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Intellectual disability syndromic and non-syndromic v0.5847 OFD1 Zornitza Stark Gene: ofd1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5847 OFD1 Zornitza Stark Phenotypes for gene: OFD1 were changed from to ciliopathy MONDO:0005308
Intellectual disability syndromic and non-syndromic v0.5846 OFD1 Zornitza Stark Publications for gene: OFD1 were set to
Intellectual disability syndromic and non-syndromic v0.5845 OFD1 Zornitza Stark Mode of inheritance for gene: OFD1 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.5844 PLP1 Zornitza Stark Marked gene: PLP1 as ready
Intellectual disability syndromic and non-syndromic v0.5844 PLP1 Zornitza Stark Gene: plp1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5844 PLP1 Zornitza Stark Phenotypes for gene: PLP1 were changed from to Pelizeaus-Merzbacher spectrum disorder MONDO:0010714
Intellectual disability syndromic and non-syndromic v0.5843 PLP1 Zornitza Stark Mode of inheritance for gene: PLP1 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.5842 PORCN Zornitza Stark Marked gene: PORCN as ready
Intellectual disability syndromic and non-syndromic v0.5842 PORCN Zornitza Stark Gene: porcn has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5842 PORCN Zornitza Stark Phenotypes for gene: PORCN were changed from to focal dermal hypoplasia MONDO:0010592
Intellectual disability syndromic and non-syndromic v0.5841 PORCN Zornitza Stark Publications for gene: PORCN were set to
Intellectual disability syndromic and non-syndromic v0.5840 PORCN Zornitza Stark Mode of inheritance for gene: PORCN 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)
Intellectual disability syndromic and non-syndromic v0.5839 PTCHD1 Zornitza Stark Marked gene: PTCHD1 as ready
Intellectual disability syndromic and non-syndromic v0.5839 PTCHD1 Zornitza Stark Gene: ptchd1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5839 PTCHD1 Zornitza Stark Phenotypes for gene: PTCHD1 were changed from to non-syndromic X-linked intellectual disability MONDO:0019181
Intellectual disability syndromic and non-syndromic v0.5838 PTCHD1 Zornitza Stark Mode of inheritance for gene: PTCHD1 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.5837 SETBP1 Zornitza Stark Marked gene: SETBP1 as ready
Intellectual disability syndromic and non-syndromic v0.5837 SETBP1 Zornitza Stark Gene: setbp1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5837 SETBP1 Zornitza Stark Phenotypes for gene: SETBP1 were changed from to Schinzel-Giedion syndrome MONDO:0010010; complex neurodevelopmental disorder MONDO:0100038
Intellectual disability syndromic and non-syndromic v0.5836 SETBP1 Zornitza Stark Publications for gene: SETBP1 were set to
Intellectual disability syndromic and non-syndromic v0.5835 SETBP1 Zornitza Stark Mode of inheritance for gene: SETBP1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5834 SHROOM4 Zornitza Stark Classified gene: SHROOM4 as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.5834 SHROOM4 Zornitza Stark Gene: shroom4 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.5833 SHROOM4 Zornitza Stark Tag disputed tag was added to gene: SHROOM4.
Intellectual disability syndromic and non-syndromic v0.5833 SLC25A15 Zornitza Stark Marked gene: SLC25A15 as ready
Intellectual disability syndromic and non-syndromic v0.5833 SLC25A15 Zornitza Stark Gene: slc25a15 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5833 SLC25A15 Zornitza Stark Phenotypes for gene: SLC25A15 were changed from to Hyperornithinemia-hyperammonemia-homocitrullinemia syndrome, MIM#238970
Intellectual disability syndromic and non-syndromic v0.5832 SLC25A15 Zornitza Stark Publications for gene: SLC25A15 were set to
Intellectual disability syndromic and non-syndromic v0.5831 SLC25A15 Zornitza Stark Mode of inheritance for gene: SLC25A15 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5830 SLC6A4 Zornitza Stark Phenotypes for gene: SLC6A4 were changed from {Obsessive-compulsive disorder}, MIM# 164230; depression; alcohol dependence to autism spectrum disorder MONDO:0005258; {Obsessive-compulsive disorder}, MIM# 164230
Intellectual disability syndromic and non-syndromic v0.5829 SLC6A4 Zornitza Stark Tag disputed tag was added to gene: SLC6A4.
Intellectual disability syndromic and non-syndromic v0.5829 WAC Zornitza Stark Publications for gene: WAC were set to 26264232
Genetic Epilepsy v0.2754 ZDHHC15 Zornitza Stark Phenotypes for gene: ZDHHC15 were changed from Mental retardation X-linked 91, 300577; cerebral palsy; intellectual disability; autism spectrum disorder; epilepsy to Intellectual disability, X-linked 91, 300577
Genetic Epilepsy v0.2753 ZDHHC15 Zornitza Stark edited their review of gene: ZDHHC15: Changed phenotypes: Intellectual disability, X-linked 91, 300577
Mendeliome v1.1791 ZDHHC15 Zornitza Stark Phenotypes for gene: ZDHHC15 were changed from Mental retardation, X-linked 91, 300577; cerebral palsy; intellectual disability; autism spectrum disorder; epilepsy to Intellectual disability, X-linked 91, 300577
Intellectual disability syndromic and non-syndromic v0.5828 ZDHHC15 Zornitza Stark Phenotypes for gene: ZDHHC15 were changed from Mental retardation, X-linked 91, 300577 to Intellectual disability, X-linked 91, 300577
Mendeliome v1.1790 ZDHHC15 Zornitza Stark Tag disputed tag was added to gene: ZDHHC15.
Mendeliome v1.1790 ZDHHC15 Zornitza Stark edited their review of gene: ZDHHC15: Changed phenotypes: Intellectual disability, X-linked 91, 300577
Intellectual disability syndromic and non-syndromic v0.5827 ZDHHC15 Zornitza Stark Tag disputed tag was added to gene: ZDHHC15.
Intellectual disability syndromic and non-syndromic v0.5827 ZNF41 Zornitza Stark Phenotypes for gene: ZNF41 were changed from to non-syndromic X-linked intellectual disability MONDO:0019181
Mendeliome v1.1790 ZNF41 Zornitza Stark Marked gene: ZNF41 as ready
Mendeliome v1.1790 ZNF41 Zornitza Stark Gene: znf41 has been classified as Red List (Low Evidence).
Mendeliome v1.1790 ZNF41 Zornitza Stark gene: ZNF41 was added
gene: ZNF41 was added to Mendeliome. Sources: Expert Review
disputed tags were added to gene: ZNF41.
Mode of inheritance for gene: ZNF41 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: ZNF41 were set to 14628291; 23871722
Phenotypes for gene: ZNF41 were set to non-syndromic X-linked intellectual disability MONDO:0019181
Review for gene: ZNF41 was set to RED
Added comment: DISPUTED by ClinGen.

Shoichet et al. (2003) described a female patient with severe nonsyndromic mental retardation and a de novo balanced translocation t(X;7)(p11.3;q11.21) in whom they cloned the DNA fragment that contained the X chromosomal and the autosomal breakpoint. In silico sequence analysis demonstrated that the ZNF41 gene was disrupted. Expression studies indicated that ZNF41 transcripts were absent in the patient cell line, suggesting that the mental disorder in this patient resulted from loss of functional ZNF41. Screening of patients with mental retardation led to the identification of 2 other ZNF41 mutations that were not found in healthy control individuals. Based on their finding of the mutations in ZNF41 identified by Shoichet et al. (2003) in a total of 7 males in the NHLBI Exome Variant Server, and the additional finding of truncating ZNF41 variants in 1 male and 1 female in that database, Piton et al. (2013) classified the involvement of ZNF41 in mental retardation as highly questionable.
Sources: Expert Review
Intellectual disability syndromic and non-syndromic v0.5826 ZNF41 Zornitza Stark Mode of inheritance for gene: ZNF41 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.5825 ZNF41 Zornitza Stark Tag disputed tag was added to gene: ZNF41.
Intellectual disability syndromic and non-syndromic v0.5825 ZNF674 Zornitza Stark Tag disputed tag was added to gene: ZNF674.
Intellectual disability syndromic and non-syndromic v0.5825 ZNF81 Zornitza Stark Phenotypes for gene: ZNF81 were changed from Intellectual disability to X-linked intellectual disability MONDO:0100284
Intellectual disability syndromic and non-syndromic v0.5824 SHANK2 Zornitza Stark Marked gene: SHANK2 as ready
Intellectual disability syndromic and non-syndromic v0.5824 SHANK2 Zornitza Stark Gene: shank2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5824 SHANK2 Zornitza Stark Phenotypes for gene: SHANK2 were changed from to Autism, susceptibility to, 17, MIM#613436; complex neurodevelopmental disorder MONDO:0100038
Intellectual disability syndromic and non-syndromic v0.5823 SHANK2 Zornitza Stark Publications for gene: SHANK2 were set to
Intellectual disability syndromic and non-syndromic v0.5822 SHANK2 Zornitza Stark Mode of inheritance for gene: SHANK2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5821 SHANK2 Zornitza Stark reviewed gene: SHANK2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: complex neurodevelopmental disorder MONDO:0100038; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Aminoacidopathy v1.9 AASS Zornitza Stark Marked gene: AASS as ready
Aminoacidopathy v1.9 AASS Zornitza Stark Gene: aass has been classified as Green List (High Evidence).
Aminoacidopathy v1.9 AASS Zornitza Stark Publications for gene: AASS were set to 23890588, 10775527, 27604308, 23570448; 35135854
Aminoacidopathy v1.8 AASS Zornitza Stark Classified gene: AASS as Green List (high evidence)
Aminoacidopathy v1.8 AASS Zornitza Stark Gene: aass has been classified as Green List (High Evidence).
Aminoacidopathy v1.7 ACSF3 Zornitza Stark Marked gene: ACSF3 as ready
Aminoacidopathy v1.7 ACSF3 Zornitza Stark Gene: acsf3 has been classified as Green List (High Evidence).
Aminoacidopathy v1.7 ACSF3 Zornitza Stark Classified gene: ACSF3 as Green List (high evidence)
Aminoacidopathy v1.7 ACSF3 Zornitza Stark Gene: acsf3 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2753 SYN1 Zornitza Stark Marked gene: SYN1 as ready
Genetic Epilepsy v0.2753 SYN1 Zornitza Stark Gene: syn1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2753 SYN1 Zornitza Stark Phenotypes for gene: SYN1 were changed from to Epilepsy, X-linked, with variable learning disabilities and behaviour disorders, MIM# 300491; Intellectual developmental disorder, X-linked 50, MIM# 300115
Aminoacidopathy v1.6 ACSF3 Sangavi Sivagnanasundram gene: ACSF3 was added
gene: ACSF3 was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: ACSF3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ACSF3 were set to 21785126, 26915364, 30740739, 26827111, 27604308, 21841779
Phenotypes for gene: ACSF3 were set to combined malonic and methylmalonic acidemia MONDO:0013661
Review for gene: ACSF3 was set to GREEN
Added comment: Established gene disease association with reported individuals showing evidence of biochemical abnormalities however some individuals do not show any other phenotypic abnormalities.
LoF is the mechanism of disease.

Definitive classification by ClinGen Aminoacidopathy GCEP on 09/10/2020 - https://search.clinicalgenome.org/CCID:004033
Sources: ClinGen
Aminoacidopathy v1.6 AASS Sangavi Sivagnanasundram gene: AASS was added
gene: AASS was added to Aminoacidopathy. Sources: ClinGen
Mode of inheritance for gene: AASS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AASS were set to 23890588, 10775527, 27604308, 23570448; 35135854
Phenotypes for gene: AASS were set to hyperlysinemia MONDO:0009388
Review for gene: AASS was set to GREEN
Added comment: Reported in individuals with affected biochemical function. Knock-in mouse model was also conducted to recapitulate the human phenotype (PMID: 35135854).

Definitive classification by ClinGen Aminoacidopathy GCEP on 14/10/2022 - https://search.clinicalgenome.org/CCID:004004
Sources: ClinGen
Intellectual disability syndromic and non-syndromic v0.5821 SHANK2 Aaron Meyers reviewed gene: SHANK2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 20473310, 22346768, 20531469, 35456494, 32987185, 25188300, 22699619, 22699620; Phenotypes: Autism, susceptibility to, 17, MIM#613436, Autism spectrum disorder; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5821 ZNF81 Sangavi Sivagnanasundram reviewed gene: ZNF81: Rating: RED; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:006590; Phenotypes: X-linked intellectual disability MONDO:0100284; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.5821 ZNF674 Sangavi Sivagnanasundram reviewed gene: ZNF674: Rating: RED; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:006588; Phenotypes: X-linked intellectual disability MONDO:0100284; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.5821 ZNF41 Sangavi Sivagnanasundram reviewed gene: ZNF41: Rating: RED; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:006585; Phenotypes: non-syndromic X-linked intellectual disability MONDO:0019181; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.5821 ZDHHC15 Sangavi Sivagnanasundram reviewed gene: ZDHHC15: Rating: RED; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:006573; Phenotypes: X-linked complex neurodevelopmental disorder MONDO:0100148; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.5821 WAC Sangavi Sivagnanasundram reviewed gene: WAC: Rating: GREEN; Mode of pathogenicity: None; Publications: 26757981, https://search.clinicalgenome.org/CCID:006532; Phenotypes: DeSanto-Shinawi syndrome MONDO:0018760; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5821 TCF7L2 Sangavi Sivagnanasundram reviewed gene: TCF7L2: Rating: GREEN; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:006339; Phenotypes: complex neurodevelopmental disorder MONDO:0100038; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Neurotransmitter Defects v1.7 SLC6A9 Bryony Thompson gene: SLC6A9 was added
gene: SLC6A9 was added to Neurotransmitter Defects. Sources: Expert Review Green
Mode of inheritance for gene: SLC6A9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC6A9 were set to 27481395; 27773429; 14622582; 33269555
Phenotypes for gene: SLC6A9 were set to Atypical glycine encephalopathy MONDO:0015010; Glycine neurotransmitter disorders
Neurotransmitter Defects v1.7 GRM1 Bryony Thompson gene: GRM1 was added
gene: GRM1 was added to Neurotransmitter Defects. Sources: Expert Review Green
Mode of inheritance for gene: GRM1 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: GRM1 were set to 26308914; 31319223; 22901947
Phenotypes for gene: GRM1 were set to Cerebellar ataxia MONDO:0000437; Glutamate neurotransmitter disorders
Neurotransmitter Defects v1.7 GRIA4 Bryony Thompson gene: GRIA4 was added
gene: GRIA4 was added to Neurotransmitter Defects. Sources: Expert Review Green
Mode of inheritance for gene: GRIA4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GRIA4 were set to 35518358; 29220673
Phenotypes for gene: GRIA4 were set to Glutamate neurotransmitter disorders; Neurodevelopmental disorder with or without seizures and gait abnormalities MONDO:0060641
Neurotransmitter Defects v1.7 GRIA3 Bryony Thompson gene: GRIA3 was added
gene: GRIA3 was added to Neurotransmitter Defects. Sources: Expert Review Green
Mode of inheritance for gene: GRIA3 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: GRIA3 were set to 38038360
Phenotypes for gene: GRIA3 were set to Glutamate neurotransmitter disorders; X-linked complex neurodevelopmental disorder MONDO:0100148
Neurotransmitter Defects v1.7 GRIN2D Bryony Thompson gene: GRIN2D was added
gene: GRIN2D was added to Neurotransmitter Defects. Sources: Expert Review Green
Mode of inheritance for gene: GRIN2D was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GRIN2D were set to 30280376; 27616483
Phenotypes for gene: GRIN2D were set to Glutamate neurotransmitter disorders; Complex neurodevelopmental disorder MONDO:0100038
Neurotransmitter Defects v1.7 GRIN2B Bryony Thompson gene: GRIN2B was added
gene: GRIN2B was added to Neurotransmitter Defects. Sources: Expert Review Green
Mode of inheritance for gene: GRIN2B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GRIN2B were set to 28377535
Phenotypes for gene: GRIN2B were set to Glutamate neurotransmitter disorders; Complex neurodevelopmental disorder MONDO:0100038
Neurotransmitter Defects v1.7 GRIN2A Bryony Thompson gene: GRIN2A was added
gene: GRIN2A was added to Neurotransmitter Defects. Sources: Expert Review Green
Mode of inheritance for gene: GRIN2A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GRIN2A were set to 30544257
Phenotypes for gene: GRIN2A were set to Glutamate neurotransmitter disorders; Complex neurodevelopmental disorder MONDO:0100038
Neurotransmitter Defects v1.7 GRIN1 Bryony Thompson gene: GRIN1 was added
gene: GRIN1 was added to Neurotransmitter Defects. Sources: Expert Review Green
Mode of inheritance for gene: GRIN1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: GRIN1 were set to 29365063; 27164704; 28051072
Phenotypes for gene: GRIN1 were set to Glutamate neurotransmitter disorders; Complex neurodevelopmental disorder MONDO:0100038
Neurotransmitter Defects v1.7 GABBR2 Bryony Thompson gene: GABBR2 was added
gene: GABBR2 was added to Neurotransmitter Defects. Sources: Expert Review Green
Mode of inheritance for gene: GABBR2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GABBR2 were set to 35850019
Phenotypes for gene: GABBR2 were set to Developmental and epileptic encephalopathy, 59 MONDO:0033368; Gamma-aminobutyric acid neurotransmitter disorders
Neurotransmitter Defects v1.7 SLC6A1 Bryony Thompson gene: SLC6A1 was added
gene: SLC6A1 was added to Neurotransmitter Defects. Sources: Expert Review Green
Mode of inheritance for gene: SLC6A1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SLC6A1 were set to 34028503
Phenotypes for gene: SLC6A1 were set to Myoclonic-atonic epilepsy MONDO:0014633
Neurotransmitter Defects v1.7 GABRB2 Bryony Thompson gene: GABRB2 was added
gene: GABRB2 was added to Neurotransmitter Defects. Sources: Expert Review Green
Mode of inheritance for gene: GABRB2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GABRB2 were set to 27789573; 35850019; 29100083
Phenotypes for gene: GABRB2 were set to Epileptic encephalopathy, infantile or early childhood, 2 MONDO:0020631; Gamma-aminobutyric acid neurotransmitter disorders
Neurotransmitter Defects v1.7 GABRB1 Bryony Thompson gene: GABRB1 was added
gene: GABRB1 was added to Neurotransmitter Defects. Sources: Expert Review Green
Mode of inheritance for gene: GABRB1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GABRB1 were set to 23934111; 27273810; 35850019; 31618474
Phenotypes for gene: GABRB1 were set to Developmental and epileptic encephalopathy, 45 MONDO:0014942; Gamma-aminobutyric acid neurotransmitter disorders
Mitochondrial disease v0.923 TMEM126A Bryony Thompson gene: TMEM126A was added
gene: TMEM126A was added to Mitochondrial disease. Sources: Expert Review Green
Mode of inheritance for gene: TMEM126A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TMEM126A were set to 29884839; 33879611
Phenotypes for gene: TMEM126A were set to Disorders of complex I subunits and assembly factors; autosomal recessive optic atrophy, OPA7 type MONDO:0013069
Mitochondrial disease v0.923 VCP Bryony Thompson gene: VCP was added
gene: VCP was added to Mitochondrial disease. Sources: Expert Review Green
Mode of inheritance for gene: VCP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: VCP were set to 29884839; 35273561; 37678339
Phenotypes for gene: VCP were set to inclusion body myopathy with Paget disease of bone and frontotemporal dementia MONDO:0000507; Disorders of mitochondrial protein quality control
Mitochondrial disease v0.923 PRKN Bryony Thompson gene: PRKN was added
gene: PRKN was added to Mitochondrial disease. Sources: Expert Review Green
Mode of inheritance for gene: PRKN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PRKN were set to 29884839; 38069350
Phenotypes for gene: PRKN were set to Disorders of mitochondrial protein quality control; Parkinson disease MONDO:0005180
Mitochondrial disease v0.923 HSPA9 Bryony Thompson gene: HSPA9 was added
gene: HSPA9 was added to Mitochondrial disease. Sources: Expert Review Green
Mode of inheritance for gene: HSPA9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HSPA9 were set to 29884839; 21123823; 26598328
Phenotypes for gene: HSPA9 were set to even-plus syndrome MONDO:0014801; Disorders of mitochondrial protein quality control
Mitochondrial disease v0.923 PAM16 Bryony Thompson gene: PAM16 was added
gene: PAM16 was added to Mitochondrial disease. Sources: Expert Review Green
Mode of inheritance for gene: PAM16 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PAM16 were set to 29884839; 24786642; 35385740; 36438081
Phenotypes for gene: PAM16 were set to autosomal recessive spondylometaphyseal dysplasia, Megarbane type MONDO:0013223; Disorders of mitochondrial protein import
Mitochondrial disease v0.923 PTRH2 Bryony Thompson gene: PTRH2 was added
gene: PTRH2 was added to Mitochondrial disease. Sources: Expert Review Green
Mode of inheritance for gene: PTRH2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PTRH2 were set to 29884839; 37239392
Phenotypes for gene: PTRH2 were set to Miscellaneous disorders associated with mitochondrial dysfunction; neurologic, endocrine, and pancreatic disease, multisystem, infantile-onset 1 MONDO:8000012
Mitochondrial disease v0.923 RMRP Bryony Thompson gene: RMRP was added
gene: RMRP was added to Mitochondrial disease. Sources: Expert Review Green
Mode of inheritance for gene: RMRP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RMRP were set to 29884839; 38337186
Phenotypes for gene: RMRP were set to Disorders of ribosomal biogenesis; cartilage-hair hypoplasia MONDO:0009595
Mitochondrial disease v0.923 SDHC Bryony Thompson gene: SDHC was added
gene: SDHC was added to Mitochondrial disease. Sources: Expert Review Red
Mode of inheritance for gene: SDHC was set to Unknown
Publications for gene: SDHC were set to 31469588; 29884839
Phenotypes for gene: SDHC were set to Mitochondrial disease MONDO:0044970
Mitochondrial disease v0.923 GPD1 Bryony Thompson gene: GPD1 was added
gene: GPD1 was added to Mitochondrial disease. Sources: Expert Review Green
Mode of inheritance for gene: GPD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GPD1 were set to 29884839; 35988808; 24549054
Phenotypes for gene: GPD1 were set to Disorders of mitochondrial shuttles and carriers; transient infantile hypertriglyceridemia and hepatosteatosis MONDO:0013771
Mitochondrial disease v0.923 L2HGDH Bryony Thompson gene: L2HGDH was added
gene: L2HGDH was added to Mitochondrial disease. Sources: Expert Review Green
Mode of inheritance for gene: L2HGDH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: L2HGDH were set to 29884839; 37995940
Phenotypes for gene: L2HGDH were set to Disorders of mitochondrial metabolite repair; L-2-hydroxyglutaric aciduria MONDO:0009370
Metal Metabolism Disorders v0.45 KCNJ10 Bryony Thompson gene: KCNJ10 was added
gene: KCNJ10 was added to Metal Metabolism Disorders. Sources: Expert Review Green
Mode of inheritance for gene: KCNJ10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KCNJ10 were set to 19289823, 21849804, 11466414
Phenotypes for gene: KCNJ10 were set to EAST syndrome MONDO:0013005, SESAME syndrome, MIM# 612780; Disorders of magnesium metabolism
Metal Metabolism Disorders v0.45 SLC12A3 Bryony Thompson gene: SLC12A3 was added
gene: SLC12A3 was added to Metal Metabolism Disorders. Sources: Expert Review Green
Mode of inheritance for gene: SLC12A3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC12A3 were set to 34604137, 35170241
Phenotypes for gene: SLC12A3 were set to Disorders of magnesium metabolism; Gitelman syndrome MONDO:0009904
Metal Metabolism Disorders v0.45 CNNM2 Bryony Thompson gene: CNNM2 was added
gene: CNNM2 was added to Metal Metabolism Disorders. Sources: Expert Review Green
Mode of inheritance for gene: CNNM2 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: CNNM2 were set to 34604137, 35170241
Phenotypes for gene: CNNM2 were set to renal hypomagnesemia 6 MONDO:0013480; Disorders of magnesium metabolism
Metal Metabolism Disorders v0.45 CLDN19 Bryony Thompson gene: CLDN19 was added
gene: CLDN19 was added to Metal Metabolism Disorders. Sources: Expert Review Green
Mode of inheritance for gene: CLDN19 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CLDN19 were set to 17033971, 22422540, 27530400
Phenotypes for gene: CLDN19 were set to Disorders of magnesium metabolism; renal hypomagnesemia 5 with ocular involvement MONDO:0009548
Metal Metabolism Disorders v0.45 CLDN16 Bryony Thompson gene: CLDN16 was added
gene: CLDN16 was added to Metal Metabolism Disorders. Sources: Expert Review Green
Mode of inheritance for gene: CLDN16 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CLDN16 were set to 26426912, 16501001, 10878661
Phenotypes for gene: CLDN16 were set to Disorders of magnesium metabolism; renal hypomagnesemia 3 MONDO:0009550
Metal Metabolism Disorders v0.45 CLDN10 Bryony Thompson gene: CLDN10 was added
gene: CLDN10 was added to Metal Metabolism Disorders. Sources: Expert Review Green
Mode of inheritance for gene: CLDN10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CLDN10 were set to 28686597
Phenotypes for gene: CLDN10 were set to Disorders of magnesium metabolism; HELIX syndrome MONDO:0060564
Metal Metabolism Disorders v0.45 FXYD2 Bryony Thompson gene: FXYD2 was added
gene: FXYD2 was added to Metal Metabolism Disorders. Sources: Expert Review Amber
Mode of inheritance for gene: FXYD2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FXYD2 were set to 17980699, 12763862, 18448590, 11062458, 25765846, 27014088
Phenotypes for gene: FXYD2 were set to Renal hypomagnesemia 2 MONDO:0007937, Disorders of magnesium metabolism
Metal Metabolism Disorders v0.45 TRPM6 Bryony Thompson gene: TRPM6 was added
gene: TRPM6 was added to Metal Metabolism Disorders. Sources: Expert Review Green
Mode of inheritance for gene: TRPM6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRPM6 were set to 23942199
Phenotypes for gene: TRPM6 were set to Hypomagnesemia 1, intestinal MONDO:0011176, Disorders of magnesium metabolism
Metal Metabolism Disorders v0.45 SEPSECS Bryony Thompson gene: SEPSECS was added
gene: SEPSECS was added to Metal Metabolism Disorders. Sources: Expert Review Green
Mode of inheritance for gene: SEPSECS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SEPSECS were set to 20920667, 25044680, 31748115, 29464431
Phenotypes for gene: SEPSECS were set to pontocerebellar hypoplasia type 2D MONDO:0013438; Other disorders of trace element metabolism
Metal Metabolism Disorders v0.45 SECISBP2 Bryony Thompson gene: SECISBP2 was added
gene: SECISBP2 was added to Metal Metabolism Disorders. Sources: Expert Review Green
Mode of inheritance for gene: SECISBP2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SECISBP2 were set to 16228000, 19602558, 21084748, 22247018
Phenotypes for gene: SECISBP2 were set to thyroid hormone metabolism, abnormal 1 MONDO:0800046; Other disorders of trace element metabolism
Metal Metabolism Disorders v0.45 SLC30A9 Bryony Thompson gene: SLC30A9 was added
gene: SLC30A9 was added to Metal Metabolism Disorders. Sources: Expert Review Green
Mode of inheritance for gene: SLC30A9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC30A9 were set to 37041080
Phenotypes for gene: SLC30A9 were set to Birk-Landau-Perez syndrome (MIM#617595); Disorders of zinc metabolism
Metal Metabolism Disorders v0.45 SLC39A13 Bryony Thompson gene: SLC39A13 was added
gene: SLC39A13 was added to Metal Metabolism Disorders. Sources: Expert Review Green
Mode of inheritance for gene: SLC39A13 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC39A13 were set to 18985159, 18513683
Phenotypes for gene: SLC39A13 were set to Ehlers-Danlos syndrome, spondylocheirodysplastic type MONDO:0012873; Disorders of zinc metabolism
Metal Metabolism Disorders v0.45 SLC30A2 Bryony Thompson gene: SLC30A2 was added
gene: SLC30A2 was added to Metal Metabolism Disorders. Sources: Expert Review Green
Mode of inheritance for gene: SLC30A2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SLC30A2 were set to 17065149, 22733820, 32278324, 30450693, 28665435
Phenotypes for gene: SLC30A2 were set to Zinc deficiency, transient neonatal , MIM#608118; Disorders of zinc metabolism
Metal Metabolism Disorders v0.45 SLC39A4 Bryony Thompson gene: SLC39A4 was added
gene: SLC39A4 was added to Metal Metabolism Disorders. Sources: Expert Review Green
Mode of inheritance for gene: SLC39A4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC39A4 were set to 19370757
Phenotypes for gene: SLC39A4 were set to acrodermatitis enteropathica MONDO:0008713; Disorders of zinc metabolism
Metal Metabolism Disorders v0.45 SLC39A8 Bryony Thompson gene: SLC39A8 was added
gene: SLC39A8 was added to Metal Metabolism Disorders. Sources: Expert Review Green
Mode of inheritance for gene: SLC39A8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC39A8 were set to 26637978, 26637979
Phenotypes for gene: SLC39A8 were set to SLC39A8-CDG MONDO:0014746; Other disorders of trace element metabolism
Metal Metabolism Disorders v0.45 SLC39A14 Bryony Thompson gene: SLC39A14 was added
gene: SLC39A14 was added to Metal Metabolism Disorders. Sources: Expert Review Green
Mode of inheritance for gene: SLC39A14 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC39A14 were set to 27231142, 29685658
Phenotypes for gene: SLC39A14 were set to hypermanganesemia with dystonia 2 MONDO:0014864; Disorders of magnesium metabolism
Metal Metabolism Disorders v0.45 SLC30A10 Bryony Thompson gene: SLC30A10 was added
gene: SLC30A10 was added to Metal Metabolism Disorders. Sources: Expert Review Green
Mode of inheritance for gene: SLC30A10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC30A10 were set to 22341972, 22341971, 29193034
Phenotypes for gene: SLC30A10 were set to hypermanganesemia syndrome MONDO:0013208; Disorders of magnesium metabolism
Metal Metabolism Disorders v0.45 TFRC Bryony Thompson gene: TFRC was added
gene: TFRC was added to Metal Metabolism Disorders. Sources: Expert Review Amber
Mode of inheritance for gene: TFRC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TFRC were set to 26642240
Phenotypes for gene: TFRC were set to Disorders of iron metabolism; TFRC-related combined immunodeficiency MONDO:0014760
Metal Metabolism Disorders v0.45 SLC33A1 Bryony Thompson gene: SLC33A1 was added
gene: SLC33A1 was added to Metal Metabolism Disorders. Sources: Expert Review Green
Mode of inheritance for gene: SLC33A1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC33A1 were set to 31194315
Phenotypes for gene: SLC33A1 were set to Disorders of copper metabolism; Huppke-Brendel syndrome MONDO:0013772
Metal Metabolism Disorders v0.45 AP1S1 Bryony Thompson gene: AP1S1 was added
gene: AP1S1 was added to Metal Metabolism Disorders. Sources: Expert Review Green
Mode of inheritance for gene: AP1S1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AP1S1 were set to 31399000
Phenotypes for gene: AP1S1 were set to MEDNIK syndrome MONDO:0012251; Disorders of copper metabolism
Metal Metabolism Disorders v0.45 ATP7A Bryony Thompson gene: ATP7A was added
gene: ATP7A was added to Metal Metabolism Disorders. Sources: Expert Review Green
Mode of inheritance for gene: ATP7A was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: ATP7A were set to 20170900, 33137485, 31969342, 31558336
Phenotypes for gene: ATP7A were set to Disorders of copper metabolism; Menkes disease MONDO:0010651, occipital Horn Syndrome (OHS, OMIM #304150), X-linked distal spinal muscular atrophy-3 (SMAX3, OMIM #300489)
Metal Metabolism Disorders v0.45 MOCOS Bryony Thompson gene: MOCOS was added
gene: MOCOS was added to Metal Metabolism Disorders. Sources: Expert Review Green
Mode of inheritance for gene: MOCOS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MOCOS were set to 25370766, 17368066, 34356852
Phenotypes for gene: MOCOS were set to Disorders of molybdenum cofactor metabolism; xanthinuria type II MONDO:0011346
Metal Metabolism Disorders v0.45 GPHN Bryony Thompson gene: GPHN was added
gene: GPHN was added to Metal Metabolism Disorders. Sources: Expert Review Green
Mode of inheritance for gene: GPHN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GPHN were set to 27604308, 11095995, 22040219, 9812897
Phenotypes for gene: GPHN were set to Disorders of molybdenum cofactor metabolism; sulfite oxidase deficiency due to molybdenum cofactor deficiency type C MONDO:0014212
Metal Metabolism Disorders v0.45 MOCS2 Bryony Thompson gene: MOCS2 was added
gene: MOCS2 was added to Metal Metabolism Disorders. Sources: Expert Review Green
Mode of inheritance for gene: MOCS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MOCS2 were set to 27604308, 10053004
Phenotypes for gene: MOCS2 were set to sulfite oxidase deficiency due to molybdenum cofactor deficiency type B MONDO:0009644; Disorders of molybdenum cofactor metabolism
Metal Metabolism Disorders v0.45 MOCS1 Bryony Thompson gene: MOCS1 was added
gene: MOCS1 was added to Metal Metabolism Disorders. Sources: Expert Review Green
Mode of inheritance for gene: MOCS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MOCS1 were set to 27604308, 9731530
Phenotypes for gene: MOCS1 were set to Disorders of molybdenum cofactor metabolism; sulfite oxidase deficiency due to molybdenum cofactor deficiency type A MONDO:0009643
Lysosomal Storage Disorder v1.11 CTSC Bryony Thompson gene: CTSC was added
gene: CTSC was added to Lysosomal Storage Disorder. Sources: Expert Review Green
Mode of inheritance for gene: CTSC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CTSC were set to 31282082; 29884839
Phenotypes for gene: CTSC were set to ectodermal dysplasia syndrome MONDO:0019287; Other disorders of complex molecule degradation
Lysosomal Storage Disorder v1.11 SCARB2 Bryony Thompson gene: SCARB2 was added
gene: SCARB2 was added to Lysosomal Storage Disorder. Sources: Expert Review Green
Mode of inheritance for gene: SCARB2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SCARB2 were set to 26677510; 29884839
Phenotypes for gene: SCARB2 were set to action myoclonus-renal failure syndrome MONDO:0009699; Other disorders of complex molecule degradation
Lysosomal Storage Disorder v1.11 KCTD7 Bryony Thompson gene: KCTD7 was added
gene: KCTD7 was added to Lysosomal Storage Disorder. Sources: Expert Review Green
Mode of inheritance for gene: KCTD7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KCTD7 were set to 36368077; 30295347; 29884839
Phenotypes for gene: KCTD7 were set to Progressive myoclonus epilepsy MONDO:0020074; Neuronal ceroid lipofuscinosis
Lysosomal Storage Disorder v1.11 GRN Bryony Thompson gene: GRN was added
gene: GRN was added to Lysosomal Storage Disorder. Sources: Expert Review Green
Mode of inheritance for gene: GRN was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: GRN were set to 37981505; 38347588; 29884839
Phenotypes for gene: GRN were set to neuronal ceroid lipofuscinosis MONDO:0016295; GRN-related frontotemporal lobar degeneration with Tdp43 inclusions MONDO:0011842
Lysosomal Storage Disorder v1.11 RAB7A Bryony Thompson gene: RAB7A was added
gene: RAB7A was added to Lysosomal Storage Disorder. Sources: Expert Review Green
Mode of inheritance for gene: RAB7A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RAB7A were set to 35159308; 36449254; 29884839
Phenotypes for gene: RAB7A were set to Disorders of autophagy; Charcot-Marie-Tooth disease type 2 MONDO:0018993
Lysosomal Storage Disorder v1.11 TBK1 Bryony Thompson gene: TBK1 was added
gene: TBK1 was added to Lysosomal Storage Disorder. Sources: Expert Review Green
Mode of inheritance for gene: TBK1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TBK1 were set to 38168426; 38517332; 29884839
Phenotypes for gene: TBK1 were set to frontotemporal dementia with motor neuron disease MONDO:0017161; Disorders of autophagy
Lysosomal Storage Disorder v1.11 TECPR2 Bryony Thompson gene: TECPR2 was added
gene: TECPR2 was added to Lysosomal Storage Disorder. Sources: Expert Review Green
Mode of inheritance for gene: TECPR2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TECPR2 were set to 33213269; 34130600; 29884839
Phenotypes for gene: TECPR2 were set to Disorders of autophagy; hereditary spastic paraplegia 49 MONDO:0014016
Lysosomal Storage Disorder v1.11 AP5Z1 Bryony Thompson gene: AP5Z1 was added
gene: AP5Z1 was added to Lysosomal Storage Disorder. Sources: Expert Review Green
Mode of inheritance for gene: AP5Z1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AP5Z1 were set to 26085577; 29884839
Phenotypes for gene: AP5Z1 were set to Disorders of autophagy; hereditary spastic paraplegia MONDO:0019064
Lysosomal Storage Disorder v1.11 ZFYVE26 Bryony Thompson gene: ZFYVE26 was added
gene: ZFYVE26 was added to Lysosomal Storage Disorder. Sources: Expert Review Green
Mode of inheritance for gene: ZFYVE26 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZFYVE26 were set to 36029068; 34130600; 29884839
Phenotypes for gene: ZFYVE26 were set to Disorders of autophagy; hereditary spastic paraplegia 15 MONDO:0010044
Lysosomal Storage Disorder v1.11 SPG11 Bryony Thompson gene: SPG11 was added
gene: SPG11 was added to Lysosomal Storage Disorder. Sources: Expert Review Green
Mode of inheritance for gene: SPG11 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SPG11 were set to 37871017; 37709208; 29884839
Phenotypes for gene: SPG11 were set to Disorders of autophagy; hereditary spastic paraplegia 11 MONDO:0011445
Lysosomal Storage Disorder v1.11 SNX14 Bryony Thompson gene: SNX14 was added
gene: SNX14 was added to Lysosomal Storage Disorder. Sources: Expert Review Green
Mode of inheritance for gene: SNX14 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SNX14 were set to 34130600; 29884839
Phenotypes for gene: SNX14 were set to Disorders of autophagy; autosomal recessive spinocerebellar ataxia 20 MONDO:0014601
Lysosomal Storage Disorder v1.11 WDR45 Bryony Thompson gene: WDR45 was added
gene: WDR45 was added to Lysosomal Storage Disorder. Sources: Expert Review Green
Mode of inheritance for gene: WDR45 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: WDR45 were set to 38465922; 29884839
Phenotypes for gene: WDR45 were set to Disorders of autophagy; X-linked complex neurodevelopmental disorder MONDO:0100148
Lysosomal Storage Disorder v1.11 EPG5 Bryony Thompson gene: EPG5 was added
gene: EPG5 was added to Lysosomal Storage Disorder. Sources: Expert Review Green
Mode of inheritance for gene: EPG5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EPG5 were set to 33674710; 34130600; 29884839
Phenotypes for gene: EPG5 were set to Disorders of autophagy; Vici syndrome MONDO:0009452
Haem degradation and bilirubin metabolism defects v0.17 SLCO1B3 Bryony Thompson gene: SLCO1B3 was added
gene: SLCO1B3 was added to Haem degradation and bilirubin metabolism defects. Sources: Expert Review Green
Mode of inheritance for gene: SLCO1B3 was set to Other
Publications for gene: SLCO1B3 were set to 36964102, 33860121
Phenotypes for gene: SLCO1B3 were set to Rotor syndrome MONDO:0009379 (MIM#237450), Disorders of bilirubin metabolism and biliary transport
Haem degradation and bilirubin metabolism defects v0.17 SLC10A2 Bryony Thompson gene: SLC10A2 was added
gene: SLC10A2 was added to Haem degradation and bilirubin metabolism defects. Sources: Expert Review Red
Mode of inheritance for gene: SLC10A2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC10A2 were set to 9109432
Phenotypes for gene: SLC10A2 were set to bile acid malabsorption, primary, 1 MONDO:0013214; Disorders of bile acid metabolism
Haem degradation and bilirubin metabolism defects v0.17 NR1H4 Bryony Thompson gene: NR1H4 was added
gene: NR1H4 was added to Haem degradation and bilirubin metabolism defects. Sources: Expert Review Green
Mode of inheritance for gene: NR1H4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NR1H4 were set to 26888176, 32443034
Phenotypes for gene: NR1H4 were set to Disorders of bile acid metabolism; cholestasis, progressive familial intrahepatic, 5 MONDO:0014884
Haem degradation and bilirubin metabolism defects v0.17 ABCB4 Bryony Thompson gene: ABCB4 was added
gene: ABCB4 was added to Haem degradation and bilirubin metabolism defects. Sources: Expert Review Green
Mode of inheritance for gene: ABCB4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ABCB4 were set to 8666348
Phenotypes for gene: ABCB4 were set to Disorders of bile acid metabolism; progressive familial intrahepatic cholestasis type 3 MONDO:0011214
Haem degradation and bilirubin metabolism defects v0.17 ABCB11 Bryony Thompson gene: ABCB11 was added
gene: ABCB11 was added to Haem degradation and bilirubin metabolism defects. Sources: Expert Review Green
Mode of inheritance for gene: ABCB11 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ABCB11 were set to 9806540
Phenotypes for gene: ABCB11 were set to progressive familial intrahepatic cholestasis type 2 MONDO:0011156; Disorders of bile acid metabolism
Haem degradation and bilirubin metabolism defects v0.17 ATP8B1 Bryony Thompson gene: ATP8B1 was added
gene: ATP8B1 was added to Haem degradation and bilirubin metabolism defects. Sources: Expert Review Green
Mode of inheritance for gene: ATP8B1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATP8B1 were set to 9500542
Phenotypes for gene: ATP8B1 were set to progressive familial intrahepatic cholestasis type 1 MONDO:0008892; Disorders of bile acid metabolism
Haem degradation and bilirubin metabolism defects v0.17 SLCO1B1 Bryony Thompson gene: SLCO1B1 was added
gene: SLCO1B1 was added to Haem degradation and bilirubin metabolism defects. Sources: Expert Review Green
Mode of inheritance for gene: SLCO1B1 was set to Other
Publications for gene: SLCO1B1 were set to 36964102, 33860121
Phenotypes for gene: SLCO1B1 were set to Rotor syndrome MONDO:0009379 (MIM#237450), Disorders of bilirubin metabolism and biliary transport
Haem degradation and bilirubin metabolism defects v0.17 ABCC2 Bryony Thompson gene: ABCC2 was added
gene: ABCC2 was added to Haem degradation and bilirubin metabolism defects. Sources: Expert Review Green
Mode of inheritance for gene: ABCC2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ABCC2 were set to 21044052, 11477083
Phenotypes for gene: ABCC2 were set to Disorders of haem degradation and bilirubin metabolism; Dubin-Johnson syndrome MONDO:0009380
Haem degradation and bilirubin metabolism defects v0.17 UGT1A1 Bryony Thompson gene: UGT1A1 was added
gene: UGT1A1 was added to Haem degradation and bilirubin metabolism defects. Sources: Expert Review Green
Mode of inheritance for gene: UGT1A1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: UGT1A1 were set to 26595536
Phenotypes for gene: UGT1A1 were set to Disorders of haem degradation and bilirubin metabolism; Crigler-Najjar syndrome type 1 MONDO:0021020, Crigler-Najjar syndrome type 2 MONDO:0011725
Haem degradation and bilirubin metabolism defects v0.17 BLVRA Bryony Thompson gene: BLVRA was added
gene: BLVRA was added to Haem degradation and bilirubin metabolism defects. Sources: Expert Review Amber
Mode of inheritance for gene: BLVRA was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: BLVRA were set to 19580635, 21278388
Phenotypes for gene: BLVRA were set to Disorders of haem degradation and bilirubin metabolism; hyperbiliverdinemia MONDO:0013595
Haem degradation and bilirubin metabolism defects v0.17 HMOX1 Bryony Thompson gene: HMOX1 was added
gene: HMOX1 was added to Haem degradation and bilirubin metabolism defects. Sources: Expert Review Green
Mode of inheritance for gene: HMOX1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HMOX1 were set to 21088618, 9884342, 20844238, 33066778
Phenotypes for gene: HMOX1 were set to Disorders of haem degradation and bilirubin metabolism; heme oxygenase 1 deficiency MONDO:0013536
Haem degradation and bilirubin metabolism defects v0.17 CYB5A Bryony Thompson gene: CYB5A was added
gene: CYB5A was added to Haem degradation and bilirubin metabolism defects. Sources: Expert Review Amber
Mode of inheritance for gene: CYB5A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CYB5A were set to 22170710, 20080843, 32051920, 3951505
Phenotypes for gene: CYB5A were set to Disorders of haem degradation and bilirubin metabolism; methemoglobinemia type 4 MONDO:0009605
Haem degradation and bilirubin metabolism defects v0.17 CYB5R3 Bryony Thompson gene: CYB5R3 was added
gene: CYB5R3 was added to Haem degradation and bilirubin metabolism defects. Sources: Expert Review Green
Mode of inheritance for gene: CYB5R3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CYB5R3 were set to 2107882, 1707593, 12393396
Phenotypes for gene: CYB5R3 were set to Disorders of haem degradation and bilirubin metabolism; methemoglobinemia due to deficiency of methemoglobin reductase MONDO:0009606
Haem degradation and bilirubin metabolism defects v0.17 ABCB6 Bryony Thompson gene: ABCB6 was added
gene: ABCB6 was added to Haem degradation and bilirubin metabolism defects. Sources: Expert Review Red
Mode of inheritance for gene: ABCB6 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ABCB6 were set to 24947683
Phenotypes for gene: ABCB6 were set to familial pseudohyperkalemia MONDO:0012204; Disorders of heme synthesis and porphyrias
Dyslipidaemia v0.41 SAR1B Bryony Thompson Marked gene: SAR1B as ready
Dyslipidaemia v0.41 SAR1B Bryony Thompson Gene: sar1b has been classified as Green List (High Evidence).
Dyslipidaemia v0.41 SAR1B Bryony Thompson Classified gene: SAR1B as Green List (high evidence)
Dyslipidaemia v0.41 SAR1B Bryony Thompson Gene: sar1b has been classified as Green List (High Evidence).
Dyslipidaemia v0.40 SAR1B Bryony Thompson gene: SAR1B was added
gene: SAR1B was added to Dyslipidaemia. Sources: Expert list
Mode of inheritance for gene: SAR1B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SAR1B were set to 12692552
Phenotypes for gene: SAR1B were set to Chylomicron retention disease, MIM# 246700
Review for gene: SAR1B was set to GREEN
gene: SAR1B was marked as current diagnostic
Added comment: Well-established inborn error of lipoprotein metabolism
Sources: Expert list
Dyslipidaemia v0.39 ANGPTL3 Bryony Thompson Classified gene: ANGPTL3 as Green List (high evidence)
Dyslipidaemia v0.39 ANGPTL3 Bryony Thompson Gene: angptl3 has been classified as Green List (High Evidence).
Dyslipidaemia v0.38 ANGPTL3 Bryony Thompson gene: ANGPTL3 was added
gene: ANGPTL3 was added to Dyslipidaemia. Sources: Expert list
Mode of inheritance for gene: ANGPTL3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ANGPTL3 were set to 23150577; 20942659; 22155345; 22062970
Phenotypes for gene: ANGPTL3 were set to Hypobetalipoproteinemia, familial, 2 MIM#605019
Review for gene: ANGPTL3 was set to GREEN
gene: ANGPTL3 was marked as current diagnostic
Added comment: Well-established inborn error of lipoprotein metabolism
Sources: Expert list
Vitamin metabolism disorders v1.2 UBIAD1 Bryony Thompson gene: UBIAD1 was added
gene: UBIAD1 was added to Vitamin metabolism disorders. Sources: Expert Review Green
Mode of inheritance for gene: UBIAD1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: UBIAD1 were set to 18176953, 23169578, 31323021, 30785396, 30223810
Phenotypes for gene: UBIAD1 were set to Schnyder corneal dystrophy MONDO:0007374 MIM#611632; Other disorders of vitamin metabolism
Vitamin metabolism disorders v1.2 EPHX1 Bryony Thompson gene: EPHX1 was added
gene: EPHX1 was added to Vitamin metabolism disorders. Sources: Expert Review Red
Mode of inheritance for gene: EPHX1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EPHX1 were set to 34342583
Phenotypes for gene: EPHX1 were set to Familial hypercholanemia MONDO:0011905; Other disorders of vitamin metabolism
Vitamin metabolism disorders v1.2 VKORC1 Bryony Thompson gene: VKORC1 was added
gene: VKORC1 was added to Vitamin metabolism disorders. Sources: Expert Review Green
Mode of inheritance for gene: VKORC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: VKORC1 were set to 14765194
Phenotypes for gene: VKORC1 were set to vitamin K-dependent clotting factors, combined deficiency of, type 2 MONDO:0011837; Other disorders of vitamin metabolism
Vitamin metabolism disorders v1.2 GGCX Bryony Thompson gene: GGCX was added
gene: GGCX was added to Vitamin metabolism disorders. Sources: Expert Review Green
Mode of inheritance for gene: GGCX was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GGCX were set to 32785662, 30531603, 26758921
Phenotypes for gene: GGCX were set to vitamin K-dependent clotting factors, combined deficiency of, type 1 MONDO:0010187; Other disorders of vitamin metabolism
Vitamin metabolism disorders v1.2 TTPA Bryony Thompson gene: TTPA was added
gene: TTPA was added to Vitamin metabolism disorders. Sources: Expert Review green
Mode of inheritance for gene: TTPA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TTPA were set to 27604308, 7719340
Phenotypes for gene: TTPA were set to familial isolated deficiency of vitamin E MONDO:0010188; Other disorders of vitamin metabolism
Vitamin metabolism disorders v1.2 CYP24A1 Bryony Thompson gene: CYP24A1 was added
gene: CYP24A1 was added to Vitamin metabolism disorders. Sources: Expert Review Green
Mode of inheritance for gene: CYP24A1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CYP24A1 were set to 21675912, 22047572, 33516786, 33186763, 32866123, 32743688
Phenotypes for gene: CYP24A1 were set to Other disorders of vitamin metabolism; hypercalcemia, infantile, 1 MONDO:0020739
Vitamin metabolism disorders v1.2 VDR Bryony Thompson gene: VDR was added
gene: VDR was added to Vitamin metabolism disorders. Sources: Expert Review Green
Mode of inheritance for gene: VDR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: VDR were set to 2849209, 9005998, 17970811
Phenotypes for gene: VDR were set to vitamin D-dependent rickets, type 2A MONDO:0010186, Other disorders of vitamin metabolism
Vitamin metabolism disorders v1.2 CYP2R1 Bryony Thompson gene: CYP2R1 was added
gene: CYP2R1 was added to Vitamin metabolism disorders. Sources: Expert Review Green
Mode of inheritance for gene: CYP2R1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CYP2R1 were set to 15128933, 28548312
Phenotypes for gene: CYP2R1 were set to vitamin D hydroxylation-deficient rickets, type 1B MONDO:0010810; Other disorders of vitamin metabolism
Vitamin metabolism disorders v1.2 CYP27B1 Bryony Thompson gene: CYP27B1 was added
gene: CYP27B1 was added to Vitamin metabolism disorders. Sources: Expert Review Green
Mode of inheritance for gene: CYP27B1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CYP27B1 were set to 9486994, 9415400, 12050193, 27473561, 34492747, 33823104
Phenotypes for gene: CYP27B1 were set to vitamin D-dependent rickets, type 1A MONDO:0020723; Other disorders of vitamin metabolism
Vitamin metabolism disorders v1.2 RLBP1 Bryony Thompson gene: RLBP1 was added
gene: RLBP1 was added to Vitamin metabolism disorders. Sources: Expert Review Green
Mode of inheritance for gene: RLBP1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: RLBP1 were set to 9326942
Phenotypes for gene: RLBP1 were set to Other disorders of vitamin metabolism; RLBP1-related retinopathy MONDO:0100444
Vitamin metabolism disorders v1.2 ALDH1A3 Bryony Thompson gene: ALDH1A3 was added
gene: ALDH1A3 was added to Vitamin metabolism disorders. Sources: Expert Review Red
Mode of inheritance for gene: ALDH1A3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ALDH1A3 were set to 23312594, 23591992, 30200890
Phenotypes for gene: ALDH1A3 were set to Isolated microphthalmia 8 MONDO:0014050; Other disorders of vitamin metabolism
Vitamin metabolism disorders v1.2 RBP3 Bryony Thompson gene: RBP3 was added
gene: RBP3 was added to Vitamin metabolism disorders. Sources: Expert Review Red
Mode of inheritance for gene: RBP3 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: RBP3 were set to Retinitis pigmentosa 66 MONDO:0014093; Other disorders of vitamin metabolism
Vitamin metabolism disorders v1.2 RDH12 Bryony Thompson gene: RDH12 was added
gene: RDH12 was added to Vitamin metabolism disorders. Sources: Expert Review Green
Mode of inheritance for gene: RDH12 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RDH12 were set to 15322982; 16269441
Phenotypes for gene: RDH12 were set to Leber congenital amaurosis 13 MONDO:0012990; Other disorders of vitamin metabolism
Vitamin metabolism disorders v1.2 RDH5 Bryony Thompson gene: RDH5 was added
gene: RDH5 was added to Vitamin metabolism disorders. Sources: Expert Review Green
Mode of inheritance for gene: RDH5 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: RDH5 were set to 32232344; 10369264
Phenotypes for gene: RDH5 were set to Fundus albipunctatus; Other disorders of vitamin metabolism
Vitamin metabolism disorders v1.2 RPE65 Bryony Thompson gene: RPE65 was added
gene: RPE65 was added to Vitamin metabolism disorders. Sources: Expert Review Green
Mode of inheritance for gene: RPE65 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RPE65 were set to 9326941
Phenotypes for gene: RPE65 were set to Disorders of vitamin A metabolism; RPE65-related recessive retinopathy MONDO:0100368
Vitamin metabolism disorders v1.2 LRAT Bryony Thompson gene: LRAT was added
gene: LRAT was added to Vitamin metabolism disorders. Sources: Expert Review Green
Mode of inheritance for gene: LRAT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LRAT were set to 11381255
Phenotypes for gene: LRAT were set to Leber congenital amaurosis 14
Vitamin metabolism disorders v1.2 STRA6 Bryony Thompson gene: STRA6 was added
gene: STRA6 was added to Vitamin metabolism disorders. Sources: Expert Review Amber
Mode of inheritance for gene: STRA6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: STRA6 were set to 21901792, 18316031, 24852372
Phenotypes for gene: STRA6 were set to Matthew-Wood syndrome MONDO:0011010; Other disorders of vitamin metabolism
Vitamin metabolism disorders v1.2 RBP4 Bryony Thompson gene: RBP4 was added
gene: RBP4 was added to Vitamin metabolism disorders. Sources: Expert Review Green
Mode of inheritance for gene: RBP4 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: RBP4 were set to Other disorders of vitamin metabolism; microphthalmia, isolated, with coloboma 10 MONDO:0014635
Vitamin metabolism disorders v1.2 BCO1 Bryony Thompson gene: BCO1 was added
gene: BCO1 was added to Vitamin metabolism disorders. Sources: Expert Review Red
Mode of inheritance for gene: BCO1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: BCO1 were set to 17951468
Phenotypes for gene: BCO1 were set to Other disorders of vitamin metabolism; hereditary hypercarotenemia and vitamin A deficiency MONDO:0007272
Vitamin metabolism disorders v1.2 SLC2A10 Bryony Thompson gene: SLC2A10 was added
gene: SLC2A10 was added to Vitamin metabolism disorders. Sources: Expert Review Green
Mode of inheritance for gene: SLC2A10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC2A10 were set to 16550171, 17935213
Phenotypes for gene: SLC2A10 were set to Arterial tortuosity syndrome MONDO:0008818; Other disorders of vitamin metabolism
Vitamin metabolism disorders v1.2 ALPL Bryony Thompson gene: ALPL was added
gene: ALPL was added to Vitamin metabolism disorders. Sources: Expert review Green
Mode of inheritance for gene: ALPL was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: ALPL were set to 3174660, 1409720
Phenotypes for gene: ALPL were set to disorder of bone metabolism; Hypophosphatasia; Disorders of pyridoxine metabolism
Vitamin metabolism disorders v1.2 PLPBP Bryony Thompson gene: PLPBP was added
gene: PLPBP was added to Vitamin metabolism disorders. Sources: Expert Review Green
Mode of inheritance for gene: PLPBP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PLPBP were set to 30668673, 36795901
Phenotypes for gene: PLPBP were set to pyridoxine-dependent epilepsy MONDO:0009945; Disorders of pyridoxine metabolism
Vitamin metabolism disorders v1.2 PNPO Bryony Thompson gene: PNPO was added
gene: PNPO was added to Vitamin metabolism disorders. Sources: Expert Review Green
Mode of inheritance for gene: PNPO was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PNPO were set to 34769443, 33981986, 33748042, 32888189
Phenotypes for gene: PNPO were set to Pyridoxal phosphate-responsive seizures MONDO:0012407; Disorders of pyridoxine metabolism
Vitamin metabolism disorders v1.2 COASY Bryony Thompson gene: COASY was added
gene: COASY was added to Vitamin metabolism disorders. Sources: Expert Review Green
Mode of inheritance for gene: COASY was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COASY were set to 24360804, 28489334, 27021474
Phenotypes for gene: COASY were set to neurodegeneration with brain iron accumulation 6 MONDO:0014290; Disorders of pantothenate and CoA metabolism
Vitamin metabolism disorders v1.2 PANK2 Bryony Thompson gene: PANK2 was added
gene: PANK2 was added to Vitamin metabolism disorders. Sources: Expert Review Green
Mode of inheritance for gene: PANK2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PANK2 were set to 25778941, 11479594, 12510040, 28863176
Phenotypes for gene: PANK2 were set to pantothenate kinase-associated neurodegeneration MONDO:0009319; Disorders of pantothenate and CoA metabolism
Vitamin metabolism disorders v1.2 NNT Bryony Thompson gene: NNT was added
gene: NNT was added to Vitamin metabolism disorders. Sources: Expert Review Green
Mode of inheritance for gene: NNT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NNT were set to 26309815, 22634753
Phenotypes for gene: NNT were set to Disorders of niacin and NAD metabolism; glucocorticoid deficiency 4 MONDO:0013874
Vitamin metabolism disorders v1.2 NAXD Bryony Thompson gene: NAXD was added
gene: NAXD was added to Vitamin metabolism disorders. Sources: Expert Review Green
Mode of inheritance for gene: NAXD was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NAXD were set to 30576410
Phenotypes for gene: NAXD were set to Disorders of niacin and NAD metabolism; Mitochondrial disease MONDO:0044970
Vitamin metabolism disorders v1.2 NAXE Bryony Thompson gene: NAXE was added
gene: NAXE was added to Vitamin metabolism disorders. Sources: Expert Review Green
Mode of inheritance for gene: NAXE was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NAXE were set to 27122014, 27616477, 31758406
Phenotypes for gene: NAXE were set to Apolipoprotein A-I binding protein deficiency; Disorders of niacin and NAD metabolism
Vitamin metabolism disorders v1.2 NADK2 Bryony Thompson gene: NADK2 was added
gene: NADK2 was added to Vitamin metabolism disorders. Sources: Expert Review Green
Mode of inheritance for gene: NADK2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NADK2 were set to 24847004, 27940755, 23212377, 28923496, 29388319
Phenotypes for gene: NADK2 were set to Disorders of niacin and NAD metabolism; 2,4-dienoyl-CoA reductase deficiency, MIM# 616034
Vitamin metabolism disorders v1.2 NMNAT1 Bryony Thompson gene: NMNAT1 was added
gene: NMNAT1 was added to Vitamin metabolism disorders. Sources: Expert Review Green
Mode of inheritance for gene: NMNAT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NMNAT1 were set to 32533184
Phenotypes for gene: NMNAT1 were set to Disorders of niacin and NAD metabolism; Leber congenital amaurosis 9 MONDO:0012056
Vitamin metabolism disorders v1.2 ETFDH Bryony Thompson gene: ETFDH was added
gene: ETFDH was added to Vitamin metabolism disorders. Sources: Expert Review Green
Mode of inheritance for gene: ETFDH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ETFDH were set to 17412732, 27038534, 19249206, 15710863, 32804429
Phenotypes for gene: ETFDH were set to multiple acyl-CoA dehydrogenase deficiency MONDO:0009282; Disorders of mitochondrial fatty acid oxidation
Vitamin metabolism disorders v1.2 ETFB Bryony Thompson gene: ETFB was added
gene: ETFB was added to Vitamin metabolism disorders. Sources: Expert Review Green
Mode of inheritance for gene: ETFB was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ETFB were set to 7912128, 12815589, 27081516, 12706375, 30626930
Phenotypes for gene: ETFB were set to multiple acyl-CoA dehydrogenase deficiency MONDO:0009282; Disorders of mitochondrial fatty acid oxidation
Vitamin metabolism disorders v1.2 ETFA Bryony Thompson gene: ETFA was added
gene: ETFA was added to Vitamin metabolism disorders. Sources: Expert Review Green
Mode of inheritance for gene: ETFA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ETFA were set to 1430199, 1882842, 21347544
Phenotypes for gene: ETFA were set to multiple acyl-CoA dehydrogenase deficiency MONDO:0009282; Disorders of mitochondrial fatty acid oxidation
Vitamin metabolism disorders v1.2 SLC25A32 Bryony Thompson gene: SLC25A32 was added
gene: SLC25A32 was added to Vitamin metabolism disorders. Sources: Expert Review Green
Mode of inheritance for gene: SLC25A32 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC25A32 were set to 26933868; 28443623
Phenotypes for gene: SLC25A32 were set to Exercise intolerance, riboflavin-responsive, MONDO:0014795; Disorders of riboflavin metabolism
Vitamin metabolism disorders v1.2 FLAD1 Bryony Thompson gene: FLAD1 was added
gene: FLAD1 was added to Vitamin metabolism disorders. Sources: Expert Review Green
Mode of inheritance for gene: FLAD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FLAD1 were set to 34454814,34718578, 31392824, 30982706, 30311138, 30427553, 28433476, 27259049, 25058219
Phenotypes for gene: FLAD1 were set to myopathy with abnormal lipid metabolism MONDO:0009703; Disorders of riboflavin metabolism
Vitamin metabolism disorders v1.2 SLC52A2 Bryony Thompson gene: SLC52A2 was added
gene: SLC52A2 was added to Vitamin metabolism disorders. Sources: Expert Review Green
Mode of inheritance for gene: SLC52A2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC52A2 were set to 26973221
Phenotypes for gene: SLC52A2 were set to Brown-Vialetto-van Laere syndrome 2 MONDO:0013867; Disorders of riboflavin metabolism
Vitamin metabolism disorders v1.2 SLC52A3 Bryony Thompson gene: SLC52A3 was added
gene: SLC52A3 was added to Vitamin metabolism disorders. Sources: Expert Review Green
Mode of inheritance for gene: SLC52A3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC52A3 were set to 26973221
Phenotypes for gene: SLC52A3 were set to Disorders of riboflavin metabolism; Brown-Vialetto-van Laere syndrome 1 MONDO:0024537
Vitamin metabolism disorders v1.2 MTHFD1 Bryony Thompson gene: MTHFD1 was added
gene: MTHFD1 was added to Vitamin metabolism disorders. Sources: Expert Review Green
Mode of inheritance for gene: MTHFD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MTHFD1 were set to 32414565; 19033438
Phenotypes for gene: MTHFD1 were set to Combined immunodeficiency and megaloblastic anemia with or without hyperhomocysteinemia MONDO:0060611; Disorders of folate metabolism
Vitamin metabolism disorders v1.2 MTHFR Bryony Thompson gene: MTHFR was added
gene: MTHFR was added to Vitamin metabolism disorders. Sources: Expert Review Green
Mode of inheritance for gene: MTHFR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MTHFR were set to 7920641; 26872964
Phenotypes for gene: MTHFR were set to Homocystinuria due to methylene tetrahydrofolate reductase deficiency MONDO:0009353; Disorders of folate metabolism
Vitamin metabolism disorders v1.2 FOLR1 Bryony Thompson gene: FOLR1 was added
gene: FOLR1 was added to Vitamin metabolism disorders. Sources: Expert Review Green
Mode of inheritance for gene: FOLR1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FOLR1 were set to 27743887; 30420205; 19732866
Phenotypes for gene: FOLR1 were set to Neurodegenerative syndrome due to cerebral folate transport deficiency MONDO:0013110; Disorders of folate metabolism
Vitamin metabolism disorders v1.2 SLC46A1 Bryony Thompson gene: SLC46A1 was added
gene: SLC46A1 was added to Vitamin metabolism disorders. Sources: Expert Review Green
Mode of inheritance for gene: SLC46A1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC46A1 were set to 17129779; 7446347; 21333572
Phenotypes for gene: SLC46A1 were set to Hereditary folate malabsorption MONDO:0009238; Disorders of folate metabolism
Vitamin metabolism disorders v1.2 MMAA Bryony Thompson gene: MMAA was added
gene: MMAA was added to Vitamin metabolism disorders. Sources: Expert Review Green
Mode of inheritance for gene: MMAA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MMAA were set to 12438653; 15523652
Phenotypes for gene: MMAA were set to Disorders of cobalamin metabolism; methylmalonic aciduria, cblA type MONDO:0009613
Vitamin metabolism disorders v1.2 CD320 Bryony Thompson gene: CD320 was added
gene: CD320 was added to Vitamin metabolism disorders. Sources: Expert Review Amber
Mode of inheritance for gene: CD320 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CD320 were set to 27604308; 29663633; 30303736
Phenotypes for gene: CD320 were set to Methylmalonic acidemia due to transcobalamin receptor defect MONDO:0013341
Vitamin metabolism disorders v1.2 HLCS Bryony Thompson gene: HLCS was added
gene: HLCS was added to Vitamin metabolism disorders. Sources: Expert Review Green,ClinGen
Mode of inheritance for gene: HLCS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HLCS were set to 10190325
Phenotypes for gene: HLCS were set to Disorders of biotin metabolism; holocarboxylase synthetase deficiency MONDO:0009666
Metabolic Disorders Superpanel v8.226 Bryony Thompson Changed child panels to: Miscellaneous Metabolic Disorders; Congenital Disorders of Glycosylation; Fatty Acid Oxidation Defects; Lysosomal Storage Disorder; Neurotransmitter Defects; Aminoacidopathy; Glycogen Storage Diseases; Vitamin metabolism disorders; Mitochondrial disease; Monogenic Diabetes; Peroxisomal Disorders; Metal Metabolism Disorders; Dyslipidaemia; Haem degradation and bilirubin metabolism defects; Hyperammonaemia; Nucleotide metabolism disorders
Nucleotide metabolism disorders v0.1 Bryony Thompson Panel status changed from internal to public
Panel types changed to Royal Melbourne Hospital; Rare Disease
Nucleotide metabolism disorders v0.0 AGXT2 Bryony Thompson gene: AGXT2 was added
gene: AGXT2 was added to Nucleotide metabolism disorders. Sources: Expert Review Red
Mode of inheritance for gene: AGXT2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AGXT2 were set to 21572414
Phenotypes for gene: AGXT2 were set to Beta-aminoisobutyric acid, urinary excretion of MIM#210100
Nucleotide metabolism disorders v0.0 UPB1 Bryony Thompson gene: UPB1 was added
gene: UPB1 was added to Nucleotide metabolism disorders. Sources: Expert Review Green
Mode of inheritance for gene: UPB1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: UPB1 were set to 24526388; 1796483; 27604308; 15385443; 25638458; 22525402
Phenotypes for gene: UPB1 were set to Beta-ureidopropionase deficiency MONDO:0013164; Disorders of pyrimidine metabolism
Nucleotide metabolism disorders v0.0 DPYS Bryony Thompson gene: DPYS was added
gene: DPYS was added to Nucleotide metabolism disorders. Sources: Expert Review Green
Mode of inheritance for gene: DPYS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DPYS were set to 9718352; 29054612; 30384990
Phenotypes for gene: DPYS were set to Dihydropyrimidinuria MONDO:0009111; Disorders of pyrimidine metabolism
Nucleotide metabolism disorders v0.0 DPYD Bryony Thompson gene: DPYD was added
gene: DPYD was added to Nucleotide metabolism disorders. Sources: Expert Review Green
Mode of inheritance for gene: DPYD was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DPYD were set to 8051923; 29152729
Phenotypes for gene: DPYD were set to Dihydropyrimidine dehydrogenase deficiency MONDO:0010130; Disorders of pyrimidine metabolism
Nucleotide metabolism disorders v0.0 SLC29A3 Bryony Thompson gene: SLC29A3 was added
gene: SLC29A3 was added to Nucleotide metabolism disorders. Sources: Expert Review Green
Mode of inheritance for gene: SLC29A3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC29A3 were set to 22238637; 18940313; 19336477
Phenotypes for gene: SLC29A3 were set to Disorders of ectonucleotide and nucleic acid metabolism; H syndrome MONDO:0011273
Nucleotide metabolism disorders v0.0 SLC29A1 Bryony Thompson gene: SLC29A1 was added
gene: SLC29A1 was added to Nucleotide metabolism disorders. Sources: Expert Review Red
Mode of inheritance for gene: SLC29A1 was set to Unknown
Nucleotide metabolism disorders v0.0 NT5E Bryony Thompson gene: NT5E was added
gene: NT5E was added to Nucleotide metabolism disorders. Sources: Expert Review Green
Mode of inheritance for gene: NT5E was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NT5E were set to 21288095
Phenotypes for gene: NT5E were set to Disorders of ectonucleotide and nucleic acid metabolism; hereditary arterial and articular multiple calcification syndrome MONDO:0008895
Nucleotide metabolism disorders v0.0 ENPP1 Bryony Thompson gene: ENPP1 was added
gene: ENPP1 was added to Nucleotide metabolism disorders. Sources: Expert Review Green
Mode of inheritance for gene: ENPP1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: ENPP1 were set to 20016754; 12881724
Phenotypes for gene: ENPP1 were set to Cole disease, MIM# 615522; Hypophosphatemic rickets, autosomal recessive, 2, MIM# 613312; Arterial calcification, generalized, of infancy, 1, MIM# 208000
Nucleotide metabolism disorders v0.0 ABCC6 Bryony Thompson gene: ABCC6 was added
gene: ABCC6 was added to Nucleotide metabolism disorders. Sources: Expert Review Green
Mode of inheritance for gene: ABCC6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ABCC6 were set to 28102862; 11536079; 33005041; 34355424
Nucleotide metabolism disorders v0.0 OAS1 Bryony Thompson gene: OAS1 was added
gene: OAS1 was added to Nucleotide metabolism disorders. Sources: Expert Review Green
Mode of inheritance for gene: OAS1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: OAS1 were set to 29455859; 34145065
Phenotypes for gene: OAS1 were set to Disorders of ectonucleotide and nucleic acid metabolism; pulmonary alveolar proteinosis with hypogammaglobulinemia MONDO:0020840
Nucleotide metabolism disorders v0.0 TMEM173 Bryony Thompson gene: TMEM173 was added
gene: TMEM173 was added to Nucleotide metabolism disorders. Sources: Expert Review Green
Mode of inheritance for gene: TMEM173 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TMEM173 were set to 25029335; 25401470
Phenotypes for gene: TMEM173 were set to STING-associated vasculopathy with onset in infancy MONDO:0014405
Nucleotide metabolism disorders v0.0 IFIH1 Bryony Thompson gene: IFIH1 was added
gene: IFIH1 was added to Nucleotide metabolism disorders. Sources: Expert Review Green
Mode of inheritance for gene: IFIH1 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: IFIH1 were set to 34185153; 24686847
Phenotypes for gene: IFIH1 were set to Disorders of ectonucleotide and nucleic acid metabolism; Aicardi-Goutieres syndrome 7, MIM#615846; Early-onset Inflammatory Bowel Disease
Nucleotide metabolism disorders v0.0 ADAR Bryony Thompson gene: ADAR was added
gene: ADAR was added to Nucleotide metabolism disorders. Sources: Expert Review Green
Mode of inheritance for gene: ADAR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADAR were set to 29221912; 23001123; 24262145
Phenotypes for gene: ADAR were set to Disorders of ectonucleotide and nucleic acid metabolism; Aicardi-Goutieres syndrome MONDO:0018866
Nucleotide metabolism disorders v0.0 SAMHD1 Bryony Thompson gene: SAMHD1 was added
gene: SAMHD1 was added to Nucleotide metabolism disorders. Sources: Expert Review Green
Mode of inheritance for gene: SAMHD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SAMHD1 were set to 33307271; 21102625; 19525956; 20301648
Phenotypes for gene: SAMHD1 were set to Disorders of mitochondrial nucleotide pool maintenance; Aicardi-Goutieres syndrome MONDO:0018866
Nucleotide metabolism disorders v0.0 RNASET2 Bryony Thompson gene: RNASET2 was added
gene: RNASET2 was added to Nucleotide metabolism disorders. Sources: Expert Review Green
Mode of inheritance for gene: RNASET2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RNASET2 were set to 19525954; 29336640; 15851732; 27091087; 31349848; 18545798
Phenotypes for gene: RNASET2 were set to Disorders of ectonucleotide and nucleic acid metabolism; cystic leukoencephalopathy without megalencephaly MONDO:0013058
Nucleotide metabolism disorders v0.0 RNASEH2A Bryony Thompson gene: RNASEH2A was added
gene: RNASEH2A was added to Nucleotide metabolism disorders. Sources: Expert Review Green
Mode of inheritance for gene: RNASEH2A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RNASEH2A were set to 25604658; 23592335; 20301648
Phenotypes for gene: RNASEH2A were set to Disorders of ectonucleotide and nucleic acid metabolism; Aicardi-Goutieres syndrome MONDO:0018866
Nucleotide metabolism disorders v0.0 RNASEH2C Bryony Thompson gene: RNASEH2C was added
gene: RNASEH2C was added to Nucleotide metabolism disorders. Sources: Expert Review Green
Mode of inheritance for gene: RNASEH2C was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RNASEH2C were set to 24183309; 23322642; 16845400
Phenotypes for gene: RNASEH2C were set to Disorders of ectonucleotide and nucleic acid metabolism; Aicardi-Goutieres syndrome MONDO:0018866
Nucleotide metabolism disorders v0.0 RNASEH2B Bryony Thompson gene: RNASEH2B was added
gene: RNASEH2B was added to Nucleotide metabolism disorders. Sources: Expert Review Green
Mode of inheritance for gene: RNASEH2B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RNASEH2B were set to 33307271; 29239743; 16845400
Phenotypes for gene: RNASEH2B were set to Disorders of ectonucleotide and nucleic acid metabolism; Aicardi-Goutieres syndrome MONDO:0018866
Nucleotide metabolism disorders v0.0 TREX1 Bryony Thompson gene: TREX1 was added
gene: TREX1 was added to Nucleotide metabolism disorders. Sources: Expert Review Green
Mode of inheritance for gene: TREX1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: TREX1 were set to 21937424; 17357087; 16845398
Phenotypes for gene: TREX1 were set to Disorder of nucleotide metabolism; Aicardi-Goutieres syndrome 1, dominant and recessive, MIM# 225750
Nucleotide metabolism disorders v0.0 SLC2A9 Bryony Thompson gene: SLC2A9 was added
gene: SLC2A9 was added to Nucleotide metabolism disorders. Sources: Expert Review Green
Mode of inheritance for gene: SLC2A9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC2A9 were set to 19926891; 19026395; 25966807; 21256783; 21810765
Phenotypes for gene: SLC2A9 were set to hereditary renal hypouricemia MONDO:0009071; Disorders of purine metabolism
Nucleotide metabolism disorders v0.0 SLC22A12 Bryony Thompson gene: SLC22A12 was added
gene: SLC22A12 was added to Nucleotide metabolism disorders. Sources: Expert Review Green
Mode of inheritance for gene: SLC22A12 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC22A12 were set to 14655203; 26821810; 34756726; 34829836; 34412930
Phenotypes for gene: SLC22A12 were set to hereditary renal hypouricemia MONDO:0009071; Disorders of purine metabolism
Nucleotide metabolism disorders v0.0 ITPA Bryony Thompson gene: ITPA was added
gene: ITPA was added to Nucleotide metabolism disorders. Sources: Expert Review Green
Mode of inheritance for gene: ITPA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ITPA were set to 12384777; 27604308
Phenotypes for gene: ITPA were set to Disorders of purine metabolism; Inosine triphosphatase deficiency MIM#613850; Developmental and epileptic encephalopathy 35 MIM#616647
Nucleotide metabolism disorders v0.0 TPMT Bryony Thompson gene: TPMT was added
gene: TPMT was added to Nucleotide metabolism disorders. Sources: Expert Review Red
Mode of inheritance for gene: TPMT was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TPMT were set to {Thiopurines, poor metabolism of, 1} 610460
Nucleotide metabolism disorders v0.0 IMPDH1 Bryony Thompson gene: IMPDH1 was added
gene: IMPDH1 was added to Nucleotide metabolism disorders. Sources: Expert Review Green
Mode of inheritance for gene: IMPDH1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: IMPDH1 were set to 11875049; 16384941; 11875050
Phenotypes for gene: IMPDH1 were set to Disorders of purine metabolism; retinitis pigmentosa MONDO:0019200
Nucleotide metabolism disorders v0.0 AK2 Bryony Thompson gene: AK2 was added
gene: AK2 was added to Nucleotide metabolism disorders. Sources: Expert Review Green
Mode of inheritance for gene: AK2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AK2 were set to 19043417; 19043416
Phenotypes for gene: AK2 were set to reticular dysgenesis MONDO:0009973; Disorders of purine metabolism
Nucleotide metabolism disorders v0.0 AK1 Bryony Thompson gene: AK1 was added
gene: AK1 was added to Nucleotide metabolism disorders. Sources: Expert Review Green
Mode of inheritance for gene: AK1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AK1 were set to 2542324; 34321014; 9432020; 10233365
Phenotypes for gene: AK1 were set to hemolytic anemia due to adenylate kinase deficiency MONDO:0012967; Disorders of purine metabolism
Nucleotide metabolism disorders v0.0 APRT Bryony Thompson gene: APRT was added
gene: APRT was added to Nucleotide metabolism disorders. Sources: Expert Review Green
Mode of inheritance for gene: APRT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: APRT were set to 7915931; 2227934; 1353080; 3680503
Phenotypes for gene: APRT were set to adenine phosphoribosyltransferase deficiency MONDO:0013869; Disorders of purine metabolism
Nucleotide metabolism disorders v0.0 HPRT1 Bryony Thompson gene: HPRT1 was added
gene: HPRT1 was added to Nucleotide metabolism disorders. Sources: Expert Review Green
Mode of inheritance for gene: HPRT1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: HPRT1 were set to 2928313; 23975452; 20176575
Phenotypes for gene: HPRT1 were set to Lesch-Nyhan syndrome MONDO:0010298; Disorders of purine metabolism
Nucleotide metabolism disorders v0.0 XDH Bryony Thompson gene: XDH was added
gene: XDH was added to Nucleotide metabolism disorders. Sources: Expert Review Green
Mode of inheritance for gene: XDH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: XDH were set to 32071838; 29723117
Phenotypes for gene: XDH were set to xanthinuria type I MONDO:0010209; Disorders of purine metabolism
Nucleotide metabolism disorders v0.0 PNP Bryony Thompson gene: PNP was added
gene: PNP was added to Nucleotide metabolism disorders. Sources: Expert Review Green
Mode of inheritance for gene: PNP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PNP were set to 1384322; 11453975; 32695102; 3029074; 32514656
Phenotypes for gene: PNP were set to Immunodeficiency due to purine nucleoside phosphorylase deficiency, MIM# 613179; Disorders of purine metabolism
Nucleotide metabolism disorders v0.0 ADA2 Bryony Thompson gene: ADA2 was added
gene: ADA2 was added to Nucleotide metabolism disorders. Sources: Expert Review Green
Mode of inheritance for gene: ADA2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADA2 were set to 24552284; 35095905
Phenotypes for gene: ADA2 were set to Disorders of purine metabolism; Deficiency of adenosine deaminase 2 MONDO:0100317
Nucleotide metabolism disorders v0.0 ADA Bryony Thompson gene: ADA was added
gene: ADA was added to Nucleotide metabolism disorders. Sources: Expert Review Green
Mode of inheritance for gene: ADA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADA were set to 3684597; 3475710; 2783588; 1680289
Phenotypes for gene: ADA were set to Severe combined immunodeficiency due to ADA deficiency MIM#102700; Adenosine deaminase deficiency, partial MIM#102700; disorder of purine metabolism
Nucleotide metabolism disorders v0.0 AMPD3 Bryony Thompson gene: AMPD3 was added
gene: AMPD3 was added to Nucleotide metabolism disorders. Sources: Expert Review Red
Mode of inheritance for gene: AMPD3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AMPD3 were set to 8004104; 24940686; 11139257
Phenotypes for gene: AMPD3 were set to adenosine monophosphate deaminase deficiency MONDO:0013028
Nucleotide metabolism disorders v0.0 AMPD2 Bryony Thompson gene: AMPD2 was added
gene: AMPD2 was added to Nucleotide metabolism disorders. Sources: Expert Review Green
Mode of inheritance for gene: AMPD2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AMPD2 were set to 27066553; 23911318
Phenotypes for gene: AMPD2 were set to pontocerebellar hypoplasia type 9 MONDO:0014351; Disorders of purine metabolism
Nucleotide metabolism disorders v0.0 AMPD1 Bryony Thompson gene: AMPD1 was added
gene: AMPD1 was added to Nucleotide metabolism disorders. Sources: Expert Review Red
Mode of inheritance for gene: AMPD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AMPD1 were set to 27296017; 21343608
Phenotypes for gene: AMPD1 were set to adenosine monophosphate deaminase deficiency MONDO:0013028
Nucleotide metabolism disorders v0.0 ADSL Bryony Thompson gene: ADSL was added
gene: ADSL was added to Nucleotide metabolism disorders. Sources: Expert Review Green
Mode of inheritance for gene: ADSL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADSL were set to 1302001; 22180458; 27626380; 18524658
Phenotypes for gene: ADSL were set to disorder of purine metabolism; Adenylosuccinase deficiency MIM#103050
Nucleotide metabolism disorders v0.0 PRPS1 Bryony Thompson gene: PRPS1 was added
gene: PRPS1 was added to Nucleotide metabolism disorders. Sources: Expert Review Green
Mode of inheritance for gene: PRPS1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: PRPS1 were set to 20380929; 17701900
Phenotypes for gene: PRPS1 were set to PRPS1 deficiency disorder MONDO:0100061; Disorders of purine metabolism
Nucleotide metabolism disorders v0.0 UNG Bryony Thompson gene: UNG was added
gene: UNG was added to Nucleotide metabolism disorders. Sources: Expert Review Green
Mode of inheritance for gene: UNG was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: UNG were set to 12958596; 23585684; 32135276
Phenotypes for gene: UNG were set to hyper-IgM syndrome type 5 MONDO:0011971; Disorders of ectonucleotide and nucleic acid metabolism
Nucleotide metabolism disorders v0.0 AICDA Bryony Thompson gene: AICDA was added
gene: AICDA was added to Nucleotide metabolism disorders. Sources: Expert Review Green
Mode of inheritance for gene: AICDA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AICDA were set to 10373455; 21700883; 14962793
Phenotypes for gene: AICDA were set to hyper-IgM syndrome type 2 MONDO:0011528; Disorders of ectonucleotide and nucleic acid metabolism
Nucleotide metabolism disorders v0.0 NT5C3A Bryony Thompson gene: NT5C3A was added
gene: NT5C3A was added to Nucleotide metabolism disorders. Sources: Expert Review Green
Mode of inheritance for gene: NT5C3A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NT5C3A were set to 11369620
Phenotypes for gene: NT5C3A were set to disorder of pyrimidine metabolism; Anemia, hemolytic, due to UMPH1 deficiency MIM#266120
Nucleotide metabolism disorders v0.0 UMPS Bryony Thompson gene: UMPS was added
gene: UMPS was added to Nucleotide metabolism disorders. Sources: Expert Review Green
Mode of inheritance for gene: UMPS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: UMPS were set to 33489760; 9042911
Phenotypes for gene: UMPS were set to Orotic aciduria, MIM# 258900
Nucleotide metabolism disorders v0.0 DHODH Bryony Thompson gene: DHODH was added
gene: DHODH was added to Nucleotide metabolism disorders. Sources: Expert Review Green
Mode of inheritance for gene: DHODH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DHODH were set to 19915526
Phenotypes for gene: DHODH were set to Miller syndrome MIM#263750; Disorders of pyrimidine metabolism
Nucleotide metabolism disorders v0.0 CAD Bryony Thompson gene: CAD was added
gene: CAD was added to Nucleotide metabolism disorders. Sources: Expert Review Green
Mode of inheritance for gene: CAD was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CAD were set to 25678555; 29884839; 28007989
Phenotypes for gene: CAD were set to Epileptic encephalopathy, early infantile, 50, MIM# 616457
Nucleotide metabolism disorders v0.0 Bryony Thompson Added panel Nucleotide metabolism disorders
Intellectual disability syndromic and non-syndromic v0.5821 SLC6A4 Sangavi Sivagnanasundram changed review comment from: DISPUTED classification by ClinGen ID and Autism GCEP on 06/01/2021 due to variants association with ASD having high frequencies in gnomAD - https://search.clinicalgenome.org/CCID:006198; to: DISPUTED classification by ClinGen ID and Autism GCEP on 06/01/2021. Variants in this gene associated with ASD having high frequencies in gnomAD - https://search.clinicalgenome.org/CCID:006198
Intellectual disability syndromic and non-syndromic v0.5821 SLC6A4 Sangavi Sivagnanasundram reviewed gene: SLC6A4: Rating: RED; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:006198; Phenotypes: autism spectrum disorder MONDO:0005258; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5821 SLC25A15 Rajkumar Krishnaswamy changed review comment from: Rare genetic disorder representing a heterogeneous disease with high clinical variability. Pyramidal dysfunction, developmental, cognitive and behavioural abnormalities have been reported. ID/mental retardation ranging from mild, moderate to severe have been reported in several cases usually manifesting in the childhood or as adult onset.; to: Rare genetic disorder representing a heterogeneous disease with high clinical variability. Lethargy, feeding difficulties, seizures, pyramidal dysfunction, developmental, cognitive and behavioural abnormalities have been reported with various features exhibited at various stages of life e.g. neonates, infantile/childhood and adults.
ID/mental retardation ranging from mild, moderate to severe have been reported in several cases usually manifesting in childhood or adults.
Intellectual disability syndromic and non-syndromic v0.5821 SHROOM4 Sangavi Sivagnanasundram reviewed gene: SHROOM4: Rating: RED; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:006141; Phenotypes: X-linked complex neurodevelopmental disorder MONDO:0100148; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.5821 SETBP1 Sangavi Sivagnanasundram reviewed gene: SETBP1: Rating: GREEN; Mode of pathogenicity: Other; Publications: 28346496, 21037274; Phenotypes: Schinzel-Giedion syndrome MONDO:0010010, complex neurodevelopmental disorder MONDO:0100038; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5821 SLC25A15 Rajkumar Krishnaswamy reviewed gene: SLC25A15: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 18978333, 25874378; Phenotypes: Hyperornithinemia-hyperammonemia-homocitrullinemia syndrome, 238970, hyperammonemia, lethargy, somnolence, refusal to feed, vomiting, tachypnea with respiratory alkalosis, seizures, protein intolerance, developmental delay, spasticity, intellectual disability / mental retardation, dysarthria, learning disabilities, spasticity, liver dysfunction; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5821 SETBP1 Sangavi Sivagnanasundram Deleted their review
Intellectual disability syndromic and non-syndromic v0.5821 SETBP1 Sangavi Sivagnanasundram commented on gene: SETBP1: Classified DEFINITIVE for both conditions by ClinGen ID and Autism GCEP.

