: pla2g16 has been classified as Green List (High Evidence).