SGS classified on 16/02/2021 - https://search.clinicalgenome.org/CCID:006117
Complex neurodevelopmental disorders on 20/10/2020 - https://search.clinicalgenome.org/CCID:006116

LoF is associated with complex neurodevelopmental disorder. There have been 20 LoF variants reported in individuals so far (nonsense, frameshift, large deletions)

GoF is proposed to be the mechanism of disease for Schinzel-Giedion syndrome (SGS) due to an increase in SETBP1 protein production. Missense variants (especially affecting p.868-871) are known to be disease causing.
Intellectual disability syndromic and non-syndromic v0.5821 SETBP1 Sangavi Sivagnanasundram commented on gene: SETBP1: Classified DEFINITIVE for both conditions by ClinGen ID and Autism GCEP.

SGS classified on 16/02/2021 - https://search.clinicalgenome.org/CCID:006117
Complex neurodevelopmental disorders on 20/10/2020 - https://search.clinicalgenome.org/CCID:006116

LoF is associated with complex neurodevelopmental disorder. There have been 20 LoF variants reported in individuals so far (nonsense, frameshift, large deletions)

GoF is proposed to be the mechanism of disease for Schinzel-Giedion syndrome (SGS) due to an increase in SETBP1 protein production. Missense variants (especially affecting p.868-871) are known to be disease causing.
Intellectual disability syndromic and non-syndromic v0.5821 SETBP1 Sangavi Sivagnanasundram reviewed gene: SETBP1: Rating: GREEN; Mode of pathogenicity: Other; Publications: 28346496, 21037274; Phenotypes: Schinzel-Giedion syndrome MONDO:0010010, complex neurodevelopmental disorder MONDO:0100038; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Vitamin metabolism disorders v1.1 Bryony Thompson Panel name changed from Inherited vitamin B12 or cobalamin deficiency to Vitamin metabolism disorders
HPO terms changed from Abnormality of vitamin B12 metabolism, HP:0004341 to Abnormality of vitamin metabolism, HP:0100508
List of related panels changed from Abnormality of vitamin B12 metabolism; HP:0004341 to Abnormality of vitamin metabolism; HP:0100508
Aminoacidopathy v1.6 Bryony Thompson Panel name changed from Disorders of branched chain amino acid metabolism to Aminoacidopathy
Metal Metabolism Disorders v0.44 Bryony Thompson Panel name changed from Iron metabolism disorders to Metal Metabolism Disorders
HPO terms changed from Abnormality of iron homeostasis, HP:0011031 to Abnormality of iron homeostasis, HP:0011031;Abnormal blood transition element cation concentration, HP:0011030
List of related panels changed from Abnormality of iron homeostasis; HP:0011031 to Abnormality of iron homeostasis; HP:0011031;Abnormal blood transition element cation concentration; HP:0011030
Haem degradation and bilirubin metabolism defects v0.16 Bryony Thompson Panel name changed from Porphyria to Haem degradation and bilirubin metabolism defects
HPO terms changed from Porphyria, MONDO:0037939;Abnormal circulating porphyrin concentration, HP:0010472 to Porphyria, MONDO:0037939;Abnormal circulating porphyrin concentration, HP:0010472;Hyperbilirubinemia, HP:0002904
List of related panels changed from Porphyria; MONDO:0037939;Abnormal circulating porphyrin concentration; HP:0010472 to Porphyria; MONDO:0037939;Abnormal circulating porphyrin concentration; HP:0010472;Hyperbilirubinemia; HP:0002904
Intellectual disability syndromic and non-syndromic v0.5821 PTCHD1 Sangavi Sivagnanasundram reviewed gene: PTCHD1: Rating: GREEN; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:005921; Phenotypes: non-syndromic X-linked intellectual disability MONDO:0019181; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.5821 PORCN Sangavi Sivagnanasundram reviewed gene: PORCN: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301712; Phenotypes: focal dermal hypoplasia MONDO:0010592; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability syndromic and non-syndromic v0.5821 PLP1 Sangavi Sivagnanasundram reviewed gene: PLP1: Rating: GREEN; Mode of pathogenicity: Other; Publications: https://search.clinicalgenome.org/CCID:005834; Phenotypes: Pelizeaus-Merzbacher spectrum disorder MONDO:0010714; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.5821 OFD1 Sangavi Sivagnanasundram reviewed gene: OFD1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24884629; Phenotypes: ciliopathy MONDO:0005308; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.5821 OCRL Sangavi Sivagnanasundram reviewed gene: OCRL: Rating: GREEN; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:005696; Phenotypes: oculocerebrorenal syndrome MONDO:0010645; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v1.1789 RBBP8 James The reviewed gene: RBBP8: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID:30561437, 34270086, 32379725; Phenotypes: Jawad syndrome, Pancreatic carcinoma, somatic, Seckel syndrome 2; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5821 NSD1 Sangavi Sivagnanasundram reviewed gene: NSD1: Rating: GREEN; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:005680; Phenotypes: Sotos syndrome MONDO:0019349; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5821 NDP Sangavi Sivagnanasundram edited their review of gene: NDP: Changed rating: GREEN
Intellectual disability syndromic and non-syndromic v0.5821 NDP Sangavi Sivagnanasundram reviewed gene: NDP: Rating: AMBER; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:005574; Phenotypes: Norrie disease MONDO:0010691; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.5821 MID1 Sangavi Sivagnanasundram reviewed gene: MID1: Rating: GREEN; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:005386; Phenotypes: X-linked Opitz G/BBB syndrome MONDO:0010222; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability syndromic and non-syndromic v0.5821 MED23 Sangavi Sivagnanasundram reviewed gene: MED23: Rating: GREEN; Mode of pathogenicity: None; Publications: 21868677, 25845469, 27311965, 27457812, 30847200, 31164858; Phenotypes: syndromic intellectual disability MONDO:0000508; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5821 MED13L Sangavi Sivagnanasundram reviewed gene: MED13L: Rating: GREEN; Mode of pathogenicity: None; Publications: 28645799, 29511999; Phenotypes: syndromic intellectual disability MONDO:0000508; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5821 MED12 Sangavi Sivagnanasundram reviewed gene: MED12: Rating: GREEN; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:005361; Phenotypes: MED12-related intellectual disability syndrome MONDO:0100000; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability syndromic and non-syndromic v0.5821 MBTPS2 Sangavi Sivagnanasundram reviewed gene: MBTPS2: Rating: GREEN; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:005345; Phenotypes: IFAP syndrome 1, with or without BRESHECK syndrome MONDO:0100213; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.5821 MAN1B1 Sangavi Sivagnanasundram reviewed gene: MAN1B1: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: MAN1B1-congenital disorder of glycosylation MONDO:0018349; Mode of inheritance: None
Intellectual disability syndromic and non-syndromic v0.5821 MAGT1 Sangavi Sivagnanasundram reviewed gene: MAGT1: Rating: RED; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:005319; Phenotypes: X-linked intellectual disability MONDO:0100284; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.5821 LAMC3 Sangavi Sivagnanasundram reviewed gene: LAMC3: Rating: RED; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:005265; Phenotypes: complex neurodevelopmental disorder MONDO:0100038; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2752 SYN1 Zornitza Stark Publications for gene: SYN1 were set to 14985377; 21441247; 28973667; 21441247; 34243774
Genetic Epilepsy v0.2752 SYN1 Zornitza Stark Publications for gene: SYN1 were set to
Genetic Epilepsy v0.2751 SYN1 Zornitza Stark Mode of inheritance for gene: SYN1 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.5821 L1CAM Sangavi Sivagnanasundram reviewed gene: L1CAM: Rating: GREEN; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:005260; Phenotypes: L1 syndrome MONDO:0017140; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Genetic Epilepsy v0.2750 SURF1 Zornitza Stark Marked gene: SURF1 as ready
Genetic Epilepsy v0.2750 SURF1 Zornitza Stark Gene: surf1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2750 SURF1 Zornitza Stark Phenotypes for gene: SURF1 were changed from to Mitochondrial complex IV deficiency, nuclear type 1, MIM# 220110
Genetic Epilepsy v0.2749 SURF1 Zornitza Stark Publications for gene: SURF1 were set to
Genetic Epilepsy v0.2748 SURF1 Zornitza Stark Mode of inheritance for gene: SURF1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2747 SURF1 Zornitza Stark changed review comment from: Well established gene-disease association with mitochondrial disease.; to: Well established gene-disease association with mitochondrial disease. Seizures are part of the phenotype.
Genetic Epilepsy v0.2747 SUOX Zornitza Stark Marked gene: SUOX as ready
Genetic Epilepsy v0.2747 SUOX Zornitza Stark Gene: suox has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2747 SUOX Zornitza Stark Phenotypes for gene: SUOX were changed from to Sulfite oxidase deficiency, MIM# 272300
Genetic Epilepsy v0.2746 SUOX Zornitza Stark Publications for gene: SUOX were set to
Intellectual disability syndromic and non-syndromic v0.5821 KIRREL3 Sangavi Sivagnanasundram reviewed gene: KIRREL3: Rating: RED; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:005235; Phenotypes: complex neurodevelopmental disorder MONDO:0100038; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2745 SUOX Zornitza Stark Mode of inheritance for gene: SUOX was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2744 SUOX Zornitza Stark changed review comment from: More than 5 unrelated families reported.; to: More than 5 unrelated families reported. Seizures are part of the phenotype.
Genetic Epilepsy v0.2744 SUCLA2 Zornitza Stark Marked gene: SUCLA2 as ready
Genetic Epilepsy v0.2744 SUCLA2 Zornitza Stark Gene: sucla2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2744 SUCLA2 Zornitza Stark Phenotypes for gene: SUCLA2 were changed from to Mitochondrial DNA depletion syndrome 5 (encephalomyopathic with or without methylmalonic aciduria), MIM# 612073, MONDO:0012791
Genetic Epilepsy v0.2743 SUCLA2 Zornitza Stark Publications for gene: SUCLA2 were set to
Genetic Epilepsy v0.2742 SUCLA2 Zornitza Stark Mode of inheritance for gene: SUCLA2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2741 STRADA Zornitza Stark Marked gene: STRADA as ready
Genetic Epilepsy v0.2741 STRADA Zornitza Stark Gene: strada has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2741 STRADA Zornitza Stark Phenotypes for gene: STRADA were changed from to Polyhydramnios, megalencephaly, and symptomatic epilepsy, OMIM:611087; Polyhydramnios, megalencephaly, and symptomatic epilepsy, MONDO:0012611
Genetic Epilepsy v0.2740 STRADA Zornitza Stark Publications for gene: STRADA were set to
Genetic Epilepsy v0.2739 STRADA Zornitza Stark Mode of inheritance for gene: STRADA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2738 STAG1 Zornitza Stark Marked gene: STAG1 as ready
Genetic Epilepsy v0.2738 STAG1 Zornitza Stark Gene: stag1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2738 STAG1 Zornitza Stark Phenotypes for gene: STAG1 were changed from to Intellectual disability, autosomal dominant 47, MIM# 617635
Genetic Epilepsy v0.2737 STAG1 Zornitza Stark Publications for gene: STAG1 were set to
Genetic Epilepsy v0.2736 STAG1 Zornitza Stark Mode of inheritance for gene: STAG1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2735 STAG1 Zornitza Stark changed review comment from: Twelve unrelated individuals reported in the original paper.; to: Twelve unrelated individuals reported in the original paper. Seizures are part of the phenotype.
Genetic Epilepsy v0.2735 STAG1 Zornitza Stark edited their review of gene: STAG1: Changed phenotypes: Intellectual disability, autosomal dominant 47, MIM# 617635
Genetic Epilepsy v0.2735 SPR Zornitza Stark Marked gene: SPR as ready
Genetic Epilepsy v0.2735 SPR Zornitza Stark Gene: spr has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2735 SPR Zornitza Stark Phenotypes for gene: SPR were changed from to Dystonia, dopa-responsive, due to sepiapterin reductase deficiency, MIM# 612716
Genetic Epilepsy v0.2734 SPR Zornitza Stark Publications for gene: SPR were set to
Genetic Epilepsy v0.2733 SPR Zornitza Stark Mode of inheritance for gene: SPR was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2732 SPR Zornitza Stark changed review comment from: Complex movement disorder, dystonia predominant, but ataxia described in some individuals. Most individuals have had bi-allelic variants identified, uncertain whether there is an association with mono-allelic variants.

Included due to phenotypic overlap.; to: Complex movement disorder, dystonia predominant, but ataxia described in some individuals. Most individuals have had bi-allelic variants identified, uncertain whether there is an association with mono-allelic variants.

Seizures reported.
Genetic Epilepsy v0.2732 SPR Zornitza Stark changed review comment from: Complex movement disorder, dystonia predominant, but ataxia described in some individuals. Most individuals have had bi-allelic variants identified, uncertain whether there is an association with mono-allelic variants.; to: Complex movement disorder, dystonia predominant, but ataxia described in some individuals. Most individuals have had bi-allelic variants identified, uncertain whether there is an association with mono-allelic variants.

Included due to phenotypic overlap.
Genetic Epilepsy v0.2732 SNAP25 Zornitza Stark Marked gene: SNAP25 as ready
Genetic Epilepsy v0.2732 SNAP25 Zornitza Stark Gene: snap25 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2732 SNAP25 Zornitza Stark Phenotypes for gene: SNAP25 were changed from to Neurodevelopmental disorder, MONDO:0700092, SNAP25-related
Genetic Epilepsy v0.2731 SNAP25 Zornitza Stark Publications for gene: SNAP25 were set to
Genetic Epilepsy v0.2730 SNAP25 Zornitza Stark Mode of inheritance for gene: SNAP25 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2729 SNAP25 Zornitza Stark changed review comment from: More than 5 unrelated individuals reported with a neurodevelopmental disorder.

Limited evidence for this being congenital myasthenic syndrome,; to: More than 5 unrelated individuals reported with a neurodevelopmental disorder, including seizures.

Limited evidence for this being congenital myasthenic syndrome,
Genetic Epilepsy v0.2729 SLC6A8 Zornitza Stark Marked gene: SLC6A8 as ready
Genetic Epilepsy v0.2729 SLC6A8 Zornitza Stark Gene: slc6a8 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2729 SLC6A8 Zornitza Stark Phenotypes for gene: SLC6A8 were changed from Cerebral creatine deficiency syndrome 1, MIM# 300352 to Cerebral creatine deficiency syndrome 1, MIM# 300352
Genetic Epilepsy v0.2728 SLC6A8 Zornitza Stark Phenotypes for gene: SLC6A8 were changed from to Cerebral creatine deficiency syndrome 1, MIM# 300352
Genetic Epilepsy v0.2727 SLC6A8 Zornitza Stark Publications for gene: SLC6A8 were set to
Genetic Epilepsy v0.2726 SLC6A8 Zornitza Stark Mode of inheritance for gene: SLC6A8 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Genetic Epilepsy v0.2725 SLC6A8 Zornitza Stark changed review comment from: Well established gene-disease association.
Sources: Expert list; to: Well established gene-disease association. Seizures are part of the phenotype.
Sources: Expert list
Genetic Epilepsy v0.2725 SLC6A19 Zornitza Stark Marked gene: SLC6A19 as ready
Genetic Epilepsy v0.2725 SLC6A19 Zornitza Stark Gene: slc6a19 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2725 SLC6A19 Zornitza Stark Phenotypes for gene: SLC6A19 were changed from to Hartnup disorder, MIM# 234500
Genetic Epilepsy v0.2724 SLC6A19 Zornitza Stark Mode of inheritance for gene: SLC6A19 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2723 SLC6A19 Zornitza Stark changed review comment from: Bi-allelic variants associated with Hartnup disorder, which is characterised by impaired transport of neutral amino acids across epithelial cells in renal proximal tubules and intestinal mucosa. Symptoms include transient manifestations of pellagra, cerebellar ataxia, and psychosis.

Hyperglycinuria/iminoglycinuria: The imino acids, proline and hydroxyproline, share a renal tubular reabsorptive mechanism with glycine. Iminoglycinuria is a benign inborn error of amino acid transport, and is also a normal finding in neonates and infants under 6 months of age (Chesney, 2001). Early studies of families with iminoglycinuria suggested genetic complexity, with homozygotes developing IG and heterozygotes manifesting only hyperglycinuria (HG)
Sources: Expert list; to: Bi-allelic variants associated with Hartnup disorder, which is characterised by impaired transport of neutral amino acids across epithelial cells in renal proximal tubules and intestinal mucosa. Symptoms include transient manifestations of pellagra, cerebellar ataxia, and psychosis. Seizures are part of the phenotype.

Hyperglycinuria/iminoglycinuria: The imino acids, proline and hydroxyproline, share a renal tubular reabsorptive mechanism with glycine. Iminoglycinuria is a benign inborn error of amino acid transport, and is also a normal finding in neonates and infants under 6 months of age (Chesney, 2001). Early studies of families with iminoglycinuria suggested genetic complexity, with homozygotes developing IG and heterozygotes manifesting only hyperglycinuria (HG)
Sources: Expert list
Genetic Epilepsy v0.2723 SLC6A19 Zornitza Stark edited their review of gene: SLC6A19: Changed phenotypes: Hartnup disorder, MIM# 234500; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2723 SLC35A2 Zornitza Stark Marked gene: SLC35A2 as ready
Genetic Epilepsy v0.2723 SLC35A2 Zornitza Stark Gene: slc35a2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2723 SLC35A2 Zornitza Stark Phenotypes for gene: SLC35A2 were changed from Congenital disorder of glycosylation, type IIm (MIM #300896) 30817854; Mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy (MOGHE) to Congenital disorder of glycosylation, type IIm (MIM #300896) 30817854; Mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy (MOGHE)
Genetic Epilepsy v0.2722 SLC35A2 Zornitza Stark Phenotypes for gene: SLC35A2 were changed from to Congenital disorder of glycosylation, type IIm (MIM #300896) 30817854; Mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy (MOGHE)
Genetic Epilepsy v0.2721 SLC35A2 Zornitza Stark Publications for gene: SLC35A2 were set to
Genetic Epilepsy v0.2720 SLC35A2 Zornitza Stark Mode of inheritance for gene: SLC35A2 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, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Genetic Epilepsy v0.2719 SLC35A2 Zornitza Stark Mode of inheritance for gene: SLC35A2 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)
Fetal anomalies v1.245 BCORL1 Zornitza Stark Marked gene: BCORL1 as ready
Fetal anomalies v1.245 BCORL1 Zornitza Stark Gene: bcorl1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.245 BCORL1 Zornitza Stark Classified gene: BCORL1 as Amber List (moderate evidence)
Fetal anomalies v1.245 BCORL1 Zornitza Stark Gene: bcorl1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.244 BCORL1 Zornitza Stark gene: BCORL1 was added
gene: BCORL1 was added to Fetal anomalies. Sources: Expert Review
Mode of inheritance for gene: BCORL1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: BCORL1 were set to Congenital anomaly of the kidney and urinary tract, MONDO:0019719, BCORL1-related
Review for gene: BCORL1 was set to AMBER
Added comment: Emerging evidence of disease association.
Sources: Expert Review
Congenital anomalies of the kidney and urinary tract (CAKUT) Nonsyndromic v0.117 BCORL1 Zornitza Stark Marked gene: BCORL1 as ready
Congenital anomalies of the kidney and urinary tract (CAKUT) Nonsyndromic v0.117 BCORL1 Zornitza Stark Gene: bcorl1 has been classified as Amber List (Moderate Evidence).
Congenital anomalies of the kidney and urinary tract (CAKUT) Nonsyndromic v0.117 BCORL1 Zornitza Stark Classified gene: BCORL1 as Amber List (moderate evidence)
Congenital anomalies of the kidney and urinary tract (CAKUT) Nonsyndromic v0.117 BCORL1 Zornitza Stark Gene: bcorl1 has been classified as Amber List (Moderate Evidence).
Congenital anomalies of the kidney and urinary tract (CAKUT) Nonsyndromic v0.116 BCORL1 Zornitza Stark gene: BCORL1 was added
gene: BCORL1 was added to Congenital anomalies of the kidney and urinary tract (CAKUT) Nonsyndromic. Sources: Expert Review
Mode of inheritance for gene: BCORL1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: BCORL1 were set to Congenital anomaly of the kidney and urinary tract, MONDO:0019719, BCORL1-related
Review for gene: BCORL1 was set to AMBER
Added comment: Emerging evidence of disease association.
Sources: Expert Review
Genetic Epilepsy v0.2718 SLC2A1 Zornitza Stark Marked gene: SLC2A1 as ready
Genetic Epilepsy v0.2718 SLC2A1 Zornitza Stark Gene: slc2a1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2718 SLC2A1 Zornitza Stark Phenotypes for gene: SLC2A1 were changed from to GLUT1 deficiency syndrome 1, infantile onset, severe, 606777; GLUT1 deficiency syndrome 2, childhood onset, 612126
Genetic Epilepsy v0.2717 SLC2A1 Zornitza Stark Publications for gene: SLC2A1 were set to
Genetic Epilepsy v0.2716 SLC2A1 Zornitza Stark Mode of inheritance for gene: SLC2A1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genetic Epilepsy v0.2715 SLC25A1 Zornitza Stark Marked gene: SLC25A1 as ready
Genetic Epilepsy v0.2715 SLC25A1 Zornitza Stark Gene: slc25a1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2715 SLC25A1 Zornitza Stark Phenotypes for gene: SLC25A1 were changed from to Combined D-2- and L-2-hydroxyglutaric aciduria MIM#: 615182, MONDO:0014072
Genetic Epilepsy v0.2714 SLC25A1 Zornitza Stark Publications for gene: SLC25A1 were set to
Genetic Epilepsy v0.2713 SLC25A1 Zornitza Stark Mode of inheritance for gene: SLC25A1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2712 SLC25A1 Zornitza Stark reviewed gene: SLC25A1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Combined D-2- and L-2-hydroxyglutaric aciduria MIM#: 615182, MONDO:0014072; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1789 SHROOM4 Zornitza Stark Phenotypes for gene: SHROOM4 were changed from Stocco dos Santos X-linked mental retardation syndrome, 300434; Intellectual disability to Congenital anomaly of the kidney and urinary tracy (CAKUT), SHROOM4-related, MONDO:0019719; epilepsy, idiopathic generalised, SHROOM4-related, MONDO:0005579
Genetic Epilepsy v0.2712 SHROOM4 Zornitza Stark Marked gene: SHROOM4 as ready
Genetic Epilepsy v0.2712 SHROOM4 Zornitza Stark Gene: shroom4 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2712 SETBP1 Zornitza Stark Marked gene: SETBP1 as ready
Genetic Epilepsy v0.2712 SETBP1 Zornitza Stark Gene: setbp1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2712 SETBP1 Zornitza Stark Phenotypes for gene: SETBP1 were changed from to Schinzel-Giedion midface retraction syndrome, MIM# 269150; Intellectual disability, autosomal dominant 29, MIM# 616078
Genetic Epilepsy v0.2711 SETBP1 Zornitza Stark Publications for gene: SETBP1 were set to
Genetic Epilepsy v0.2710 SETBP1 Zornitza Stark Mode of inheritance for gene: SETBP1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2709 SEPSECS Zornitza Stark Marked gene: SEPSECS as ready
Genetic Epilepsy v0.2709 SEPSECS Zornitza Stark Gene: sepsecs has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2709 SEPSECS Zornitza Stark Phenotypes for gene: SEPSECS were changed from to Pontocerebellar hypoplasia type 2D, MIM# 613811
Genetic Epilepsy v0.2708 SEPSECS Zornitza Stark Publications for gene: SEPSECS were set to
Genetic Epilepsy v0.2707 SEPSECS Zornitza Stark Mode of inheritance for gene: SEPSECS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2706 SEPSECS Zornitza Stark changed review comment from: PCH2D is an autosomal recessive disorder characterized by progressive microcephaly, postnatal onset of progressive atrophy of the cerebrum and cerebellum, profound mental retardation, spasticity, and variable seizures. At least 5 unrelated families reported.; to: PCH2D is an autosomal recessive disorder characterized by progressive microcephaly, postnatal onset of progressive atrophy of the cerebrum and cerebellum, profound ID, spasticity, and variable seizures. At least 5 unrelated families reported.
Genetic Epilepsy v0.2706 SCO2 Zornitza Stark Marked gene: SCO2 as ready
Genetic Epilepsy v0.2706 SCO2 Zornitza Stark Gene: sco2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2706 SCO2 Zornitza Stark Phenotypes for gene: SCO2 were changed from to Mitochondrial complex IV deficiency, nuclear type 2, MIM# 604377
Genetic Epilepsy v0.2705 SCO2 Zornitza Stark Mode of inheritance for gene: SCO2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2704 SCO2 Zornitza Stark reviewed gene: SCO2: Rating: GREEN; Mode of pathogenicity: None; Publications: 10545952, 10749987, 18924171; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 2, MIM# 604377; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2704 SCN2A Zornitza Stark Marked gene: SCN2A as ready
Genetic Epilepsy v0.2704 SCN2A Zornitza Stark Gene: scn2a has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2704 SCN2A Zornitza Stark Phenotypes for gene: SCN2A were changed from to Seizures, benign familial infantile, 3, MIM# 607745; Developmental and epileptic encephalopathy 11, MIM# 613721
Genetic Epilepsy v0.2703 SCN2A Zornitza Stark Publications for gene: SCN2A were set to
Genetic Epilepsy v0.2702 SCN2A Zornitza Stark Mode of inheritance for gene: SCN2A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2701 SCN2A Zornitza Stark changed review comment from: Classically presents with seizures and DD/ID although a range of other manifestations reported, including movement abnormalities, including ataxia. Rather than being discrete disorders, these probably represent a continuum of manifestations of a single brain channelopathy disorder.

Multiple families reported.; to: Classically presents with seizures and DD/ID although a range of other manifestations reported, including movement abnormalities, including DEE. Rather than being discrete disorders, these probably represent a continuum of manifestations of a single brain channelopathy disorder.

Multiple families reported.
Cerebellar and Pontocerebellar Hypoplasia v1.64 RARS2 sailajah vishwanathan reviewed gene: RARS2: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: PubMed: 17847012, PubMed: 25809939, PubMed: 20635367, PubMed: 7607232; Phenotypes: pontocerebellar hypoplasia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Speech apraxia v0.0 Zornitza Stark Added Panel Speech apraxia
Genetic Epilepsy v0.2701 SAMHD1 Zornitza Stark Marked gene: SAMHD1 as ready
Genetic Epilepsy v0.2701 SAMHD1 Zornitza Stark Gene: samhd1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2701 SAMHD1 Zornitza Stark Phenotypes for gene: SAMHD1 were changed from to Aicardi-Goutieres syndrome 5, MIM# 612952
Genetic Epilepsy v0.2700 SAMHD1 Zornitza Stark Publications for gene: SAMHD1 were set to
Genetic Epilepsy v0.2699 SAMHD1 Zornitza Stark Mode of inheritance for gene: SAMHD1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2698 RTTN Zornitza Stark Marked gene: RTTN as ready
Genetic Epilepsy v0.2698 RTTN Zornitza Stark Gene: rttn has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2698 RTTN Zornitza Stark Phenotypes for gene: RTTN were changed from to Microcephaly, short stature, and polymicrogyria with seizures, MIM# 614833
Genetic Epilepsy v0.2697 RTTN Zornitza Stark Publications for gene: RTTN were set to
Genetic Epilepsy v0.2696 RTTN Zornitza Stark Mode of inheritance for gene: RTTN was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2695 RTTN Zornitza Stark reviewed gene: RTTN: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Microcephaly, short stature, and polymicrogyria with seizures, MIM# 614833; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2695 RTN4IP1 Zornitza Stark Marked gene: RTN4IP1 as ready
Genetic Epilepsy v0.2695 RTN4IP1 Zornitza Stark Gene: rtn4ip1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2695 RTN4IP1 Zornitza Stark Phenotypes for gene: RTN4IP1 were changed from to Optic atrophy 10 with or without ataxia, mental retardation, and seizures, MIM#616732
Genetic Epilepsy v0.2694 RTN4IP1 Zornitza Stark Publications for gene: RTN4IP1 were set to
Genetic Epilepsy v0.2693 RTN4IP1 Zornitza Stark Mode of inheritance for gene: RTN4IP1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2692 RRM2B Zornitza Stark Marked gene: RRM2B as ready
Genetic Epilepsy v0.2692 RRM2B Zornitza Stark Gene: rrm2b has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2692 RRM2B Zornitza Stark Phenotypes for gene: RRM2B were changed from to Mitochondrial DNA depletion syndrome 8A (encephalomyopathic type with renal tubulopathy) MIM#612075; Mitochondrial DNA depletion syndrome 8B (MNGIE type) MIM#612075
Genetic Epilepsy v0.2691 RRM2B Zornitza Stark Publications for gene: RRM2B were set to
Genetic Epilepsy v0.2690 RRM2B Zornitza Stark Mode of inheritance for gene: RRM2B was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2689 RRM2B Zornitza Stark Deleted their review
Genetic Epilepsy v0.2689 RNU4ATAC Zornitza Stark Marked gene: RNU4ATAC as ready
Genetic Epilepsy v0.2689 RNU4ATAC Zornitza Stark Gene: rnu4atac has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2689 RNU4ATAC Zornitza Stark Phenotypes for gene: RNU4ATAC were changed from to Microcephalic osteodysplastic primordial dwarfism, type I (MIM# 210710); Roifman syndrome (MIM# 616651); Lowry-Wood syndrome, MIM# 226960
Genetic Epilepsy v0.2688 RNU4ATAC Zornitza Stark Publications for gene: RNU4ATAC were set to
Genetic Epilepsy v0.2687 RNU4ATAC Zornitza Stark Mode of inheritance for gene: RNU4ATAC was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2686 RNU4ATAC Zornitza Stark edited their review of gene: RNU4ATAC: Changed phenotypes: Microcephalic osteodysplastic primordial dwarfism, type I, MIM# 210710, Lowry-Wood syndrome, MIM# 226960
Genetic Epilepsy v0.2686 RNU4ATAC Zornitza Stark changed review comment from: Lowry-Wood syndrome (LWS) is characterized by multiple epiphyseal dysplasia and microcephaly. Patients exhibit intrauterine growth retardation and short stature, as well as developmental delay and intellectual disability. Retinal degeneration has been reported in some patients.

Four unrelated families reported.

Note features between the three RNU4ATAC-related conditions overlap and they may not represent distinct disorders.; to: Lowry-Wood syndrome (LWS) is characterized by multiple epiphyseal dysplasia and microcephaly. Patients exhibit intrauterine growth retardation and short stature, as well as developmental delay and intellectual disability. Retinal degeneration has been reported in some patients.

Four unrelated families reported.

Note features between the three RNU4ATAC-related conditions overlap and they may not represent distinct disorders.

Seizures reported with the Microcephalic osteodysplastic primordial dwarfism, type I, MIM# 210710 phenotype.
Genetic Epilepsy v0.2686 RNASET2 Zornitza Stark Marked gene: RNASET2 as ready
Genetic Epilepsy v0.2686 RNASET2 Zornitza Stark Gene: rnaset2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2686 RNASET2 Zornitza Stark Phenotypes for gene: RNASET2 were changed from to Leukoencephalopathy, cystic, without megalencephaly MIM#612951
Genetic Epilepsy v0.2685 RNASET2 Zornitza Stark Publications for gene: RNASET2 were set to
Genetic Epilepsy v0.2684 RNASET2 Zornitza Stark Mode of inheritance for gene: RNASET2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2683 RNASEH2C Zornitza Stark Marked gene: RNASEH2C as ready
Genetic Epilepsy v0.2683 RNASEH2C Zornitza Stark Gene: rnaseh2c has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2683 RNASEH2C Zornitza Stark Phenotypes for gene: RNASEH2C were changed from to Aicardi-Goutieres syndrome 3 (MIM# 610329)
Genetic Epilepsy v0.2682 RNASEH2C Zornitza Stark Publications for gene: RNASEH2C were set to
Genetic Epilepsy v0.2681 RNASEH2C Zornitza Stark Mode of inheritance for gene: RNASEH2C was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2680 RNASEH2B Zornitza Stark Marked gene: RNASEH2B as ready
Genetic Epilepsy v0.2680 RNASEH2B Zornitza Stark Gene: rnaseh2b has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2680 RNASEH2B Zornitza Stark Phenotypes for gene: RNASEH2B were changed from to Aicardi-Goutieres syndrome 2, MIM# 610181
Genetic Epilepsy v0.2679 RNASEH2B Zornitza Stark Publications for gene: RNASEH2B were set to
Genetic Epilepsy v0.2678 RNASEH2B Zornitza Stark Mode of inheritance for gene: RNASEH2B was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2677 RNASEH2A Zornitza Stark Marked gene: RNASEH2A as ready
Genetic Epilepsy v0.2677 RNASEH2A Zornitza Stark Gene: rnaseh2a has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2677 RNASEH2A Zornitza Stark Marked gene: RNASEH2A as ready
Genetic Epilepsy v0.2677 RNASEH2A Zornitza Stark Gene: rnaseh2a has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2677 RNASEH2A Zornitza Stark Phenotypes for gene: RNASEH2A were changed from to Aicardi-Goutieres syndrome 4 MIM#610333
Genetic Epilepsy v0.2676 RNASEH2A Zornitza Stark Publications for gene: RNASEH2A were set to
Genetic Epilepsy v0.2675 RNASEH2A Zornitza Stark Mode of inheritance for gene: RNASEH2A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2674 POMT1 Zornitza Stark Marked gene: POMT1 as ready
Genetic Epilepsy v0.2674 POMT1 Zornitza Stark Gene: pomt1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2674 POMT1 Zornitza Stark Phenotypes for gene: POMT1 were changed from to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 1, MIM# 236670
Genetic Epilepsy v0.2673 POMT1 Zornitza Stark Mode of inheritance for gene: POMT1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2672 POMT1 Zornitza Stark edited their review of gene: POMT1: Changed phenotypes: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 1 236670
Genetic Epilepsy v0.2672 POMT1 Zornitza Stark changed review comment from: Well established gene-disease association.; to: Well established gene-disease association. Seizures are part of the more severe end of the phenotype.
Genetic Epilepsy v0.2672 POMGNT1 Zornitza Stark Marked gene: POMGNT1 as ready
Genetic Epilepsy v0.2672 POMGNT1 Zornitza Stark Gene: pomgnt1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2672 POMGNT1 Zornitza Stark Phenotypes for gene: POMGNT1 were changed from to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies, type A, 8 MIM#614830
Genetic Epilepsy v0.2671 POMGNT1 Zornitza Stark Publications for gene: POMGNT1 were set to
Genetic Epilepsy v0.2670 POMGNT1 Zornitza Stark Mode of inheritance for gene: POMGNT1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2669 POMGNT1 Zornitza Stark changed review comment from: PMID 26908613 and 27391550: 4 unrelated families with isolated RP in adults.

Well established association with dystroglycanopathy.; to: Well established association with dystroglycanopathy. Seizures are a feature of the more severe end of the spectrum.
Genetic Epilepsy v0.2669 POLG Zornitza Stark Marked gene: POLG as ready
Genetic Epilepsy v0.2669 POLG Zornitza Stark Gene: polg has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2669 POLG Zornitza Stark Phenotypes for gene: POLG were changed from to Mitochondrial DNA depletion syndrome 4A (Alpers type), MIM# 203700; Mitochondrial DNA depletion syndrome 4B (MNGIE type), MIM# 613662
Genetic Epilepsy v0.2668 POLG Zornitza Stark Publications for gene: POLG were set to
Genetic Epilepsy v0.2667 POLG Zornitza Stark Mode of inheritance for gene: POLG was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2666 POLG Zornitza Stark edited their review of gene: POLG: Added comment: Seizures are a feature of the more severe, recessive disorders associated with this gene.; Changed phenotypes: Mitochondrial DNA depletion syndrome 4A (Alpers type), MIM# 203700, Mitochondrial DNA depletion syndrome 4B (MNGIE type), MIM# 613662; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Renal Macrocystic Disease v0.69 ALG9 Ain Roesley Phenotypes for gene: ALG9 were changed from Congenital disorder of glycosylation, type Il, MIM# 608776; Gillessen-Kaesbach-Nishimura syndrome, MIM#263210; Polycystic kidney disease to Congenital disorder of glycosylation, type Il, MIM#608776; Gillessen-Kaesbach-Nishimura syndrome, MIM#263210; Polycystic kidney disease; ALG9-associated autosomal dominant polycystic kidney disease MONDO:0700000
Mendeliome v1.1788 ALG9 Ain Roesley Phenotypes for gene: ALG9 were changed from Congenital disorder of glycosylation, type Il, MIM#608776; Gillessen-Kaesbach-Nishimura syndrome, MIM# 263210; Polycystic kidney disease to Congenital disorder of glycosylation, type Il, MIM#608776; Gillessen-Kaesbach-Nishimura syndrome, MIM# 263210; Polycystic kidney disease; ALG9-associated autosomal dominant polycystic kidney disease MONDO:0700000
Intellectual disability syndromic and non-syndromic v0.5821 KATNAL2 Sangavi Sivagnanasundram reviewed gene: KATNAL2: Rating: RED; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:005176; Phenotypes: complex neurodevelopmental disorder MONDO:0100038; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5821 KAT6B Sangavi Sivagnanasundram reviewed gene: KAT6B: Rating: GREEN; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:005174; Phenotypes: KAT6B-related multiple congenital anomalies syndrome MONDO:0036042; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5821 KAT6A Sangavi Sivagnanasundram reviewed gene: KAT6A: Rating: GREEN; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:005173; Phenotypes: syndromic intellectual disability MONDO:0000508; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5821 IGBP1 Sangavi Sivagnanasundram reviewed gene: IGBP1: Rating: RED; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:005117; Phenotypes: corpus callosum agenesis-intellectual disability-coloboma-micrognathia syndrome MONDO:0010333; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.5821 IDS Sangavi Sivagnanasundram reviewed gene: IDS: Rating: GREEN; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:005112; Phenotypes: mucopolysaccharidosis type 2 MONDO:0010674; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability syndromic and non-syndromic v0.5821 HPRT1 Sangavi Sivagnanasundram reviewed gene: HPRT1: Rating: GREEN; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:005082; Phenotypes: Lesch-Nyhan syndrome MONDO:0010298; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.5821 HOXA1 Sangavi Sivagnanasundram reviewed gene: HOXA1: Rating: GREEN; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:005077; Phenotypes: syndromic intellectual disability MONDO:0000508; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hyperinsulinism v1.16 EP300 Chirag Patel Classified gene: EP300 as Green List (high evidence)
Hyperinsulinism v1.16 EP300 Chirag Patel Gene: ep300 has been classified as Green List (High Evidence).
Hyperinsulinism v1.15 CREBBP Chirag Patel Classified gene: CREBBP as Green List (high evidence)
Hyperinsulinism v1.15 CREBBP Chirag Patel Gene: crebbp has been classified as Green List (High Evidence).
Hyperinsulinism v1.14 CREBBP Chirag Patel gene: CREBBP was added
gene: CREBBP was added to Hyperinsulinism. Sources: Literature
Mode of inheritance for gene: CREBBP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CREBBP were set to PMID: 31137009, 33442921, 2240025, 31414570, 33043588
Phenotypes for gene: CREBBP were set to Rubinstein-Taybi syndrome 1, OMIM #180849
Review for gene: CREBBP was set to GREEN
gene: CREBBP was marked as current diagnostic
Added comment: Established gene-disease association.
Hyperinsulinaemic hypoglycaemia reported in less than 5%.
Sources: Literature
Hyperinsulinism v1.14 EP300 Chirag Patel gene: EP300 was added
gene: EP300 was added to Hyperinsulinism. Sources: Literature
Mode of inheritance for gene: EP300 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: EP300 were set to PMID: 31137009, 33442921, 2240025, 31414570, 33043588
Phenotypes for gene: EP300 were set to Rubinstein-Taybi syndrome 2, OMIM #613684
Review for gene: EP300 was set to GREEN
gene: EP300 was marked as current diagnostic
Added comment: Established gene-disease association.
Hyperinsulinaemic hypoglycaemia reported in less than 5%.
Sources: Literature
Hyperinsulinism v1.13 Chirag Patel Panel types changed to Victorian Clinical Genetics Services; Genetic Health Queensland; Royal Melbourne Hospital; Rare Disease
Hyperinsulinism v1.12 CACNA1D Chirag Patel Classified gene: CACNA1D as Amber List (moderate evidence)
Hyperinsulinism v1.12 CACNA1D Chirag Patel Gene: cacna1d has been classified as Amber List (Moderate Evidence).
Hyperinsulinism v1.11 CACNA1D Chirag Patel reviewed gene: CACNA1D: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 32336187; Phenotypes: congenital hyperinsulinism, primary hyperaldosteronism, and neurologic abnormalities; Mode of inheritance: None
Intellectual disability syndromic and non-syndromic v0.5821 HNRNPK Sangavi Sivagnanasundram reviewed gene: HNRNPK: Rating: GREEN; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:005073; Phenotypes: neurodevelopmental disorder-craniofacial dysmorphism-cardiac defect-hip dysplasia syndrome (Au-Kline syndrome) MONDO:0018681; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5821 HIST1H1E Sangavi Sivagnanasundram commented on gene: HIST1H1E
Hyperinsulinism v1.11 UCP2 Chirag Patel reviewed gene: UCP2: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 27967291, 23275527, 19065272, 28681398; Phenotypes: congenital hyperinsulinism; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5821 GPC3 Sangavi Sivagnanasundram reviewed gene: GPC3: Rating: GREEN; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:004990; Phenotypes: Simpson-Golabi-Behmel syndrome MONDO:0010731; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability syndromic and non-syndromic v0.5821 GDI1 Sangavi Sivagnanasundram reviewed gene: GDI1: Rating: ; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:004941; Phenotypes: non-syndromic X-linked intellectual disability MONDO:0019181; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability syndromic and non-syndromic v0.5821 FTSJ1 Sangavi Sivagnanasundram reviewed gene: FTSJ1: Rating: GREEN; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:004892; Phenotypes: X-linked complex neurodevelopmental disorder MONDO:0100148; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Hyperinsulinism v1.11 PGM1 Chirag Patel Classified gene: PGM1 as Green List (high evidence)
Hyperinsulinism v1.11 PGM1 Chirag Patel Gene: pgm1 has been classified as Green List (High Evidence).
Hyperinsulinism v1.10 PGM1 Chirag Patel gene: PGM1 was added
gene: PGM1 was added to Hyperinsulinism. Sources: Literature
Mode of inheritance for gene: PGM1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PGM1 were set to PMID: 24499211, 27206562
Phenotypes for gene: PGM1 were set to Congenital disorder of glycosylation, type It, OMIM# 614921
Review for gene: PGM1 was set to GREEN
gene: PGM1 was marked as current diagnostic
Added comment: Well established gene-disease association. Individuals can present with hypoglycaemia (+/- hyperinsulinism) and may not have all the syndromic features at presentation.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5821 FMR1 Sangavi Sivagnanasundram reviewed gene: FMR1: Rating: GREEN; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:004870; Phenotypes: fragile X syndrome MONDO:0010383; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.5821 SPR Zornitza Stark Marked gene: SPR as ready
Intellectual disability syndromic and non-syndromic v0.5821 SPR Zornitza Stark Gene: spr has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5821 SPR Zornitza Stark Phenotypes for gene: SPR were changed from to Dystonia, dopa-responsive, due to sepiapterin reductase deficiency, MIM# 612716
Intellectual disability syndromic and non-syndromic v0.5820 SPR Zornitza Stark Publications for gene: SPR were set to
Intellectual disability syndromic and non-syndromic v0.5819 SPR Zornitza Stark Mode of inheritance for gene: SPR was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5818 SPR Zornitza Stark reviewed gene: SPR: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Dystonia, dopa-responsive, due to sepiapterin reductase deficiency, MIM# 612716; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5818 MAST3 Zornitza Stark Publications for gene: MAST3 were set to 34185323
Mendeliome v1.1787 AGTR2 Zornitza Stark Marked gene: AGTR2 as ready
Mendeliome v1.1787 AGTR2 Zornitza Stark Gene: agtr2 has been classified as Red List (Low Evidence).
Mendeliome v1.1787 AGTR2 Zornitza Stark changed review comment from: Variants in AGTR2 have been reported in individuals presenting various neurodevelopmental phenotypes, including intellectual disability, autistic features, epileptic seizures, speech delay, restlessness, and hyperactivity, as early as 2002. Per criteria outlined by the ClinGen Lumping and Splitting Working Group, we found no difference in molecular mechanism, inheritance pattern, or phenotypic variability. Therefore, for the purposes of this curation, all of these features have been lumped into one disease entity, X-linked complex neurodevelopmental disorder. Although eight unique variants, including missense and truncating, have been reported in affected humans, the majority (six) have been ruled out from disease-causality based on high frequency in control populations (Piton et al., PMID 23871722), occurrence in unaffected males (Erdmann et al., PMID 14722754), non-segregation within a family (Bienvenu et al., PMID 12746399), and lack of enrichment in patients in a case-control study (Huang et al., PMID 16283672). Given that the two remaining variants are missense with no supporting functional evidence, and AGTR2 was the only gene sequenced in each case, the ClinGen Intellectual Disability and Autism Working Group recommended awarding 0 points for these variants. There are two AGTR2 mouse models which collectively show altered neuronal spine morphology, spatial memory impairment, delayed learning, and reduced exploratory behavior (PMIDs 18335189 and 7477267).
Sources: Expert Review; to: DISPUTED by ClinGen:

Variants in AGTR2 have been reported in individuals presenting various neurodevelopmental phenotypes, including intellectual disability, autistic features, epileptic seizures, speech delay, restlessness, and hyperactivity, as early as 2002. Per criteria outlined by the ClinGen Lumping and Splitting Working Group, we found no difference in molecular mechanism, inheritance pattern, or phenotypic variability. Therefore, for the purposes of this curation, all of these features have been lumped into one disease entity, X-linked complex neurodevelopmental disorder. Although eight unique variants, including missense and truncating, have been reported in affected humans, the majority (six) have been ruled out from disease-causality based on high frequency in control populations (Piton et al., PMID 23871722), occurrence in unaffected males (Erdmann et al., PMID 14722754), non-segregation within a family (Bienvenu et al., PMID 12746399), and lack of enrichment in patients in a case-control study (Huang et al., PMID 16283672). Given that the two remaining variants are missense with no supporting functional evidence, and AGTR2 was the only gene sequenced in each case, the ClinGen Intellectual Disability and Autism Working Group recommended awarding 0 points for these variants. There are two AGTR2 mouse models which collectively show altered neuronal spine morphology, spatial memory impairment, delayed learning, and reduced exploratory behavior (PMIDs 18335189 and 7477267).
Sources: Expert Review
Mendeliome v1.1787 AGTR2 Zornitza Stark gene: AGTR2 was added
gene: AGTR2 was added to Mendeliome. Sources: Expert Review
disputed tags were added to gene: AGTR2.
Mode of inheritance for gene: AGTR2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: AGTR2 were set to X-linked complex neurodevelopmental disorder MONDO:0100148
Review for gene: AGTR2 was set to RED
Added comment: Variants in AGTR2 have been reported in individuals presenting various neurodevelopmental phenotypes, including intellectual disability, autistic features, epileptic seizures, speech delay, restlessness, and hyperactivity, as early as 2002. Per criteria outlined by the ClinGen Lumping and Splitting Working Group, we found no difference in molecular mechanism, inheritance pattern, or phenotypic variability. Therefore, for the purposes of this curation, all of these features have been lumped into one disease entity, X-linked complex neurodevelopmental disorder. Although eight unique variants, including missense and truncating, have been reported in affected humans, the majority (six) have been ruled out from disease-causality based on high frequency in control populations (Piton et al., PMID 23871722), occurrence in unaffected males (Erdmann et al., PMID 14722754), non-segregation within a family (Bienvenu et al., PMID 12746399), and lack of enrichment in patients in a case-control study (Huang et al., PMID 16283672). Given that the two remaining variants are missense with no supporting functional evidence, and AGTR2 was the only gene sequenced in each case, the ClinGen Intellectual Disability and Autism Working Group recommended awarding 0 points for these variants. There are two AGTR2 mouse models which collectively show altered neuronal spine morphology, spatial memory impairment, delayed learning, and reduced exploratory behavior (PMIDs 18335189 and 7477267).
Sources: Expert Review
Intellectual disability syndromic and non-syndromic v0.5817 AGTR2 Zornitza Stark Phenotypes for gene: AGTR2 were changed from to X-linked complex neurodevelopmental disorder MONDO:0100148
Intellectual disability syndromic and non-syndromic v0.5816 AGTR2 Zornitza Stark Mode of inheritance for gene: AGTR2 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.5815 AGTR2 Zornitza Stark Tag disputed tag was added to gene: AGTR2.
Monogenic Diabetes v0.121 LIPC Zornitza Stark Marked gene: LIPC as ready
Monogenic Diabetes v0.121 LIPC Zornitza Stark Gene: lipc has been classified as Red List (Low Evidence).
Monogenic Diabetes v0.121 LIPC Zornitza Stark Phenotypes for gene: LIPC were changed from {Diabetes mellitus, noninsulin-dependent}, 125853; [High density lipoprotein cholesterol level QTL 12], 612797; Hepatic lipase deficiency, 614025 to {Diabetes mellitus, noninsulin-dependent}, MIM#125853
Monogenic Diabetes v0.120 LIPC Zornitza Stark Publications for gene: LIPC were set to
Monogenic Diabetes v0.119 COQ2 Zornitza Stark Marked gene: COQ2 as ready
Monogenic Diabetes v0.119 COQ2 Zornitza Stark Gene: coq2 has been classified as Green List (High Evidence).
Monogenic Diabetes v0.119 COQ2 Zornitza Stark Phenotypes for gene: COQ2 were changed from neonatal hyperglycaemia, Primary Coenzyme Q10 Deficiency to coenzyme Q10 deficiency, primary, 1 MONDO:0011829
Monogenic Diabetes v0.118 COQ2 Zornitza Stark Publications for gene: COQ2 were set to
Monogenic Diabetes v0.117 COQ2 Zornitza Stark Classified gene: COQ2 as Green List (high evidence)
Monogenic Diabetes v0.117 COQ2 Zornitza Stark Gene: coq2 has been classified as Green List (High Evidence).
Monogenic Diabetes v0.116 CIDEC Zornitza Stark Marked gene: CIDEC as ready
Monogenic Diabetes v0.116 CIDEC Zornitza Stark Gene: cidec has been classified as Red List (Low Evidence).
Monogenic Diabetes v0.116 CIDEC Zornitza Stark Phenotypes for gene: CIDEC were changed from Lipodystrophy, familial partial, type 5 to CIDEC-related familial partial lipodystrophy MONDO:0014098
Monogenic Diabetes v0.115 CAV1 Zornitza Stark Marked gene: CAV1 as ready
Monogenic Diabetes v0.115 CAV1 Zornitza Stark Gene: cav1 has been classified as Red List (Low Evidence).
Monogenic Diabetes v0.115 CAV1 Zornitza Stark Mode of inheritance for gene: CAV1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Monogenic Diabetes v0.114 CAV1 Zornitza Stark changed review comment from: Single family reported.; to: Single family reported in 2008.
Monogenic Diabetes v0.114 CAV1 Zornitza Stark reviewed gene: CAV1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Monogenic Diabetes v0.114 ZFP57 Zornitza Stark Marked gene: ZFP57 as ready
Monogenic Diabetes v0.114 ZFP57 Zornitza Stark Gene: zfp57 has been classified as Green List (High Evidence).
Monogenic Diabetes v0.114 ZFP57 Zornitza Stark Phenotypes for gene: ZFP57 were changed from Diabetes mellitus, transient neonatal, 1, 601410; Transient Neonatal Diabetes; Transient Neonatal Diabetes, Recessive to Diabetes mellitus, transient neonatal, 1, MIM#601410
Monogenic Diabetes v0.113 ZFP57 Zornitza Stark Publications for gene: ZFP57 were set to
Monogenic Diabetes v0.112 PTF1A Zornitza Stark Marked gene: PTF1A as ready
Monogenic Diabetes v0.112 PTF1A Zornitza Stark Gene: ptf1a has been classified as Green List (High Evidence).
Monogenic Diabetes v0.112 PTF1A Zornitza Stark Phenotypes for gene: PTF1A were changed from Permanent neonatal diabetes mellitus (PNDM); Diabetes mellitus, permanent neonatal, with cerebellar agenesis, 609069 to Diabetes mellitus, permanent neonatal, with cerebellar agenesis, MIM#609069
Monogenic Diabetes v0.111 PTF1A Zornitza Stark Publications for gene: PTF1A were set to
Monogenic Diabetes v0.110 PDX1 Zornitza Stark Marked gene: PDX1 as ready
Monogenic Diabetes v0.110 PDX1 Zornitza Stark Gene: pdx1 has been classified as Green List (High Evidence).
Monogenic Diabetes v0.110 PDX1 Zornitza Stark Phenotypes for gene: PDX1 were changed from Permanent neonatal diabetes; Maturity-Onset Diabetes Of The Young; Maturity-onset diabetes of the young (MODY); MODY type IV; Recessive neonatal diabetes, pancreatic agenesis and dominant MODY, 606392; MODY4; Pancreatic agenesis 1; MATURITY-ONSET DIABETES OF THE YOUNG, TYPE 4 to maturity-onset diabetes of the young type 4 MONDO:0011667
Monogenic Diabetes v0.109 PDX1 Zornitza Stark Publications for gene: PDX1 were set to
Monogenic Diabetes v0.108 NEUROD1 Zornitza Stark Marked gene: NEUROD1 as ready
Monogenic Diabetes v0.108 NEUROD1 Zornitza Stark Gene: neurod1 has been classified as Green List (High Evidence).
Monogenic Diabetes v0.108 NEUROD1 Zornitza Stark Phenotypes for gene: NEUROD1 were changed from MODY6; Maturity-Onset Diabetes Of The Young; MATURITY-ONSET DIABETES OF THE YOUNG, TYPE 6; {Diabetes mellitus, noninsulin-dependent}, 125853; Maturity Onset Diabetes of the Young; Maturity-onset diabetes of the young 6, 606394; Permanent neonatal diabetes and cerebellar agenesis to maturity-onset diabetes of the young type 6 MONDO:0011668
Mendeliome v1.1786 AVPR1A Zornitza Stark Tag disputed tag was added to gene: AVPR1A.
Mendeliome v1.1786 AVPR1A Zornitza Stark Marked gene: AVPR1A as ready
Mendeliome v1.1786 AVPR1A Zornitza Stark Gene: avpr1a has been classified as Red List (Low Evidence).
Mendeliome v1.1786 AVPR1A Zornitza Stark gene: AVPR1A was added
gene: AVPR1A was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: AVPR1A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: AVPR1A were set to 24924430
Phenotypes for gene: AVPR1A were set to Autism spectrum disorder MONDO:0005258
Review for gene: AVPR1A was set to RED
Added comment: DISPUTED by ClinGen:

The Arginine Vasopressin Receptor 1A (AVPR1A) was considered a candidate gene in autism spectrum disorder (ASD) based on reports focused on linkage intervals and animal models. Additionally, experimental evidence showed that AVPR1A is possibly involved in social behaviors, including affiliation and attachment (PMID: 24924430). However, these association studies were underpowered—sequencing more individuals may have identified variants of functional significance. In two studies, transmission disequilibrium between AVPR1A microsatellites and autism were found but most were not statistically significant (PMID: 12082568, 16520824). In another study, investigators screened AVPR1A exons in 125 independent autistic probands (PMID: 15098001). However, the study did not demonstrate a disease-causing variant in the coding sequence, and the authors noted that differences in AVPR1A at the amino-acid level are unlikely to confer genetic vulnerability to autism. Experimental evidence is available, but, in the absence of human genetic evidence, such data were not utilized in the scoring. In summary, there is no valid genetic evidence to support an association between AVPR1A and autism spectrum disorder.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.5815 AVPR1A Zornitza Stark Tag disputed tag was added to gene: AVPR1A.
Intellectual disability syndromic and non-syndromic v0.5815 BAZ2B Zornitza Stark Classified gene: BAZ2B as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.5815 BAZ2B Zornitza Stark Gene: baz2b has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1785 BCORL1 Zornitza Stark Classified gene: BCORL1 as Amber List (moderate evidence)
Mendeliome v1.1785 BCORL1 Zornitza Stark Gene: bcorl1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1784 BCORL1 Zornitza Stark edited their review of gene: BCORL1: Added comment: Classified as LIMITED by ClinGen.; Changed rating: AMBER
Intellectual disability syndromic and non-syndromic v0.5814 BCORL1 Zornitza Stark Classified gene: BCORL1 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.5814 BCORL1 Zornitza Stark Gene: bcorl1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5813 CASK Zornitza Stark Publications for gene: CASK were set to
Intellectual disability syndromic and non-syndromic v0.5812 CASK Zornitza Stark Marked gene: CASK as ready
Intellectual disability syndromic and non-syndromic v0.5812 CASK Zornitza Stark Added comment: Comment when marking as ready: Microcephaly with pontine and cerebellar hypoplasia (MICPCH), generally associated with pathogenic loss-of-function variants in CASK
X-linked intellectual disability (XLID) with or without nystagmus, generally associated with hypomorphic CASK pathogenic variants
Intellectual disability syndromic and non-syndromic v0.5812 CASK Zornitza Stark Gene: cask has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5812 CASK Zornitza Stark Phenotypes for gene: CASK were changed from to FG syndrome 4 MIM#300422; Intellectual developmental disorder and microcephaly with pontine and cerebellar hypoplasia MIM#300749; Intellectual disability, with or without nystagmus MIM#300422
Intellectual disability syndromic and non-syndromic v0.5811 CASK Zornitza Stark Mode of inheritance for gene: CASK was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Bone Marrow Failure v1.91 LCP1 Zornitza Stark Marked gene: LCP1 as ready
Bone Marrow Failure v1.91 LCP1 Zornitza Stark Gene: lcp1 has been classified as Amber List (Moderate Evidence).
Bone Marrow Failure v1.91 LCP1 Zornitza Stark Classified gene: LCP1 as Amber List (moderate evidence)
Bone Marrow Failure v1.91 LCP1 Zornitza Stark Gene: lcp1 has been classified as Amber List (Moderate Evidence).
Bone Marrow Failure v1.90 LCP1 Zornitza Stark gene: LCP1 was added
gene: LCP1 was added to Bone Marrow Failure. Sources: Literature
Mode of inheritance for gene: LCP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: LCP1 were set to 38710235
Phenotypes for gene: LCP1 were set to Bone marrow failure syndrome, MONDO:0000159, LCP1-related
Review for gene: LCP1 was set to AMBER
Added comment: 3 individuals from single kindred presenting with fevers, recurrent infections ,lymphopenia, neutropenia and thrombocytopenia. Murine model with similar phenotype. heterozygous LCP1c.740 -1G>A splice site variant hypothesized to cause dominant negative mode of inheritance
Sources: Literature
Mendeliome v1.1784 LCP1 Zornitza Stark Marked gene: LCP1 as ready
Mendeliome v1.1784 LCP1 Zornitza Stark Gene: lcp1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1784 LCP1 Zornitza Stark Classified gene: LCP1 as Amber List (moderate evidence)
Mendeliome v1.1784 LCP1 Zornitza Stark Gene: lcp1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1783 LCP1 Zornitza Stark gene: LCP1 was added
gene: LCP1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: LCP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: LCP1 were set to 38710235
Phenotypes for gene: LCP1 were set to Bone marrow failure syndrome, MONDO:0000159, LCP1-related
Review for gene: LCP1 was set to AMBER
Added comment: 3 individuals from single kindred presenting with fevers, recurrent infections ,lymphopenia, neutropenia and thrombocytopenia. Murine model with similar phenotype. heterozygous LCP1c.740 -1G>A splice site variant hypothesized to cause dominant negative mode of inheritance
Sources: Literature
Combined Immunodeficiency v1.61 LCP1 Zornitza Stark Marked gene: LCP1 as ready
Combined Immunodeficiency v1.61 LCP1 Zornitza Stark Gene: lcp1 has been classified as Amber List (Moderate Evidence).
Combined Immunodeficiency v1.61 LCP1 Zornitza Stark Phenotypes for gene: LCP1 were changed from lymphopaenia and neutropaenia to Bone marrow failure syndrome, MONDO:0000159, LCP1-related
Combined Immunodeficiency v1.60 LCP1 Zornitza Stark Classified gene: LCP1 as Amber List (moderate evidence)
Combined Immunodeficiency v1.60 LCP1 Zornitza Stark Gene: lcp1 has been classified as Amber List (Moderate Evidence).
Combined Immunodeficiency v1.59 LCP1 Zornitza Stark reviewed gene: LCP1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Bone marrow failure syndrome, MONDO:0000159, LCP1-related; Mode of inheritance: None
Mendeliome v1.1782 CLIC2 Zornitza Stark edited their review of gene: CLIC2: Added comment: DISPUTED by ClinGen.; Changed phenotypes: Intellectual disability, X-linked, syndromic 32, 300886
Intellectual disability syndromic and non-syndromic v0.5810 CLIC2 Zornitza Stark Phenotypes for gene: CLIC2 were changed from Mental retardation, X-linked, syndromic 32, 300886 to Intellectual disability, X-linked, syndromic 32, 300886
Intellectual disability syndromic and non-syndromic v0.5809 CLIC2 Zornitza Stark Tag disputed tag was added to gene: CLIC2.
Mendeliome v1.1782 UFSP2 Zornitza Stark Publications for gene: UFSP2 were set to 33473208; 26428751; 28892125; 32755715
Mendeliome v1.1781 UFSP2 Zornitza Stark edited their review of gene: UFSP2: Added comment: PMID: 37214758:

Additional patient with spondyloepimetaphyseal dysplasia type Di Rocco:
- het missense Cys302Ser
- confirmed de novo in segregation analyses
- absent in gnomAD
- no functional studies on the missense.

Four AD missense reported in the literature so far are located in the C-term catalytic domain - 1x hip dysplasia, Beukes type and 3x spondyloepimetaphyseal dysplasia type Di Rocco.

The well reported AR missense (associated with neurodevelopmental anomalies and epilepsy) is located in the N-terminal domain possibly involved in substrate binding.; Changed publications: 33473208, 26428751, 28892125, 32755715, 37214758
Skeletal dysplasia v0.274 UFSP2 Zornitza Stark Publications for gene: UFSP2 were set to 28892125; 26428751; 32755715
Skeletal dysplasia v0.273 UFSP2 Zornitza Stark Classified gene: UFSP2 as Green List (high evidence)
Skeletal dysplasia v0.273 UFSP2 Zornitza Stark Gene: ufsp2 has been classified as Green List (High Evidence).
Mendeliome v1.1781 CNTN6 Zornitza Stark Tag disputed tag was added to gene: CNTN6.
Intellectual disability syndromic and non-syndromic v0.5809 CNTN6 Zornitza Stark Tag disputed tag was added to gene: CNTN6.
Intellectual disability syndromic and non-syndromic v0.5809 DHCR7 Zornitza Stark Marked gene: DHCR7 as ready
Intellectual disability syndromic and non-syndromic v0.5809 DHCR7 Zornitza Stark Gene: dhcr7 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5809 DHCR7 Zornitza Stark Publications for gene: DHCR7 were set to
Intellectual disability syndromic and non-syndromic v0.5808 DHCR7 Zornitza Stark Phenotypes for gene: DHCR7 were changed from to Smith-Lemli-Opitz syndrome MONDO:0010035
Intellectual disability syndromic and non-syndromic v0.5807 DHCR7 Zornitza Stark Mode of inheritance for gene: DHCR7 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5806 DKC1 Zornitza Stark Marked gene: DKC1 as ready
Intellectual disability syndromic and non-syndromic v0.5806 DKC1 Zornitza Stark Gene: dkc1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5806 DKC1 Zornitza Stark Publications for gene: DKC1 were set to
Intellectual disability syndromic and non-syndromic v0.5805 DKC1 Zornitza Stark Phenotypes for gene: DKC1 were changed from to DKC1-related disorder MONDO:0100152
Intellectual disability syndromic and non-syndromic v0.5804 DKC1 Zornitza Stark Mode of inheritance for gene: DKC1 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Microcephaly v1.260 DPP6 Zornitza Stark Tag disputed tag was added to gene: DPP6.
Mendeliome v1.1781 DPP6 Zornitza Stark Phenotypes for gene: DPP6 were changed from Mental retardation, autosomal dominant 33 (MIM#616311) to Intellectual disability, autosomal dominant 33 (MIM#616311)
Mendeliome v1.1780 DPP6 Zornitza Stark Classified gene: DPP6 as Red List (low evidence)
Mendeliome v1.1780 DPP6 Zornitza Stark Gene: dpp6 has been classified as Red List (Low Evidence).
Mendeliome v1.1779 DPP6 Zornitza Stark Tag disputed tag was added to gene: DPP6.
Mendeliome v1.1779 DPP6 Zornitza Stark edited their review of gene: DPP6: Added comment: DISPUTED by ClinGen.; Changed rating: RED; Changed phenotypes: Intellectual disability, autosomal dominant 33 (MIM#616311)
Microcephaly v1.260 DPP6 Zornitza Stark Phenotypes for gene: DPP6 were changed from Mental retardation, autosomal dominant 33 (MIM#616311) to Intellectual disability, autosomal dominant 33 (MIM#616311)
Microcephaly v1.259 DPP6 Zornitza Stark Classified gene: DPP6 as Red List (low evidence)
Microcephaly v1.259 DPP6 Zornitza Stark Gene: dpp6 has been classified as Red List (Low Evidence).
Microcephaly v1.258 DPP6 Zornitza Stark edited their review of gene: DPP6: Added comment: DISPUTED by ClinGen.; Changed rating: RED; Changed phenotypes: Intellectual disability, autosomal dominant 33 (MIM#616311); Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5803 DPP6 Zornitza Stark Phenotypes for gene: DPP6 were changed from Mental retardation, autosomal dominant 33 (MIM#616311) to Intellectual disability, autosomal dominant 33 (MIM#616311)
Intellectual disability syndromic and non-syndromic v0.5802 DPP6 Zornitza Stark Classified gene: DPP6 as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.5802 DPP6 Zornitza Stark Gene: dpp6 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.5801 DPP6 Zornitza Stark Tag disputed tag was added to gene: DPP6.
Intellectual disability syndromic and non-syndromic v0.5801 FBN1 Zornitza Stark Tag disputed tag was added to gene: FBN1.
Intellectual disability syndromic and non-syndromic v0.5801 FLNA Zornitza Stark Marked gene: FLNA as ready
Intellectual disability syndromic and non-syndromic v0.5801 FLNA Zornitza Stark Gene: flna has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5801 FLNA Zornitza Stark Phenotypes for gene: FLNA were changed from to Heterotopia, periventricular, 1, MIM# 300049
Intellectual disability syndromic and non-syndromic v0.5800 FLNA Zornitza Stark Publications for gene: FLNA were set to
Intellectual disability syndromic and non-syndromic v0.5799 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)
Intellectual disability syndromic and non-syndromic v0.5798 FLNA Sangavi Sivagnanasundram reviewed gene: FLNA: Rating: GREEN; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:004863; Phenotypes: periventricular nodular heterotopia MONDO:0020341; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability syndromic and non-syndromic v0.5798 FBN1 Sangavi Sivagnanasundram reviewed gene: FBN1: Rating: RED; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:004823; Phenotypes: Shprintzen-Goldberg syndrome MONDO:0008426; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5798 DPP6 Sangavi Sivagnanasundram reviewed gene: DPP6: Rating: RED; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:004701; Phenotypes: complex neurodevelopmental disorder MONDO:0100038; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5798 DKC1 Sangavi Sivagnanasundram reviewed gene: DKC1: Rating: GREEN; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:004651; Phenotypes: DKC1-related disorder MONDO:0100152; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.5798 DHCR7 Sangavi Sivagnanasundram reviewed gene: DHCR7: Rating: GREEN; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:004643; Phenotypes: Smith-Lemli-Opitz syndrome MONDO:0010035; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5798 CNTN6 Sangavi Sivagnanasundram reviewed gene: CNTN6: Rating: RED; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:004489; Phenotypes: complex neurodevelopmental disorder MONDO:0100038; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v0.272 UFSP2 Chern Lim reviewed gene: UFSP2: Rating: GREEN; Mode of pathogenicity: None; Publications: 37214758; Phenotypes: Spondyloepimetaphyseal dysplasia, Di Rocco type, MIM# 617974; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.5798 CLIC2 Sangavi Sivagnanasundram reviewed gene: CLIC2: Rating: RED; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:004469; Phenotypes: X-linked complex neurodevelopmental disorder MONDO:0100148; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Combined Immunodeficiency v1.59 LCP1 Peter McNaughton gene: LCP1 was added
gene: LCP1 was added to Combined Immunodeficiency. Sources: Literature
Mode of inheritance for gene: LCP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: LCP1 were set to PMID: 38710235
Phenotypes for gene: LCP1 were set to lymphopaenia and neutropaenia
Mode of pathogenicity for gene: LCP1 was set to Other
Review for gene: LCP1 was set to AMBER
Added comment: 3 individuals from single kindred presenting with fevers, recurrent infections ,lymphopaenia, neutropaenia and thrombocytopaenia. Murine model with similar phenotype.
heterozygous LCP1c.740 -1G>A splice site variant hypothesized to cause dominant negative mode of inheritance
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5798 CDH15 Sangavi Sivagnanasundram reviewed gene: CDH15: Rating: RED; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:004393; Phenotypes: intellectual disability MONDO:0001071; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5798 CASK Sangavi Sivagnanasundram reviewed gene: CASK: Rating: GREEN; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:004345; Phenotypes: X-linked syndromic intellectual disability MONDO:0020119; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.5798 BCORL1 Sangavi Sivagnanasundram reviewed gene: BCORL1: Rating: ; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:004254; Phenotypes: Shukla-Vernon syndrome MONDO:0026727; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability syndromic and non-syndromic v0.5798 BAZ2B Sangavi Sivagnanasundram reviewed gene: BAZ2B: Rating: AMBER; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:004237; Phenotypes: complex neurodevelopmental disorder MONDO:0100038; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5798 AVPR1A Sangavi Sivagnanasundram reviewed gene: AVPR1A: Rating: RED; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:004223; Phenotypes: autism spectrum disorder MONDO:0005258; Mode of inheritance: Unknown
Intellectual disability syndromic and non-syndromic v0.5798 KDM5A Zornitza Stark Phenotypes for gene: KDM5A were changed from Neurodevelopmental disorder MONDO:0700092, KDM5A-related to Neurodevelopmental disorder MONDO:0700092, KDM5A-related; El Hayek-Chahrour neurodevelopmental syndrome, MIM# 620820
Intellectual disability syndromic and non-syndromic v0.5797 KDM5A Zornitza Stark edited their review of gene: KDM5A: Changed phenotypes: Neurodevelopmental disorder MONDO:0700092, KDM5A-related, El Hayek-Chahrour neurodevelopmental syndrome, MIM# 620820
Mendeliome v1.1779 KDM5A Zornitza Stark Phenotypes for gene: KDM5A were changed from autism spectrum disorder, MONDO:0005258; Neurodevelopmental disorder MONDO:0700092, KDM5A-related to El Hayek-Chahrour neurodevelopmental syndrome, MIM# 620820; Neurodevelopmental disorder MONDO:0700092, KDM5A-related
Mendeliome v1.1778 KDM5A Zornitza Stark reviewed gene: KDM5A: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: El Hayek-Chahrour neurodevelopmental syndrome, MIM# 620820; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v0.192 GTPBP3 Zornitza Stark Marked gene: GTPBP3 as ready
Cardiomyopathy_Paediatric v0.192 GTPBP3 Zornitza Stark Gene: gtpbp3 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v0.192 GTPBP3 Zornitza Stark Classified gene: GTPBP3 as Green List (high evidence)
Cardiomyopathy_Paediatric v0.192 GTPBP3 Zornitza Stark Gene: gtpbp3 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v0.191 GTPBP3 Zornitza Stark gene: GTPBP3 was added
gene: GTPBP3 was added to Cardiomyopathy_Paediatric. Sources: Expert Review
Mode of inheritance for gene: GTPBP3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GTPBP3 were set to 34276756; 25434004
Phenotypes for gene: GTPBP3 were set to Combined oxidative phosphorylation deficiency 23 MIM#616198
Review for gene: GTPBP3 was set to GREEN
Added comment: Clinical presentation: early childhood onset of hypertrophic cardiomyopathy and/or neurologic symptoms, including hypotonia and delayed psychomotor development. Laboratory investigations are consistent with a defect in mitochondrial function resulting in lactic acidosis, impaired activities of respiratory complexes I and IV, and defective translation of mitochondrial proteins. Brain imaging shows abnormal lesions in the basal ganglia, thalamus, and brainstem.

At least 12 unrelated individuals reported.
Sources: Expert Review
Malignant Hyperthermia Susceptibility v1.8 Zornitza Stark Panel types changed to Victorian Clinical Genetics Services; Royal Melbourne Hospital; Rare Disease
Genetic Epilepsy v0.2666 STAT3 Ain Roesley Marked gene: STAT3 as ready
Genetic Epilepsy v0.2666 STAT3 Ain Roesley Gene: stat3 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2666 STAT3 Ain Roesley gene: STAT3 was added
gene: STAT3 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: STAT3 was set to Unknown
Publications for gene: STAT3 were set to 36935347
Review for gene: STAT3 was set to RED
gene: STAT3 was marked as current diagnostic
Added comment: No evidence of STAT3 being reported in individuals with seizures/epilepsy. Only mouse models.
Sources: Literature
Genetic Epilepsy v0.2665 KCNIP4 Ain Roesley Marked gene: KCNIP4 as ready
Genetic Epilepsy v0.2665 KCNIP4 Ain Roesley Gene: kcnip4 has been classified as Red List (Low Evidence).
Mendeliome v1.1778 KCNIP4 Ain Roesley Marked gene: KCNIP4 as ready
Mendeliome v1.1778 KCNIP4 Ain Roesley Gene: kcnip4 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2665 KCNIP4 Ain Roesley gene: KCNIP4 was added
gene: KCNIP4 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: KCNIP4 was set to Unknown
Publications for gene: KCNIP4 were set to 33826137
Phenotypes for gene: KCNIP4 were set to seizures; epilepsy
Review for gene: KCNIP4 was set to RED
gene: KCNIP4 was marked as current diagnostic
Added comment: single paper describing insertions of L1 retrotransposons in KCNIP4
samples were post-mortem of resected temporal cortex from individuals with idiopathic temporal lobe epilepsy

1x de novo insertion of L1 in KCNIP4 however ddPCR revealed that this did NOT alter KCNIP4 mRNA expression
Sources: Literature
Mendeliome v1.1778 KCNIP4 Ain Roesley gene: KCNIP4 was added
gene: KCNIP4 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: KCNIP4 was set to Unknown
Publications for gene: KCNIP4 were set to 33826137
Phenotypes for gene: KCNIP4 were set to seizures; epilepsy
Review for gene: KCNIP4 was set to RED
gene: KCNIP4 was marked as current diagnostic
Added comment: single paper describing insertions of L1 retrotransposons in KCNIP4
samples were post-mortem of resected temporal cortex from individuals with idiopathic temporal lobe epilepsy

1x de novo insertion of L1 in KCNIP4 however ddPCR revealed that this did NOT alter KCNIP4 mRNA expression
Sources: Literature
Genetic Epilepsy v0.2664 IDH1 Ain Roesley Marked gene: IDH1 as ready
Genetic Epilepsy v0.2664 IDH1 Ain Roesley Gene: idh1 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2664 IDH1 Ain Roesley gene: IDH1 was added
gene: IDH1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: IDH1 was set to Other
Phenotypes for gene: IDH1 were set to Ollier disease MONDO:0008145; Maffucci syndromeMONDO:0013808
Review for gene: IDH1 was set to RED
gene: IDH1 was marked as current diagnostic
Added comment: unable to find evidence of seizures/epilepsy for Ollier or Maffucci syndrome
Sources: Literature
Genetic Epilepsy v0.2663 FGFR1 Ain Roesley Marked gene: FGFR1 as ready
Genetic Epilepsy v0.2663 FGFR1 Ain Roesley Gene: fgfr1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2663 FGFR1 Ain Roesley Classified gene: FGFR1 as Green List (high evidence)
Genetic Epilepsy v0.2663 FGFR1 Ain Roesley Gene: fgfr1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2662 FGFR1 Ain Roesley gene: FGFR1 was added
gene: FGFR1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: FGFR1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: FGFR1 were set to 26937548; 31512363; 23812909; 26931467
Phenotypes for gene: FGFR1 were set to Hartsfield syndrome (MIM#615465)
Review for gene: FGFR1 was set to GREEN
gene: FGFR1 was marked as current diagnostic
Added comment: Seizures is part of the phenotypic spectrum of Hartsfield Syndrome

*rare reports of AR Hartsfield
Sources: Literature
Mendeliome v1.1777 CHRNA7 Ain Roesley Marked gene: CHRNA7 as ready
Mendeliome v1.1777 CHRNA7 Ain Roesley Gene: chrna7 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2661 CHRNA7 Ain Roesley Marked gene: CHRNA7 as ready
Genetic Epilepsy v0.2661 CHRNA7 Ain Roesley Gene: chrna7 has been classified as Red List (Low Evidence).
Mendeliome v1.1777 CHRNA7 Ain Roesley gene: CHRNA7 was added
gene: CHRNA7 was added to Mendeliome. Sources: Literature
cnv tags were added to gene: CHRNA7.
Mode of inheritance for gene: CHRNA7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CHRNA7 were set to 20979196; 21596161; 21290787
Phenotypes for gene: CHRNA7 were set to intellectual disability; seizures; hypotonia
Review for gene: CHRNA7 was set to RED
gene: CHRNA7 was marked as current diagnostic
Added comment: Homozygous deletion of 15q13.3, which includes CHRNA7, causes ID, hypotonia, seizures, encephalopathy
Sources: Literature
Genetic Epilepsy v0.2661 CHRNA7 Ain Roesley gene: CHRNA7 was added
gene: CHRNA7 was added to Genetic Epilepsy. Sources: Literature
cnv tags were added to gene: CHRNA7.
Mode of inheritance for gene: CHRNA7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CHRNA7 were set to 20979196; 21596161; 21290787
Phenotypes for gene: CHRNA7 were set to intellectual disability; seizures; hypotonia
Review for gene: CHRNA7 was set to RED
gene: CHRNA7 was marked as current diagnostic
Added comment: Homozygous deletion of 15q13.3, which includes CHRNA7, causes ID, hypotonia, seizures, encephalopathy
Sources: Literature
Monogenic Diabetes v0.107 NEUROD1 Hali Van Niel reviewed gene: NEUROD1: Rating: GREEN; Mode of pathogenicity: None; Publications: 22784109, 29521454, 10545951, 11575290; Phenotypes: maturity-onset diabetes of the young type 6 MONDO:0011668; Mode of inheritance: Unknown
Monogenic Diabetes v0.107 PDX1 Hali Van Niel reviewed gene: PDX1: Rating: GREEN; Mode of pathogenicity: None; Publications: 9326926, 10545531, 10720084, 12970316, 20009086, 19496967; Phenotypes: maturity-onset diabetes of the young type 4 MONDO:0011667; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Monogenic Diabetes v0.107 PTF1A Hali Van Niel edited their review of gene: PTF1A: Changed publications: 24212882, 21749365, 10507728, 15543146, 19650412, 37854477
Monogenic Diabetes v0.107 PTF1A Hali Van Niel edited their review of gene: PTF1A: Changed rating: GREEN
Monogenic Diabetes v0.107 PTF1A Hali Van Niel reviewed gene: PTF1A: Rating: ; Mode of pathogenicity: None; Publications: 24212882, 21749365, 10507728, 15543146, 19650412; Phenotypes: permanent neonatal diabetes mellitus-pancreatic and cerebellar agenesis syndrome MONDO:0012192; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Monogenic Diabetes v0.107 ZFP57 Hali Van Niel reviewed gene: ZFP57: Rating: GREEN; Mode of pathogenicity: None; Publications: 18622393, 27075368, 23150280, 30315371, 35218690, 28334746; Phenotypes: transient neonatal diabetes mellitus MONDO:0020525; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Monogenic Diabetes v0.107 CAV1 Hali Van Niel reviewed gene: CAV1: Rating: AMBER; Mode of pathogenicity: None; Publications: 18211975; Phenotypes: diabetes mellitus MONDO:0005015, congenital generalized lipodystrophy type 1 MONDO:0012071; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Monogenic Diabetes v0.107 CIDEC Hali Van Niel reviewed gene: CIDEC: Rating: RED; Mode of pathogenicity: None; Publications: 20049731; Phenotypes: CIDEC-related familial partial lipodystrophy MONDO:0014098; Mode of inheritance: Unknown
Monogenic Diabetes v0.107 COQ2 Hali Van Niel reviewed gene: COQ2: Rating: GREEN; Mode of pathogenicity: None; Publications: 16400613, 30337132, 26296322; Phenotypes: neonatal diabetes mellitus MONDO:0016391, coenzyme Q10 deficiency, primary, 1 MONDO:0011829; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5797 ANKRD11 Sangavi Sivagnanasundram reviewed gene: ANKRD11: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 25413698, https://search.clinicalgenome.org/CCID:004133; Phenotypes: KBG syndrome MONDO:0007846; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Monogenic Diabetes v0.107 LIPC Hali Van Niel edited their review of gene: LIPC: Changed publications: 1671786, 12777476, 1883393, 22798447, 15126514, 18364377, 32617858
Monogenic Diabetes v0.107 LIPC Hali Van Niel reviewed gene: LIPC: Rating: RED; Mode of pathogenicity: None; Publications: 1671786, 12777476, 1883393, 22798447; Phenotypes: diabetes mellitus MONDO:0005015; Mode of inheritance: Unknown
Intellectual disability syndromic and non-syndromic v0.5797 AGTR2 Sangavi Sivagnanasundram reviewed gene: AGTR2: Rating: RED; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:004075; Phenotypes: X-linked complex neurodevelopmental disorder MONDO:0100148; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v1.1776 DNA2 Zornitza Stark Phenotypes for gene: DNA2 were changed from Seckel syndrome 8, MIM#615807; Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 6 MIM#615156 to Rothmund-Thomson syndrome, type 4, MIM# 620819; Seckel syndrome 8, MIM#615807; Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 6 MIM#615156
Mendeliome v1.1775 DNA2 Zornitza Stark Publications for gene: DNA2 were set to 24389050; 31045292; 23352259; 25635128; 28554558
Mendeliome v1.1774 DNA2 Zornitza Stark reviewed gene: DNA2: Rating: AMBER; Mode of pathogenicity: None; Publications: 37133451; Phenotypes: Rothmund-Thomson syndrome, type 4, MIM# 620819; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cataract v0.366 DNA2 Zornitza Stark Phenotypes for gene: DNA2 were changed from Rothmund-Thomson syndrome, MONDO:0010002, DNA2 associated to Rothmund-Thomson syndrome, type 4, MIM# 620819
Cataract v0.365 DNA2 Zornitza Stark reviewed gene: DNA2: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Rothmund-Thomson syndrome, type 4, MIM# 620819; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5797 MAST3 Sarah Leigh reviewed gene: MAST3: Rating: GREEN; Mode of pathogenicity: None; Publications: 35095415; Phenotypes: ; Mode of inheritance: None
Genetic Epilepsy v0.2660 MAST3 Sarah Leigh reviewed gene: MAST3: Rating: GREEN; Mode of pathogenicity: None; Publications: 35095415; Phenotypes: ; Mode of inheritance: None
Intellectual disability syndromic and non-syndromic v0.5797 SPR Amy Chiang edited their review of gene: SPR: Added comment: SPR has been classified to have definitive association with dopa-responsive dystonia (reviewed by the Aminoacidopathy Expert Panel on 06/04/2021).

Clinical phenotypes are mainly neuromuscular with characteristic features of axial hypotonia, dystonia, delayed psychomotor development, oculogyric crises, diurnal fluctuation with improvement after sleep; though cognitive impairment ranging from mild to severe levels have been reported in patients with sepiapterin reductase deficiency (PMID: 16049044, 17188538) - 7 Maltese patients with the same homozygous spice variants in SPR (founder effect due to relative small Maltese population); note there was no significant improvement in cognitive ability with L-dopa treatment in these patients despite improvement in their motor abilities (PMID: 16049044) - ? other causes to cognitive impairment in these patients other than SPR associated sepiapterin reductase deficiency

There are 271 SPR variants registered in ClinVar to date with only 1 submission from a research lab reported 2 affected individuals with intellectual disability + family history (ClinVar # 625209) - no publication available to verify, ? from BRIDGE consortium study: SPEED project cohort
A start loss variant detected in 5 affected individuals with ID & epilepsy from a Persian consanguineous family - LOD score = 4.027 (PMID: 29302074); Changed publications: PMID: 29302074, 16049044, 17188538; Changed phenotypes: MONDO #0012994, OMIM #612716, axial hypotonia, dystonia with diurnal fluctuation, oculogyric crises, delayed psychomotor development, sepiapterin reductase deficiency
Fetal anomalies v1.243 CCDC114 Zornitza Stark Tag new gene name tag was added to gene: CCDC114.
Mendeliome v1.1774 CCDC114 Zornitza Stark Tag new gene name tag was added to gene: CCDC114.
Heterotaxy v1.32 CCDC114 Zornitza Stark Tag new gene name tag was added to gene: CCDC114.
Ciliary Dyskinesia v1.39 CCDC114 Zornitza Stark Tag new gene name tag was added to gene: CCDC114.
Prepair 1000+ v1.6 ARMC4 Zornitza Stark Tag new gene name tag was added to gene: ARMC4.
Fetal anomalies v1.243 ARMC4 Zornitza Stark Tag new gene name tag was added to gene: ARMC4.
Mendeliome v1.1774 ARMC4 Zornitza Stark Tag new gene name tag was added to gene: ARMC4.
Heterotaxy v1.32 ARMC4 Zornitza Stark Tag new gene name tag was added to gene: ARMC4.
Ciliary Dyskinesia v1.39 ARMC4 Zornitza Stark Tag new gene name tag was added to gene: ARMC4.
Fetal anomalies v1.243 CCDC151 Zornitza Stark Tag new gene name tag was added to gene: CCDC151.
Mendeliome v1.1774 CCDC151 Zornitza Stark Tag new gene name tag was added to gene: CCDC151.
Heterotaxy v1.32 CCDC151 Zornitza Stark Tag new gene name tag was added to gene: CCDC151.
Ciliary Dyskinesia v1.39 CCDC151 Zornitza Stark Tag new gene name tag was added to gene: CCDC151.
Fetal anomalies v1.243 TTC25 Zornitza Stark Tag new gene name tag was added to gene: TTC25.
Heterotaxy v1.32 TTC25 Zornitza Stark Tag new gene name tag was added to gene: TTC25.
Ciliary Dyskinesia v1.39 TTC25 Zornitza Stark Tag new gene name tag was added to gene: TTC25.
Congenital Heart Defect v0.418 TTC25 Zornitza Stark Tag new gene name tag was added to gene: TTC25.
Mendeliome v1.1774 TTC25 Zornitza Stark Tag new gene name tag was added to gene: TTC25.
Syndromic Retinopathy v0.209 ADAMTS18 Zornitza Stark Marked gene: ADAMTS18 as ready
Syndromic Retinopathy v0.209 ADAMTS18 Zornitza Stark Gene: adamts18 has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.209 ADAMTS18 Zornitza Stark Phenotypes for gene: ADAMTS18 were changed from Microcornea, myopic chorioretinal atrophy, and telecanthus; Genetic Retinal Degeneration Conditions to microcornea-myopic chorioretinal atrophy (MONDO:0014195)
Mendeliome v1.1774 ADAMTS18 Zornitza Stark Marked gene: ADAMTS18 as ready
Mendeliome v1.1774 ADAMTS18 Zornitza Stark Gene: adamts18 has been classified as Green List (High Evidence).
Mendeliome v1.1774 ADAMTS18 Zornitza Stark Classified gene: ADAMTS18 as Green List (high evidence)
Mendeliome v1.1774 ADAMTS18 Zornitza Stark Gene: adamts18 has been classified as Green List (High Evidence).
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.147 AIPL1 Zornitza Stark Marked gene: AIPL1 as ready
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.147 AIPL1 Zornitza Stark Gene: aipl1 has been classified as Green List (High Evidence).
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.147 AIPL1 Zornitza Stark Phenotypes for gene: AIPL1 were changed from Retinitis pigmentosa, juvenile; Leber congenital amaurosis 4; Cone-rod dystrophy to AIPL1-related retinopathy (MONDO:0100438)
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.146 AIPL1 Zornitza Stark Publications for gene: AIPL1 were set to
Mendeliome v1.1773 FOXD3 Zornitza Stark Tag disputed tag was added to gene: FOXD3.
Mendeliome v1.1773 NTF4 Zornitza Stark Tag disputed tag was added to gene: NTF4.
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.145 C2orf71 Zornitza Stark Tag new gene name tag was added to gene: C2orf71.
Mendeliome v1.1773 C2orf71 Zornitza Stark Tag new gene name tag was added to gene: C2orf71.
Mendeliome v1.1773 SPATA13 Zornitza Stark Phenotypes for gene: SPATA13 were changed from primary angle-closure glaucoma to primary angle-closure glaucoma MONDO:0001868
Mendeliome v1.1772 SPATA13 Zornitza Stark Classified gene: SPATA13 as Amber List (moderate evidence)
Mendeliome v1.1772 SPATA13 Zornitza Stark Gene: spata13 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1771 WDR36 Zornitza Stark Classified gene: WDR36 as Red List (low evidence)
Mendeliome v1.1771 WDR36 Zornitza Stark Gene: wdr36 has been classified as Red List (Low Evidence).
Mendeliome v1.1770 WDR36 Zornitza Stark Tag disputed tag was added to gene: WDR36.
Deafness_IsolatedAndComplex v1.182 KARS Zornitza Stark Tag new gene name tag was added to gene: KARS.
Deafness_IsolatedAndComplex v1.182 TCOF1 Zornitza Stark Classified gene: TCOF1 as Green List (high evidence)
Deafness_IsolatedAndComplex v1.182 TCOF1 Zornitza Stark Gene: tcof1 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.181 TCOF1 Zornitza Stark Classified gene: TCOF1 as Green List (high evidence)
Deafness_IsolatedAndComplex v1.181 TCOF1 Zornitza Stark Gene: tcof1 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.180 TCOF1 Zornitza Stark Marked gene: TCOF1 as ready
Deafness_IsolatedAndComplex v1.180 TCOF1 Zornitza Stark Gene: tcof1 has been removed from the panel.
Deafness_IsolatedAndComplex v1.180 TJP2 Sangavi Sivagnanasundram reviewed gene: TJP2: Rating: RED; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:006375; Phenotypes: nonsyndromic genetic hearing loss MONDO:0019497; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Deafness_IsolatedAndComplex v1.180 TCOF1 Sangavi Sivagnanasundram gene: TCOF1 was added
gene: TCOF1 was added to Deafness_IsolatedAndComplex. Sources: Other
Mode of inheritance for gene: TCOF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TCOF1 were set to https://search.clinicalgenome.org/CCID:006342
Phenotypes for gene: TCOF1 were set to Treacher-Collins syndrome (MONDO:0002457)
Review for gene: TCOF1 was set to GREEN
Added comment: Classified DEFINITIVE by ClinGen Hearing Loss on 17/09/2019 - https://search.clinicalgenome.org/CCID:006342

The mechanism of disease is haploinsufficiency.
Sources: Other
Deafness_IsolatedAndComplex v1.180 KARS Sangavi Sivagnanasundram commented on gene: KARS
Mendeliome v1.1770 WDR36 Sangavi Sivagnanasundram reviewed gene: WDR36: Rating: RED; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:006545; Phenotypes: glaucoma 1, open angle, G MONDO:0012357; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.1770 SPATA13 Sangavi Sivagnanasundram reviewed gene: SPATA13: Rating: AMBER; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:006261; Phenotypes: primary angle-closure glaucoma MONDO:0001868; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.1770 C2orf71 Sangavi Sivagnanasundram reviewed gene: C2orf71: Rating: ; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:005738; Phenotypes: PCARE-related retinopathy MONDO:0800404; Mode of inheritance: None
Mendeliome v1.1770 NTF4 Sangavi Sivagnanasundram reviewed gene: NTF4: Rating: RED; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:005684; Phenotypes: glaucoma 1, open angle, O MONDO:0013134; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.1770 FOXD3 Sangavi Sivagnanasundram reviewed gene: FOXD3: Rating: RED; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:004877; Phenotypes: aniridia MONDO:0019172; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Macular Dystrophy/Stargardt Disease v0.45 CDH3 Sangavi Sivagnanasundram reviewed gene: CDH3: Rating: GREEN; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:004398; Phenotypes: EEM syndrome MONDO:0009155; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.145 AIPL1 Sangavi Sivagnanasundram reviewed gene: AIPL1: Rating: GREEN; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:004084; Phenotypes: AIPL1-related retinopathy (MONDO:0100438); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1770 ADAMTS18 Sangavi Sivagnanasundram gene: ADAMTS18 was added
gene: ADAMTS18 was added to Mendeliome. Sources: Other
Mode of inheritance for gene: ADAMTS18 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADAMTS18 were set to https://search.clinicalgenome.org/CCID:004057
Phenotypes for gene: ADAMTS18 were set to microcornea-myopic chorioretinal atrophy (MONDO:0014195)
Review for gene: ADAMTS18 was set to GREEN
Added comment: Classified DEFINITIVE by ClinGen Retina GCEP on 02/03/20222 - https://search.clinicalgenome.org/CCID:004057
Sources: Other
Syndromic Retinopathy v0.208 ADAMTS18 Sangavi Sivagnanasundram reviewed gene: ADAMTS18: Rating: GREEN; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:004057; Phenotypes: microcornea-myopic chorioretinal atrophy (MONDO:0014195); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1770 TTC25 Sangavi Sivagnanasundram reviewed gene: TTC25: Rating: ; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:005700; Phenotypes: primary ciliary dyskinesia 35 MONDO:0014910; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ciliary Dyskinesia v1.39 TTC25 Sangavi Sivagnanasundram reviewed gene: TTC25: Rating: ; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:005700; Phenotypes: primary ciliary dyskinesia 35 MONDO:0014910; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ciliary Dyskinesia v1.39 CCDC151 Sangavi Sivagnanasundram reviewed gene: CCDC151: Rating: ; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:005699; Phenotypes: primary ciliary dyskinesia 30 MONDO:0014465; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5797 COG4 Zornitza Stark Marked gene: COG4 as ready
Intellectual disability syndromic and non-syndromic v0.5797 COG4 Zornitza Stark Gene: cog4 has been classified as Green List (High Evidence).
Mendeliome v1.1770 CCDC151 Sangavi Sivagnanasundram reviewed gene: CCDC151: Rating: ; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:005699; Phenotypes: primary ciliary dyskinesia 30 MONDO:0014465; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5797 COG4 Zornitza Stark Phenotypes for gene: COG4 were changed from to Saul-Wilson syndrome, OMIM #618150; Congenital disorder of glycosylation, type IIj, OMIM #613489
Ciliary Dyskinesia v1.39 ARMC4 Sangavi Sivagnanasundram reviewed gene: ARMC4: Rating: ; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:005698; Phenotypes: primary ciliary dyskinesia 23 MONDO:0014193; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1770 ARMC4 Sangavi Sivagnanasundram reviewed gene: ARMC4: Rating: ; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:005698; Phenotypes: primary ciliary dyskinesia 23 MONDO:0014193; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ciliary Dyskinesia v1.39 CCDC114 Sangavi Sivagnanasundram commented on gene: CCDC114
Ciliary Dyskinesia v1.39 DNAH8 Sangavi Sivagnanasundram reviewed gene: DNAH8: Rating: RED; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:004671; Phenotypes: primary ciliary dyskinesia (MONDO:0016575); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1770 DNAH8 Sangavi Sivagnanasundram reviewed gene: DNAH8: Rating: ; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:004671; Phenotypes: primary ciliary dyskinesia (MONDO:0016575), spermatogenic failure 46 (MONDO:0033673); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1770 DNAH17 Sangavi Sivagnanasundram changed review comment from: Classified DEFINITIVE by ClinGen on 08/09/2022 - https://search.clinicalgenome.org/CCID:004669
Sources: Other; to: Classified DEFINITIVE by ClinGen Motile Ciliopathies GCEP on 08/09/2022 - https://search.clinicalgenome.org/CCID:004669
Sources: Other
Ciliary Dyskinesia v1.39 DNAH17 Sangavi Sivagnanasundram changed review comment from: Classified DEFINITIVE by ClinGen on 08/09/2022 - https://search.clinicalgenome.org/CCID:004669
Sources: Other; to: Classified DEFINITIVE by ClinGen Motile Ciliopathies GCEP on 08/09/2022 - https://search.clinicalgenome.org/CCID:004669
Sources: Other
Ciliary Dyskinesia v1.39 DNAH5 Sangavi Sivagnanasundram reviewed gene: DNAH5: Rating: GREEN; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:004670; Phenotypes: primary ciliary dyskinesia 3 (MONDO:0012085); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1770 DNAH17 Sangavi Sivagnanasundram gene: DNAH17 was added
gene: DNAH17 was added to Mendeliome. Sources: Other
Mode of inheritance for gene: DNAH17 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DNAH17 were set to https://search.clinicalgenome.org/CCID:004669
Phenotypes for gene: DNAH17 were set to spermatogenic failure 39 (MONDO:0032845)
Review for gene: DNAH17 was set to GREEN
Added comment: Classified DEFINITIVE by ClinGen on 08/09/2022 - https://search.clinicalgenome.org/CCID:004669
Sources: Other
Ciliary Dyskinesia v1.39 DNAH17 Sangavi Sivagnanasundram gene: DNAH17 was added
gene: DNAH17 was added to Ciliary Dyskinesia. Sources: Other
Mode of inheritance for gene: DNAH17 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DNAH17 were set to https://search.clinicalgenome.org/CCID:004669
Phenotypes for gene: DNAH17 were set to spermatogenic failure 39 (MONDO:0032845)
Review for gene: DNAH17 was set to GREEN
Added comment: Classified DEFINITIVE by ClinGen on 08/09/2022 - https://search.clinicalgenome.org/CCID:004669
Sources: Other
Ciliary Dyskinesia v1.39 LRRC6 Sangavi Sivagnanasundram reviewed gene: LRRC6: Rating: ; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:004663; Phenotypes: ; Mode of inheritance: None
Intellectual disability syndromic and non-syndromic v0.5796 SPR Amy Chiang changed review comment from: SPR has been classified to have definitive association with dopa-responsive dystonia. This was reviewed by the Aminoacidopathy Expert Panel on 06/04/2021.
There are 271 SPR variants registered in ClinVar to date with only 1 submission from a research lab reported 2 affected individuals with intellectual disability + family history (ClinVar # 625209) - no publication available to verify, ? from BRIDGE consortium study: SPEED project cohort
A start loss variant detected in 5 affected individuals with ID & epilepsy from a Persian consanguineous family - LOD score = 4.027 (PMID: 29302074); to: SPR has been classified to have definitive association with dopa-responsive dystonia. This was reviewed by the Aminoacidopathy Expert Panel on 06/04/2021.
There are 271 SPR variants registered in ClinVar to date with only 1 submission from a research lab reported 2 affected individuals with intellectual disability + family history (ClinVar # 625209) - no publication available to verify, ? from BRIDGE consortium study: SPEED project cohort
A start loss variant detected in 5 affected individuals with ID & epilepsy from a Persian consanguineous family - LOD score = 4.027 (PMID: 29302074)
Intellectual disability syndromic and non-syndromic v0.5796 SPR Amy Chiang reviewed gene: SPR: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 29302074; Phenotypes: dopa-responsive dystonia due to sepiapterin reductase deficiency, MONDO: 0012994, Dystonia, dopa-responsive, due to sepiapterin reductase deficiency, OMIM: 612716; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1770 SLC52A1 Bryony Thompson Classified gene: SLC52A1 as Amber List (moderate evidence)
Mendeliome v1.1770 SLC52A1 Bryony Thompson Added comment: Comment on list classification: Moderate gene-disease classification by ClinGen - https://search.clinicalgenome.org/CCID:006192
Mendeliome v1.1770 SLC52A1 Bryony Thompson Gene: slc52a1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1769 SLC52A1 Bryony Thompson Publications for gene: SLC52A1 were set to 29122468; 17689999
Mendeliome v1.1768 SLC52A1 Bryony Thompson reviewed gene: SLC52A1: Rating: AMBER; Mode of pathogenicity: None; Publications: 37510312, 29122468, 21089064; Phenotypes: Maternal riboflavin deficiency MONDO:0014013, Disorders of riboflavin metabolism; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary Neuropathy - complex v1.14 SLC25A19 Bryony Thompson Marked gene: SLC25A19 as ready
Hereditary Neuropathy - complex v1.14 SLC25A19 Bryony Thompson Gene: slc25a19 has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v1.14 SLC25A19 Bryony Thompson Classified gene: SLC25A19 as Green List (high evidence)
Hereditary Neuropathy - complex v1.14 SLC25A19 Bryony Thompson Gene: slc25a19 has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v1.13 SLC25A19 Bryony Thompson gene: SLC25A19 was added
gene: SLC25A19 was added to Hereditary Neuropathy - complex. Sources: Literature
Mode of inheritance for gene: SLC25A19 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC25A19 were set to 20301539
Phenotypes for gene: SLC25A19 were set to Progressive demyelinating neuropathy with bilateral striatal necrosis MONDO:0013382
Review for gene: SLC25A19 was set to GREEN
gene: SLC25A19 was marked as current diagnostic
Added comment: Neuropathy is a feature of the condition
Sources: Literature
Monogenic Diabetes v0.107 SLC2A2 Zornitza Stark Marked gene: SLC2A2 as ready
Monogenic Diabetes v0.107 SLC2A2 Zornitza Stark Gene: slc2a2 has been classified as Green List (High Evidence).
Monogenic Diabetes v0.107 SLC2A2 Zornitza Stark Phenotypes for gene: SLC2A2 were changed from {Diabetes mellitus, noninsulin-dependent}; Fanconi-Bickel syndrome to Fanconi-Bickel syndrome, MIM# 227810
Monogenic Diabetes v0.106 AGPAT2 Zornitza Stark Marked gene: AGPAT2 as ready
Monogenic Diabetes v0.106 AGPAT2 Zornitza Stark Gene: agpat2 has been classified as Green List (High Evidence).
Monogenic Diabetes v0.106 AGPAT2 Zornitza Stark Phenotypes for gene: AGPAT2 were changed from neonatal diabetes mellitus to congenital generalized lipodystrophy type 1 MONDO:0012071
Monogenic Diabetes v0.105 AGPAT2 Zornitza Stark Publications for gene: AGPAT2 were set to PubMed PMID: 11967537, PubMed PMID: 12765973.
Monogenic Diabetes v0.104 SLC40A1 Zornitza Stark Marked gene: SLC40A1 as ready
Monogenic Diabetes v0.104 SLC40A1 Zornitza Stark Gene: slc40a1 has been classified as Green List (High Evidence).
Monogenic Diabetes v0.104 SLC40A1 Zornitza Stark Phenotypes for gene: SLC40A1 were changed from Hemochromatosis, type 4 606069 to Hemochromatosis, type 4, MIM# 606069
Monogenic Diabetes v0.103 SLC40A1 Zornitza Stark Publications for gene: SLC40A1 were set to
Monogenic Diabetes v0.102 SLC40A1 Zornitza Stark Mode of pathogenicity for gene: SLC40A1 was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Monogenic Diabetes v0.101 SLC29A3 Zornitza Stark Marked gene: SLC29A3 as ready
Monogenic Diabetes v0.101 SLC29A3 Zornitza Stark Gene: slc29a3 has been classified as Green List (High Evidence).
Monogenic Diabetes v0.101 SLC29A3 Zornitza Stark Phenotypes for gene: SLC29A3 were changed from Histiocytosis-lymphadenopathy plus syndrome,602782; Pigmented hypertrichotic dermatosis with insulin-dependent diabetes (PHID) syndrome; H syndrome (hyperpigmentation, hypertrichosis, hepatosplenomegaly, heart anomalies, hearing loss, hypogonadism, low height, and hyperglycaemia) and PHID syndrome (pigmented hypertrichosis with insulin dependent diabetes) to Histiocytosis-lymphadenopathy plus syndrome, MIM#602782
Monogenic Diabetes v0.100 SLC29A3 Zornitza Stark Publications for gene: SLC29A3 were set to 19336477
Monogenic Diabetes v0.99 SLC19A2 Zornitza Stark Marked gene: SLC19A2 as ready
Monogenic Diabetes v0.99 SLC19A2 Zornitza Stark Gene: slc19a2 has been classified as Green List (High Evidence).
Monogenic Diabetes v0.99 SLC19A2 Zornitza Stark Phenotypes for gene: SLC19A2 were changed from Thiamine-responsive megaloblastic anemia syndrome; MEGALOBLASTIC ANEMIA, THIAMINE-RESPONSIVE, WITH DIABETES MELLITUS AND SENSORINEURAL DEAFNESS ROGERS SYNDROME to thiamine-responsive megaloblastic anemia syndrome MONDO:0009575
Monogenic Diabetes v0.98 SLC19A2 Zornitza Stark Publications for gene: SLC19A2 were set to 26549656; 26839896
Monogenic Diabetes v0.97 BSCL2 Zornitza Stark Marked gene: BSCL2 as ready
Monogenic Diabetes v0.97 BSCL2 Zornitza Stark Gene: bscl2 has been classified as Green List (High Evidence).
Monogenic Diabetes v0.97 BSCL2 Zornitza Stark Phenotypes for gene: BSCL2 were changed from Berardinelli-Seip congenital lipodystrophy to congenital generalized lipodystrophy type 2 MONDO:0010020; diabetes mellitus MONDO:0005015
Monogenic Diabetes v0.96 BSCL2 Zornitza Stark Publications for gene: BSCL2 were set to 11479539
Early-onset Dementia v1.22 POLG Zornitza Stark Classified gene: POLG as Amber List (moderate evidence)
Early-onset Dementia v1.22 POLG Zornitza Stark Gene: polg has been classified as Amber List (Moderate Evidence).
Monogenic Diabetes v0.95 PPP1R15B Zornitza Stark Marked gene: PPP1R15B as ready
Monogenic Diabetes v0.95 PPP1R15B Zornitza Stark Gene: ppp1r15b has been classified as Amber List (Moderate Evidence).
Monogenic Diabetes v0.95 PPP1R15B Zornitza Stark Classified gene: PPP1R15B as Amber List (moderate evidence)
Monogenic Diabetes v0.95 PPP1R15B Zornitza Stark Gene: ppp1r15b has been classified as Amber List (Moderate Evidence).
Monogenic Diabetes v0.94 PPP1R15B Zornitza Stark Publications for gene: PPP1R15B were set to
Early-onset Dementia v1.21 COL4A2 Zornitza Stark Classified gene: COL4A2 as Amber List (moderate evidence)
Early-onset Dementia v1.21 COL4A2 Zornitza Stark Gene: col4a2 has been classified as Amber List (Moderate Evidence).
Monogenic Diabetes v0.93 PAX6 Zornitza Stark Marked gene: PAX6 as ready
Monogenic Diabetes v0.93 PAX6 Zornitza Stark Gene: pax6 has been classified as Red List (Low Evidence).
Monogenic Diabetes v0.93 PAX6 Zornitza Stark Phenotypes for gene: PAX6 were changed from Aniridia 106210; diabetes to Monogenic diabetes, MONDO:0015967, PAX6-related
Monogenic Diabetes v0.92 PAX6 Zornitza Stark Publications for gene: PAX6 were set to
Monogenic Diabetes v0.91 PAX6 Zornitza Stark Classified gene: PAX6 as Red List (low evidence)
Monogenic Diabetes v0.91 PAX6 Zornitza Stark Gene: pax6 has been classified as Red List (Low Evidence).
Monogenic Diabetes v0.90 PAX6 Zornitza Stark reviewed gene: PAX6: Rating: RED; Mode of pathogenicity: None; Publications: 36202929; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Monogenic Diabetes v0.90 HNF4A Zornitza Stark Marked gene: HNF4A as ready
Monogenic Diabetes v0.90 HNF4A Zornitza Stark Gene: hnf4a has been classified as Green List (High Evidence).
Monogenic Diabetes v0.90 HNF4A Zornitza Stark Phenotypes for gene: HNF4A were changed from Fanconi renotubular syndrome 4, with maturity-onset diabetes of the young 616026; Maturity-Onset Diabetes Of The Young, Type 1; MODY1, 125850; {Diabetes mellitus, noninsulin-dependent}, 125853 to Fanconi renotubular syndrome 4, with maturity-onset diabetes of the young 616026; Maturity-Onset Diabetes Of The Young, Type 1; MODY1, 125850; {Diabetes mellitus, noninsulin-dependent}, 125853
Monogenic Diabetes v0.89 HNF4A Zornitza Stark Publications for gene: HNF4A were set to 28242437
Monogenic Diabetes v0.88 ALMS1 Zornitza Stark Marked gene: ALMS1 as ready
Monogenic Diabetes v0.88 ALMS1 Zornitza Stark Gene: alms1 has been classified as Green List (High Evidence).
Monogenic Diabetes v0.88 ALMS1 Zornitza Stark Phenotypes for gene: ALMS1 were changed from Alstrom syndrome to Alstrom syndrome MONDO:0008763
Monogenic Diabetes v0.87 ALMS1 Zornitza Stark Publications for gene: ALMS1 were set to
Monogenic Diabetes v0.86 CISD2 Zornitza Stark Marked gene: CISD2 as ready
Monogenic Diabetes v0.86 CISD2 Zornitza Stark Gene: cisd2 has been classified as Green List (High Evidence).
Monogenic Diabetes v0.86 CISD2 Zornitza Stark Phenotypes for gene: CISD2 were changed from Wolfram syndrome 2604928 to Wolfram syndrome, MIM#2604928
Monogenic Diabetes v0.85 CISD2 Zornitza Stark Publications for gene: CISD2 were set to 25056293; 17846994
Monogenic Diabetes v0.84 DMXL2 Zornitza Stark Marked gene: DMXL2 as ready
Monogenic Diabetes v0.84 DMXL2 Zornitza Stark Gene: dmxl2 has been classified as Red List (Low Evidence).
Monogenic Diabetes v0.84 DMXL2 Zornitza Stark Phenotypes for gene: DMXL2 were changed from Sensorineural Hearing Loss; OMIM:612186; ORPHA90636 to Polyendocrine-polyneuropathy syndrome , MIM# 616113
Monogenic Diabetes v0.83 DMXL2 Zornitza Stark Publications for gene: DMXL2 were set to 22875945; 27657680; 25248098
Monogenic Diabetes v0.82 DMXL2 Zornitza Stark Classified gene: DMXL2 as Red List (low evidence)
Monogenic Diabetes v0.82 DMXL2 Zornitza Stark Gene: dmxl2 has been classified as Red List (Low Evidence).
Monogenic Diabetes v0.81 STAT3 Zornitza Stark Marked gene: STAT3 as ready
Monogenic Diabetes v0.81 STAT3 Zornitza Stark Gene: stat3 has been classified as Green List (High Evidence).
Monogenic Diabetes v0.81 STAT3 Zornitza Stark Phenotypes for gene: STAT3 were changed from to STAT3-related early-onset multisystem autoimmune disease MONDO:0014414
Monogenic Diabetes v0.80 STAT3 Zornitza Stark Publications for gene: STAT3 were set to 25038750; 27167055
Monogenic Diabetes v0.79 STAT1 Zornitza Stark Marked gene: STAT1 as ready
Monogenic Diabetes v0.79 STAT1 Zornitza Stark Gene: stat1 has been classified as Amber List (Moderate Evidence).
Monogenic Diabetes v0.79 STAT1 Zornitza Stark Phenotypes for gene: STAT1 were changed from to autoimmune enteropathy and endocrinopathy - susceptibility to chronic infections syndrome MONDO:0013599
Monogenic Diabetes v0.78 STAT1 Zornitza Stark Publications for gene: STAT1 were set to 23534974
Monogenic Diabetes v0.77 STAT1 Zornitza Stark Classified gene: STAT1 as Amber List (moderate evidence)
Monogenic Diabetes v0.77 STAT1 Zornitza Stark Gene: stat1 has been classified as Amber List (Moderate Evidence).
Monogenic Diabetes v0.76 TRMT10A Zornitza Stark Marked gene: TRMT10A as ready
Monogenic Diabetes v0.76 TRMT10A Zornitza Stark Gene: trmt10a has been classified as Green List (High Evidence).
Monogenic Diabetes v0.76 TRMT10A Zornitza Stark Phenotypes for gene: TRMT10A were changed from Autosomal recessive juvenile-onset diabetes with microcephaly, epilepsy and intellectual disability; failure to thrive and microcephaly, ketoacidosis at onset of diabetes and islet cell autoantibodies; young onset diabetes, short stature and microcephaly with intellectual disability; Microcephaly, short stature, and impaired glucose metabolism 1, 616033 to Microcephaly, short stature, and impaired glucose metabolism 1, 616033
Monogenic Diabetes v0.75 TRMT10A Zornitza Stark Publications for gene: TRMT10A were set to 26297882; 24204302
Paroxysmal Dyskinesia v0.131 SCN8A Zornitza Stark Marked gene: SCN8A as ready
Paroxysmal Dyskinesia v0.131 SCN8A Zornitza Stark Gene: scn8a has been classified as Green List (High Evidence).
Paroxysmal Dyskinesia v0.131 SCN8A Zornitza Stark Phenotypes for gene: SCN8A were changed from to Complex neurodevelopmental disorder MONDO:0100038
Paroxysmal Dyskinesia v0.130 SCN8A Zornitza Stark Publications for gene: SCN8A were set to
Paroxysmal Dyskinesia v0.129 SCN8A Zornitza Stark Mode of inheritance for gene: SCN8A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Paroxysmal Dyskinesia v0.128 SLC2A1 Zornitza Stark Marked gene: SLC2A1 as ready
Paroxysmal Dyskinesia v0.128 SLC2A1 Zornitza Stark Gene: slc2a1 has been classified as Green List (High Evidence).
Paroxysmal Dyskinesia v0.128 SLC2A1 Zornitza Stark Phenotypes for gene: SLC2A1 were changed from to GLUT1 deficiency syndrome MONDO:0000188
Paroxysmal Dyskinesia v0.127 SLC2A1 Zornitza Stark Publications for gene: SLC2A1 were set to
Paroxysmal Dyskinesia v0.126 SLC2A1 Zornitza Stark Mode of inheritance for gene: SLC2A1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v1.243 BRWD1 Zornitza Stark changed review comment from: Single individual with situs inversus.; to: Single individual with situs inversus.

Whole gene-disease relationship assessed as DISPUTED by ClinGen.
Fetal anomalies v1.243 BRWD1 Zornitza Stark Tag disputed tag was added to gene: BRWD1.
Mendeliome v1.1768 BRWD1 Zornitza Stark Tag disputed tag was added to gene: BRWD1.
Ciliary Dyskinesia v1.39 BRWD1 Zornitza Stark Tag disputed tag was added to gene: BRWD1.
Ciliary Dyskinesia v1.39 BRWD1 Zornitza Stark Classified gene: BRWD1 as Red List (low evidence)
Ciliary Dyskinesia v1.39 BRWD1 Zornitza Stark Gene: brwd1 has been classified as Red List (Low Evidence).
Mendeliome v1.1768 BRWD1 Zornitza Stark Classified gene: BRWD1 as Red List (low evidence)
Mendeliome v1.1768 BRWD1 Zornitza Stark Gene: brwd1 has been classified as Red List (Low Evidence).
Renal Tubulopathies and related disorders v1.14 SLC6A20 Bryony Thompson Marked gene: SLC6A20 as ready
Renal Tubulopathies and related disorders v1.14 SLC6A20 Bryony Thompson Gene: slc6a20 has been classified as Red List (Low Evidence).
Renal Tubulopathies and related disorders v1.14 SLC6A20 Bryony Thompson Publications for gene: SLC6A20 were set to 24816252; 19033659
Renal Tubulopathies and related disorders v1.13 SLC6A20 Bryony Thompson Classified gene: SLC6A20 as Red List (low evidence)
Renal Tubulopathies and related disorders v1.13 SLC6A20 Bryony Thompson Gene: slc6a20 has been classified as Red List (Low Evidence).
Renal Tubulopathies and related disorders v1.12 SLC6A20 Bryony Thompson reviewed gene: SLC6A20: Rating: RED; Mode of pathogenicity: None; Publications: 19033659, 36820062, 24816252; Phenotypes: Hyperglycinuria MONDO:0007677; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.1767 SLC6A20 Bryony Thompson Publications for gene: SLC6A20 were set to 24816252; 19033659
Mendeliome v1.1766 SLC6A20 Bryony Thompson Classified gene: SLC6A20 as Red List (low evidence)
Mendeliome v1.1766 SLC6A20 Bryony Thompson Gene: slc6a20 has been classified as Red List (Low Evidence).
Mendeliome v1.1765 SLC6A20 Bryony Thompson reviewed gene: SLC6A20: Rating: RED; Mode of pathogenicity: None; Publications: 19033659, 36820062, 24816252; Phenotypes: Hyperglycinuria MONDO:0007677; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Leukodystrophy - paediatric v0.308 NFE2L2 Bryony Thompson Marked gene: NFE2L2 as ready
Leukodystrophy - paediatric v0.308 NFE2L2 Bryony Thompson Gene: nfe2l2 has been classified as Green List (High Evidence).
Leukodystrophy - paediatric v0.308 NFE2L2 Bryony Thompson Classified gene: NFE2L2 as Green List (high evidence)
Leukodystrophy - paediatric v0.308 NFE2L2 Bryony Thompson Gene: nfe2l2 has been classified as Green List (High Evidence).
Leukodystrophy - paediatric v0.307 NFE2L2 Bryony Thompson gene: NFE2L2 was added
gene: NFE2L2 was added to Leukodystrophy - paediatric. Sources: Literature
Mode of inheritance for gene: NFE2L2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NFE2L2 were set to 29018201
Phenotypes for gene: NFE2L2 were set to Immunodeficiency, developmental delay, and hypohomocysteinemia MONDO:0060591; Disorders of glutathione metabolism
Mode of pathogenicity for gene: NFE2L2 was set to Other
Review for gene: NFE2L2 was set to GREEN
gene: NFE2L2 was marked as current diagnostic
Added comment: Paediatric-onset leukoencephalopathy is a feature of the condition.
Sources: Literature
Mendeliome v1.1765 NFE2L2 Bryony Thompson Tag treatable tag was added to gene: NFE2L2.
Mendeliome v1.1765 BRWD1 Sangavi Sivagnanasundram reviewed gene: BRWD1: Rating: RED; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:004289; Phenotypes: primary ciliary dyskinesia MONDO:0016575; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ciliary Dyskinesia v1.38 BRWD1 Sangavi Sivagnanasundram reviewed gene: BRWD1: Rating: RED; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:004289; Phenotypes: primary ciliary dyskinesia MONDO:0016575; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2660 PNPO Zornitza Stark Marked gene: PNPO as ready
Genetic Epilepsy v0.2660 PNPO Zornitza Stark Gene: pnpo has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2660 PNPO Zornitza Stark Phenotypes for gene: PNPO were changed from Pyridoxamine 5'-phosphate oxidase deficiency, MIM# 610090 to Pyridoxamine 5'-phosphate oxidase deficiency, MIM# 610090
Genetic Epilepsy v0.2659 PNPO Zornitza Stark Phenotypes for gene: PNPO were changed from to Pyridoxamine 5'-phosphate oxidase deficiency, MIM# 610090
Genetic Epilepsy v0.2658 PNPO Zornitza Stark Publications for gene: PNPO were set to 34769443; 33981986; 33748042; 32888189
Genetic Epilepsy v0.2657 PNPO Zornitza Stark Publications for gene: PNPO were set to
Genetic Epilepsy v0.2656 PNPO Zornitza Stark Mode of inheritance for gene: PNPO was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2655 PNKP Zornitza Stark Marked gene: PNKP as ready
Genetic Epilepsy v0.2655 PNKP Zornitza Stark Gene: pnkp has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2655 PNKP Zornitza Stark Phenotypes for gene: PNKP were changed from to Microcephaly, seizures, and developmental delay, MIM# 613402
Genetic Epilepsy v0.2654 PNKP Zornitza Stark Publications for gene: PNKP were set to
Genetic Epilepsy v0.2653 PNKP Zornitza Stark Mode of inheritance for gene: PNKP was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2652 PMM2 Zornitza Stark Marked gene: PMM2 as ready
Genetic Epilepsy v0.2652 PMM2 Zornitza Stark Gene: pmm2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2652 PMM2 Zornitza Stark Phenotypes for gene: PMM2 were changed from to Congenital disorder of glycosylation, type Ia (MIM#212065); Hyperinsulinaemic Hypoglycaemia and Polycystic Kidney Disease (HIPKD), MONDO:0020642, PMM2-related
Genetic Epilepsy v0.2651 PMM2 Zornitza Stark Publications for gene: PMM2 were set to
Genetic Epilepsy v0.2650 PMM2 Zornitza Stark Mode of inheritance for gene: PMM2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2649 PIK3R2 Zornitza Stark Marked gene: PIK3R2 as ready
Genetic Epilepsy v0.2649 PIK3R2 Zornitza Stark Gene: pik3r2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2649 PIK3R2 Zornitza Stark Phenotypes for gene: PIK3R2 were changed from to Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1, MIM# 603387
Genetic Epilepsy v0.2648 PIK3R2 Zornitza Stark Publications for gene: PIK3R2 were set to
Genetic Epilepsy v0.2647 PIK3R2 Zornitza Stark Mode of inheritance for gene: PIK3R2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2646 PIK3R2 Zornitza Stark changed review comment from: More than 10 affected individuals reported. Some variants are recurrent.; to: More than 10 affected individuals reported. Some variants are recurrent. Seizures are part of the phenotype.
Genetic Epilepsy v0.2646 PIGC Zornitza Stark Marked gene: PIGC as ready
Genetic Epilepsy v0.2646 PIGC Zornitza Stark Gene: pigc has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2646 PIGC Zornitza Stark Phenotypes for gene: PIGC were changed from Glycosylphosphatidylinositol biosynthesis defect 16, MIM# 617816 to Glycosylphosphatidylinositol biosynthesis defect 16, MIM# 617816
Genetic Epilepsy v0.2645 PIGC Zornitza Stark Phenotypes for gene: PIGC were changed from to Glycosylphosphatidylinositol biosynthesis defect 16, MIM# 617816
Genetic Epilepsy v0.2644 PIGC Zornitza Stark Publications for gene: PIGC were set to 27694521; 32707268
Genetic Epilepsy v0.2643 PIGC Zornitza Stark Publications for gene: PIGC were set to
Genetic Epilepsy v0.2642 PIGC Zornitza Stark Mode of inheritance for gene: PIGC was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2641 PHGDH Zornitza Stark Marked gene: PHGDH as ready
Genetic Epilepsy v0.2641 PHGDH Zornitza Stark Gene: phgdh has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2641 PHGDH Zornitza Stark Phenotypes for gene: PHGDH were changed from to Neu-Laxova syndrome 1, MIM# 256520; Phosphoglycerate dehydrogenase deficiency, MIM# 601815
Genetic Epilepsy v0.2640 PHGDH Zornitza Stark Publications for gene: PHGDH were set to
Genetic Epilepsy v0.2639 PHGDH Zornitza Stark Mode of inheritance for gene: PHGDH was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2638 PHGDH Zornitza Stark Mode of inheritance for gene: PHGDH was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2637 PHGDH Zornitza Stark changed review comment from: Well established gene-disease association, severity depends on amount of residual enzyme activity.; to: Well established gene-disease association, severity depends on amount of residual enzyme activity, seizures are part of the phenotype.
Genetic Epilepsy v0.2637 PEX7 Zornitza Stark Phenotypes for gene: PEX7 were changed from Peroxisome biogenesis disorder 9B, MIM# 614879 to Peroxisome biogenesis disorder 9B, MIM# 614879
Genetic Epilepsy v0.2636 PEX7 Zornitza Stark Marked gene: PEX7 as ready
Genetic Epilepsy v0.2636 PEX7 Zornitza Stark Gene: pex7 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2636 PEX7 Zornitza Stark Phenotypes for gene: PEX7 were changed from Peroxisome biogenesis disorder 9B, MIM# 614879 to Peroxisome biogenesis disorder 9B, MIM# 614879
Genetic Epilepsy v0.2635 PEX7 Zornitza Stark Phenotypes for gene: PEX7 were changed from to Peroxisome biogenesis disorder 9B, MIM# 614879
Genetic Epilepsy v0.2634 PEX7 Zornitza Stark Publications for gene: PEX7 were set to
Genetic Epilepsy v0.2633 PEX7 Zornitza Stark Mode of inheritance for gene: PEX7 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2632 PEX6 Zornitza Stark Marked gene: PEX6 as ready
Genetic Epilepsy v0.2632 PEX6 Zornitza Stark Gene: pex6 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2632 PEX6 Zornitza Stark Phenotypes for gene: PEX6 were changed from to Peroxisome biogenesis disorder 4A (Zellweger), MIM# 614862
Genetic Epilepsy v0.2631 PEX6 Zornitza Stark Publications for gene: PEX6 were set to
Genetic Epilepsy v0.2630 PEX6 Zornitza Stark Mode of inheritance for gene: PEX6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2629 PEX5 Zornitza Stark Marked gene: PEX5 as ready
Genetic Epilepsy v0.2629 PEX5 Zornitza Stark Gene: pex5 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2629 PEX5 Zornitza Stark Phenotypes for gene: PEX5 were changed from to Peroxisome biogenesis disorder 2A (Zellweger), MIM# 214110; Peroxisome biogenesis disorder 2B, MIM# 202370
Genetic Epilepsy v0.2628 PEX5 Zornitza Stark Publications for gene: PEX5 were set to
Genetic Epilepsy v0.2627 PEX5 Zornitza Stark Mode of inheritance for gene: PEX5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2626 PEX3 Zornitza Stark Marked gene: PEX3 as ready
Genetic Epilepsy v0.2626 PEX3 Zornitza Stark Gene: pex3 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2626 PEX3 Zornitza Stark Phenotypes for gene: PEX3 were changed from to Peroxisome biogenesis disorder 10A (Zellweger), MIM# 614882; Peroxisome biogenesis disorder 10B , MIM# 617370
Genetic Epilepsy v0.2625 PEX3 Zornitza Stark Publications for gene: PEX3 were set to
Genetic Epilepsy v0.2624 PEX3 Zornitza Stark Mode of inheritance for gene: PEX3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2623 MOCS2 Zornitza Stark Marked gene: MOCS2 as ready
Genetic Epilepsy v0.2623 MOCS2 Zornitza Stark Gene: mocs2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2623 MOCS2 Zornitza Stark Phenotypes for gene: MOCS2 were changed from to Molybdenum cofactor deficiency B MIM#252160
Genetic Epilepsy v0.2622 SGCE Zornitza Stark Marked gene: SGCE as ready
Genetic Epilepsy v0.2622 SGCE Zornitza Stark Gene: sgce has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2622 SGCE Zornitza Stark Classified gene: SGCE as Green List (high evidence)
Genetic Epilepsy v0.2622 SGCE Zornitza Stark Gene: sgce has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2621 SGCE Zornitza Stark gene: SGCE was added
gene: SGCE was added to Genetic Epilepsy. Sources: Expert list
Mode of inheritance for gene: SGCE was set to MONOALLELIC, autosomal or pseudoautosomal, maternally imprinted (paternal allele expressed)
Publications for gene: SGCE were set to 15389977; 12821748; 24297365
Phenotypes for gene: SGCE were set to Dystonia-11, myoclonic, MIM# 159900
Review for gene: SGCE was set to GREEN
Added comment: Occasional reports of epilepsy in this disorder; however, also included due to possible phenotypic overlap.
Sources: Expert list
Genetic Epilepsy v0.2620 SRD5A3 Zornitza Stark Marked gene: SRD5A3 as ready
Genetic Epilepsy v0.2620 SRD5A3 Zornitza Stark Gene: srd5a3 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2620 SRD5A3 Zornitza Stark Classified gene: SRD5A3 as Amber List (moderate evidence)
Genetic Epilepsy v0.2620 SRD5A3 Zornitza Stark Gene: srd5a3 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2619 SRD5A3 Zornitza Stark gene: SRD5A3 was added
gene: SRD5A3 was added to Genetic Epilepsy. Sources: Expert list
Mode of inheritance for gene: SRD5A3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SRD5A3 were set to 26219881
Phenotypes for gene: SRD5A3 were set to Congenital disorder of glycosylation, type Iq, MIM# 612379
Review for gene: SRD5A3 was set to AMBER
Added comment: Many CDGs have epilepsy as a feature, and note brain abnormalities with this particular CDG,w which may be expected to contribute to the development of epilepsy. However, paucity of reports of patients with molecularly confirmed diagnosis and epilepsy.
Sources: Expert list
Genetic Epilepsy v0.2618 MAGI2 Zornitza Stark Marked gene: MAGI2 as ready
Genetic Epilepsy v0.2618 MAGI2 Zornitza Stark Gene: magi2 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2618 MAGI2 Zornitza Stark gene: MAGI2 was added
gene: MAGI2 was added to Genetic Epilepsy. Sources: Expert list
Mode of inheritance for gene: MAGI2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAGI2 were set to 26030165; 25497044; 31056551
Phenotypes for gene: MAGI2 were set to Monogenic epilepsy, MONDO:0015653, MAGI2-related
Review for gene: MAGI2 was set to RED
Added comment: Reported as a candidate gene for epilepsy but evidence is contradictory.
Sources: Expert list
Genetic Epilepsy v0.2617 CACNB4 Zornitza Stark Marked gene: CACNB4 as ready
Genetic Epilepsy v0.2617 CACNB4 Zornitza Stark Gene: cacnb4 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2617 CACNB4 Zornitza Stark Classified gene: CACNB4 as Amber List (moderate evidence)
Genetic Epilepsy v0.2617 CACNB4 Zornitza Stark Gene: cacnb4 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2616 CACNB4 Zornitza Stark gene: CACNB4 was added
gene: CACNB4 was added to Genetic Epilepsy. Sources: Expert list
Mode of inheritance for gene: CACNB4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CACNB4 were set to 10762541; 35813387; 31056551; 22892567
Phenotypes for gene: CACNB4 were set to {Epilepsy, idiopathic generalized, susceptibility to, 9} 607682; {Epilepsy, juvenile myoclonic, susceptibility to, 6} 607682
Review for gene: CACNB4 was set to AMBER
Added comment: Good biological candidate but may be a susceptibility locus. Some of the variants reported have relatively high frequencies in gnomAD, and others are reported as part of large cohort studies with little supporting information regarding pathogenicity.
Sources: Expert list
Miscellaneous Metabolic Disorders v1.46 GLUL Zornitza Stark Phenotypes for gene: GLUL were changed from Glutamine deficiency, congenital MIM#610015; disorder of amino acid metabolism to Glutamine deficiency, congenital MIM#610015; Developmental and epileptic encephalopathy 116, MIM# 620806
Miscellaneous Metabolic Disorders v1.45 GLUL Zornitza Stark Mode of inheritance for gene: GLUL was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Miscellaneous Metabolic Disorders v1.44 GLUL Zornitza Stark reviewed gene: GLUL: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Glutamine deficiency, congenital MIM#610015, Developmental and epileptic encephalopathy 116, MIM# 620806; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5796 GLUL Zornitza Stark Phenotypes for gene: GLUL were changed from Developmental and epileptic encephalopathy, MONDO:0100062, GLUL-related; Glutamine deficiency, congenital MIM#610015 to Glutamine deficiency, congenital MIM#610015; Developmental and epileptic encephalopathy 116, MIM# 620806
Intellectual disability syndromic and non-syndromic v0.5795 GLUL Zornitza Stark edited their review of gene: GLUL: Changed phenotypes: Glutamine deficiency, congenital MIM#610015, Developmental and epileptic encephalopathy 116, MIM# 620806
Genetic Epilepsy v0.2615 GLUL Zornitza Stark Phenotypes for gene: GLUL were changed from Glutamine deficiency, congenital MIM#610015; Developmental and epileptic encephalopathy, MONDO:0100062, GLUL-related to Glutamine deficiency, congenital MIM#610015; Developmental and epileptic encephalopathy 116, MIM# 620806
Genetic Epilepsy v0.2614 GLUL Zornitza Stark edited their review of gene: GLUL: Changed phenotypes: Glutamine deficiency, congenital MIM#610015, Developmental and epileptic encephalopathy 116, MIM# 620806
Mendeliome v1.1765 GLUL Zornitza Stark Phenotypes for gene: GLUL were changed from Developmental and epileptic encephalopathy, MONDO:0100062, GLUL-related; Glutamine deficiency, congenital MIM#610015; disorder of amino acid metabolism to Developmental and epileptic encephalopathy 116, MIM# 620806; Glutamine deficiency, congenital MIM#610015; disorder of amino acid metabolism
Mendeliome v1.1764 GLUL Zornitza Stark edited their review of gene: GLUL: Changed phenotypes: Developmental and epileptic encephalopathy 116, MIM# 620806
Ataxia - paediatric v1.21 DAGLA Zornitza Stark Marked gene: DAGLA as ready
Ataxia - paediatric v1.21 DAGLA Zornitza Stark Gene: dagla has been classified as Green List (High Evidence).
Ataxia - paediatric v1.21 DAGLA Zornitza Stark Classified gene: DAGLA as Green List (high evidence)
Ataxia - paediatric v1.21 DAGLA Zornitza Stark Gene: dagla has been classified as Green List (High Evidence).
Ataxia - paediatric v1.20 DAGLA Zornitza Stark gene: DAGLA was added
gene: DAGLA was added to Ataxia - paediatric. Sources: Literature
Mode of inheritance for gene: DAGLA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DAGLA were set to 35737950
Phenotypes for gene: DAGLA were set to Neuroocular syndrome 2, paroxysmal type, MIM# 168885
Review for gene: DAGLA was set to GREEN
Added comment: 9 individuals from 8 families reported with daily paroxysmal spells characterized by eye deviation or nystagmus with abnormal head posturing apparent from birth or early infancy. The episodes tend to be triggered after sleeping, and most patients show improvement of the ocular symptoms over time. Affected individuals also have hypotonia, mild developmental delay, dysarthria, and gait ataxia; most have mildly impaired intellectual development. Seizures are not observed.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5795 DAGLA Zornitza Stark Marked gene: DAGLA as ready
Intellectual disability syndromic and non-syndromic v0.5795 DAGLA Zornitza Stark Gene: dagla has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5795 DAGLA Zornitza Stark Classified gene: DAGLA as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5795 DAGLA Zornitza Stark Gene: dagla has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5794 DAGLA Zornitza Stark gene: DAGLA was added
gene: DAGLA was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: DAGLA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DAGLA were set to 35737950
Phenotypes for gene: DAGLA were set to Neuroocular syndrome 2, paroxysmal type, MIM# 168885
Review for gene: DAGLA was set to GREEN
Added comment: 9 individuals from 8 families reported with daily paroxysmal spells characterized by eye deviation or nystagmus with abnormal head posturing apparent from birth or early infancy. The episodes tend to be triggered after sleeping, and most patients show improvement of the ocular symptoms over time. Affected individuals also have hypotonia, mild developmental delay, dysarthria, and gait ataxia; most have mildly impaired intellectual development. Seizures are not observed.
Sources: Literature
Mendeliome v1.1764 DAGLA Zornitza Stark Marked gene: DAGLA as ready
Mendeliome v1.1764 DAGLA Zornitza Stark Gene: dagla has been classified as Green List (High Evidence).
Mendeliome v1.1764 DAGLA Zornitza Stark Classified gene: DAGLA as Green List (high evidence)
Mendeliome v1.1764 DAGLA Zornitza Stark Gene: dagla has been classified as Green List (High Evidence).
Mendeliome v1.1763 DAGLA Zornitza Stark gene: DAGLA was added
gene: DAGLA was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: DAGLA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DAGLA were set to 35737950
Phenotypes for gene: DAGLA were set to Neuroocular syndrome 2, paroxysmal type, MIM# 168885
Review for gene: DAGLA was set to GREEN
Added comment: 9 individuals from 8 families reported with daily paroxysmal spells characterized by eye deviation or nystagmus with abnormal head posturing apparent from birth or early infancy. The episodes tend to be triggered after sleeping, and most patients show improvement of the ocular symptoms over time. Affected individuals also have hypotonia, mild developmental delay, dysarthria, and gait ataxia; most have mildly impaired intellectual development. Seizures are not observed.
Sources: Literature
Paroxysmal Dyskinesia v0.125 SLC2A1 Lynn Tan reviewed gene: SLC2A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 18451999, 34279792, 18577546, 34305802, 27098784; Phenotypes: GLUT1 deficiency syndrome MONDO:0000188; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Paroxysmal Dyskinesia v0.125 SCN8A Lynn Tan changed review comment from: PMID: 26677014 (2016)
3 families 16 individuals, cosegregating het missense SCN8A:c.4447G>A; p.E1483K (founder effect excluded by linkage analysis). 15/16 individuals seizures in first to second year of life, 1/16 seizures at school age. 5/16 patients developed additional brief paroxysmal episodes in puberty, either dystonic/dyskinetic or "shivering" attacks, triggered by stretching or motor initiation (3 patients from 2 families), or emotional stimuli (2 patients who were both from the same family).

PMID: 29356177 (2018)
De novo SCN8A mutation c.3640G>A (p.A1214T) in 23M with PKD

PMID: 25799905 (2015)
De novo dominant SCN8A (c.3979A>G; p.Ile1327Val) in male with in utero onset of movement disorder (exaggerated startle, paroxysmal posturing and jittery movements subsiding in sleep that on clinical and encephalographic grounds were not epileptic in nature), with evolving epilepsy, epileptic encephalopathy and developmental delay; to: PMID: 26677014 (2016)
3 families 16 individuals, cosegregating het missense SCN8A:c.4447G>A; p.E1483K (founder effect excluded by linkage analysis). All patients had seizures (15/16 individuals seizures in first to second year of life, 1/16 seizures at school age). 5/16 patients developed additional brief paroxysmal episodes in puberty, either dystonic/dyskinetic or "shivering" attacks, triggered by stretching or motor initiation (3 patients from 2 families), or emotional stimuli (2 patients who were both from the same family).

PMID: 29356177 (2018)
De novo SCN8A mutation c.3640G>A (p.A1214T) in 23M with PKD

PMID: 25799905 (2015)
De novo dominant SCN8A (c.3979A>G; p.Ile1327Val) in male with in utero onset of movement disorder (exaggerated startle, paroxysmal posturing and jittery movements subsiding in sleep that on clinical and encephalographic grounds were not epileptic in nature), with evolving epilepsy, epileptic encephalopathy and developmental delay
Paroxysmal Dyskinesia v0.125 SCN8A Lynn Tan reviewed gene: SCN8A: Rating: GREEN; Mode of pathogenicity: None; Publications: 26677014, 29356177, 25799905; Phenotypes: Complex neurodevelopmental disorder MONDO:0100038; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Monogenic Diabetes v0.74 TRMT10A Hali Van Niel reviewed gene: TRMT10A: Rating: GREEN; Mode of pathogenicity: None; Publications: 34541035, 24204302, 25053765, 26297882, 35137278; Phenotypes: microcephaly, short stature, and impaired glucose metabolism 1 MONDO:0000208; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Monogenic Diabetes v0.74 STAT1 Hali Van Niel Deleted their comment
Monogenic Diabetes v0.74 STAT1 Hali Van Niel edited their review of gene: STAT1: Added comment: STAT1 associated with 3 types of immonodeficiencies
Immonodeficiency 31A (AD, LoF), Immonodeficiency 31B (AR, LoF) and
Immonodeficiency 31C (autoimmune enteropathy and endocrinopathy - susceptibility to chronic infections syndrome), AD, GoF variants in STAT1

23534974: 5 patients w GOF mutation in STAT1, 3 developed type 1 diabetes mellitus
33027576: 1 patient with type 1 diabetes

Well established gene disease association, type 1 diabetes mellitus may present with disease; Changed mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Monogenic Diabetes v0.74 STAT1 Hali Van Niel reviewed gene: STAT1: Rating: AMBER; Mode of pathogenicity: Other; Publications: 23534974, 33027576; Phenotypes: autoimmune enteropathy and endocrinopathy - susceptibility to chronic infections syndrome MONDO:0013599; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Monogenic Diabetes v0.74 STAT1 Hali Van Niel Deleted their review
Monogenic Diabetes v0.74 STAT1 Hali Van Niel reviewed gene: STAT1: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: 23534974, 33027576; Phenotypes: autoimmune enteropathy and endocrinopathy - susceptibility to chronic infections syndrome MONDO:0013599; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Monogenic Diabetes v0.74 STAT3 Hali Van Niel reviewed gene: STAT3: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: 25038750, 25359994, 38020118, 30825606; Phenotypes: STAT3-related early-onset multisystem autoimmune disease MONDO:0014414; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Monogenic Diabetes v0.74 DMXL2 Hali Van Niel reviewed gene: DMXL2: Rating: RED; Mode of pathogenicity: None; Publications: 30237576, 31688942, 27657680, 25248098; Phenotypes: ; Mode of inheritance: Unknown
Monogenic Diabetes v0.74 POLD1 Zornitza Stark Marked gene: POLD1 as ready
Monogenic Diabetes v0.74 POLD1 Zornitza Stark Gene: pold1 has been classified as Green List (High Evidence).
Monogenic Diabetes v0.74 POLD1 Zornitza Stark Phenotypes for gene: POLD1 were changed from Mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome; Mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome, 615381; multisystem disorder that includes subcutaneous lipodystrophy, deafness, mandibular hypoplasia and hypogonadism in males to mandibular hypoplasia-deafness-progeroid syndrome MONDO:0014157
Monogenic Diabetes v0.73 POLD1 Zornitza Stark Publications for gene: POLD1 were set to 23770608
Monogenic Diabetes v0.72 DCAF17 Zornitza Stark Marked gene: DCAF17 as ready
Monogenic Diabetes v0.72 DCAF17 Zornitza Stark Gene: dcaf17 has been classified as Green List (High Evidence).
Monogenic Diabetes v0.72 DCAF17 Zornitza Stark Phenotypes for gene: DCAF17 were changed from Woodhouse-Sakati syndrome (hypogonadism, partial alopecia, diabetes mellitus, mental retardation, and deafness); Woodhouse-Sakati syndrome, 241080 to Woodhouse-Sakati syndrome MONDO:0009419
Monogenic Diabetes v0.71 DCAF17 Zornitza Stark Publications for gene: DCAF17 were set to 24464444; 19026396; 20507343
Monogenic Diabetes v0.70 DNAJC3 Zornitza Stark Marked gene: DNAJC3 as ready
Monogenic Diabetes v0.70 DNAJC3 Zornitza Stark Gene: dnajc3 has been classified as Green List (High Evidence).
Monogenic Diabetes v0.70 DNAJC3 Zornitza Stark Phenotypes for gene: DNAJC3 were changed from Autosomal recessive juvenile-onset diabetes with central and peripheral neurodegeneration; ?Ataxia, combined cerebellar and peripheral, with hearing loss and diabetes mellitus, 616192 to juvenile-onset diabetes mellitus-central and peripheral neurodegeneration syndrome MONDO:0014523
Monogenic Diabetes v0.69 DNAJC3 Zornitza Stark Publications for gene: DNAJC3 were set to
Monogenic Diabetes v0.68 FOXP3 Zornitza Stark Marked gene: FOXP3 as ready
Monogenic Diabetes v0.68 FOXP3 Zornitza Stark Gene: foxp3 has been classified as Green List (High Evidence).
Monogenic Diabetes v0.68 FOXP3 Zornitza Stark Phenotypes for gene: FOXP3 were changed from to immune dysregulation-polyendocrinopathy-enteropathy-X-linked syndrome MONDO:0010580
Monogenic Diabetes v0.67 FOXP3 Zornitza Stark Publications for gene: FOXP3 were set to
Monogenic Diabetes v0.66 GLIS3 Zornitza Stark Marked gene: GLIS3 as ready
Monogenic Diabetes v0.66 GLIS3 Zornitza Stark Gene: glis3 has been classified as Green List (High Evidence).
Monogenic Diabetes v0.66 GLIS3 Zornitza Stark Phenotypes for gene: GLIS3 were changed from Diabetes Mellitus, Neonatal, with Congenital Hypothyroidism; Diabetes mellitus, neonatal, with congenital hypothyroidism, 610199 -3 to neonatal diabetes mellitus with congenital hypothyroidism MONDO:0012436
Monogenic Diabetes v0.65 GLIS3 Zornitza Stark Publications for gene: GLIS3 were set to
Monogenic Diabetes v0.64 HFE Zornitza Stark Marked gene: HFE as ready
Monogenic Diabetes v0.64 HFE Zornitza Stark Gene: hfe has been classified as Green List (High Evidence).
Monogenic Diabetes v0.64 HFE Zornitza Stark Phenotypes for gene: HFE were changed from {Porphyria variegata, susceptibility to}, 176200; Hemochromatosis, 235200; {Microvascular complications of diabetes 7}, 612635; {Porphyria cutanea tarda, susceptibility to}, 176100; {Alzheimer disease, susceptibility to}, 104300 to haemochromatosis type 1 MONDO:0021001
Monogenic Diabetes v0.63 HFE Zornitza Stark Publications for gene: HFE were set to
Monogenic Diabetes v0.62 TFR2 Zornitza Stark Marked gene: TFR2 as ready
Monogenic Diabetes v0.62 TFR2 Zornitza Stark Gene: tfr2 has been classified as Green List (High Evidence).
Monogenic Diabetes v0.62 TFR2 Zornitza Stark Publications for gene: TFR2 were set to
Monogenic Diabetes v0.61 HAMP Zornitza Stark Marked gene: HAMP as ready
Monogenic Diabetes v0.61 HAMP Zornitza Stark Gene: hamp has been classified as Green List (High Evidence).
Monogenic Diabetes v0.61 HAMP Zornitza Stark Publications for gene: HAMP were set to
Monogenic Diabetes v0.60 COQ9 Zornitza Stark Marked gene: COQ9 as ready
Monogenic Diabetes v0.60 COQ9 Zornitza Stark Gene: coq9 has been classified as Red List (Low Evidence).
Monogenic Diabetes v0.60 COQ9 Zornitza Stark Phenotypes for gene: COQ9 were changed from Primary Coenzyme Q10 Deficiency; neonatal hyperglycaemia to encephalopathy-hypertrophic cardiomyopathy-renal tubular disease syndrome MONDO:0013840
Monogenic Diabetes v0.59 COQ9 Zornitza Stark Publications for gene: COQ9 were set to
Fetal anomalies v1.243 HOXD12 Zornitza Stark Marked gene: HOXD12 as ready
Fetal anomalies v1.243 HOXD12 Zornitza Stark Gene: hoxd12 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.243 HOXD12 Zornitza Stark Classified gene: HOXD12 as Amber List (moderate evidence)
Fetal anomalies v1.243 HOXD12 Zornitza Stark Gene: hoxd12 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.242 HOXD12 Zornitza Stark gene: HOXD12 was added
gene: HOXD12 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: HOXD12 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HOXD12 were set to 38663984
Phenotypes for gene: HOXD12 were set to Clubfoot (non-syndromic) MONDO:0007342
Review for gene: HOXD12 was set to AMBER
Added comment: Identified as a candidate gene in a large cohort due to enrichment of rare variants.


PMID: 38663984
Around 9 individuals from 4 unrelated families have been reported with clubfoot and the variants were shown to segregate. Cohort of over 1000 individuals, with several novel candidates identified.

N-terminal region and C-terminal homeobox domain of HOXD12 are known to be clusters for pathogenic variants related to clubfoot.
Loss of function variants are less likely to contribute to clubfoot pathogenesis therefore mechanism of disease is suggested as dominant negative but is not confirmed.
Sources: Literature
Mendeliome v1.1762 HOXD12 Zornitza Stark Marked gene: HOXD12 as ready
Mendeliome v1.1762 HOXD12 Zornitza Stark Gene: hoxd12 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1762 HOXD12 Zornitza Stark Classified gene: HOXD12 as Amber List (moderate evidence)
Mendeliome v1.1762 HOXD12 Zornitza Stark Gene: hoxd12 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1761 HOXD12 Zornitza Stark reviewed gene: HOXD12: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Clubfoot (non-syndromic) MONDO:0007342; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hand and foot malformations v0.74 HOXD12 Zornitza Stark Marked gene: HOXD12 as ready
Hand and foot malformations v0.74 HOXD12 Zornitza Stark Gene: hoxd12 has been classified as Amber List (Moderate Evidence).
Hand and foot malformations v0.74 HOXD12 Zornitza Stark Classified gene: HOXD12 as Amber List (moderate evidence)
Hand and foot malformations v0.74 HOXD12 Zornitza Stark Gene: hoxd12 has been classified as Amber List (Moderate Evidence).
Hand and foot malformations v0.73 HOXD12 Zornitza Stark reviewed gene: HOXD12: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Clubfoot (non-syndromic) MONDO:0007342; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Deafness_Isolated v1.59 PKHD1L1 Zornitza Stark Marked gene: PKHD1L1 as ready
Deafness_Isolated v1.59 PKHD1L1 Zornitza Stark Gene: pkhd1l1 has been classified as Green List (High Evidence).
Deafness_Isolated v1.59 PKHD1L1 Zornitza Stark Classified gene: PKHD1L1 as Green List (high evidence)
Deafness_Isolated v1.59 PKHD1L1 Zornitza Stark Gene: pkhd1l1 has been classified as Green List (High Evidence).
Deafness_Isolated v1.58 PKHD1L1 Zornitza Stark gene: PKHD1L1 was added
gene: PKHD1L1 was added to Deafness_Isolated. Sources: Literature
Mode of inheritance for gene: PKHD1L1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PKHD1L1 were set to 38459354
Phenotypes for gene: PKHD1L1 were set to non syndromic hearing loss (MONDO:0020678)
Review for gene: PKHD1L1 was set to GREEN
Added comment: At least 4 individuals from unrelated families with sensorineural hearing loss (SNHL) (2 of the reported probands were from consanguineous parents).
The individuals are either homozygous or compound heterozygous for mutations in PKHD1L1 (missense, frameshift and nonsense mutations have been reported).

In vitro functional assessment as well as a mini-gene assay of Gly605Arg was conducted. The mini-gene assay on Gly605Arg showed that exon skipping occurs resulting in an in-frame deletion of 48 aa. Both studies didn't use a positive control however loss of function or disruption to protein stability is the speculated mechanism of disease.
Sources: Literature
Mendeliome v1.1761 PKHD1L1 Zornitza Stark Marked gene: PKHD1L1 as ready
Mendeliome v1.1761 PKHD1L1 Zornitza Stark Gene: pkhd1l1 has been classified as Green List (High Evidence).
Mendeliome v1.1761 PKHD1L1 Zornitza Stark Publications for gene: PKHD1L1 were set to
Mendeliome v1.1760 PKHD1L1 Zornitza Stark Classified gene: PKHD1L1 as Green List (high evidence)
Mendeliome v1.1760 PKHD1L1 Zornitza Stark Gene: pkhd1l1 has been classified as Green List (High Evidence).
Monogenic Diabetes v0.58 FOXC2 Hali Van Niel reviewed gene: FOXC2: Rating: AMBER; Mode of pathogenicity: None; Publications: 15523639, 27349002, 11551504; Phenotypes: lymphedema-distichiasis syndrome MONDO:0007922; Mode of inheritance: Unknown
Monogenic Diabetes v0.58 EPHX1 Lauren Rogers Deleted their review
Lipodystrophy_Lipoatrophy v1.17 EPHX1 Ain Roesley Classified gene: EPHX1 as Green List (high evidence)
Lipodystrophy_Lipoatrophy v1.17 EPHX1 Ain Roesley Gene: ephx1 has been classified as Green List (High Evidence).
Mendeliome v1.1759 EPHX1 Ain Roesley Classified gene: EPHX1 as Green List (high evidence)
Mendeliome v1.1759 EPHX1 Ain Roesley Gene: ephx1 has been classified as Green List (High Evidence).
Monogenic Diabetes v0.58 COQ9 Hali Van Niel reviewed gene: COQ9: Rating: RED; Mode of pathogenicity: None; Publications: 19375058, 26081641, 31821167, 11562630; Phenotypes: encephalopathy-hypertrophic cardiomyopathy-renal tubular disease syndrome MONDO:0013840; Mode of inheritance: Unknown
Early-onset Dementia v1.20 TREX1 Bryony Thompson Marked gene: TREX1 as ready
Early-onset Dementia v1.20 TREX1 Bryony Thompson Gene: trex1 has been classified as Green List (High Evidence).
Early-onset Dementia v1.20 TREX1 Bryony Thompson Classified gene: TREX1 as Green List (high evidence)
Early-onset Dementia v1.20 TREX1 Bryony Thompson Gene: trex1 has been classified as Green List (High Evidence).
Early-onset Dementia v1.19 POLG Bryony Thompson Marked gene: POLG as ready
Early-onset Dementia v1.19 POLG Bryony Thompson Gene: polg has been classified as Red List (Low Evidence).
Early-onset Dementia v1.19 POLG Bryony Thompson Classified gene: POLG as Red List (low evidence)
Early-onset Dementia v1.19 POLG Bryony Thompson Gene: polg has been classified as Red List (Low Evidence).
Early-onset Dementia v1.18 COL4A2 Bryony Thompson Marked gene: COL4A2 as ready
Early-onset Dementia v1.18 COL4A2 Bryony Thompson Gene: col4a2 has been classified as Red List (Low Evidence).
Early-onset Dementia v1.18 COL4A2 Bryony Thompson Classified gene: COL4A2 as Red List (low evidence)
Early-onset Dementia v1.18 COL4A2 Bryony Thompson Gene: col4a2 has been classified as Red List (Low Evidence).
Early-onset Dementia v1.17 COL4A1 Bryony Thompson Marked gene: COL4A1 as ready
Early-onset Dementia v1.17 COL4A1 Bryony Thompson Gene: col4a1 has been classified as Green List (High Evidence).
Early-onset Dementia v1.17 COL4A1 Bryony Thompson Classified gene: COL4A1 as Green List (high evidence)
Early-onset Dementia v1.17 COL4A1 Bryony Thompson Gene: col4a1 has been classified as Green List (High Evidence).
Monogenic Diabetes v0.58 HAMP Hali Van Niel reviewed gene: HAMP: Rating: GREEN; Mode of pathogenicity: None; Publications: 33861982, 12469120, 34828384, 15198949, 33016646; Phenotypes: hemochromatosis type 2B MONDO:0013220; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Monogenic Diabetes v0.58 TFR2 Hali Van Niel reviewed gene: TFR2: Rating: GREEN; Mode of pathogenicity: None; Publications: 10802645, 12130528, 35065677, 29985876, 26029709, 24055163; Phenotypes: hemochromatosis type 3 MONDO:0011417; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Monogenic Diabetes v0.58 HFE Hali Van Niel reviewed gene: HFE: Rating: GREEN; Mode of pathogenicity: None; Publications: 8696333, 10575540, 20301613, 38560130; Phenotypes: hemochromatosis type 1 MONDO:0021001; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Lipodystrophy_Lipoatrophy v1.16 EPHX1 Lauren Rogers reviewed gene: EPHX1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Hereditary lipodystrophy, MONDO:0020087, EPHX1-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Monogenic Diabetes v0.58 EPHX1 Lauren Rogers reviewed gene: EPHX1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Hereditary lipodystrophy, MONDO:0020087, EPHX1-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.1758 EPHX1 Lauren Rogers reviewed gene: EPHX1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Hereditary lipodystrophy, MONDO:0020087, EPHX1-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Monogenic Diabetes v0.58 GLIS3 Hali Van Niel reviewed gene: GLIS3: Rating: GREEN; Mode of pathogenicity: None; Publications: 16715098, 21139041, 35394098; Phenotypes: neonatal diabetes mellitus with congenital hypothyroidism MONDO:0012436; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Monogenic Diabetes v0.58 FOXP3 Hali Van Niel reviewed gene: FOXP3: Rating: GREEN; Mode of pathogenicity: None; Publications: 11137992, 32234571, 11137993, 33614561; Phenotypes: immune dysregulation-polyendocrinopathy-enteropathy-X-linked syndrome MONDO:0010580; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Monogenic Diabetes v0.58 DNAJC3 Hali Van Niel reviewed gene: DNAJC3: Rating: GREEN; Mode of pathogenicity: None; Publications: 33486469, 34630333, 34654017, 32738013, 29767246; Phenotypes: juvenile-onset diabetes mellitus-central and peripheral neurodegeneration syndrome MONDO:0014523; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Monogenic Diabetes v0.58 DCAF17 Hali Van Niel changed review comment from: Established gene disease association for Woodhouse-Sakati syndrome (also referred to as C2ORF37 gene), diabetes mellitus common presentation is syndrome; to: Established gene disease association for Woodhouse-Sakati syndrome (also referred to as C2ORF37 gene), diabetes mellitus common presentation of syndrome
Monogenic Diabetes v0.58 DCAF17 Hali Van Niel reviewed gene: DCAF17: Rating: GREEN; Mode of pathogenicity: None; Publications: 19026396, 20507343, 35002959, 34732557, 34590781; Phenotypes: Woodhouse-Sakati syndrome MONDO:0009419; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Monogenic Diabetes v0.58 POLD1 Hali Van Niel reviewed gene: POLD1: Rating: GREEN; Mode of pathogenicity: None; Publications: 23770608, 33369179, 32826474, 30023403, 29199204, 28791128; Phenotypes: mandibular hypoplasia-deafness-progeroid syndrome MONDO:0014157; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Monogenic Diabetes v0.58 CISD2 Hali Van Niel reviewed gene: CISD2: Rating: GREEN; Mode of pathogenicity: None; Publications: 10739754, 17846994, 25056293, 25371195, 7490992; Phenotypes: Wolfram syndrome 2 MONDO:0011502; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Monogenic Diabetes v0.58 ALMS1 Hali Van Niel reviewed gene: ALMS1: Rating: GREEN; Mode of pathogenicity: None; Publications: 11941369, 17594715; Phenotypes: Alstrom syndrome MONDO:0008763; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hand and foot malformations v0.73 HOXD12 Sangavi Sivagnanasundram gene: HOXD12 was added
gene: HOXD12 was added to Hand and foot malformations. Sources: Other
Mode of inheritance for gene: HOXD12 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HOXD12 were set to 38663984
Phenotypes for gene: HOXD12 were set to Clubfoot (non-syndromic) MONDO:0007342
Mode of pathogenicity for gene: HOXD12 was set to Other
Review for gene: HOXD12 was set to GREEN
Added comment: Novel gene-disease association with non-syndromic clubfoot.

10 variants in HOXD12 have been reported in individuals with clubfoot (variants are predominantly missense variants however one rare deletion has been reported).

PMID: 38663984
Around 9 individuals from 4 unrelated families have been reported with clubfoot and the variants were shown to segregate.

N-terminal region and C-terminal homeobox domain of HOXD12 are known to be clusters for pathogenic variants related to clubfoot.
Loss of function variants are less likely to contribute to clubfoot pathogenesis therefore mechanism of disease is suggested as dominant negative but is not confirmed.
Sources: Other
Mendeliome v1.1758 HOXD12 Sangavi Sivagnanasundram gene: HOXD12 was added
gene: HOXD12 was added to Mendeliome. Sources: Other
Mode of inheritance for gene: HOXD12 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HOXD12 were set to 38663984
Phenotypes for gene: HOXD12 were set to Clubfoot (non-syndromic) MONDO:0007342
Mode of pathogenicity for gene: HOXD12 was set to Other
Review for gene: HOXD12 was set to GREEN
Added comment: Novel gene-disease association with non-syndromic clubfoot.

10 variants in HOXD12 have been reported in individuals with clubfoot (variants are predominantly missense variants however one rare deletion has been reported).

PMID: 38663984
Around 9 individuals from 4 unrelated families have been reported with clubfoot and the variants were shown to segregate.

N-terminal region and C-terminal homeobox domain of HOXD12 are known to be clusters for pathogenic variants related to clubfoot.
Loss of function variants are less likely to contribute to clubfoot pathogenesis therefore mechanism of disease is suggested as dominant negative but is not confirmed.
Sources: Other
Mendeliome v1.1758 PKHD1L1 Sangavi Sivagnanasundram edited their review of gene: PKHD1L1: Changed publications: 38459354
Genetic Epilepsy v0.2614 MBOAT7 Zornitza Stark Mode of inheritance for gene: MBOAT7 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2613 MBOAT7 Zornitza Stark reviewed gene: MBOAT7: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1758 PKHD1L1 Sangavi Sivagnanasundram gene: PKHD1L1 was added
gene: PKHD1L1 was added to Mendeliome. Sources: Other
Mode of inheritance for gene: PKHD1L1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PKHD1L1 were set to non syndromic hearing loss (MONDO:0020678)
Review for gene: PKHD1L1 was set to GREEN
Added comment: At least 4 individuals from unrelated families with sensorineural hearing loss (SNHL) (2 of the reported probands were from consanguineous parents).
The individuals are either homozygous or compound heterozygous for mutations in PKHD1L1 (missense, frameshift and nonsense mutations have been reported).

In vitro functional assessment as well as a mini-gene assay of Gly605Arg was conducted. The mini-gene assay on Gly605Arg showed that exon skipping occurs resulting in an in-frame deletion of 48 aa. Both studies didn't use a positive control however loss of function or disruption to protein stability is the speculated mechanism of disease.
Sources: Other
Mendeliome v1.1758 RAB32 Bryony Thompson Marked gene: RAB32 as ready
Mendeliome v1.1758 RAB32 Bryony Thompson Gene: rab32 has been classified as Red List (Low Evidence).
Mendeliome v1.1758 RAB32 Bryony Thompson gene: RAB32 was added
gene: RAB32 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RAB32 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RAB32 were set to 38614108
Phenotypes for gene: RAB32 were set to Parkinson disease MONDO:0005180
Mode of pathogenicity for gene: RAB32 was set to Other
Review for gene: RAB32 was set to RED
Added comment: A single variant in RAB32 - c.213C>G p.(Ser71Arg) with a significant association with PD (odds ratio [OR] 13.17, 95% CI 2.15-87.23; p=0.0055, 6,043 PD cases and 62,549 controls). The variant cosegregated with autosomal dominant PD in 3 families (9 affected individuals), with incomplete penetrance. In vitro studies demonstrate that RAB32 Ser71Arg activates LRRK2 kinase. The variant is reported as a novel reduced penetrance PD risk factor. The 95% CI for the OR estimate are very wide. A confirmatory study is required for this variant.
Sources: Literature
Early-onset Parkinson disease v2.1 RAB32 Bryony Thompson Marked gene: RAB32 as ready
Early-onset Parkinson disease v2.1 RAB32 Bryony Thompson Gene: rab32 has been classified as Red List (Low Evidence).
Early-onset Parkinson disease v2.1 RAB32 Bryony Thompson changed review comment from: A single variant in RAB32 - c.213C>G p.(Ser71Arg) with a significant association with PD (odds ratio [OR] 13.17, 95% CI 2.15-87.23; p=0.0055, 6,043 PD cases and 62,549 controls).
The variant cosegregated with autosomal dominant PD in 3 families (9 affected individuals), with incomplete penetrance. In vitro studies demonstrate that RAB32 Ser71Arg activates LRRK2 kinase.
Sources: Literature; to: A single variant in RAB32 - c.213C>G p.(Ser71Arg) with a significant association with PD (odds ratio [OR] 13.17, 95% CI 2.15-87.23; p=0.0055, 6,043 PD cases and 62,549 controls).
The variant cosegregated with autosomal dominant PD in 3 families (9 affected individuals), with incomplete penetrance. In vitro studies demonstrate that RAB32 Ser71Arg activates LRRK2 kinase.
The variant is reported as a novel reduced penetrance PD risk factor. The 95% CI for the OR estimate are very wide. A confirmatory study is required for this variant.
Sources: Literature
Early-onset Parkinson disease v2.1 RAB32 Bryony Thompson edited their review of gene: RAB32: Changed rating: RED
Monogenic Diabetes v0.58 HNF1B Zornitza Stark Marked gene: HNF1B as ready
Monogenic Diabetes v0.58 HNF1B Zornitza Stark Gene: hnf1b has been classified as Green List (High Evidence).
Monogenic Diabetes v0.58 HNF1B Zornitza Stark Phenotypes for gene: HNF1B were changed from RENAL CYSTS AND DIABETES SYNDROME; Maturity-Onset Diabetes Of The Young; renal malformation; Diabetes mellitus, noninsulin-dependent, 125853; Renal Cysts and Diabetes Syndrome; Renal cysts and diabetes syndrome, 137920; Transient neonatal diabetes; RCAD; {Renal cell carcinoma}, 144700 to renal cysts and diabetes syndrome MONDO:0007669
Monogenic Diabetes v0.57 HNF1B Zornitza Stark Publications for gene: HNF1B were set to
Monogenic Diabetes v0.56 HNF1B Zornitza Stark Tag SV/CNV tag was added to gene: HNF1B.
Monogenic Diabetes v0.56 AKT2 Zornitza Stark Marked gene: AKT2 as ready
Monogenic Diabetes v0.56 AKT2 Zornitza Stark Gene: akt2 has been classified as Red List (Low Evidence).
Monogenic Diabetes v0.56 AKT2 Zornitza Stark Phenotypes for gene: AKT2 were changed from Diabetes mellitus, type II, 125853; Severe insulin resistance, partial lipodystrophy and diabetes to Diabetes mellitus, type II, 125853
Monogenic Diabetes v0.55 AKT2 Zornitza Stark Classified gene: AKT2 as Red List (low evidence)
Monogenic Diabetes v0.55 AKT2 Zornitza Stark Gene: akt2 has been classified as Red List (Low Evidence).
Monogenic Diabetes v0.54 KCNJ11 Zornitza Stark Phenotypes for gene: KCNJ11 were changed from Hyperinsulinemic hypoglycemia, familial, 2, 601820Diabetes, permanent neonatal, 606176Diabetes mellitus, permanent neonatal, with neurologic features, 606176{Diabetes mellitus, type 2, susceptibility to}, 125853Diabetes mellitus, transient neonatal, 3, 610582; {Diabetes mellitus, type 2, susceptibility to}, 125853; Transient Neonatal Diabetes, Dominant; Diabetes, permanent neonatal, 606176; Diabetes mellitus, permanent neonatal, with neurologic features, 606176; Transient Neonatal, 3; Maturity Onset Diabetes of the Young (Dominant); Hyperinsulinemic hypoglycemia, familial, 2, 601820; Diabetes Mellitus, Permanent Neonatal; Diabetes mellitus, trans; Diabetes Mellitus, Transient Neonatal, 3; Diabetes mellitus, transient neonatal, 3, 610582; Maturity Onset Diabetes of the Young; Diabetes Mellitus, Permanent Neonatal diabetes mellitus (Dominant and recessive); Transient Neonatal diabetes mellitus (Dominant) to permanent neonatal diabetes mellitus MONDO:0100164
Monogenic Diabetes v0.53 KCNJ11 Zornitza Stark Publications for gene: KCNJ11 were set to
Early-onset Dementia v1.16 GLA Zornitza Stark Marked gene: GLA as ready
Early-onset Dementia v1.16 GLA Zornitza Stark Gene: gla has been classified as Green List (High Evidence).
Early-onset Dementia v1.16 GLA Zornitza Stark Classified gene: GLA as Green List (high evidence)
Early-onset Dementia v1.16 GLA Zornitza Stark Gene: gla has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5793 CYHR1 Zornitza Stark Tag new gene name tag was added to gene: CYHR1.
Microcephaly v1.258 CYHR1 Zornitza Stark Tag new gene name tag was added to gene: CYHR1.
Mendeliome v1.1757 CYHR1 Zornitza Stark Tag new gene name tag was added to gene: CYHR1.
Early-onset Parkinson disease v2.1 RAB32 Bryony Thompson gene: RAB32 was added
gene: RAB32 was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: RAB32 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RAB32 were set to 38614108
Phenotypes for gene: RAB32 were set to Parkinson disease MONDO:0005180
Mode of pathogenicity for gene: RAB32 was set to Other
Review for gene: RAB32 was set to AMBER
Added comment: A single variant in RAB32 - c.213C>G p.(Ser71Arg) with a significant association with PD (odds ratio [OR] 13.17, 95% CI 2.15-87.23; p=0.0055, 6,043 PD cases and 62,549 controls).
The variant cosegregated with autosomal dominant PD in 3 families (9 affected individuals), with incomplete penetrance. In vitro studies demonstrate that RAB32 Ser71Arg activates LRRK2 kinase.
Sources: Literature
Mendeliome v1.1757 CCDC91 Bryony Thompson Marked gene: CCDC91 as ready
Mendeliome v1.1757 CCDC91 Bryony Thompson Gene: ccdc91 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1757 CCDC91 Bryony Thompson Classified gene: CCDC91 as Amber List (moderate evidence)
Mendeliome v1.1757 CCDC91 Bryony Thompson Gene: ccdc91 has been classified as Amber List (Moderate Evidence).
Palmoplantar Keratoderma and Erythrokeratoderma v0.132 CCDC91 Bryony Thompson changed review comment from: A single 3 generation Chinese acrokeratoelastoidosis family segregates c.1101 + 1 G > A (causes exon 11 skipping). In vitro knockdown experiments in cell lines demonstrated distended Golgi cisternae, cytoplasmic vesicle accumulation, and lysosome presence.
Sources: Literature; to: A single 3-generation Chinese acrokeratoelastoidosis family segregates c.1101 + 1 G > A (causes exon 11 skipping). In vitro knockdown experiments in cell lines demonstrated distended Golgi cisternae, cytoplasmic vesicle accumulation, and lysosome presence. Immnunostaining of si-CCDC91-human skin fibroblasts cells demonstrated tropoelastin accumulation in the Golgi and abnormal extracellular aggregates.
Sources: Literature
Mendeliome v1.1756 CCDC91 Bryony Thompson gene: CCDC91 was added
gene: CCDC91 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CCDC91 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CCDC91 were set to 38627542
Phenotypes for gene: CCDC91 were set to Punctate palmoplantar keratoderma type III MONDO:0007047
Review for gene: CCDC91 was set to AMBER
Added comment: A single 3-generation Chinese acrokeratoelastoidosis family segregates c.1101 + 1 G > A (causes exon 11 skipping). In vitro knockdown experiments in cell lines demonstrated distended Golgi cisternae, cytoplasmic vesicle accumulation, and lysosome presence. Immnunostaining of si-CCDC91-human skin fibroblasts cells demonstrated tropoelastin accumulation in the Golgi and abnormal extracellular aggregates
Sources: Literature
Palmoplantar Keratoderma and Erythrokeratoderma v0.132 CCDC91 Bryony Thompson Marked gene: CCDC91 as ready
Palmoplantar Keratoderma and Erythrokeratoderma v0.132 CCDC91 Bryony Thompson Gene: ccdc91 has been classified as Amber List (Moderate Evidence).
Palmoplantar Keratoderma and Erythrokeratoderma v0.132 CCDC91 Bryony Thompson Classified gene: CCDC91 as Amber List (moderate evidence)
Palmoplantar Keratoderma and Erythrokeratoderma v0.132 CCDC91 Bryony Thompson Gene: ccdc91 has been classified as Amber List (Moderate Evidence).
Palmoplantar Keratoderma and Erythrokeratoderma v0.131 CCDC91 Bryony Thompson gene: CCDC91 was added
gene: CCDC91 was added to Palmoplantar Keratoderma and Erythrokeratoderma. Sources: Literature
Mode of inheritance for gene: CCDC91 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CCDC91 were set to 38627542
Phenotypes for gene: CCDC91 were set to Punctate palmoplantar keratoderma type III MONDO:0007047
Review for gene: CCDC91 was set to AMBER
Added comment: A single 3 generation Chinese acrokeratoelastoidosis family segregates c.1101 + 1 G > A (causes exon 11 skipping). In vitro knockdown experiments in cell lines demonstrated distended Golgi cisternae, cytoplasmic vesicle accumulation, and lysosome presence.
Sources: Literature
Mendeliome v1.1755 CYHR1 Bryony Thompson Phenotypes for gene: CYHR1 were changed from Neurodevelopmental disorder and microcephaly, MONDO:0700092, CYHR1-related to Neurodevelopmental disorder, MONDO:0700092, ZTRAF1-related
Mendeliome v1.1754 CYHR1 Bryony Thompson Publications for gene: CYHR1 were set to
Intellectual disability syndromic and non-syndromic v0.5793 CYHR1 Bryony Thompson Classified gene: CYHR1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5793 CYHR1 Bryony Thompson Gene: cyhr1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5792 CYHR1 Bryony Thompson reviewed gene: CYHR1: Rating: GREEN; Mode of pathogenicity: None; Publications: 38641995; Phenotypes: neurodevelopmental disorder MONDO:0700092, ZTRAF1-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v1.258 CYHR1 Bryony Thompson reviewed gene: CYHR1: Rating: AMBER; Mode of pathogenicity: None; Publications: 38641995; Phenotypes: neurodevelopmental disorder MONDO:0700092, ZTRAF1-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1753 CYHR1 Bryony Thompson Classified gene: CYHR1 as Green List (high evidence)
Mendeliome v1.1753 CYHR1 Bryony Thompson Gene: cyhr1 has been classified as Green List (High Evidence).
Mendeliome v1.1752 CYHR1 Bryony Thompson reviewed gene: CYHR1: Rating: GREEN; Mode of pathogenicity: None; Publications: 38641995; Phenotypes: neurodevelopmental disorder MONDO:0700092, ZTRAF1-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early-onset Dementia v1.15 GLA Lynn Tan gene: GLA was added
gene: GLA was added to Early-onset Dementia. Sources: Literature
Mode of inheritance for gene: GLA 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: GLA were set to 36927868; 38254927; 9213072; 23949010; 32510623
Phenotypes for gene: GLA were set to Fabry disease MONDO:0010526
Review for gene: GLA was set to GREEN
gene: GLA was marked as current diagnostic
Added comment: PMID 36927868 (2023)
Index patient with GLA T410A (α-Gal A activity 32%) developed dementia and died of stroke in her 70s

PMID: 9213072 (1997)
47M biochemically confirmed Fabry’s with predominant manifestation being a dementing illness

PMID: 23949010 (2014)
Systematic review on cognitive dysfunction in Fabry's disease: patients with Fabry disease may be impaired in: executive functioning assessed by two standardised tests, the Stroop test and the Trail Making test part B, information processing speed and attention. Five case studies documenting neuropsychological impairment also described.

PMID: 32510623
Prospective cohort study to describe cognitive function changes in Fabry's over a year. Eighty‐one patients were included of which 76 patients (94%) completed both assessments (age: 44 years, 34% men, 75% classical phenotype). Four patients (5.3%) showed reliable decrease in cognitive functioning, two women and one man with classical disease and one woman with non‐classical disease (age range: 19‐41 years). Changes were from excellent to good/average and from good to average. None had a history of stroke or extensive WMLs. Follow‐up CESD scores were similar in two patients (+0 and +1) and increased in two others (+6, +11).

PMID: 38254927 (2023)
"This vasculopathy, along with elevating the risk of cerebral ischemia and stroke, is likely the pathophysiological basis for cognitive impairments in FD patients. Nevertheless, there is currently insufficient evidence indicating a direct association between neuropsychological findings and alterations in morphology in the CNS of FD patients as determined by brain imaging techniques such as magnetic resonance imaging."
Sources: Literature
Monogenic Diabetes v0.52 KCNJ11 Hali Van Niel reviewed gene: KCNJ11: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: 30086875, 20922570, 28824061, 15115830, 23626843; Phenotypes: permanent neonatal diabetes mellitus MONDO:0100164; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Monogenic Diabetes v0.52 AKT2 Hali Van Niel reviewed gene: AKT2: Rating: RED; Mode of pathogenicity: None; Publications: 37105912, 28341696, 15166380; Phenotypes: type 2 diabetes mellitus MONDO:0005148; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Monogenic Diabetes v0.52 HNF1B Hali Van Niel reviewed gene: HNF1B: Rating: GREEN; Mode of pathogenicity: None; Publications: 25536396, 9703339, 10484768; Phenotypes: renal cysts and diabetes syndrome MONDO:0007669; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hydrops fetalis v0.311 EHBP1L1 Ain Roesley Phenotypes for gene: EHBP1L1 were changed from Non-immune hydrops fetalis, MONDO:0015193, EHBP1L1-related to non-immune hydrops fetalis MONDO:0009369, EHBP1L1-related
Fetal anomalies v1.241 EHBP1L1 Ain Roesley Phenotypes for gene: EHBP1L1 were changed from Non-immune hydrops fetalis, MONDO:0015193, EHBP1L1-related to non-immune hydrops fetalis MONDO:0009369, EHBP1L1-related
Mendeliome v1.1752 EHBP1L1 Ain Roesley Phenotypes for gene: EHBP1L1 were changed from non-immune hydrops fetalis MONDO:0009369, EHBP1L1-related to non-immune hydrops fetalis MONDO:0009369, EHBP1L1-related
Mendeliome v1.1751 EHBP1L1 Ain Roesley Phenotypes for gene: EHBP1L1 were changed from Non-immune hydrops fetalis, MONDO:0015193, EHBP1L1-related to non-immune hydrops fetalis MONDO:0009369, EHBP1L1-related
Early-onset Dementia v1.15 NOTCH3 Ain Roesley Mode of inheritance for gene: NOTCH3 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
Leukodystrophy - adult onset v0.140 NOTCH3 Ain Roesley Phenotypes for gene: NOTCH3 were changed from neurodevelopmental disorder MONDO:0700092, NOTCH3-related; Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy 1 MIM#125310 to neurodevelopmental disorder MONDO:0700092, NOTCH3-related; Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy 1 MIM#125310
Leukodystrophy - adult onset v0.139 NOTCH3 Ain Roesley Phenotypes for gene: NOTCH3 were changed from Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy 1, 125310 to neurodevelopmental disorder MONDO:0700092, NOTCH3-related; Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy 1 MIM#125310
Early-onset Dementia v1.14 NOTCH3 Ain Roesley reviewed gene: NOTCH3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy 1 MIM#125310; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal; Current diagnostic: yes
Leukodystrophy - adult onset v0.138 NOTCH3 Ain Roesley Mode of inheritance for gene: NOTCH3 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
Leukodystrophy - adult onset v0.137 NOTCH3 Ain Roesley reviewed gene: NOTCH3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: neurodevelopmental disorder MONDO:0700092, NOTCH3-related, Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy 1 MIM#125310; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal; Current diagnostic: yes
Monogenic Diabetes v0.52 HNF4A Hali Van Niel reviewed gene: HNF4A: Rating: GREEN; Mode of pathogenicity: None; Publications: 8945471, 11590126; Phenotypes: maturity-onset diabetes of the young type 1 MONDO:0007452; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Vasculitis v0.82 NOTCH3 Ain Roesley Phenotypes for gene: NOTCH3 were changed from Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy 1 125310 to neurodevelopmental disorder MONDO:0700092, NOTCH3-related; Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy 1 MIM#125310
Susceptibility to Viral Infections v0.117 IL27RA Ain Roesley Marked gene: IL27RA as ready
Susceptibility to Viral Infections v0.117 IL27RA Ain Roesley Gene: il27ra has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1750 IL27RA Ain Roesley Marked gene: IL27RA as ready
Mendeliome v1.1750 IL27RA Ain Roesley Gene: il27ra has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1750 IL27RA Ain Roesley Classified gene: IL27RA as Amber List (moderate evidence)
Mendeliome v1.1750 IL27RA Ain Roesley Gene: il27ra has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1749 IL27RA Ain Roesley gene: IL27RA was added
gene: IL27RA was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: IL27RA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IL27RA were set to 38509369
Phenotypes for gene: IL27RA were set to Epstein-Barr virus infection MONDO:0005111 , IL27RA-related
Review for gene: IL27RA was set to AMBER
gene: IL27RA was marked as current diagnostic
Added comment: 3 children from 2 families with severe acute EBV infection.

fam1: homozygous for p.(Gln96*) (NMD-pred)
fam2: chet for p.(Arg446Gly) and c.1142-2A>C

the splice variant in fam2 was found to to result in an in-frame deletion p.(Gln381_Ala395del)
the missense in fam2 is hypothesised to be a hypomorphic allele:
- out of 15 Homs in the Finnish database, 2 had hospital diagnoses of EBV IM
- expression of this variant on its own results in a weak but detectable IL-27RA expression associated with significant increase in STAT1/3 phosphorus in response to IL-27 stimulation

borderline amber/green due to functional studies performed
Sources: Literature
Susceptibility to Viral Infections v0.117 IL27RA Ain Roesley Classified gene: IL27RA as Amber List (moderate evidence)
Susceptibility to Viral Infections v0.117 IL27RA Ain Roesley Gene: il27ra has been classified as Amber List (Moderate Evidence).
Susceptibility to Viral Infections v0.116 IL27RA Ain Roesley gene: IL27RA was added
gene: IL27RA was added to Susceptibility to Viral Infections. Sources: Literature
Mode of inheritance for gene: IL27RA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IL27RA were set to 38509369
Phenotypes for gene: IL27RA were set to Epstein-Barr virus infection MONDO:0005111 , IL27RA-related
Review for gene: IL27RA was set to AMBER
gene: IL27RA was marked as current diagnostic
Added comment: 3 children from 2 families with severe acute EBV infection.

fam1: homozygous for p.(Gln96*) (NMD-pred)
fam2: chet for p.(Arg446Gly) and c.1142-2A>C

the splice variant in fam2 was found to to result in an in-frame deletion p.(Gln381_Ala395del)
the missense in fam2 is hypothesised to be a hypomorphic allele:
- out of 15 Homs in the Finnish database, 2 had hospital diagnoses of EBV IM
- expression of this variant on its own results in a weak but detectable IL-27RA expression associated with significant increase in STAT1/3 phosphorus in response to IL-27 stimulation

borderline amber/green due to functional studies performed
Sources: Literature
Monogenic Diabetes v0.52 HNF1A Hali Van Niel reviewed gene: HNF1A: Rating: GREEN; Mode of pathogenicity: None; Publications: 11162430, 11575290, 36257325; Phenotypes: maturity-onset diabetes of the young type 3 MONDO:0010894, diabetes mellitus MONDO:0005015; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Monogenic Diabetes v0.52 PAX6 Hali Van Niel changed review comment from: PAX6 well established gene disease association for Aniridia
No evidence of association with monogenic diabetes
PMID: 22153401: out of 83 patients with Aniridia, did not find increased incidence of diabetes beyond normal population
PMID: 11756345: one family with cosegregation of T2D and arnidia with PAX6 SNP; to: PAX6 well established gene disease association for Aniridia
No evidence of association with monogenic diabetes
PMID: 22153401: out of 83 patients with Aniridia, did not find increased incidence of diabetes beyond normal population
PMID: 11756345: one family with cosegregation of T2D and Aniridia with PAX6 SNP
Monogenic Diabetes v0.52 PAX6 Hali Van Niel reviewed gene: PAX6: Rating: RED; Mode of pathogenicity: None; Publications: 22153401, 11756345; Phenotypes: aniridia MONDO:0019172; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2613 NOTCH3 Ain Roesley Phenotypes for gene: NOTCH3 were changed from neurodevelopmental disorder MONDO:0700092, NOTCH3-related; Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy 1 - 125310 to neurodevelopmental disorder MONDO:0700092, NOTCH3-related; Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy 1 - 125310
Genetic Epilepsy v0.2612 NOTCH3 Ain Roesley Phenotypes for gene: NOTCH3 were changed from Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy 1 - 125310 to neurodevelopmental disorder MONDO:0700092, NOTCH3-related; Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy 1 - 125310
Genetic Epilepsy v0.2612 NOTCH3 Ain Roesley Mode of inheritance for gene: NOTCH3 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2612 NOTCH3 Ain Roesley Classified gene: NOTCH3 as Green List (high evidence)
Genetic Epilepsy v0.2612 NOTCH3 Ain Roesley Gene: notch3 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2611 NOTCH3 Ain Roesley reviewed gene: NOTCH3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: neurodevelopmental disorder MONDO:0700092, NOTCH3-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Vasculitis v0.81 NOTCH3 Ain Roesley Mode of inheritance for gene: NOTCH3 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
Intellectual disability syndromic and non-syndromic v0.5792 NOTCH3 Ain Roesley Phenotypes for gene: NOTCH3 were changed from neurodevelopmental disorder MONDO:0700092, NOTCH3-related; Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy 1, MIM#125310 to neurodevelopmental disorder MONDO:0700092, NOTCH3-related; Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy 1, MIM#125310
Intellectual disability syndromic and non-syndromic v0.5791 NOTCH3 Ain Roesley Phenotypes for gene: NOTCH3 were changed from Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy 1, MIM#125310 to neurodevelopmental disorder MONDO:0700092, NOTCH3-related; Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy 1, MIM#125310
Intellectual disability syndromic and non-syndromic v0.5791 NOTCH3 Ain Roesley Mode of inheritance for gene: NOTCH3 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5791 NOTCH3 Ain Roesley Classified gene: NOTCH3 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5791 NOTCH3 Ain Roesley Gene: notch3 has been classified as Green List (High Evidence).
Vasculitis v0.80 NOTCH3 Ain Roesley reviewed gene: NOTCH3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: neurodevelopmental disorder MONDO:0700092, NOTCH3-related, Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy 1 MIM#125310; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.5790 NOTCH3 Ain Roesley changed review comment from: Pre-print (https://sciprofiles.com/publication/view/62eb776390415f0166f73fae7cd172ed)

Review of research and diagnostic databases and literature review found 50 individuals from 31 families with biallelic variants.

13 PTCS (including splice) and 15 missense resulting in gain or loss of Cys residue.

AR PTCs are associated with early onset leukoencephalopathy including cognitive decline, dev delay/ID and dysmorphism

AR missense are associated with CADASIL-like phenotype; to: Pre-print (https://sciprofiles.com/publication/view/62eb776390415f0166f73fae7cd172ed)

Review of research and diagnostic databases and literature review found 50 individuals from 31 families with biallelic variants.

13 PTCS (including splice) and 15 missense resulting in gain or loss of Cys residue.

AR PTCs are associated with early onset leukoencephalopathy including cognitive decline, dev delay/ID and dysmorphism; seizures, spasticity, hypotonia, ataxia

AR missense are associated with CADASIL-like phenotype
Intellectual disability syndromic and non-syndromic v0.5790 NOTCH3 Ain Roesley reviewed gene: NOTCH3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: neurodevelopmental disorder MONDO:0700092, NOTCH3-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Early-onset Dementia v1.14 COL4A2 Lynn Tan edited their review of gene: COL4A2: Added comment: PMID: 35699195
The frequency of cognitive features in COL4A2 was 27% [11/41 individuals from 22 pedigrees]. These 11 patients all had developmental delay.

PMID: 37272523
Ontario Neurodegenerative Disease Research Initiative (ONDRI) sample size 510: 8 patients with COL4A1/2 variants had Alzheimer's disease/mild cognitive impairment, 3 patients with COL4A1/2 variants had frontotemporal dementia

PMID: 36300346
UK Biobank cohort study (n = 454 756): 2 patients with COL4A1/2 variants had vascular dementia, 8 patients with COL4A1/2 variants had all-cause dementia

Dev delay vs early-onset dementia
PMID: 37272523 and PMID: 36300346 -combined cohort with both COL4A1 and COL4A2

Sources: Literature; Changed rating: AMBER
Mendeliome v1.1748 SHH Ain Roesley Publications for gene: SHH were set to 21976454; 12503095; 22791840; 19057928; 19533790; 38562108; 29321670, 32703609
Mendeliome v1.1747 SHH Ain Roesley edited their review of gene: SHH: Changed publications: 38562108, 29321670, 32703609
Mendeliome v1.1747 SHH Ain Roesley Publications for gene: SHH were set to 21976454; 12503095; 22791840; 19057928; 19533790,38562108, 29321670, 32703609
Mendeliome v1.1746 SHH Ain Roesley Phenotypes for gene: SHH were changed from Holoprosencephaly 3, MIM#142945; Microphthalmia with coloboma 5, MIM#611638; Single median maxillary central incisor, MIM#147250 to Holoprosencephaly 3, MIM#142945; Microphthalmia with coloboma 5, MIM#611638; Single median maxillary central incisor, MIM#147250; Hypertelorism, ACC, intellectual disability
Mendeliome v1.1745 SHH Ain Roesley Publications for gene: SHH were set to 21976454; 12503095; 22791840; 19057928; 19533790
Mendeliome v1.1744 SHH Ain Roesley reviewed gene: SHH: Rating: GREEN; Mode of pathogenicity: None; Publications: 38562108, 29321670, 32703609; Phenotypes: Hypertelorism, ACC, intellectual disability; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Monogenic Diabetes v0.52 PPP1R15B Hali Van Niel reviewed gene: PPP1R15B: Rating: RED; Mode of pathogenicity: None; Publications: 26159176, 26307080, 27640355; Phenotypes: microcephaly MONDO:0001149; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early-onset Dementia v1.14 POLG Lynn Tan gene: POLG was added
gene: POLG was added to Early-onset Dementia. Sources: Literature
Mode of inheritance for gene: POLG was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POLG were set to 15477547; 14694057; 16638794
Phenotypes for gene: POLG were set to Mitochondrial DNA depletion syndrome 4a MONDO:0008758
Review for gene: POLG was set to AMBER
gene: POLG was marked as current diagnostic
Added comment: PMID: 15477547
5 patients with "cognitive impairment" in their 30s-50s, one male "had mild cognitive decline in the fifth decade".

PMID: 14694057
Biallelic POLG A467T variants: The 18-year-old patient is the elder son of nonconsanguineous parents, aged 45 and 41 years. The clinical features of myoclonus, seizure, axonal sensory ataxic neuropathy, and hepatotoxicity induced by valproate and mild cognitive decline and cardiomyopathy were indicative of a multisystem disorder and suggestive of mitochondrial disease.

PMID: 16638794
We studied 26 patients belonging to 20 families with a disorder caused by biallelic mutations in the POLG gene. Mild cognitive abnormalities were clinically suspected in eight patients. In four a mild cognitive impairment was confirmed by neuropsychological examination.

Cognitive impairment -developmental delay/regression/ID in childhood vs dementia (and decline from a baseline) later in life
Sources: Literature
Monogenic Diabetes v0.52 BSCL2 Hali Van Niel reviewed gene: BSCL2: Rating: GREEN; Mode of pathogenicity: None; Publications: 11479539, 26239609; Phenotypes: congenital generalized lipodystrophy type 2 MONDO:0010020, diabetes mellitus MONDO:0005015; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Monogenic Diabetes v0.52 SLC19A2 Hali Van Niel reviewed gene: SLC19A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 10391221, 14994241, 22369132, 35114785; Phenotypes: thiamine-responsive megaloblastic anemia syndrome MONDO:0009575, neonatal diabetes mellitus MONDO:0016391, diabetes mellitus MONDO:0005015; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Monogenic Diabetes v0.52 SLC29A3 Hali Van Niel reviewed gene: SLC29A3: Rating: GREEN; Mode of pathogenicity: None; Publications: 19336477, 22238637, 38163427, 24894595; Phenotypes: H syndrome MONDO:0011273; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early-onset Dementia v1.14 COL4A2 Lynn Tan gene: COL4A2 was added
gene: COL4A2 was added to Early-onset Dementia. Sources: Literature
Mode of inheritance for gene: COL4A2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: COL4A2 were set to 35699195; 37272523; 36300346
Phenotypes for gene: COL4A2 were set to Familial porencephaly MONDO:0020496
Review for gene: COL4A2 was set to GREEN
gene: COL4A2 was marked as current diagnostic
Added comment: PMID: 35699195
The frequency of cognitive features in COL4A2 was 27% [11/41 individuals from 22 pedigrees]. Developmental delay was present in over 80% of individuals with COL4A1/2 with cognitive features.

PMID: 37272523
Ontario Neurodegenerative Disease Research Initiative (ONDRI) sample size 510: 8 patients with COL4A1/2 variants had Alzheimer's disease/mild cognitive impairment, 3 patients with COL4A1/2 variants had frontotemporal dementia

PMID: 36300346
UK Biobank cohort study (n = 454 756): 2 patients with COL4A1/2 variants had vascular dementia, 8 patients with COL4A1/2 variants had all-cause dementia
Sources: Literature
Monogenic Diabetes v0.52 SLC40A1 Hali Van Niel reviewed gene: SLC40A1: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: 34601591, 33341511, 2258529; Phenotypes: hemochromatosis type 4 MONDO:0011631, diabetes mellitus MONDO:0005015; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Dementia v1.14 COL4A1 Lynn Tan gene: COL4A1 was added
gene: COL4A1 was added to Early-onset Dementia. Sources: Literature
Mode of inheritance for gene: COL4A1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: COL4A1 were set to 35699195; 37272523; 36300346; 30413629
Phenotypes for gene: COL4A1 were set to Brain small vessel disease 1 with or without ocular anomalies MONDO:0008289; Microangiopathy and leukoencephalopathy, pontine, autosomal dominant MONDO:0032814
Review for gene: COL4A1 was set to GREEN
gene: COL4A1 was marked as current diagnostic
Added comment: PMID: 35699195
Systematic review: frequency of cognitive features in COL4A1 was 33% [128/390 individuals from 233 pedigrees]. Developmental delay was present in over 80% of individuals with COL4A1/2 with cognitive features.

PMID: 37272523
Ontario Neurodegenerative Disease Research Initiative (ONDRI) sample size 510: 8 patients with COL4A1/2 variants had Alzheimer's disease/mild cognitive impairment, 3 patients with COL4A1/2 variants had frontotemporal dementia

PMID: 36300346
UK Biobank cohort study (n = 454 756): 2 patients with COL4A1/2 variants had vascular dementia, 8 patients with COL4A1/2 variants had all-cause dementia

PMID: 30413629
Child with COL4A1 p. G601S variant: developmental delay, moderate cognitive impairment, autism, and normal neurologic examination. Focal-onset drug-resistant seizures started at 11 years of age.
3-year-old girl with de novo COL4A1 p.G1239R: Surgical delivery was performed because prenatal hydrocephalus was suspected. The child developed microcephaly, severe cognitive impairment, and drug-resistant epileptic spasms.
Sources: Literature
Monogenic Diabetes v0.52 AGPAT2 Hali Van Niel reviewed gene: AGPAT2: Rating: GREEN; Mode of pathogenicity: None; Publications: 33651552, 30296183, 35857714, 21847459; Phenotypes: diabetes mellitus MONDO:0005015, congenital generalized lipodystrophy type 1 MONDO:0012071; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.240 PIP5K1C Zornitza Stark Publications for gene: PIP5K1C were set to 17701898
Fetal anomalies v1.239 PIP5K1C Zornitza Stark Classified gene: PIP5K1C as Green List (high evidence)
Fetal anomalies v1.239 PIP5K1C Zornitza Stark Gene: pip5k1c has been classified as Green List (High Evidence).
Fetal anomalies v1.238 PIP5K1C Zornitza Stark reviewed gene: PIP5K1C: Rating: GREEN; Mode of pathogenicity: None; Publications: 38491417; Phenotypes: Lethal congenital contractural syndrome 3, OMIM:611369; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Multiple pterygium syndrome_Fetal akinesia sequence v1.5 PIP5K1C Zornitza Stark Classified gene: PIP5K1C as Green List (high evidence)
Multiple pterygium syndrome_Fetal akinesia sequence v1.5 PIP5K1C Zornitza Stark Gene: pip5k1c has been classified as Green List (High Evidence).
Multiple pterygium syndrome_Fetal akinesia sequence v1.4 PIP5K1C Zornitza Stark edited their review of gene: PIP5K1C: Added comment: PMID 38491417: reported a novel variant (p.S318Ifs*28) and a different variant which has been reported in ClinVar (p.G230Qfs*114) has been identified in two foetuses with contractures and other joint abnormalities. The variants were confirmed to be in trans through parental testing.; Changed rating: GREEN; Changed publications: 17701898, 38491417
Arthrogryposis v0.409 PIP5K1C Zornitza Stark Publications for gene: PIP5K1C were set to 17701898
Arthrogryposis v0.408 PIP5K1C Zornitza Stark Classified gene: PIP5K1C as Green List (high evidence)
Arthrogryposis v0.408 PIP5K1C Zornitza Stark Gene: pip5k1c has been classified as Green List (High Evidence).
Monogenic Diabetes v0.52 SLC2A2 Hali Van Niel changed review comment from: Rare presenting feature for recessive Fanconi-Bickel syndrome.
From 104 patients with neonatal diabetes, five (5%) were found to have homozygous SLC2A2 mutations (PMID: 22660720)
Three further patient with neonatal diabetes with SLC2A2 variant detected (PMID: 22060631, PMID: 23456528; 29116606); to: Rare presenting feature for recessive Fanconi-Bickel syndrome.
From 104 patients with neonatal diabetes, five (5%) were found to have homozygous SLC2A2 mutations (PMID: 22660720)
Three further patients with neonatal diabetes with SLC2A2 variant detected (PMID: 22060631, PMID: 23456528; 29116606)
Arthrogryposis v0.407 PIP5K1C Zornitza Stark Classified gene: PIP5K1C as Green List (high evidence)
Arthrogryposis v0.407 PIP5K1C Zornitza Stark Gene: pip5k1c has been classified as Green List (High Evidence).
Monogenic Diabetes v0.52 SLC2A2 Hali Van Niel reviewed gene: SLC2A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 22060631, 23456528, 29116606, 22660720; Phenotypes: neonatal diabetes mellitus MONDO:0016391; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Maturity-onset Diabetes of the Young v1.21 BLK Zornitza Stark Deleted their review
Maturity-onset Diabetes of the Young v1.21 BLK Zornitza Stark Marked gene: BLK as ready
Maturity-onset Diabetes of the Young v1.21 BLK Zornitza Stark Gene: blk has been classified as Red List (Low Evidence).
Maturity-onset Diabetes of the Young v1.21 BLK Zornitza Stark Phenotypes for gene: BLK were changed from Maturity Onset Diabetes of the Young; Maturity-onset diabetes of the young, type 11, 613375 to Maturity-onset diabetes of the young, type 11 MIM#613375
Maturity-onset Diabetes of the Young v1.20 BLK Zornitza Stark Publications for gene: BLK were set to
Maturity-onset Diabetes of the Young v1.19 BLK Zornitza Stark Tag refuted tag was added to gene: BLK.
Maturity-onset Diabetes of the Young v1.19 INS Zornitza Stark Phenotypes for gene: INS were changed from Maturity Onset Diabetes of the Young (Dominant); Maturity Onset Diabetes of the Young; Transient Neonatal Diabetes, Dominant/Recessive; Hyperproinsulinemia, familial, with or without diabetes to monogenic diabetes MONDO:0015967; Diabetes mellitus, insulin-dependent, 2, MIM# 125852; Diabetes mellitus, permanent neonatal 4, MIM# 618858; Maturity-onset diabetes of the young, type 10, MIM# 613370
Maturity-onset Diabetes of the Young v1.18 INS Zornitza Stark Publications for gene: INS were set to 18162506
Intellectual disability syndromic and non-syndromic v0.5790 SLC35C1 Zornitza Stark Marked gene: SLC35C1 as ready
Intellectual disability syndromic and non-syndromic v0.5790 SLC35C1 Zornitza Stark Gene: slc35c1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5790 SLC35C1 Zornitza Stark Phenotypes for gene: SLC35C1 were changed from to Congenital disorder of glycosylation, type IIc, MIM# 266265, MONDO:0009953
Intellectual disability syndromic and non-syndromic v0.5789 SLC35C1 Zornitza Stark Publications for gene: SLC35C1 were set to
Intellectual disability syndromic and non-syndromic v0.5788 SLC35C1 Zornitza Stark Mode of inheritance for gene: SLC35C1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Osteogenesis Imperfecta and Osteoporosis v0.114 P3H1 Zornitza Stark Publications for gene: P3H1 were set to 17277775; 18566967
Osteogenesis Imperfecta and Osteoporosis v0.113 P3H1 Zornitza Stark Tag founder tag was added to gene: P3H1.
Intellectual disability syndromic and non-syndromic v0.5787 PRMT9 Zornitza Stark Marked gene: PRMT9 as ready
Intellectual disability syndromic and non-syndromic v0.5787 PRMT9 Zornitza Stark Gene: prmt9 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.5787 PRMT9 Zornitza Stark Phenotypes for gene: PRMT9 were changed from Neurodevelopmental disorder, MONDO:0100500 to Neurodevelopmental disorder, MONDO:0100500, PRMT9-related
Mendeliome v1.1744 PRMT9 Zornitza Stark Marked gene: PRMT9 as ready
Mendeliome v1.1744 PRMT9 Zornitza Stark Gene: prmt9 has been classified as Red List (Low Evidence).
Mendeliome v1.1744 PRMT9 Zornitza Stark Phenotypes for gene: PRMT9 were changed from Neurodevelopmental disorder, MONDO:0100500 to Neurodevelopmental disorder, MONDO:0100500, PRMT9-related
Lipodystrophy_Lipoatrophy v1.16 SUPT7L Zornitza Stark Marked gene: SUPT7L as ready
Lipodystrophy_Lipoatrophy v1.16 SUPT7L Zornitza Stark Gene: supt7l has been classified as Red List (Low Evidence).
Lipodystrophy_Lipoatrophy v1.16 SUPT7L Zornitza Stark Phenotypes for gene: SUPT7L were changed from lipodystrophy, MONDO:0006573 to lipodystrophy, MONDO:0006573, SUPT7L-related
Mendeliome v1.1743 SUPT7L Zornitza Stark Marked gene: SUPT7L as ready
Mendeliome v1.1743 SUPT7L Zornitza Stark Gene: supt7l has been classified as Red List (Low Evidence).
Mendeliome v1.1743 SUPT7L Zornitza Stark Phenotypes for gene: SUPT7L were changed from Lipodystrophy, MONDO:0006573 to Lipodystrophy, MONDO:0006573, SUPT7L-related
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.145 PQLC2 Zornitza Stark Marked gene: PQLC2 as ready
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.145 PQLC2 Zornitza Stark Gene: pqlc2 has been classified as Green List (High Evidence).
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.145 PQLC2 Zornitza Stark Phenotypes for gene: PQLC2 were changed from Retinitis pigmentosa, MONDO:0019200 to Retinitis pigmentosa, MONDO:0019200, PQLC2-related
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.144 PQLC2 Zornitza Stark Publications for gene: PQLC2 were set to PMID: 35486108; and online publication GiM Feb 2024
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.143 PQLC2 Zornitza Stark Tag new gene name tag was added to gene: PQLC2.
Mendeliome v1.1742 PQLC2 Zornitza Stark Marked gene: PQLC2 as ready
Mendeliome v1.1742 PQLC2 Zornitza Stark Gene: pqlc2 has been classified as Green List (High Evidence).
Mendeliome v1.1742 PQLC2 Zornitza Stark Phenotypes for gene: PQLC2 were changed from Retinitis pigmentosa, MONDO:0019200 to Retinitis pigmentosa, MONDO:0019200, PQLC2-related
Mendeliome v1.1741 PQLC2 Zornitza Stark Publications for gene: PQLC2 were set to PMID: 35486108; and online publication GiM Feb 2024
Mendeliome v1.1740 PQLC2 Zornitza Stark Tag new gene name tag was added to gene: PQLC2.
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.143 SLC39A12 Zornitza Stark Marked gene: SLC39A12 as ready
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.143 SLC39A12 Zornitza Stark Gene: slc39a12 has been classified as Red List (Low Evidence).
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.143 SLC39A12 Zornitza Stark Phenotypes for gene: SLC39A12 were changed from Retinitis pigmentosa, MONDO:0019200 to Retinitis pigmentosa, MONDO:0019200, SLC39A12-related
Mendeliome v1.1740 SLC39A12 Zornitza Stark Marked gene: SLC39A12 as ready
Mendeliome v1.1740 SLC39A12 Zornitza Stark Gene: slc39a12 has been classified as Red List (Low Evidence).
Mendeliome v1.1740 SLC39A12 Zornitza Stark Phenotypes for gene: SLC39A12 were changed from Retinitis pigmentosa, MONDO:0019200 to Retinitis pigmentosa, MONDO:0019200, SLC39A12-related
Early-onset Dementia v1.14 TREX1 Lynn Tan gene: TREX1 was added
gene: TREX1 was added to Early-onset Dementia. Sources: Literature
Mode of inheritance for gene: TREX1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TREX1 were set to 29380913; 35699195; 36586737; 35307828
Phenotypes for gene: TREX1 were set to Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations MONDO:0008641
Review for gene: TREX1 was set to GREEN
gene: TREX1 was marked as current diagnostic
Added comment: PMID: 35699195
Systematic review: frequency of cognitive features in TREX1 was 29% [36/123 individuals from 34 pedigrees]

PMID: 29380913
Symptoms for this disorder start in adulthood and frequently include rapid loss of vision, multifocal strokes and dementia.

PMID: 36586737
1. Female patient displayed the first symptoms at a very early-age, 57 years old, and originated from Serbia. She presented with mild cognitive impairment.
2. 53-year old Dutch patient who displayed presenile dementia
3. 39-year old Finnish patient presenting migrane without aura, severe and pervasive cognitive impairment

PMID: 35307828
First stroke at age 39, diagnosed with severe amyloid angiopathy, and he also started suffering from migraines without aura and was later diagnosed with cognitive impairment
Sources: Literature
Bleeding and Platelet Disorders v1.43 CBS Zornitza Stark Publications for gene: CBS were set to
Bleeding and Platelet Disorders v1.42 CBS Zornitza Stark Classified gene: CBS as Green List (high evidence)
Bleeding and Platelet Disorders v1.42 CBS Zornitza Stark Gene: cbs has been classified as Green List (High Evidence).
Bleeding and Platelet Disorders v1.41 CBS Zornitza Stark edited their review of gene: CBS: Changed rating: GREEN
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.142 SLC4A7 Zornitza Stark Marked gene: SLC4A7 as ready
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.142 SLC4A7 Zornitza Stark Gene: slc4a7 has been classified as Amber List (Moderate Evidence).
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.142 SLC4A7 Zornitza Stark Phenotypes for gene: SLC4A7 were changed from Retinitis pigmentosa, MONDO:0019200 to Retinitis pigmentosa, MONDO:0019200, SLC4A7-related
Mendeliome v1.1739 SLC4A7 Zornitza Stark Marked gene: SLC4A7 as ready
Mendeliome v1.1739 SLC4A7 Zornitza Stark Gene: slc4a7 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1739 SLC4A7 Zornitza Stark Phenotypes for gene: SLC4A7 were changed from Retinitis pigmentosa, MONDO:0019200 to Retinitis pigmentosa, MONDO:0019200, SLC4A7-related
Monogenic Diabetes v0.52 ABCC8 Zornitza Stark Marked gene: ABCC8 as ready
Monogenic Diabetes v0.52 ABCC8 Zornitza Stark Gene: abcc8 has been classified as Green List (High Evidence).
Monogenic Diabetes v0.52 ABCC8 Zornitza Stark Phenotypes for gene: ABCC8 were changed from DIABETES MELLITUS, NONINSULIN-DEPENDENT; Transient Neonatal Diabetes, Dominant; Diabetes mellitus, permanent neonatal, 6; Hyperinsulinemic hypoglycemia, familial, 1, 256450; Diabetes mellitus, noninsulin-dependent, 125853; Permanent Neonatal Diabetes Mellitus; Permanent neonatal diabetes mellitus; transient neonatal diabetes (Dominant); Hypoglycemia of infancy, leucine-sensitive, 240800; Permanent Neonatal Diabetes Mellitus (recessive); Diabetes mellitus, transient neonatal 2, 610374; Hyperinsulinemic hypoglycemia, familial, 1, 256450Hypoglycemia of infancy, leucine-sensitive, 240800Diabetes mellitus, transient neonatal 2, 610374Diabetes mellitus, noninsulin-dependent, 125853Diabetes mellitus, permanent neonatal, 6 to permanent neonatal diabetes mellitus MONDO:0100164; transient neonatal diabetes mellitus MONDO:0020525
Monogenic Diabetes v0.51 ABCC8 Zornitza Stark Publications for gene: ABCC8 were set to
Bleeding and Platelet Disorders v1.41 PLG Zornitza Stark Publications for gene: PLG were set to
Bleeding and Platelet Disorders v1.40 PLG Zornitza Stark Mode of inheritance for gene: PLG was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Bleeding and Platelet Disorders v1.39 PLG Zornitza Stark Classified gene: PLG as Amber List (moderate evidence)
Bleeding and Platelet Disorders v1.39 PLG Zornitza Stark Gene: plg has been classified as Amber List (Moderate Evidence).
Bleeding and Platelet Disorders v1.38 PLG Zornitza Stark reviewed gene: PLG: Rating: AMBER; Mode of pathogenicity: None; Publications: 35244080, 27976734; Phenotypes: Dysplasminogenemia 217090; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Monogenic Diabetes v0.50 ABCC8 Hali Van Niel reviewed gene: ABCC8: Rating: GREEN; Mode of pathogenicity: None; Publications: (PMID: 21054355, 32027066, 32376986); Phenotypes: permanent neonatal diabetes mellitus MONDO:0100164, transient neonatal diabetes mellitus MONDO:0020525; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Bleeding and Platelet Disorders v1.38 PLG Jane Lin gene: PLG was added
gene: PLG was added to Bleeding and Platelet Disorders. Sources: Expert Review
Mode of inheritance for gene: PLG was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PLG were set to Plasminogen deficiency, type I; Dysplasminogenemia; MIM#217090
gene: PLG was marked as current diagnostic
Added comment: Included in Genomics England PanelApp "Thrombophilia with a likely monogenic cause" panel. Adding to this panel as this gene has a gene-disease association with thrombophilia.
Sources: Expert Review
Mendeliome v1.1738 SLC4A7 Chirag Patel Classified gene: SLC4A7 as Amber List (moderate evidence)
Mendeliome v1.1738 SLC4A7 Chirag Patel Gene: slc4a7 has been classified as Amber List (Moderate Evidence).
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.141 SLC4A7 Chirag Patel Classified gene: SLC4A7 as Amber List (moderate evidence)
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.141 SLC4A7 Chirag Patel Gene: slc4a7 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1737 SLC4A7 Chirag Patel gene: SLC4A7 was added
gene: SLC4A7 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SLC4A7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC4A7 were set to PMID: 35486108, 32594822
Phenotypes for gene: SLC4A7 were set to Retinitis pigmentosa, MONDO:0019200
Review for gene: SLC4A7 was set to AMBER
Added comment: Total 4 individuals from 3 families (2 known to be from same ethnic origin: Oriental-Jewish) with adult onset retinitis pigmentosa. All individuals had same homozygous frameshift variant in SLC4A7 gene (p.P670Sfs*6). RNA seq analysis revealed retinal expression in human and mouse samples. Immunohistochemistry of human and mouse retina revealed relatively strong expression in various retinal layers. Western blot analysis in fibroblasts from 1 patient showed absence of encoded protein.
Sources: Literature
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.140 SLC4A7 Chirag Patel gene: SLC4A7 was added
gene: SLC4A7 was added to Retinitis pigmentosa_Autosomal Recessive/X-linked. Sources: Literature
Mode of inheritance for gene: SLC4A7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC4A7 were set to PMID: 35486108, 32594822
Phenotypes for gene: SLC4A7 were set to Retinitis pigmentosa, MONDO:0019200
Review for gene: SLC4A7 was set to AMBER
Added comment: Total 4 individuals from 3 families (2 known to be from same ethnic origin: Oriental-Jewish) with adult onset retinitis pigmentosa. All individuals had same homozygous frameshift variant in SLC4A7 gene (p.P670Sfs*6). RNA seq analysis revealed retinal expression in human and mouse samples. Immunohistochemistry of human and mouse retina revealed relatively strong expression in various retinal layers. Western blot analysis in fibroblasts from 1 patient showed absence of encoded protein.
Sources: Literature
Bleeding and Platelet Disorders v1.38 CBS Jane Lin reviewed gene: CBS: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Thrombosis, HOMOCYSTINURIA, MIM# 236200; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1736 SLC39A12 Chirag Patel gene: SLC39A12 was added
gene: SLC39A12 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SLC39A12 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC39A12 were set to PMID: 35486108
Phenotypes for gene: SLC39A12 were set to Retinitis pigmentosa, MONDO:0019200
Review for gene: SLC39A12 was set to RED
Added comment: WES (with targeted analysis of SLC genes) in 913 cases from 785 families with inherited retinal dystrophy. They identified 1 homozygous variant in SLC39A12 in 1 individual with adult-onset mild widespread retinal degeneration with marked macular involvement. No functional data. RNA seq analysis revealed retinal expression in human samples. Immunohistochemistry of human and mouse retina revealed comprehensive expression in various retinal cells including retinal pigment epithelium.
Sources: Literature
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.139 SLC39A12 Chirag Patel gene: SLC39A12 was added
gene: SLC39A12 was added to Retinitis pigmentosa_Autosomal Recessive/X-linked. Sources: Literature
Mode of inheritance for gene: SLC39A12 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC39A12 were set to PMID: 35486108
Phenotypes for gene: SLC39A12 were set to Retinitis pigmentosa, MONDO:0019200
Review for gene: SLC39A12 was set to RED
Added comment: WES (with targeted analysis of SLC genes) in 913 cases from 785 families with inherited retinal dystrophy. They identified 1 homozygous variant in SLC39A12 in 1 individual with adult-onset mild widespread retinal degeneration with marked macular involvement. No functional data. RNA seq analysis revealed retinal expression in human samples. Immunohistochemistry of human and mouse retina revealed comprehensive expression in various retinal cells including retinal pigment epithelium.
Sources: Literature
Mendeliome v1.1735 PQLC2 Chirag Patel Classified gene: PQLC2 as Green List (high evidence)
Mendeliome v1.1735 PQLC2 Chirag Patel Gene: pqlc2 has been classified as Green List (High Evidence).
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.138 PQLC2 Chirag Patel Classified gene: PQLC2 as Green List (high evidence)
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.138 PQLC2 Chirag Patel Gene: pqlc2 has been classified as Green List (High Evidence).
Mendeliome v1.1734 PQLC2 Chirag Patel gene: PQLC2 was added
gene: PQLC2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PQLC2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PQLC2 were set to PMID: 35486108; and online publication GiM Feb 2024
Phenotypes for gene: PQLC2 were set to Retinitis pigmentosa, MONDO:0019200
Review for gene: PQLC2 was set to GREEN
gene: PQLC2 was marked as current diagnostic
Added comment: HGNC Gene Symbol: SLC66A1
Total 8 individuals from 6 families.

Millo et al. (2022)(PMID: 35486108) -
WES (with targeted analysis of SLC genes) in 913 cases from 785 families with inherited retinal dystrophy. They identified 2 different homozygous variants in SLC66A1 in 3 individuals from 2 families with adult-onset retinal dystrophy. No functional data.


Olinger et al. (2024)(https://www.sciencedirect.com/science/article/pii/S2949774424009804) -
CNV analysis of trio and non-trio WGS data from Genomics England 100K genomes project. They identified homozygous 21kb deletion spanning nearly entire SLC66A1 gene in 2 siblings with adult-onset rod-cone dystrophy (parents HTZ carriers). Review of cohort data then identified homozygous LOF variants (1 nonsense, 2 frameshift) in another 3 individuals with rod-cone dystrophy.
Sources: Literature
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.137 PQLC2 Chirag Patel gene: PQLC2 was added
gene: PQLC2 was added to Retinitis pigmentosa_Autosomal Recessive/X-linked. Sources: Literature
Mode of inheritance for gene: PQLC2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PQLC2 were set to PMID: 35486108; and online publication GiM Feb 2024
Phenotypes for gene: PQLC2 were set to Retinitis pigmentosa, MONDO:0019200
Review for gene: PQLC2 was set to GREEN
gene: PQLC2 was marked as current diagnostic
Added comment: HGNC Gene Symbol: SLC66A1
Total 8 individuals from 6 families.

Millo et al. (2022)(PMID: 35486108) -
WES (with targeted analysis of SLC genes) in 913 cases from 785 families with inherited retinal dystrophy. They identified 2 different homozygous variants in SLC66A1 in 3 individuals from 2 families with adult-onset retinal dystrophy. No functional data.


Olinger et al. (2024)(https://www.sciencedirect.com/science/article/pii/S2949774424009804) -
CNV analysis of trio and non-trio WGS data from Genomics England 100K genomes project. They identified homozygous 21kb deletion spanning nearly entire SLC66A1 gene in 2 siblings with adult-onset rod-cone dystrophy (parents HTZ carriers). Review of cohort data then identified homozygous LOF variants (1 nonsense, 2 frameshift) in another 3 individuals with rod-cone dystrophy.
Sources: Literature
Mendeliome v1.1733 SUPT7L Chirag Patel gene: SUPT7L was added
gene: SUPT7L was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SUPT7L was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SUPT7L were set to PMID: 38592547
Phenotypes for gene: SUPT7L were set to Lipodystrophy, MONDO:0006573
Review for gene: SUPT7L was set to RED
Added comment: 1 case with generalised lipodystrophy, growth retardation, congenital cataracts, severe developmental delay and progeriod features. Trio WGS identified compound heterozygous variants in SUPT7L (missense causing abnormal splicing + frameshift). Variants validated with Sanger. SUPT7L encodes a component of the core structural module of the STAGA complex - a nuclear multifunctional protein complex that plays a role in various cellular processes (e.g. transcription factor binding, protein acetylation, splicing, and DNA damage control). Immunolabelling in fibroblasts from patient showed complete absence of SUPT7L protein. Transcriptome data from individual revealed downregulation of several gene sets associated with DNA replication, DNA repair, cell cycle, and transcription.
Sources: Literature
Mendeliome v1.1732 PRMT9 Chirag Patel gene: PRMT9 was added
gene: PRMT9 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PRMT9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PRMT9 were set to PMID: 38561334
Phenotypes for gene: PRMT9 were set to Neurodevelopmental disorder, MONDO:0100500
Review for gene: PRMT9 was set to RED
Added comment: A homozygous variant (G189R) in PRMT9 is reported based on large WGS study in 136 consanguineous families - unclear if only found in 1 family and no clinical information on case(s).

PMRTs (protein arginine methyltransferases) catalyse post translational modification via arginine methylation. Functional studies showed that the G189R variant abolishes PRMT9's methyltransferase activity - specifically at the R508 residue of SF3B2 RNA (exclusively methylated by PRMT9) - and leads to heavy PRMT9 ubiquitination, and abnormal splicing activity of SF3B2. Knock out mouse model showed PRMT9 loss in excitatory neurons leads to aberrant synapse development and impaired learning and memory.
Sources: Literature
Lipodystrophy_Lipoatrophy v1.15 SUPT7L Chirag Patel gene: SUPT7L was added
gene: SUPT7L was added to Lipodystrophy_Lipoatrophy. Sources: Literature
Mode of inheritance for gene: SUPT7L was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SUPT7L were set to PMID: 38592547
Phenotypes for gene: SUPT7L were set to lipodystrophy, MONDO:0006573
Review for gene: SUPT7L was set to RED
Added comment: 1 case with generalised lipodystrophy, growth retardation, congenital cataracts, severe developmental delay and progeriod features. Trio WGS identified compound heterozygous variants in SUPT7L (missense causing abnormal splicing + frameshift). Variants validated with Sanger. SUPT7L encodes a component of the core structural module of the STAGA complex - a nuclear multifunctional protein complex that plays a role in various cellular processes (e.g. transcription factor binding, protein acetylation, splicing, and DNA damage control). Immunolabelling in fibroblasts from patient showed complete absence of SUPT7L protein. Transcriptome data from individual revealed downregulation of several gene sets associated with DNA replication, DNA repair, cell cycle, and transcription.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5786 PRMT9 Chirag Patel gene: PRMT9 was added
gene: PRMT9 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: PRMT9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PRMT9 were set to PMID: 38561334
Phenotypes for gene: PRMT9 were set to Neurodevelopmental disorder, MONDO:0100500
Review for gene: PRMT9 was set to RED
Added comment: A homozygous variant (G189R) in PRMT9 is reported based on large WGS study in 136 consanguineous families - unclear if only found in 1 family and no clinical information on case(s).

PMRTs (protein arginine methyltransferases) catalyse post translational modification via arginine methylation. Functional studies showed that the G189R variant abolishes PRMT9's methyltransferase activity - specifically at the R508 residue of SF3B2 RNA (exclusively methylated by PRMT9) - and leads to heavy PRMT9 ubiquitination, and abnormal splicing activity of SF3B2. Knock out mouse model showed PRMT9 loss in excitatory neurons leads to aberrant synapse development and impaired learning and memory.
Sources: Literature
Osteogenesis Imperfecta and Osteoporosis v0.113 P3H1 Tashunka Taylor-Miller reviewed gene: P3H1: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 36833249; Phenotypes: Osteopenia HP:0000938, Platyspondyly HP:0000926, MONDO:0012581; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Systemic Autoinflammatory Disease_Periodic Fever v1.47 JAK1 Zornitza Stark Marked gene: JAK1 as ready
Systemic Autoinflammatory Disease_Periodic Fever v1.47 JAK1 Zornitza Stark Gene: jak1 has been classified as Green List (High Evidence).
Systemic Autoinflammatory Disease_Periodic Fever v1.47 JAK1 Zornitza Stark Classified gene: JAK1 as Green List (high evidence)
Systemic Autoinflammatory Disease_Periodic Fever v1.47 JAK1 Zornitza Stark Gene: jak1 has been classified as Green List (High Evidence).
Systemic Autoinflammatory Disease_Periodic Fever v1.46 JAK1 Zornitza Stark gene: JAK1 was added
gene: JAK1 was added to Systemic Autoinflammatory Disease_Periodic Fever. Sources: Literature
Mode of inheritance for gene: JAK1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: JAK1 were set to 38563820; 28111307
Phenotypes for gene: JAK1 were set to Autoinflammation, immunde dysregulation, and eosinophilia, MIM# 618999
Review for gene: JAK1 was set to GREEN
Added comment: PMID 38563820: 59 individuals presenting with autoimmunity, atopy, colitis, and/or dermatitis and one of four JAK1 variants.
Sources: Literature
Disorders of immune dysregulation v0.186 JAK1 Zornitza Stark Classified gene: JAK1 as Green List (high evidence)
Disorders of immune dysregulation v0.186 JAK1 Zornitza Stark Gene: jak1 has been classified as Green List (High Evidence).
Disorders of immune dysregulation v0.185 JAK1 Zornitza Stark edited their review of gene: JAK1: Added comment: PMID 38563820: 59 individuals presenting with autoimmunity, atopy, colitis, and/or dermatitis and one of four JAK1 variants.; Changed rating: GREEN; Changed phenotypes: Autoinflammation, immunde dysregulation, and eosinophilia, MIM# 618999, Eosinophilia, Eosinophilic enteritis, Thyroid disease, Poor growth, Viral infections, Autoinflammation, immunde dysregulation, and eosinophilia, MIM# 618999
Mendeliome v1.1731 JAK1 Zornitza Stark Phenotypes for gene: JAK1 were changed from Eosinophilia; Eosinophilic enteritis; Thyroid disease; Poor growth; Viral infections; Susceptibility to mycobacteria and viruses to Autoinflammation, immunde dysregulation, and eosinophilia, MIM# 618999; Eosinophilia; Eosinophilic enteritis; Thyroid disease; Poor growth; Viral infections; Susceptibility to mycobacteria and viruses
Mendeliome v1.1730 JAK1 Zornitza Stark Publications for gene: JAK1 were set to 28111307; 28008925; 30671064
Mendeliome v1.1729 JAK1 Zornitza Stark Classified gene: JAK1 as Green List (high evidence)
Mendeliome v1.1729 JAK1 Zornitza Stark Gene: jak1 has been classified as Green List (High Evidence).
Mendeliome v1.1728 JAK1 Zornitza Stark edited their review of gene: JAK1: Added comment: PMID 38563820: 59 individuals presenting with autoimmunity, atopy, colitis, and/or dermatitis and one of four JAK1 variants.; Changed rating: GREEN; Changed publications: 28111307, 28008925, 30671064, 38563820; Changed phenotypes: Autoinflammatory syndrome, MONDO:0019751, JAK1-related, Eosinophilia, Eosinophilic enteritis, Thyroid disease, Poor growth, Viral infections, Susceptibility to mycobacteria and viruses, Autoinflammation, immunde dysregulation, and eosinophilia, MIM# 618999
Mendeliome v1.1728 SRPK3 Zornitza Stark Marked gene: SRPK3 as ready
Mendeliome v1.1728 SRPK3 Zornitza Stark Gene: srpk3 has been classified as Green List (High Evidence).
Mendeliome v1.1728 SRPK3 Zornitza Stark Classified gene: SRPK3 as Green List (high evidence)
Mendeliome v1.1728 SRPK3 Zornitza Stark Gene: srpk3 has been classified as Green List (High Evidence).
Mendeliome v1.1727 SRPK3 Zornitza Stark gene: SRPK3 was added
gene: SRPK3 was added to Mendeliome. Sources: Literature
digenic tags were added to gene: SRPK3.
Mode of inheritance for gene: SRPK3 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: SRPK3 were set to 38429495
Phenotypes for gene: SRPK3 were set to Myopathy, MONDO:0005336, digenic SRPK3- and TTN-related
Review for gene: SRPK3 was set to GREEN
Added comment: 33 individuals reported with SRPK3 variants but myopathy only occurred when TTN variant also present (most truncating). Zebrafish model supports digenic model of inheritance.
Sources: Literature
Muscular dystrophy and myopathy_Paediatric v1.33 SRPK3 Zornitza Stark Marked gene: SRPK3 as ready
Muscular dystrophy and myopathy_Paediatric v1.33 SRPK3 Zornitza Stark Gene: srpk3 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v1.33 SRPK3 Zornitza Stark Classified gene: SRPK3 as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v1.33 SRPK3 Zornitza Stark Gene: srpk3 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v1.32 SRPK3 Zornitza Stark Tag digenic tag was added to gene: SRPK3.
Muscular dystrophy and myopathy_Paediatric v1.32 SRPK3 Zornitza Stark gene: SRPK3 was added
gene: SRPK3 was added to Muscular dystrophy and myopathy_Paediatric. Sources: Literature
Mode of inheritance for gene: SRPK3 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: SRPK3 were set to 38429495
Phenotypes for gene: SRPK3 were set to Myopathy, MONDO:0005336, digenic SRPK3- and TTN-related
Review for gene: SRPK3 was set to GREEN
Added comment: 33 individuals reported with SRPK3 variants but myopathy only occurred when TTN variant also present (most truncating). Zebrafish model supports digenic model of inheritance.
Sources: Literature
Mendeliome v1.1726 OTULIN Zornitza Stark Publications for gene: OTULIN were set to 27523608; 27559085; 35587511
Mendeliome v1.1725 OTULIN Zornitza Stark edited their review of gene: OTULIN: Added comment: Three individuals reported with de novo missense variants and auto inflammatory syndrome. Two had at the same variant, p.Cys129Ser. Experimental data supports dominant negative mechanism. Fourth individual with heterozygous variant in PMID 38129331 and severe fasciitis.; Changed publications: 27523608, 27559085, 35587511, 38630025, 38652464, 38129331
Systemic Autoinflammatory Disease_Periodic Fever v1.45 OTULIN Zornitza Stark Publications for gene: OTULIN were set to 27523608; 27559085
Systemic Autoinflammatory Disease_Periodic Fever v1.44 OTULIN Zornitza Stark Mode of inheritance for gene: OTULIN was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Systemic Autoinflammatory Disease_Periodic Fever v1.43 OTULIN Zornitza Stark edited their review of gene: OTULIN: Added comment: Three individuals reported with de novo missense variants and auto inflammatory syndrome. Two had at the same variant, p.Cys129Ser. Experimental data supports dominant negative mechanism. Fourth individual with heterozygous variant in PMID 38129331 and severe fasciitis.; Changed publications: 27523608, 27559085, 38630025, 38652464, 38129331; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Bleeding and Platelet Disorders v1.38 CFI Zornitza Stark Marked gene: CFI as ready
Bleeding and Platelet Disorders v1.38 CFI Zornitza Stark Gene: cfi has been classified as Green List (High Evidence).
Bleeding and Platelet Disorders v1.38 CFI Zornitza Stark Classified gene: CFI as Green List (high evidence)
Bleeding and Platelet Disorders v1.38 CFI Zornitza Stark Gene: cfi has been classified as Green List (High Evidence).
Bleeding and Platelet Disorders v1.37 CFI Zornitza Stark gene: CFI was added
gene: CFI was added to Bleeding and Platelet Disorders. Sources: Expert Review
Mode of inheritance for gene: CFI was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: CFI were set to {Haemolytic uremic syndrome, atypical, susceptibility to, 3}, MIM# 612923
Review for gene: CFI was set to GREEN
Added comment: Thrombotic microangiopathy is part of the phenotype. Note this is a susceptibility locus.
Sources: Expert Review
Bleeding and Platelet Disorders v1.36 CFB Zornitza Stark Marked gene: CFB as ready
Bleeding and Platelet Disorders v1.36 CFB Zornitza Stark Gene: cfb has been classified as Green List (High Evidence).
Bleeding and Platelet Disorders v1.36 CFB Zornitza Stark Classified gene: CFB as Green List (high evidence)
Bleeding and Platelet Disorders v1.36 CFB Zornitza Stark Gene: cfb has been classified as Green List (High Evidence).
Bleeding and Platelet Disorders v1.35 CFB Zornitza Stark gene: CFB was added
gene: CFB was added to Bleeding and Platelet Disorders. Sources: Expert Review
Mode of inheritance for gene: CFB was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: CFB were set to {Hemolytic uremic syndrome, atypical, susceptibility to, 4}, MIM# 612924
Review for gene: CFB was set to GREEN
Added comment: Thrombotic microangiopathy is part of the phenotype. Note this is a susceptibility locus.
Sources: Expert Review
Bleeding and Platelet Disorders v1.34 C3 Zornitza Stark Marked gene: C3 as ready
Bleeding and Platelet Disorders v1.34 C3 Zornitza Stark Gene: c3 has been classified as Green List (High Evidence).
Bleeding and Platelet Disorders v1.34 C3 Zornitza Stark Classified gene: C3 as Green List (high evidence)
Bleeding and Platelet Disorders v1.34 C3 Zornitza Stark Gene: c3 has been classified as Green List (High Evidence).
Bleeding and Platelet Disorders v1.33 C3 Zornitza Stark gene: C3 was added
gene: C3 was added to Bleeding and Platelet Disorders. Sources: Expert Review
Mode of inheritance for gene: C3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: C3 were set to {Hemolytic uremic syndrome, atypical, susceptibility to, 5}, MIM# 612925
Review for gene: C3 was set to GREEN
Added comment: Thrombotic microangiopathy is part of the clinical presentation. Note this is a susceptibility locus.
Sources: Expert Review
Mitochondrial disease v0.922 SPG7 Zornitza Stark Marked gene: SPG7 as ready
Mitochondrial disease v0.922 SPG7 Zornitza Stark Gene: spg7 has been classified as Green List (High Evidence).
Mitochondrial disease v0.922 SPG7 Zornitza Stark Phenotypes for gene: SPG7 were changed from to Spastic paraplegia 7, autosomal recessive, MIM# 607259; Autosomal dominant optic atrophy, MONDO:0020250
Mitochondrial disease v0.921 SPG7 Zornitza Stark Publications for gene: SPG7 were set to 9635427; 9635427; 16534102; 18799786; 22571692; 34500365; 33598982; 32548275; 24727571
Mitochondrial disease v0.920 SPG7 Zornitza Stark Publications for gene: SPG7 were set to
Mitochondrial disease v0.919 SPG7 Zornitza Stark Mode of inheritance for gene: SPG7 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mitochondrial disease v0.918 SPG7 Zornitza Stark edited their review of gene: SPG7: Added comment: Please note PEO can be a feature +/- multiple mito deletions in skeletal muscle. PMID 24727571; Changed publications: 9635427, 9635427, 16534102, 18799786, 22571692, 34500365, 33598982, 32548275, 24727571
Systemic Autoinflammatory Disease_Periodic Fever v1.43 SHARPIN Zornitza Stark Phenotypes for gene: SHARPIN were changed from Autoinflammatory syndrome, MONDO:0019751, SHARPIN-related to Autoinflammation with episodic fever and immune dysregulation, MIM# 620795
Systemic Autoinflammatory Disease_Periodic Fever v1.42 SHARPIN Zornitza Stark edited their review of gene: SHARPIN: Changed phenotypes: Autoinflammation with episodic fever and immune dysregulation, MIM# 620795
Mendeliome v1.1725 SHARPIN Zornitza Stark Phenotypes for gene: SHARPIN were changed from Autoinflammatory syndrome, MONDO:0019751, SHARPIN-related to Autoinflammation with episodic fever and immune dysregulation, MIM# 620795
Mendeliome v1.1724 SHARPIN Zornitza Stark edited their review of gene: SHARPIN: Changed phenotypes: Autoinflammation with episodic fever and immune dysregulation, MIM# 620795
Intellectual disability syndromic and non-syndromic v0.5785 OTUD7A Zornitza Stark Phenotypes for gene: OTUD7A were changed from Intellectual disability; Epilepsy to Neurodevelopmental disorder with hypotonia and seizures, MIM# 620790
Intellectual disability syndromic and non-syndromic v0.5784 OTUD7A Zornitza Stark edited their review of gene: OTUD7A: Changed phenotypes: Neurodevelopmental disorder with hypotonia and seizures, MIM# 620790
Genetic Epilepsy v0.2611 OTUD7A Zornitza Stark Phenotypes for gene: OTUD7A were changed from Intellectual disability; Epilepsy to Neurodevelopmental disorder with hypotonia and seizures, MIM# 620790
Genetic Epilepsy v0.2610 OTUD7A Zornitza Stark edited their review of gene: OTUD7A: Changed phenotypes: Neurodevelopmental disorder with hypotonia and seizures, MIM# 620790
Mendeliome v1.1724 OTUD7A Zornitza Stark Phenotypes for gene: OTUD7A were changed from Intellectual disability; Epilepsy to Neurodevelopmental disorder with hypotonia and seizures, MIM# 620790
Mendeliome v1.1723 OTUD7A Zornitza Stark edited their review of gene: OTUD7A: Changed phenotypes: Neurodevelopmental disorder with hypotonia and seizures, MIM# 620790
Cardiomyopathy_Paediatric v0.190 MYPN Zornitza Stark Marked gene: MYPN as ready
Cardiomyopathy_Paediatric v0.190 MYPN Zornitza Stark Gene: mypn has been classified as Amber List (Moderate Evidence).
Cardiomyopathy_Paediatric v0.190 MYPN Zornitza Stark Phenotypes for gene: MYPN were changed from Cardiomyopathy, dilated, 1KK, MIM# 615248; Cardiomyopathy, hypertrophic, 22, MIM# 615248 to Congenital myopathy 24, MIM# 617336; Cardiomyopathy, dilated, 1KK, MIM# 615248; Cardiomyopathy, hypertrophic, 22, MIM# 615248
Cardiomyopathy_Paediatric v0.189 MYPN Zornitza Stark Mode of inheritance for gene: MYPN was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v0.188 MYPN Zornitza Stark Classified gene: MYPN as Amber List (moderate evidence)
Cardiomyopathy_Paediatric v0.188 MYPN Zornitza Stark Gene: mypn has been classified as Amber List (Moderate Evidence).
Cardiomyopathy_Paediatric v0.187 MYPN Zornitza Stark edited their review of gene: MYPN: Added comment: However, note that the AR skeletal myopathy condition has some reports of HCM in association.; Changed rating: AMBER; Changed phenotypes: Congenital myopathy 24, MIM# 617336, Cardiomyopathy, dilated, 1KK, MIM# 615248, Cardiomyopathy, hypertrophic, 22, MIM# 615248; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v0.187 MYPN Zornitza Stark Phenotypes for gene: MYPN were changed from Cardiomyopathy, dilated, 1KK; Cardiomypathy, familial hypertrophic, 22, to Cardiomyopathy, dilated, 1KK, MIM# 615248; Cardiomyopathy, hypertrophic, 22, MIM# 615248
Cardiomyopathy_Paediatric v0.186 MYPN Zornitza Stark Mode of inheritance for gene: MYPN was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cardiomyopathy_Paediatric v0.185 MYPN Zornitza Stark Classified gene: MYPN as Red List (low evidence)
Cardiomyopathy_Paediatric v0.185 MYPN Zornitza Stark Gene: mypn has been classified as Red List (Low Evidence).
Cardiomyopathy_Paediatric v0.184 MYPN Zornitza Stark reviewed gene: MYPN: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Cardiomyopathy, dilated, 1KK, MIM# 615248, Cardiomyopathy, hypertrophic, 22, MIM# 615248; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5784 SLC35C1 Yixin JIANG reviewed gene: SLC35C1: Rating: GREEN; Mode of pathogenicity: None; Publications: 33836758, 32313197, 34389986; Phenotypes: Congenital disorder of glycosylation, type IIc, MIM# 266265, MONDO:0009953; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1723 AMPD2 Bryony Thompson Deleted their review
Mendeliome v1.1723 AMPD2 Bryony Thompson commented on gene: AMPD2
Mendeliome v1.1723 AMPD2 Bryony Thompson Deleted their review
Metabolic Disorders Superpanel v8.143 Bryony Thompson Changed child panels to: Congenital Disorders of Glycosylation; Miscellaneous Metabolic Disorders; Calcium and Phosphate disorders; Fatty Acid Oxidation Defects; Hypertension and Aldosterone disorders; Lysosomal Storage Disorder; Neurotransmitter Defects; Disorders of branched chain amino acid metabolism; Glycogen Storage Diseases; Inherited vitamin B12 or cobalamin deficiency; Mitochondrial disease; Peroxisomal Disorders; Monogenic Diabetes; Iron metabolism disorders; Dyslipidaemia; Vitamin C Pathway Disorders; Porphyria; Hyperammonaemia
Mendeliome v1.1723 SAR1B Bryony Thompson Deleted their review
Mendeliome v1.1723 SAR1B Bryony Thompson commented on gene: SAR1B
Mendeliome v1.1723 SAR1B Bryony Thompson Deleted their review
Dyslipidaemia v0.37 STAP1 Bryony Thompson Marked gene: STAP1 as ready
Dyslipidaemia v0.37 STAP1 Bryony Thompson Gene: stap1 has been classified as Red List (Low Evidence).
Dyslipidaemia v0.37 STAP1 Bryony Thompson gene: STAP1 was added
gene: STAP1 was added to Dyslipidaemia. Sources: Literature
Mode of inheritance for gene: STAP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: STAP1 were set to 31809983; 31996024; 32208993
Phenotypes for gene: STAP1 were set to Familial hypercholesterolemia MONDO:0005439
Review for gene: STAP1 was set to RED
Added comment: The gene appears to fulfil the criteria for a refuted gene-disease association
Sources: Literature
Metal Metabolism Disorders v0.43 Bryony Thompson removed gene:PLA2G6 from the panel
Metal Metabolism Disorders v0.42 Bryony Thompson removed gene:PANK2 from the panel
Metal Metabolism Disorders v0.41 Bryony Thompson removed gene:FA2H from the panel
Metal Metabolism Disorders v0.40 Bryony Thompson removed gene:C19orf12 from the panel
Metal Metabolism Disorders v0.39 Bryony Thompson removed gene:ATP13A2 from the panel
Liverome Superpanel v1.6 Zornitza Stark Panel types changed to Melbourne Genomics; Victorian Clinical Genetics Services; Royal Melbourne Hospital
Intellectual disability syndromic and non-syndromic v0.5784 PTRH2 Bryony Thompson Publications for gene: PTRH2 were set to 25574476; 28175314; 28328138; 25558065; 27129381
Intellectual disability syndromic and non-syndromic v0.5783 PTRH2 Bryony Thompson Classified gene: PTRH2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5783 PTRH2 Bryony Thompson Gene: ptrh2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5782 PTRH2 Bryony Thompson reviewed gene: PTRH2: Rating: GREEN; Mode of pathogenicity: None; Publications: 33092935, 37239392; Phenotypes: neurologic, endocrine, and pancreatic disease, multisystem, infantile-onset 1 MONDO:8000012; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Proteinuria v0.225 SCARB2 Bryony Thompson Marked gene: SCARB2 as ready
Proteinuria v0.225 SCARB2 Bryony Thompson Gene: scarb2 has been classified as Green List (High Evidence).
Proteinuria v0.225 SCARB2 Bryony Thompson Phenotypes for gene: SCARB2 were changed from to Progressive Myoclonus Epilepsy, MONDO:0020074; Epilepsy, progressive myoclonic 4, with or without renal failure, MIM #254900
Proteinuria v0.224 SCARB2 Bryony Thompson Publications for gene: SCARB2 were set to
Proteinuria v0.223 SCARB2 Bryony Thompson Mode of inheritance for gene: SCARB2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Maturity-onset Diabetes of the Young v1.17 INS Sangavi Sivagnanasundram reviewed gene: INS: Rating: GREEN; Mode of pathogenicity: None; Publications: 9884331; Phenotypes: monogenic diabetes MONDO:0015967; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Maturity-onset Diabetes of the Young v1.17 BLK Sangavi Sivagnanasundram reviewed gene: BLK: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: monogenic diabetes MONDO:0015967; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Metal Metabolism Disorders v0.38 Bryony Thompson removed gene:WDR45 from the panel
Early-onset Dementia v1.14 VPS13C Bryony Thompson Marked gene: VPS13C as ready
Early-onset Dementia v1.14 VPS13C Bryony Thompson Gene: vps13c has been classified as Green List (High Evidence).
Early-onset Dementia v1.14 VPS13C Bryony Thompson Classified gene: VPS13C as Green List (high evidence)
Early-onset Dementia v1.14 VPS13C Bryony Thompson Gene: vps13c has been classified as Green List (High Evidence).
Early-onset Dementia v1.14 VPS13C Bryony Thompson Classified gene: VPS13C as Green List (high evidence)
Early-onset Dementia v1.14 VPS13C Bryony Thompson Gene: vps13c has been classified as Green List (High Evidence).
Early-onset Dementia v1.13 VPS13C Bryony Thompson gene: VPS13C was added
gene: VPS13C was added to Early-onset Dementia. Sources: Literature
Mode of inheritance for gene: VPS13C was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: VPS13C were set to 33579389; 37330543; 34875562
Phenotypes for gene: VPS13C were set to autosomal recessive early-onset Parkinson disease 23 MONDO:0014796
Review for gene: VPS13C was set to GREEN
gene: VPS13C was marked as current diagnostic
Added comment: Multiple cases with biallelic variants and dementia with Lewy bodies have been reported.
Sources: Literature
Arthrogryposis v0.406 PIP5K1C Achchuthan Shanmugasundram reviewed gene: PIP5K1C: Rating: GREEN; Mode of pathogenicity: None; Publications: 38491417; Phenotypes: Lethal congenital contractural syndrome 3, OMIM:611369; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1723 KIAA1024L Zornitza Stark Tag new gene name tag was added to gene: KIAA1024L.
Deafness_IsolatedAndComplex v1.180 KIAA1024L Zornitza Stark Marked gene: KIAA1024L as ready
Deafness_IsolatedAndComplex v1.180 KIAA1024L Zornitza Stark Gene: kiaa1024l has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.180 KIAA1024L Zornitza Stark Classified gene: KIAA1024L as Green List (high evidence)
Deafness_IsolatedAndComplex v1.180 KIAA1024L Zornitza Stark Gene: kiaa1024l has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.179 KIAA1024L Zornitza Stark gene: KIAA1024L was added
gene: KIAA1024L was added to Deafness_IsolatedAndComplex. Sources: Literature
new gene name tags were added to gene: KIAA1024L.
Mode of inheritance for gene: KIAA1024L was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIAA1024L were set to 35727972
Phenotypes for gene: KIAA1024L were set to Deafness, autosomal recessive 120, OMIM:620238
Review for gene: KIAA1024L was set to GREEN
Added comment: New gene name - MINAR2

PMID:35727972 reported 13 patients from four unrelated families with non-syndromic sensorineural hearing loss. Four of these patients had prelingual onset of severe to profound, progressive bilateral hearing loss. The other nine patients had congenital onset of severe to profound bilateral hearing loss, which was not progressive on one patient, while data was not available for the other.

Three different homozygous variants (c.144G > A/ p.Trp48Ter, c.412_419delCGGTTTTG/ p.Arg138Valfs*10 and c.393G > T/ p.Lys131Asn) were identified in MINAR2/ KIAA1024L gene in these patients.

There is some functional evidence available for the p.Lys131Asn variant. In addition, mice with loss of function of the Minar2 protein present with rapidly progressive sensorineural hearing loss.
Sources: Literature
Deafness_Isolated v1.57 KIAA1024L Zornitza Stark Marked gene: KIAA1024L as ready
Deafness_Isolated v1.57 KIAA1024L Zornitza Stark Gene: kiaa1024l has been classified as Green List (High Evidence).
Deafness_Isolated v1.57 KIAA1024L Zornitza Stark Classified gene: KIAA1024L as Green List (high evidence)
Deafness_Isolated v1.57 KIAA1024L Zornitza Stark Gene: kiaa1024l has been classified as Green List (High Evidence).
Deafness_Isolated v1.56 KIAA1024L Zornitza Stark gene: KIAA1024L was added
gene: KIAA1024L was added to Deafness_Isolated. Sources: Literature
new gene name tags were added to gene: KIAA1024L.
Mode of inheritance for gene: KIAA1024L was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIAA1024L were set to 35727972
Phenotypes for gene: KIAA1024L were set to Deafness, autosomal recessive 120, OMIM:620238
Review for gene: KIAA1024L was set to GREEN
Added comment: New gene name - MINAR2

PMID:35727972 reported 13 patients from four unrelated families with non-syndromic sensorineural hearing loss. Four of these patients had prelingual onset of severe to profound, progressive bilateral hearing loss. The other nine patients had congenital onset of severe to profound bilateral hearing loss, which was not progressive on one patient, while data was not available for the other.

Three different homozygous variants (c.144G > A/ p.Trp48Ter, c.412_419delCGGTTTTG/ p.Arg138Valfs*10 and c.393G > T/ p.Lys131Asn) were identified in MINAR2/ KIAA1024L gene in these patients.

There is some functional evidence available for the p.Lys131Asn variant. In addition, mice with loss of function of the Minar2 protein present with rapidly progressive sensorineural hearing loss.
Sources: Literature
Mendeliome v1.1723 KIAA1024L Zornitza Stark Marked gene: KIAA1024L as ready
Mendeliome v1.1723 KIAA1024L Zornitza Stark Gene: kiaa1024l has been classified as Green List (High Evidence).
Mendeliome v1.1723 KIAA1024L Zornitza Stark Classified gene: KIAA1024L as Green List (high evidence)
Mendeliome v1.1723 KIAA1024L Zornitza Stark Gene: kiaa1024l has been classified as Green List (High Evidence).
Fetal anomalies v1.238 EHBP1L1 Zornitza Stark Phenotypes for gene: EHBP1L1 were changed from Non-immune hydrops fetalis MONDO:0009369 to Non-immune hydrops fetalis, MONDO:0015193, EHBP1L1-related
Fetal anomalies v1.237 EHBP1L1 Zornitza Stark Classified gene: EHBP1L1 as Green List (high evidence)
Fetal anomalies v1.237 EHBP1L1 Zornitza Stark Gene: ehbp1l1 has been classified as Green List (High Evidence).
Fetal anomalies v1.236 EHBP1L1 Zornitza Stark reviewed gene: EHBP1L1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Non-immune hydrops fetalis, MONDO:0015193, EHBP1L1-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1722 EHBP1L1 Zornitza Stark Phenotypes for gene: EHBP1L1 were changed from Non-immune hydrops fetalis, MONDO:0015193, EHBP1l1-related to Non-immune hydrops fetalis, MONDO:0015193, EHBP1L1-related
Mendeliome v1.1721 EHBP1L1 Zornitza Stark Classified gene: EHBP1L1 as Green List (high evidence)
Mendeliome v1.1721 EHBP1L1 Zornitza Stark Gene: ehbp1l1 has been classified as Green List (High Evidence).
Mendeliome v1.1720 EHBP1L1 Zornitza Stark reviewed gene: EHBP1L1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Non-immune hydrops fetalis, MONDO:0015193, EHBP1L1-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hydrops fetalis v0.310 EHBP1L1 Zornitza Stark Phenotypes for gene: EHBP1L1 were changed from Non-immune hydrops fetalis, MONDO:0015193, EHBP1l1-related to Non-immune hydrops fetalis, MONDO:0015193, EHBP1L1-related
Hydrops fetalis v0.309 EHBP1L1 Zornitza Stark Classified gene: EHBP1L1 as Green List (high evidence)
Hydrops fetalis v0.309 EHBP1L1 Zornitza Stark Gene: ehbp1l1 has been classified as Green List (High Evidence).
Hydrops fetalis v0.308 EHBP1L1 Zornitza Stark reviewed gene: EHBP1L1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Non-immune hydrops fetalis, MONDO:0015193, EHBP1L1-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5782 DMAP1 Ben Lundie reviewed gene: DMAP1: Rating: AMBER; Mode of pathogenicity: Other; Publications: ; Phenotypes: Unknown.; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2610 EFHC1 Zornitza Stark Tag disputed was removed from gene: EFHC1.
Tag refuted tag was added to gene: EFHC1.
Genetic Epilepsy v0.2610 SCN1A Zornitza Stark Publications for gene: SCN1A were set to 30368457; 12754708; 25754450; 32928894
Genetic Epilepsy v0.2609 SCN1A Zornitza Stark Publications for gene: SCN1A were set to
Genetic Epilepsy v0.2608 SCN1B Zornitza Stark Marked gene: SCN1B as ready
Genetic Epilepsy v0.2608 SCN1B Zornitza Stark Gene: scn1b has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2608 SCN1B Zornitza Stark Phenotypes for gene: SCN1B were changed from Developmental and epileptic encephalopathy (MONDO:0100062); generalized epilepsy with febrile seizures plus (MONDO:0018214) to Developmental and epileptic encephalopathy (MONDO:0100062); generalized epilepsy with febrile seizures plus (MONDO:0018214)
Genetic Epilepsy v0.2607 SCN1B Zornitza Stark Phenotypes for gene: SCN1B were changed from to Developmental and epileptic encephalopathy (MONDO:0100062); generalized epilepsy with febrile seizures plus (MONDO:0018214)
Genetic Epilepsy v0.2606 SCN1B Zornitza Stark Publications for gene: SCN1B were set to
Genetic Epilepsy v0.2605 SCN1B Zornitza Stark Mode of inheritance for gene: SCN1B was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genetic Epilepsy v0.2604 SLC12A5 Zornitza Stark Marked gene: SLC12A5 as ready
Genetic Epilepsy v0.2604 SLC12A5 Zornitza Stark Gene: slc12a5 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2604 SLC12A5 Zornitza Stark Phenotypes for gene: SLC12A5 were changed from Developmental and epileptic encephalopathy 34, MIM# 616645; {Epilepsy, idiopathic generalized, susceptibility to, 14}, MIM# 616685 to Developmental and epileptic encephalopathy 34, MIM# 616645; {Epilepsy, idiopathic generalized, susceptibility to, 14}, MIM# 616685
Genetic Epilepsy v0.2603 SLC12A5 Zornitza Stark Phenotypes for gene: SLC12A5 were changed from Developmental and epileptic encephalopathy 34, MIM# 616645; {Epilepsy, idiopathic generalized, susceptibility to, 14}, MIM# 616685 to Developmental and epileptic encephalopathy 34, MIM# 616645; {Epilepsy, idiopathic generalized, susceptibility to, 14}, MIM# 616685
Genetic Epilepsy v0.2602 SLC12A5 Zornitza Stark Phenotypes for gene: SLC12A5 were changed from to Developmental and epileptic encephalopathy 34, MIM# 616645; {Epilepsy, idiopathic generalized, susceptibility to, 14}, MIM# 616685
Genetic Epilepsy v0.2601 SLC12A5 Zornitza Stark Publications for gene: SLC12A5 were set to
Genetic Epilepsy v0.2600 SLC12A5 Zornitza Stark Mode of inheritance for gene: SLC12A5 was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Osteogenesis Imperfecta and Osteoporosis v0.113 ALPL Zornitza Stark Marked gene: ALPL as ready
Osteogenesis Imperfecta and Osteoporosis v0.113 ALPL Zornitza Stark Gene: alpl has been classified as Green List (High Evidence).
Osteogenesis Imperfecta and Osteoporosis v0.113 ALPL Zornitza Stark Phenotypes for gene: ALPL were changed from to Hypophosphatasia, adult 146300 (AD, AR); Hypophosphatasia, childhood 241510 AR; Hypophosphatasia, infantile 241500 AR; Odontohypophosphatasia 146300 AD, AR
Osteogenesis Imperfecta and Osteoporosis v0.112 ALPL Zornitza Stark Publications for gene: ALPL were set to
Osteogenesis Imperfecta and Osteoporosis v0.111 ALPL Zornitza Stark Mode of inheritance for gene: ALPL was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Autonomic neuropathy v0.50 DST Zornitza Stark Publications for gene: DST were set to
Autonomic neuropathy v0.49 DST Zornitza Stark Classified gene: DST as Green List (high evidence)
Autonomic neuropathy v0.49 DST Zornitza Stark Gene: dst has been classified as Green List (High Evidence).
Systemic Autoinflammatory Disease_Periodic Fever v1.42 PSMB9 Zornitza Stark Phenotypes for gene: PSMB9 were changed from Proteasome-associated autoinflammatory syndrome 3, digenic, MIM# 617591 to Proteasome-associated autoinflammatory syndrome 3, digenic, MIM# 617591; Proteasome-associated autoinflammatory syndrome 6, MIM# 620796
Systemic Autoinflammatory Disease_Periodic Fever v1.41 PSMB9 Zornitza Stark edited their review of gene: PSMB9: Changed phenotypes: Proteasome-associated autoinflammatory syndrome 3, digenic, MIM# 617591, Proteasome-associated autoinflammatory syndrome 6, MIM# 620796
Mendeliome v1.1720 PSMB9 Zornitza Stark Phenotypes for gene: PSMB9 were changed from Proteasome-associated autoinflammatory syndrome 3, digenic, MIM# 617591 to Proteasome-associated autoinflammatory syndrome 3, digenic, MIM# 617591; Proteasome-associated autoinflammatory syndrome 6, MIM# 620796
Mendeliome v1.1719 PSMB9 Zornitza Stark edited their review of gene: PSMB9: Changed phenotypes: Proteasome-associated autoinflammatory syndrome 3, digenic, MIM# 617591, Proteasome-associated autoinflammatory syndrome 6, MIM# 620796
Systemic Autoinflammatory Disease_Periodic Fever v1.41 OTULIN Peter McNaughton reviewed gene: OTULIN: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38630025; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5782 SLC1A1 Bryony Thompson Classified gene: SLC1A1 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.5782 SLC1A1 Bryony Thompson Gene: slc1a1 has been classified as Amber List (Moderate Evidence).
Hypertrophic cardiomyopathy_HCM v0.178 TCAP Bryony Thompson Tag disputed tag was added to gene: TCAP.
Hypertrophic cardiomyopathy_HCM v0.178 TCAP Bryony Thompson Classified gene: TCAP as Red List (low evidence)
Hypertrophic cardiomyopathy_HCM v0.178 TCAP Bryony Thompson Added comment: Comment on list classification: Now DISPUTED gene-disease association by ClinGen Hereditary Cardiovascular Disease GCEP
Hypertrophic cardiomyopathy_HCM v0.178 TCAP Bryony Thompson Gene: tcap has been classified as Red List (Low Evidence).
Autonomic neuropathy v0.48 DST Alison Yeung edited their review of gene: DST: Added comment: Since first family published in 2012, there have been two other families published. This is a green gene in the hereditary neuropathy panel.; Changed rating: GREEN; Changed publications: 30371979, 28468842
Rhabdomyolysis and Metabolic Myopathy v1.3 PACSIN3 Zornitza Stark Marked gene: PACSIN3 as ready
Rhabdomyolysis and Metabolic Myopathy v1.3 PACSIN3 Zornitza Stark Gene: pacsin3 has been classified as Amber List (Moderate Evidence).
Rhabdomyolysis and Metabolic Myopathy v1.3 PACSIN3 Zornitza Stark Classified gene: PACSIN3 as Amber List (moderate evidence)
Rhabdomyolysis and Metabolic Myopathy v1.3 PACSIN3 Zornitza Stark Gene: pacsin3 has been classified as Amber List (Moderate Evidence).
Rhabdomyolysis and Metabolic Myopathy v1.2 PACSIN3 Zornitza Stark gene: PACSIN3 was added
gene: PACSIN3 was added to Rhabdomyolysis and Metabolic Myopathy. Sources: Literature
Mode of inheritance for gene: PACSIN3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PACSIN3 were set to 38637313
Phenotypes for gene: PACSIN3 were set to Myopathy, MONDO:0005336, PACSIN3-related
Review for gene: PACSIN3 was set to AMBER
Added comment: Two unrelated families with LoF variants, one homozygous. Muscle phenotype including raised CK. Supportive mouse model.
Sources: Literature
Mendeliome v1.1719 PACSIN3 Zornitza Stark Marked gene: PACSIN3 as ready
Mendeliome v1.1719 PACSIN3 Zornitza Stark Gene: pacsin3 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1719 PACSIN3 Zornitza Stark Classified gene: PACSIN3 as Amber List (moderate evidence)
Mendeliome v1.1719 PACSIN3 Zornitza Stark Gene: pacsin3 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1718 PACSIN3 Zornitza Stark gene: PACSIN3 was added
gene: PACSIN3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PACSIN3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PACSIN3 were set to 38637313
Phenotypes for gene: PACSIN3 were set to Myopathy, MONDO:0005336, PACSIN3-related
Review for gene: PACSIN3 was set to AMBER
Added comment: Two unrelated families with LoF variants, one homozygous. Muscle phenotype including raised CK. Supportive mouse model.
Sources: Literature
Muscular dystrophy and myopathy_Paediatric v1.31 PACSIN3 Zornitza Stark Marked gene: PACSIN3 as ready
Muscular dystrophy and myopathy_Paediatric v1.31 PACSIN3 Zornitza Stark Gene: pacsin3 has been classified as Amber List (Moderate Evidence).
Muscular dystrophy and myopathy_Paediatric v1.31 PACSIN3 Zornitza Stark Classified gene: PACSIN3 as Amber List (moderate evidence)
Muscular dystrophy and myopathy_Paediatric v1.31 PACSIN3 Zornitza Stark Gene: pacsin3 has been classified as Amber List (Moderate Evidence).
Muscular dystrophy and myopathy_Paediatric v1.30 PACSIN3 Zornitza Stark gene: PACSIN3 was added
gene: PACSIN3 was added to Muscular dystrophy and myopathy_Paediatric. Sources: Literature
Mode of inheritance for gene: PACSIN3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PACSIN3 were set to 38637313
Phenotypes for gene: PACSIN3 were set to Myopathy, MONDO:0005336, PACSIN3-related
Review for gene: PACSIN3 was set to AMBER
Added comment: Two unrelated families with LoF variants, one homozygous. Muscle phenotype including raised CK. Supportive mouse model.
Sources: Literature
Angelman Rett like syndromes v1.10 MECP2 Zornitza Stark changed review comment from: Well established gene-disease association, XLD.; to: Well established gene-disease association, XLD.
Metabolic Disorders Superpanel v8.132 Bryony Thompson Changed child panels to: Miscellaneous Metabolic Disorders; Congenital Disorders of Glycosylation; Calcium and Phosphate disorders; Fatty Acid Oxidation Defects; Hypertension and Aldosterone disorders; Lysosomal Storage Disorder; Neurotransmitter Defects; Disorders of branched chain amino acid metabolism; Glycogen Storage Diseases; Rhabdomyolysis and Metabolic Myopathy; Inherited vitamin B12 or cobalamin deficiency; Mitochondrial disease; Peroxisomal Disorders; Monogenic Diabetes; Iron metabolism disorders; Dyslipidaemia; Vitamin C Pathway Disorders; Porphyria; Hyperammonaemia
Intellectual disability syndromic and non-syndromic v0.5781 RNU4-2 Zornitza Stark changed review comment from: Emerging evidence that de novo variants in this gene cause ID.
Sources: Literature; to: Over 100 individuals with ID found to have de novo variants in this gene. Please note difficult to identify on ES.
Sources: Literature
Mendeliome v1.1717 RNU4-2 Zornitza Stark changed review comment from: Emerging evidence that de novo variants in this gene cause ID.
Sources: Literature; to: Over 100 individuals with ID found to have de novo variants in this gene. Please note difficult to identify on ES.
Sources: Literature
Mendeliome v1.1717 RNU4-2 Zornitza Stark Publications for gene: RNU4-2 were set to
Mendeliome v1.1716 RNU4-2 Zornitza Stark edited their review of gene: RNU4-2: Changed publications: 38645094
Intellectual disability syndromic and non-syndromic v0.5781 RNU4-2 Zornitza Stark Publications for gene: RNU4-2 were set to
Intellectual disability syndromic and non-syndromic v0.5780 RNU4-2 Zornitza Stark edited their review of gene: RNU4-2: Changed publications: 38645094
Intellectual disability syndromic and non-syndromic v0.5780 MAB21L1 Zornitza Stark reviewed gene: MAB21L1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cerebellar, ocular, craniofacial, and genital syndrome MIM#618479; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Osteogenesis Imperfecta and Osteoporosis v0.110 ALPL Chirag Patel reviewed gene: ALPL: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 19500388, 23688511; Phenotypes: Hypophosphatasia, adult 146300 (AD, AR), Hypophosphatasia, childhood 241510 AR, Hypophosphatasia, infantile 241500 AR, Odontohypophosphatasia 146300 AD, AR; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Genetic Epilepsy v0.2599 SLC12A5 Sangavi Sivagnanasundram reviewed gene: SLC12A5: Rating: AMBER; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:006147; Phenotypes: developmental and epileptic encephalopathy MONDO:0100062; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2599 SERPINI1 Sangavi Sivagnanasundram reviewed gene: SERPINI1: Rating: GREEN; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:006114; Phenotypes: progressive myoclonus epilepsy MONDO:0020074; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2599 SCN1B Sangavi Sivagnanasundram reviewed gene: SCN1B: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 19710327, 28218389, 23148524; Phenotypes: Developmental and epileptic encephalopathy (MONDO:0100062), generalized epilepsy with febrile seizures plus (MONDO:0018214); Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genetic Epilepsy v0.2599 SCN1A Sangavi Sivagnanasundram reviewed gene: SCN1A: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: generalized epilepsy with febrile seizures plus (MONDO:0018214), Dravet syndrome (MONDO:0100135), developmental and epileptic encephalopathy (MONDO:0100062), familial hemiplegic migraine (MONDO:0000700); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2599 RORB Sangavi Sivagnanasundram reviewed gene: RORB: Rating: ; Mode of pathogenicity: None; Publications: 27352968; Phenotypes: epilepsy MONDO:0005027; Mode of inheritance: None
Genetic Epilepsy v0.2599 NECAP1 Sangavi Sivagnanasundram reviewed gene: NECAP1: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 24399846, 30626896; Phenotypes: developmental and epileptic encephalopathy MONDO:0100062; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2599 KCNT1 Sangavi Sivagnanasundram reviewed gene: KCNT1: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: PMID: 23086397, 26725113; Phenotypes: childhood-onset epilepsy syndrome MONDO:0020072; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2599 EFHC1 Sangavi Sivagnanasundram reviewed gene: EFHC1: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 31056551, https://search.clinicalgenome.org/CCID:004730; Phenotypes: epilepsy MONDO:0005027; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Progressive Neurological Conditions v16.1 Bryony Thompson Changed child panels to: Early-onset Parkinson disease; Brain Calcification; Hereditary Spastic Paraplegia - paediatric; Hereditary Neuropathy_CMT - isolated; Congenital Disorders of Glycosylation; Miscellaneous Metabolic Disorders; Dystonia - isolated/combined; Limb-Girdle Muscular Dystrophy and Distal Myopathy; Motor Neurone Disease; Ataxia - paediatric; Fatty Acid Oxidation Defects; Early-onset Dementia; Hereditary Neuropathy - complex; Lysosomal Storage Disorder; Ataxia - adult onset; Hereditary Spastic Paraplegia - adult onset; Neurotransmitter Defects; Brain Channelopathies; Glycogen Storage Diseases; Rhabdomyolysis and Metabolic Myopathy; Genetic Epilepsy; Mitochondrial disease; Leukodystrophy - paediatric; Dystonia - complex; Leukodystrophy - adult onset; Peroxisomal Disorders; Cerebral vascular malformations; Iron metabolism disorders; Neurodegeneration with brain iron accumulation; Pain syndromes
Early-onset Parkinson disease v2.0 Bryony Thompson promoted panel to version 2.0
Early-onset Parkinson disease v1.0 Bryony Thompson promoted panel to version 1.0
Early-onset Parkinson disease v0.347 WDR45 Bryony Thompson Marked gene: WDR45 as ready
Early-onset Parkinson disease v0.347 WDR45 Bryony Thompson Gene: wdr45 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.347 WDR45 Bryony Thompson Phenotypes for gene: WDR45 were changed from to X-linked complex neurodevelopmental disorder MONDO:0100148
Early-onset Parkinson disease v0.346 WDR45 Bryony Thompson Publications for gene: WDR45 were set to
Early-onset Parkinson disease v0.345 WDR45 Bryony Thompson Mode of inheritance for gene: WDR45 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)
Early-onset Parkinson disease v0.344 VPS13A Bryony Thompson Marked gene: VPS13A as ready
Early-onset Parkinson disease v0.344 VPS13A Bryony Thompson Gene: vps13a has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.344 VPS13A Bryony Thompson Phenotypes for gene: VPS13A were changed from to chorea-acanthocytosis MONDO:0008695
Early-onset Parkinson disease v0.343 VPS13A Bryony Thompson Publications for gene: VPS13A were set to
Early-onset Parkinson disease v0.342 VPS13A Bryony Thompson Mode of inheritance for gene: VPS13A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.341 TUBB4A Bryony Thompson Mode of inheritance for gene: TUBB4A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.340 TUBB4A Bryony Thompson Marked gene: TUBB4A as ready
Early-onset Parkinson disease v0.340 TUBB4A Bryony Thompson Gene: tubb4a has been classified as Red List (Low Evidence).
Early-onset Parkinson disease v0.340 TUBB4A Bryony Thompson Classified gene: TUBB4A as Red List (low evidence)
Early-onset Parkinson disease v0.340 TUBB4A Bryony Thompson Added comment: Comment on list classification: More suitable for the dystonia panel
Early-onset Parkinson disease v0.340 TUBB4A Bryony Thompson Gene: tubb4a has been classified as Red List (Low Evidence).
Early-onset Parkinson disease v0.339 TH Bryony Thompson Marked gene: TH as ready
Early-onset Parkinson disease v0.339 TH Bryony Thompson Gene: th has been classified as Green List (High Evidence).
Motor Neurone Disease v1.21 OPTN Bryony Thompson Marked gene: OPTN as ready
Motor Neurone Disease v1.21 OPTN Bryony Thompson Gene: optn has been classified as Green List (High Evidence).
Motor Neurone Disease v1.21 OPTN Bryony Thompson Phenotypes for gene: OPTN were changed from to Amyotrophic lateral sclerosis 12 with or without frontotemporal dementia (MONDO: 0013264, MIM#613435)
Early-onset Parkinson disease v0.339 TH Bryony Thompson Phenotypes for gene: TH were changed from to Tyrosine hydroxylase deficiency MONDO:0100064
Motor Neurone Disease v1.20 OPTN Bryony Thompson Publications for gene: OPTN were set to
Early-onset Parkinson disease v0.338 TH Bryony Thompson Publications for gene: TH were set to 20301334; 20301610
Motor Neurone Disease v1.19 OPTN Bryony Thompson Mode of inheritance for gene: OPTN was changed from BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Early-onset Parkinson disease v0.337 TH Bryony Thompson Publications for gene: TH were set to
Motor Neurone Disease v1.19 OPTN Bryony Thompson Mode of inheritance for gene: OPTN 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 v0.336 TH Bryony Thompson Mode of inheritance for gene: TH was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.335 SPR Bryony Thompson Marked gene: SPR as ready
Early-onset Parkinson disease v0.335 SPR Bryony Thompson Gene: spr has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.335 SPR Bryony Thompson Phenotypes for gene: SPR were changed from to Dopa-responsive dystonia due to sepiapterin reductase deficiency MONDO:0012994
Early-onset Parkinson disease v0.334 SPR Bryony Thompson Publications for gene: SPR were set to
Early-onset Parkinson disease v0.333 SPR Bryony Thompson Mode of inheritance for gene: SPR was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.332 SLC30A10 Bryony Thompson Marked gene: SLC30A10 as ready
Early-onset Parkinson disease v0.332 SLC30A10 Bryony Thompson Gene: slc30a10 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.332 SLC30A10 Bryony Thompson Mode of inheritance for gene: SLC30A10 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Motor Neurone Disease v1.18 UBQLN2 Bryony Thompson Mode of inheritance for gene: UBQLN2 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, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Early-onset Parkinson disease v0.332 SLC30A10 Bryony Thompson Mode of inheritance for gene: SLC30A10 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Motor Neurone Disease v1.18 UBQLN2 Bryony Thompson Mode of inheritance for gene: UBQLN2 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Early-onset Parkinson disease v0.331 SLC30A10 Bryony Thompson Publications for gene: SLC30A10 were set to
Early-onset Parkinson disease v0.330 SLC30A10 Bryony Thompson Phenotypes for gene: SLC30A10 were changed from to cirrhosis - dystonia - polycythemia - hypermanganesemia syndrome MONDO:0013208
Early-onset Parkinson disease v0.329 SPG11 Bryony Thompson Marked gene: SPG11 as ready
Early-onset Parkinson disease v0.329 SPG11 Bryony Thompson Gene: spg11 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.329 SPG11 Bryony Thompson Mode of inheritance for gene: SPG11 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.328 SPG11 Bryony Thompson Publications for gene: SPG11 were set to
Early-onset Parkinson disease v0.328 SPG11 Bryony Thompson Phenotypes for gene: SPG11 were changed from hereditary spastic paraplegia 11 MONDO:0011445 to hereditary spastic paraplegia 11 MONDO:0011445
Early-onset Parkinson disease v0.327 SPG11 Bryony Thompson Phenotypes for gene: SPG11 were changed from hereditary spastic paraplegia 11 MONDO:0011445 to hereditary spastic paraplegia 11 MONDO:0011445
Early-onset Parkinson disease v0.327 SPG11 Bryony Thompson Phenotypes for gene: SPG11 were changed from to hereditary spastic paraplegia 11 MONDO:0011445
Early-onset Parkinson disease v0.326 RAB39B Bryony Thompson Marked gene: RAB39B as ready
Early-onset Parkinson disease v0.326 RAB39B Bryony Thompson Gene: rab39b has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.326 RAB39B Bryony Thompson Mode of inheritance for gene: RAB39B was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Early-onset Parkinson disease v0.325 RAB39B Bryony Thompson Publications for gene: RAB39B were set to
Early-onset Parkinson disease v0.324 RAB39B Bryony Thompson Phenotypes for gene: RAB39B were changed from to Early-onset parkinsonism-intellectual disability syndrome MONDO:0010709
Motor Neurone Disease v1.17 NEFH Bryony Thompson Marked gene: NEFH as ready
Motor Neurone Disease v1.17 NEFH Bryony Thompson Gene: nefh has been classified as Red List (Low Evidence).
Early-onset Parkinson disease v0.323 PSEN1 Bryony Thompson Marked gene: PSEN1 as ready
Early-onset Parkinson disease v0.323 PSEN1 Bryony Thompson Gene: psen1 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.323 PSEN1 Bryony Thompson Mode of inheritance for gene: PSEN1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.322 PSEN1 Bryony Thompson Mode of inheritance for gene: PSEN1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Motor Neurone Disease v1.17 NEFH Bryony Thompson gene: NEFH was added
gene: NEFH was added to Motor Neurone Disease. Sources: ClinGen
Mode of inheritance for gene: NEFH was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: NEFH were set to amyotrophic lateral sclerosis MONDO:0004976
Review for gene: NEFH was set to RED
Added comment: Limited gene-disease validity classification by ClinGen ALS spectrum disorders GCEP - 23/03/2023
https://search.clinicalgenome.org/CCID:005612
Sources: ClinGen
Early-onset Parkinson disease v0.321 PSEN1 Bryony Thompson Publications for gene: PSEN1 were set to
Early-onset Parkinson disease v0.320 PSEN1 Bryony Thompson Phenotypes for gene: PSEN1 were changed from to Alzheimer disease 3 MONDO:0011913
Early-onset Parkinson disease v0.319 PRKN Bryony Thompson Marked gene: PRKN as ready
Early-onset Parkinson disease v0.319 PRKN Bryony Thompson Gene: prkn has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.319 PRKN Bryony Thompson Phenotypes for gene: PRKN were changed from to autosomal recessive juvenile Parkinson disease 2 MONDO:0010820
Early-onset Parkinson disease v0.318 PRKN Bryony Thompson Mode of inheritance for gene: PRKN was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.317 PARK7 Bryony Thompson Marked gene: PARK7 as ready
Early-onset Parkinson disease v0.317 PARK7 Bryony Thompson Gene: park7 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.317 PARK7 Bryony Thompson Phenotypes for gene: PARK7 were changed from to autosomal recessive early-onset Parkinson disease 7 MONDO:0011658
Fetal anomalies v1.236 FOSL2 Zornitza Stark Phenotypes for gene: FOSL2 were changed from Neurodevelopmental disorder, MONDO:0700092, FOSL2-related to Aplasia cutis-enamel dysplasia syndrome, MIM# 620789
Fetal anomalies v1.235 FOSL2 Zornitza Stark reviewed gene: FOSL2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Aplasia cutis-enamel dysplasia syndrome, MIM# 620789; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Growth failure v1.76 FOSL2 Zornitza Stark Phenotypes for gene: FOSL2 were changed from Neurodevelopmental disorder, MONDO:0700092, FOSL2-related to Aplasia cutis-enamel dysplasia syndrome, MIM# 620789
Growth failure v1.75 FOSL2 Zornitza Stark reviewed gene: FOSL2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Aplasia cutis-enamel dysplasia syndrome, MIM# 620789; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Ectodermal Dysplasia v0.86 FOSL2 Zornitza Stark Phenotypes for gene: FOSL2 were changed from Neurodevelopmental disorder, MONDO:0700092, FOSL2-related to Aplasia cutis-enamel dysplasia syndrome, MIM# 620789
Ectodermal Dysplasia v0.85 FOSL2 Zornitza Stark reviewed gene: FOSL2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Aplasia cutis-enamel dysplasia syndrome, MIM# 620789; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5780 FOSL2 Zornitza Stark Phenotypes for gene: FOSL2 were changed from Neurodevelopmental disorder, MONDO:0700092, FOSL2-related to Aplasia cutis-enamel dysplasia syndrome, MIM# 620789
Intellectual disability syndromic and non-syndromic v0.5779 FOSL2 Zornitza Stark reviewed gene: FOSL2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Aplasia cutis-enamel dysplasia syndrome, MIM# 620789; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.1716 FOSL2 Zornitza Stark Phenotypes for gene: FOSL2 were changed from Neurodevelopmental disorder, MONDO:0700092, FOSL2-related to Aplasia cutis-enamel dysplasia syndrome, MIM# 620789
Mendeliome v1.1715 FOSL2 Zornitza Stark reviewed gene: FOSL2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Aplasia cutis-enamel dysplasia syndrome, MIM# 620789; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cataract v0.365 FOSL2 Zornitza Stark Phenotypes for gene: FOSL2 were changed from Neurodevelopmental disorder, MONDO:0700092, FOSL2-related to Aplasia cutis-enamel dysplasia syndrome, MIM# 620789
Cataract v0.364 FOSL2 Zornitza Stark reviewed gene: FOSL2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Aplasia cutis-enamel dysplasia syndrome, MIM# 620789; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.316 PARK7 Bryony Thompson Publications for gene: PARK7 were set to
Early-onset Parkinson disease v0.315 PARK7 Bryony Thompson Mode of inheritance for gene: PARK7 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Motor Neurone Disease v1.16 SETX Bryony Thompson Marked gene: SETX as ready
Motor Neurone Disease v1.16 SETX Bryony Thompson Gene: setx has been classified as Green List (High Evidence).
Motor Neurone Disease v1.16 SETX Bryony Thompson Phenotypes for gene: SETX were changed from to Amyotrophic Lateral Sclerosis 4, juvenile (MIM#602433)
Motor Neurone Disease v1.15 SETX Bryony Thompson Publications for gene: SETX were set to
Motor Neurone Disease v1.14 SETX Bryony Thompson Mode of inheritance for gene: SETX was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.314 ANG Bryony Thompson Marked gene: ANG as ready
Early-onset Parkinson disease v0.314 ANG Bryony Thompson Gene: ang has been classified as Red List (Low Evidence).
Early-onset Parkinson disease v0.314 ANG Bryony Thompson gene: ANG was added
gene: ANG was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: ANG was set to Unknown
Publications for gene: ANG were set to 33875291; 25386690
Phenotypes for gene: ANG were set to Parkinson disease MONDO:0005180
Review for gene: ANG was set to RED
Added comment: Multiple large studies not finding an association with PD
Sources: Literature
Early-onset Parkinson disease v0.313 FUS Bryony Thompson changed review comment from: A single family reported p.Gln290* segregating (incomplete penetrance) with essential tremor, also two missense variants reported in 2 probands which are too common in gnomAD and have been classified as LB in ClinVar. A reported ET risk variant Met392Ile in a Chinese population - set 1 odds ratio = 4.72 [95% confidence interval = 1.90-11.71], p = 0.0037). Validation set 2 (joint analysis odds ratio = 3.92 [95% confidence interval = 1.57-9.82], p = 8.6 × 10(-4). This variant has been classified as LB in ClinVar.
Sources: Literature; to: A single family reported p.Gln290* segregating (incomplete penetrance) with essential tremor, also two missense variants reported in 2 probands which are too common in gnomAD and have been classified as LB in ClinVar. One of these (Pro431Leu) was also reported in an Italian family. A reported ET risk variant Met392Ile in a Chinese population - set 1 odds ratio = 4.72 [95% confidence interval = 1.90-11.71], p = 0.0037). Validation set 2 (joint analysis odds ratio = 3.92 [95% confidence interval = 1.57-9.82], p = 8.6 × 10(-4). This variant has been classified as LB in ClinVar.
Sources: Literature
Early-onset Parkinson disease v0.313 FUS Bryony Thompson edited their review of gene: FUS: Changed publications: 22863194, 23834483, 23825177, 38626532
Early-onset Parkinson disease v0.313 FUS Bryony Thompson Publications for gene: FUS were set to 22863194
Early-onset Parkinson disease v0.312 FUS Bryony Thompson Marked gene: FUS as ready
Early-onset Parkinson disease v0.312 FUS Bryony Thompson Gene: fus has been classified as Red List (Low Evidence).
Early-onset Parkinson disease v0.312 FUS Bryony Thompson gene: FUS was added
gene: FUS was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: FUS was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FUS were set to 22863194
Phenotypes for gene: FUS were set to tremor, hereditary essential, 4 MONDO:0013888
Review for gene: FUS was set to RED
Added comment: A single family reported p.Gln290* segregating (incomplete penetrance) with essential tremor, also two missense variants reported in 2 probands which are too common in gnomAD and have been classified as LB in ClinVar. A reported ET risk variant Met392Ile in a Chinese population - set 1 odds ratio = 4.72 [95% confidence interval = 1.90-11.71], p = 0.0037). Validation set 2 (joint analysis odds ratio = 3.92 [95% confidence interval = 1.57-9.82], p = 8.6 × 10(-4). This variant has been classified as LB in ClinVar.
Sources: Literature
Early-onset Parkinson disease v0.311 MAPT Bryony Thompson Marked gene: MAPT as ready
Early-onset Parkinson disease v0.311 MAPT Bryony Thompson Gene: mapt has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.311 MAPT Bryony Thompson Phenotypes for gene: MAPT were changed from to late-onset Parkinson disease MONDO:0008199
Early-onset Parkinson disease v0.310 MAPT Bryony Thompson Mode of inheritance for gene: MAPT was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.309 MAPT Bryony Thompson Mode of inheritance for gene: MAPT was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Motor Neurone Disease v1.13 FUS Bryony Thompson Marked gene: FUS as ready
Motor Neurone Disease v1.13 FUS Bryony Thompson Gene: fus has been classified as Green List (High Evidence).
Motor Neurone Disease v1.13 FUS Bryony Thompson Phenotypes for gene: FUS were changed from to Amyotrophic lateral sclerosis 6, with or without frontotemporal dementia (MIM#608030)
Early-onset Parkinson disease v0.308 MAPT Bryony Thompson Publications for gene: MAPT were set to
Motor Neurone Disease v1.12 FUS Bryony Thompson Publications for gene: FUS were set to
Motor Neurone Disease v1.11 FUS Bryony Thompson Mode of inheritance for gene: FUS was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.307 VCP Bryony Thompson Marked gene: VCP as ready
Early-onset Parkinson disease v0.307 VCP Bryony Thompson Gene: vcp has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.307 VCP Bryony Thompson Classified gene: VCP as Green List (high evidence)
Early-onset Parkinson disease v0.307 VCP Bryony Thompson Gene: vcp has been classified as Green List (High Evidence).
Neurodegeneration with brain iron accumulation v0.35 THAP1 Bryony Thompson Marked gene: THAP1 as ready
Neurodegeneration with brain iron accumulation v0.35 THAP1 Bryony Thompson Gene: thap1 has been classified as Amber List (Moderate Evidence).
Early-onset Parkinson disease v0.306 VCP Bryony Thompson gene: VCP was added
gene: VCP was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: VCP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: VCP were set to 38283104; 38145206
Phenotypes for gene: VCP were set to Inclusion body myopathy with Paget disease of bone and frontotemporal dementia MONDO:0000507
Mode of pathogenicity for gene: VCP was set to Other
Review for gene: VCP was set to GREEN
gene: VCP was marked as current diagnostic
Added comment: Parkinsonism is a rare feature of VCP-related multisystem proteinopathy, but has been reported in at least 15 individuals with VCP variants.
Sources: Literature
Early-onset Parkinson disease v0.305 LYST Bryony Thompson Marked gene: LYST as ready
Early-onset Parkinson disease v0.305 LYST Bryony Thompson Gene: lyst has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.305 LYST Bryony Thompson Publications for gene: LYST were set to
Neurodegeneration with brain iron accumulation v0.35 THAP1 Bryony Thompson Classified gene: THAP1 as Amber List (moderate evidence)
Neurodegeneration with brain iron accumulation v0.35 THAP1 Bryony Thompson Gene: thap1 has been classified as Amber List (Moderate Evidence).
Neurodegeneration with brain iron accumulation v0.34 DDHD1 Bryony Thompson Marked gene: DDHD1 as ready
Neurodegeneration with brain iron accumulation v0.34 DDHD1 Bryony Thompson Gene: ddhd1 has been classified as Red List (Low Evidence).
Neurodegeneration with brain iron accumulation v0.34 DDHD1 Bryony Thompson Classified gene: DDHD1 as Red List (low evidence)
Neurodegeneration with brain iron accumulation v0.34 DDHD1 Bryony Thompson Added comment: Comment on list classification: Only single case reported with iron accumulation
Neurodegeneration with brain iron accumulation v0.34 DDHD1 Bryony Thompson Gene: ddhd1 has been classified as Red List (Low Evidence).
Early-onset Parkinson disease v0.304 LYST Bryony Thompson Phenotypes for gene: LYST were changed from to Chediak-Higashi syndrome MONDO:0008963
Early-onset Parkinson disease v0.303 LYST Bryony Thompson Mode of inheritance for gene: LYST was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Neurodegeneration with brain iron accumulation v0.33 SQSTM1 Bryony Thompson Marked gene: SQSTM1 as ready
Neurodegeneration with brain iron accumulation v0.33 SQSTM1 Bryony Thompson Gene: sqstm1 has been classified as Red List (Low Evidence).
Neurodegeneration with brain iron accumulation v0.33 SQSTM1 Bryony Thompson Classified gene: SQSTM1 as Red List (low evidence)
Neurodegeneration with brain iron accumulation v0.33 SQSTM1 Bryony Thompson Added comment: Comment on list classification: Only single family reported with iron accumulation
Neurodegeneration with brain iron accumulation v0.33 SQSTM1 Bryony Thompson Gene: sqstm1 has been classified as Red List (Low Evidence).
Early-onset Parkinson disease v0.302 LYST Bryony Thompson Classified gene: LYST as Green List (high evidence)
Early-onset Parkinson disease v0.302 LYST Bryony Thompson Added comment: Comment on list classification: Parkinsonism is a feature of the condition
Early-onset Parkinson disease v0.302 LYST Bryony Thompson Gene: lyst has been classified as Green List (High Evidence).
Ataxia - adult onset v1.9 CHCHD10 Bryony Thompson Marked gene: CHCHD10 as ready
Ataxia - adult onset v1.9 CHCHD10 Bryony Thompson Gene: chchd10 has been classified as Red List (Low Evidence).
Ataxia - adult onset v1.9 CHCHD10 Bryony Thompson gene: CHCHD10 was added
gene: CHCHD10 was added to Ataxia - adult onset. Sources: Literature
Mode of inheritance for gene: CHCHD10 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CHCHD10 were set to 24934289
Phenotypes for gene: CHCHD10 were set to autosomal dominant mitochondrial myopathy with exercise intolerance MONDO:0014532
Review for gene: CHCHD10 was set to RED
Added comment: A single family with ataxia as a feature of the phenotype.
Sources: Literature
Early-onset Parkinson disease v0.301 EPM2A Bryony Thompson Publications for gene: EPM2A were set to PMID: 27574708
Early-onset Parkinson disease v0.300 KIF5A Bryony Thompson Phenotypes for gene: KIF5A were changed from to Spastic paraplegia 10, autosomal dominant MIM#604187
Early-onset Parkinson disease v0.299 KIF5A Bryony Thompson Publications for gene: KIF5A were set to
Early-onset Parkinson disease v0.298 KIF5A Bryony Thompson Mode of inheritance for gene: KIF5A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.297 NHLRC1 Bryony Thompson Publications for gene: NHLRC1 were set to PMID: 22425593
Mendeliome v1.1715 KIAA1024L Achchuthan Shanmugasundram gene: KIAA1024L was added
gene: KIAA1024L was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: KIAA1024L was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIAA1024L were set to 35727972
Phenotypes for gene: KIAA1024L were set to Deafness, autosomal recessive 120, OMIM:620238
Review for gene: KIAA1024L was set to GREEN
Added comment: New gene name - MINAR2

PMID:35727972 reported 13 patients from four unrelated families with non-syndromic sensorineural hearing loss. Four of these patients had prelingual onset of severe to profound, progressive bilateral hearing loss. The other nine patients had congenital onset of severe to profound bilateral hearing loss, which was not progressive on one patient, while data was not available for the other.

Three different homozygous variants (c.144G > A/ p.Trp48Ter, c.412_419delCGGTTTTG/ p.Arg138Valfs*10 and c.393G > T/ p.Lys131Asn) were identified in MINAR2/ KIAA1024L gene in these patients.

There is some functional evidence available for the p.Lys131Asn variant. In addition, mice with loss of function of the Minar2 protein present with rapidly progressive sensorineural hearing loss.

This gene has also been associated with relevant phenotype in OMIM (MIM #620238).
Sources: Literature
Pulmonary Arterial Hypertension v1.39 FLNA Zornitza Stark Marked gene: FLNA as ready
Pulmonary Arterial Hypertension v1.39 FLNA Zornitza Stark Gene: flna has been classified as Green List (High Evidence).
Pulmonary Arterial Hypertension v1.39 FLNA Zornitza Stark Classified gene: FLNA as Green List (high evidence)
Pulmonary Arterial Hypertension v1.39 FLNA Zornitza Stark Gene: flna has been classified as Green List (High Evidence).
Pulmonary Arterial Hypertension v1.38 FLNA Zornitza Stark gene: FLNA was added
gene: FLNA was added to Pulmonary Arterial Hypertension. Sources: Expert Review
Mode of inheritance for gene: FLNA 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: FLNA were set to 33143682
Phenotypes for gene: FLNA were set to congenital emphysematous lung disease due to Filamin A loss-of-function variant, MONDO:0800135; Melnick-Needles syndrome, MIM# 309350
Review for gene: FLNA was set to GREEN
Added comment: Severe PAH can be a rare feature of FLNA-related disorders.
Sources: Expert Review
Interstitial Lung Disease v1.0 FLNA Zornitza Stark edited their review of gene: FLNA: Changed phenotypes: congenital emphysematous lung disease due to Filamin A loss-of-function variant, MONDO:0800135
Motor Neurone Disease v1.10 CYLD Zornitza Stark Marked gene: CYLD as ready
Motor Neurone Disease v1.10 CYLD Zornitza Stark Gene: cyld has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1715 CYLD Zornitza Stark Classified gene: CYLD as Green List (high evidence)
Mendeliome v1.1715 CYLD Zornitza Stark Gene: cyld has been classified as Green List (High Evidence).
Mendeliome v1.1714 CYLD Zornitza Stark Classified gene: CYLD as Amber List (moderate evidence)
Mendeliome v1.1714 CYLD Zornitza Stark Gene: cyld has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1713 CYLD Zornitza Stark commented on gene: CYLD: DEFINITIVE by ClinGen for the cutaneous disorder, Brooke-Spiegler syndrome, 605041.
LIMITED for FTD/ALS -- rated as Amber due to multiple affected individuals and experimental data.
Motor Neurone Disease v1.10 CYLD Zornitza Stark Marked gene: CYLD as ready
Motor Neurone Disease v1.10 CYLD Zornitza Stark Gene: cyld has been classified as Amber List (Moderate Evidence).
Incidentalome v0.301 SS18L1 Zornitza Stark Marked gene: SS18L1 as ready
Incidentalome v0.301 SS18L1 Zornitza Stark Gene: ss18l1 has been classified as Amber List (Moderate Evidence).
Incidentalome v0.301 SS18L1 Zornitza Stark Classified gene: SS18L1 as Amber List (moderate evidence)
Incidentalome v0.301 SS18L1 Zornitza Stark Gene: ss18l1 has been classified as Amber List (Moderate Evidence).
Incidentalome v0.300 SS18L1 Zornitza Stark gene: SS18L1 was added
gene: SS18L1 was added to Incidentalome. Sources: Expert Review
Mode of inheritance for gene: SS18L1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SS18L1 were set to 25888396; 24360741; 23708140; 30976389
Phenotypes for gene: SS18L1 were set to amyotrophic lateral sclerosis (MONDO:0004976)
Review for gene: SS18L1 was set to AMBER
Added comment: ClinGen has curated as LIMITED:

There are 5 variants (one nonsense, three missense, and one in-frame del) that have been reported in 5 probands in 3 publications (PMIDs: 23708140, 24360741, 31522742) that are included in this curation, one of which was not scored due to the patient harboring a variant in another ALS-causing gene and a high minor allele frequency in population databases. ALS-associated SS18L1 variants are suggested to dysregulate neuronal function by inhibiting dendrite outgrowth and microglial activation through a dominant-negative mechanism, however there is an absence of functional data from primary tissue of SS18L1 mutation carriers. This gene-disease relationship is also supported by experimental evidence (mouse models, expression, and protein interactions; PMIDs: 30976389, 14716005, 23708140). CREST knockout (Crest +/− ) and Q394X knock-in mice generated through CRISPR/Cas9 system displayed deficits in motor coordination and partially recapitulated ALS phenotypes (PMID: 30976389). In summary, there is limited evidence to support this gene-disease relationship. Although more evidence is needed to support a causal role, no convincing evidence has emerged that contradicts the gene-disease relationship.
Sources: Expert Review
Motor Neurone Disease v1.10 SS18L1 Zornitza Stark Phenotypes for gene: SS18L1 were changed from amyotrophic lateral sclerosis to amyotrophic lateral sclerosis (MONDO:0004976)
Motor Neurone Disease v1.9 SS18L1 Zornitza Stark Classified gene: SS18L1 as Amber List (moderate evidence)
Motor Neurone Disease v1.9 SS18L1 Zornitza Stark Gene: ss18l1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1713 MARS Zornitza Stark Mode of inheritance for gene: MARS was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1712 MARS Zornitza Stark edited their review of gene: MARS: Added comment: The mono-allelic gene-disease associations have LIMITED evidence.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Neuropathy_CMT - isolated v1.47 MARS Zornitza Stark Classified gene: MARS as Red List (low evidence)
Hereditary Neuropathy_CMT - isolated v1.47 MARS Zornitza Stark Gene: mars has been classified as Red List (Low Evidence).
Hereditary Neuropathy_CMT - isolated v1.46 MED25 Zornitza Stark Tag disputed tag was added to gene: MED25.
Hereditary Neuropathy_CMT - isolated v1.46 MED25 Zornitza Stark reviewed gene: MED25: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Hereditary Neuropathy_CMT - isolated v1.46 MED25 Zornitza Stark Deleted their review
Vascular Malformations_Somatic v1.13 PIK3R1 Bryony Thompson Phenotypes for gene: PIK3R1 were changed from capillary and lymphatic malformation to capillary malformation MONDO:0016231, PIK3R1-related
Vascular Malformations_Somatic v1.12 PIK3R1 Bryony Thompson Publications for gene: PIK3R1 were set to 29174369
Vascular Malformations_Somatic v1.11 PIK3R1 Bryony Thompson Classified gene: PIK3R1 as Green List (high evidence)
Vascular Malformations_Somatic v1.11 PIK3R1 Bryony Thompson Gene: pik3r1 has been classified as Green List (High Evidence).
Vascular Malformations_Somatic v1.10 PIK3R1 Bryony Thompson edited their review of gene: PIK3R1: Added comment: Many reports now of somatic variants in individuals with capillary malformation with dilated veins. Loss of function is the expected mechanism of malformation formation.; Changed rating: GREEN; Changed publications: 29174369, 34040190, 37641480, 38431221
Mendeliome v1.1712 PMP2 Zornitza Stark Mode of pathogenicity for gene: PMP2 was changed from None to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Mendeliome v1.1711 PMP2 Zornitza Stark Classified gene: PMP2 as Amber List (moderate evidence)
Mendeliome v1.1711 PMP2 Zornitza Stark Gene: pmp2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1710 PMP2 Zornitza Stark reviewed gene: PMP2: Rating: AMBER; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: 26257172, 27009151, 30249361, 31412900, 26828946, 32277537; Phenotypes: Charcot-Marie-Tooth disease, demyelinating, type 1G, 618279; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary Neuropathy_CMT - isolated v1.46 PMP2 Zornitza Stark Mode of pathogenicity for gene: PMP2 was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Hereditary Neuropathy_CMT - isolated v1.45 PMP2 Zornitza Stark Classified gene: PMP2 as Amber List (moderate evidence)
Hereditary Neuropathy_CMT - isolated v1.45 PMP2 Zornitza Stark Gene: pmp2 has been classified as Amber List (Moderate Evidence).
Hereditary Neuropathy_CMT - isolated v1.44 PMP2 Zornitza Stark reviewed gene: PMP2: Rating: AMBER; Mode of pathogenicity: None; Publications: 26257172, 27009151, 30249361, 31412900, 26828946, 32277537; Phenotypes: Charcot-Marie-Tooth disease MONDO:0015626; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary Neuropathy_CMT - isolated v1.44 WARS Zornitza Stark Classified gene: WARS as Amber List (moderate evidence)
Hereditary Neuropathy_CMT - isolated v1.44 WARS Zornitza Stark Gene: wars has been classified as Amber List (Moderate Evidence).
Hereditary Neuropathy_CMT - isolated v1.43 WARS Zornitza Stark edited their review of gene: WARS: Added comment: ClinGen curation:

In 2017, three families, two Taiwanese and one Belgian, were shown to carry the same heterozygous His257Arg missense variant in WARS1 co-segregating with a juvenile onset distal motor neuropathy phenotype (PMID: 28369220). The authors show evidence of a dominant-negative effect of the His257Arg mutation capable of dimerizing with the wild-type protein and impairing the overall aminoacylation function. When transfected into neuronal-like cells, an effect on neurite length was also observed. Two other WARS1 missense variants have been linked with this consistent juvenile onset HMN phenotype since then (PMID: 31321409). In these two families, significant segregation or de novo inheritance was shown, but functional evidence was absent. The phenotype in all five published WARS1 families is very consistent, a juvenile onset motor neuropathy phenotype affecting both upper and lower limbs without any sensory involvement.

The panel concludes that the evidence for the pathogenicity of the His257Arg mutation is sufficient to link WARS1 to the motor neuropathy phenotype. More reports will solidify the gene-disease relationship in the future. Based on the curated evidence, we classify the gene-disease relationship of WARS1 and autosomal dominant motor neuropathy as limited, but with the advice to include it on panels.; Changed rating: AMBER
BabyScreen+ newborn screening v1.111 ELANE Zornitza Stark Mode of pathogenicity for gene: ELANE was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
BabyScreen+ newborn screening v1.110 ELANE Zornitza Stark commented on gene: ELANE: ClinGen: there is little evidence for haploinsufficiency. gnomAD pLI score is zero and there are NMD predicted variants in the population.

Entire gene deletion is not described in the context of neutropenia, including deletion of 19p terminal (encompassing ELANE) (PMID: 33968054).

Maturation arrest, the failure of the marrow myeloid progenitors to form mature neutrophils, is a consistent feature of ELANE associated congenital neutropenia. Knock-out of the mutant allele in hematopoietic stem cells derived from SCN patients restores neutrophils maturation (PMID: 3124897).
BabyScreen+ newborn screening v1.110 ELANE Zornitza Stark edited their review of gene: ELANE: Changed mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
IBMDx study v0.23 ELANE Zornitza Stark Marked gene: ELANE as ready
IBMDx study v0.23 ELANE Zornitza Stark Gene: elane has been classified as Green List (High Evidence).
IBMDx study v0.23 ELANE Zornitza Stark Publications for gene: ELANE were set to
IBMDx study v0.22 ELANE Zornitza Stark Mode of pathogenicity for gene: ELANE was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
IBMDx study v0.21 ELANE Zornitza Stark Mode of inheritance for gene: ELANE was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
IBMDx study v0.20 ELANE Zornitza Stark edited their review of gene: ELANE: Changed mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Systemic Autoinflammatory Disease_Periodic Fever v1.41 ELANE Zornitza Stark Mode of pathogenicity for gene: ELANE was changed from Other to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Systemic Autoinflammatory Disease_Periodic Fever v1.40 ELANE Zornitza Stark edited their review of gene: ELANE: Changed mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Phagocyte Defects v1.26 ELANE Zornitza Stark Mode of pathogenicity for gene: ELANE was changed from Other to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Phagocyte Defects v1.25 ELANE Zornitza Stark edited their review of gene: ELANE: Changed mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Mendeliome v1.1710 ELANE Zornitza Stark Publications for gene: ELANE were set to 19036076
Mendeliome v1.1709 ELANE Zornitza Stark Mode of pathogenicity for gene: ELANE was changed from Other to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Mendeliome v1.1708 ELANE Zornitza Stark edited their review of gene: ELANE: Changed mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Bone Marrow Failure v1.89 ELANE Zornitza Stark Mode of pathogenicity for gene: ELANE was changed from Other to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Bone Marrow Failure v1.88 ELANE Zornitza Stark edited their review of gene: ELANE: Changed mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Early-onset Parkinson disease v0.296 LRRK2 Zornitza Stark Mode of inheritance for gene: LRRK2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Regression v0.551 ABCD1 Zornitza Stark Marked gene: ABCD1 as ready
Regression v0.551 ABCD1 Zornitza Stark Gene: abcd1 has been classified as Green List (High Evidence).
Regression v0.551 ABCD1 Zornitza Stark Phenotypes for gene: ABCD1 were changed from to adrenoleukodystrophy (MONDO:0018544)
Regression v0.550 ABCD1 Zornitza Stark Publications for gene: ABCD1 were set to
Regression v0.549 ABCD1 Zornitza Stark Mode of inheritance for gene: ABCD1 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Regression v0.548 ABCD1 Zornitza Stark reviewed gene: ABCD1: Rating: GREEN; Mode of pathogenicity: None; Publications: 15811009, 8651290, 7825602, 21700483; Phenotypes: adrenoleukodystrophy (MONDO:0018544); Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Peroxisomal Disorders v0.53 ABCD1 Zornitza Stark Marked gene: ABCD1 as ready
Peroxisomal Disorders v0.53 ABCD1 Zornitza Stark Gene: abcd1 has been classified as Green List (High Evidence).
Peroxisomal Disorders v0.53 ABCD1 Zornitza Stark Publications for gene: ABCD1 were set to 15811009; 8651290; 7825602; 21700483
Peroxisomal Disorders v0.52 ABCD1 Zornitza Stark Publications for gene: ABCD1 were set to 15811009; 8651290; 7825602, 21700483
Peroxisomal Disorders v0.51 ABCD1 Zornitza Stark Publications for gene: ABCD1 were set to
Peroxisomal Disorders v0.50 ABCD1 Zornitza Stark Phenotypes for gene: ABCD1 were changed from to adrenoleukodystrophy (MONDO:0018544)
Peroxisomal Disorders v0.49 ABCD1 Zornitza Stark Mode of inheritance for gene: ABCD1 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Peroxisomal Disorders v0.48 ABCD1 Zornitza Stark Mode of inheritance for gene: ABCD1 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Fetal anomalies v1.235 CNOT1 Zornitza Stark Classified gene: CNOT1 as Amber List (moderate evidence)
Fetal anomalies v1.235 CNOT1 Zornitza Stark Gene: cnot1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.234 CNOT1 Zornitza Stark edited their review of gene: CNOT1: Added comment: LIMITED by ClinGen for holoprosencephaly 12 with or without pancreatic agenesis, MONDO:0032787

ClinGen curation: CNOT1 was originally reported in cases of holoprosencephaly and/or pancreatic agenesis/insufficiency in 2019 (PMID: 31006513, 31006510). One of the papers included 3 individuals with heterozygous p.Arg535Cys (PMID: 31006513), confirmed to be de novo in 2 individuals. One of these individuals was not scored due to a lack of documentation of holoprosencephaly. The other paper included 2 individuals with de novo p.Arg535Cys, both of whom with holoprosencephaly. A knock-in mouse model of this variant showed neurological and pancreatic abnormalities at E14.5, and this evidence was used to augment the genetic evidence. A mouse brain expression study (PMID: 31006510) was scored as functional evidence. In total, there is Limited evidence to support the gene-disease relationship between CNOT1 and holoprosencephaly with or without pancreatic agenesis. Of note, this gene has also been implicated in Vissers-Bodmer syndrome, which is characterized by global developmental delay and behavioral abnormalities apparent from infancy. As the condition is clinically distinct from holoprosencephaly and/or pancreatic agenesis/insufficiency, lacks specific structural brain anomalies, and likely has different molecular mechanisms, this will be/have been assessed separately.; Changed rating: AMBER; Changed phenotypes: Holoprosencephaly 12 with or without pancreatic agenesis MONDO:0032787
Holoprosencephaly and septo-optic dysplasia v1.16 CNOT1 Zornitza Stark Phenotypes for gene: CNOT1 were changed from Holoprosencephaly 12 with or without pancreatic agenesis MONDO:0032787 to Holoprosencephaly 12 with or without pancreatic agenesis MONDO:0032787
Holoprosencephaly and septo-optic dysplasia v1.16 CNOT1 Zornitza Stark Phenotypes for gene: CNOT1 were changed from HOLOPROSENCEPHALY 12 WITH OR WITHOUT PANCREATIC AGENESIS; HPE12; OMIM# 618500 to Holoprosencephaly 12 with or without pancreatic agenesis MONDO:0032787
Holoprosencephaly and septo-optic dysplasia v1.15 CNOT1 Zornitza Stark Classified gene: CNOT1 as Amber List (moderate evidence)
Holoprosencephaly and septo-optic dysplasia v1.15 CNOT1 Zornitza Stark Gene: cnot1 has been classified as Amber List (Moderate Evidence).
Holoprosencephaly and septo-optic dysplasia v1.14 CNOT1 Zornitza Stark edited their review of gene: CNOT1: Changed rating: AMBER
Holoprosencephaly and septo-optic dysplasia v1.14 CNOT1 Zornitza Stark edited their review of gene: CNOT1: Added comment: LIMITED by ClinGen for holoprosencephaly 12 with or without pancreatic agenesis, MONDO:0032787

ClinGen curation:
CNOT1 was originally reported in cases of holoprosencephaly and/or pancreatic agenesis/insufficiency in 2019 (PMID: 31006513, 31006510). One of the papers included 3 individuals with heterozygous p.Arg535Cys (PMID: 31006513), confirmed to be de novo in 2 individuals. One of these individuals was not scored due to a lack of documentation of holoprosencephaly. The other paper included 2 individuals with de novo p.Arg535Cys, both of whom with holoprosencephaly. A knock-in mouse model of this variant showed neurological and pancreatic abnormalities at E14.5, and this evidence was used to augment the genetic evidence. A mouse brain expression study (PMID: 31006510) was scored as functional evidence. In total, there is Limited evidence to support the gene-disease relationship between CNOT1 and holoprosencephaly with or without pancreatic agenesis. Of note, this gene has also been implicated in Vissers-Bodmer syndrome, which is characterized by global developmental delay and behavioral abnormalities apparent from infancy. As the condition is clinically distinct from holoprosencephaly and/or pancreatic agenesis/insufficiency, lacks specific structural brain anomalies, and likely has different molecular mechanisms, this will be/have been assessed separately.; Changed phenotypes: Holoprosencephaly 12 with or without pancreatic agenesis MONDO:0032787
Mendeliome v1.1708 CNOT1 Zornitza Stark commented on gene: CNOT1: DEFINITIVE by ClinGen for Neurodevelopmental disorder.
Mendeliome v1.1708 SHARPIN Zornitza Stark Marked gene: SHARPIN as ready
Mendeliome v1.1708 SHARPIN Zornitza Stark Gene: sharpin has been classified as Green List (High Evidence).
Mendeliome v1.1708 SHARPIN Zornitza Stark Classified gene: SHARPIN as Green List (high evidence)
Mendeliome v1.1708 SHARPIN Zornitza Stark Gene: sharpin has been classified as Green List (High Evidence).
Mendeliome v1.1707 SHARPIN Zornitza Stark gene: SHARPIN was added
gene: SHARPIN was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SHARPIN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SHARPIN were set to 38609546
Phenotypes for gene: SHARPIN were set to Autoinflammatory syndrome, MONDO:0019751, SHARPIN-related
Review for gene: SHARPIN was set to GREEN
Added comment: Two unrelated patients with homozygous frameshift variants presenting with: P1 - recurrent fever, parotitis, joint inflammation, colitis and chronic otitis media necessitating tympanoplasty P2 - recurrent fever episodes with lymphadenopathy and vomiting every 2–3 weeks. Extensive functional data and mouse model.
Sources: Literature
Systemic Autoinflammatory Disease_Periodic Fever v1.40 SHARPIN Zornitza Stark Marked gene: SHARPIN as ready
Systemic Autoinflammatory Disease_Periodic Fever v1.40 SHARPIN Zornitza Stark Gene: sharpin has been classified as Green List (High Evidence).
Systemic Autoinflammatory Disease_Periodic Fever v1.40 SHARPIN Zornitza Stark Phenotypes for gene: SHARPIN were changed from recurrent fever to Autoinflammatory syndrome, MONDO:0019751, SHARPIN-related
Systemic Autoinflammatory Disease_Periodic Fever v1.39 SHARPIN Zornitza Stark Classified gene: SHARPIN as Green List (high evidence)
Systemic Autoinflammatory Disease_Periodic Fever v1.39 SHARPIN Zornitza Stark Gene: sharpin has been classified as Green List (High Evidence).
Systemic Autoinflammatory Disease_Periodic Fever v1.38 SHARPIN Zornitza Stark reviewed gene: SHARPIN: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Autoinflammatory syndrome, MONDO:0019751, SHARPIN-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Neuropathy_CMT - isolated v1.43 RTN2 Zornitza Stark Marked gene: RTN2 as ready
Hereditary Neuropathy_CMT - isolated v1.43 RTN2 Zornitza Stark Gene: rtn2 has been classified as Green List (High Evidence).
Hereditary Neuropathy_CMT - isolated v1.43 RTN2 Zornitza Stark Classified gene: RTN2 as Green List (high evidence)
Hereditary Neuropathy_CMT - isolated v1.43 RTN2 Zornitza Stark Gene: rtn2 has been classified as Green List (High Evidence).
Hereditary Neuropathy_CMT - isolated v1.42 RTN2 Zornitza Stark gene: RTN2 was added
gene: RTN2 was added to Hereditary Neuropathy_CMT - isolated. Sources: Literature
Mode of inheritance for gene: RTN2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RTN2 were set to 38527963
Phenotypes for gene: RTN2 were set to distal hereditary motor neuropathy, MONDO:0018894, RTN2-related
Review for gene: RTN2 was set to GREEN
Added comment: PMID:38527963 reported the identification of seven novel or ultra-rare homozygous loss-of-function RTN2 variants in 14 individuals from seven unrelated families with distal hereditary motor neuropathy.

All affected individuals exhibited weakness in the distal upper and lower limbs, lower limb spasticity, hyperreflexia, with an onset in the first decade of life. Nerve conduction studies revealed axonal motor neuropathy with neurogenic changes in the electromyography.

Characterisation of C. elegans RTN2 homolog loss-of-function variants demonstrated morphological and behavioural differences compared to the parental strain, and treatment with an endoplasmic/sarcoplasmic reticulum Ca(2+) re-uptake inhibitor (2,5-di-tert-butylhydroquinone) rescued key phenotypic differences.
Sources: Literature
Mendeliome v1.1706 RTN2 Zornitza Stark Phenotypes for gene: RTN2 were changed from Spastic paraplegia 12, autosomal dominant, 604805; MONDO:0011489 to Spastic paraplegia 12, autosomal dominant, 604805; MONDO:0011489; distal hereditary motor neuropathy, MONDO:0018894
Mendeliome v1.1705 RTN2 Zornitza Stark Publications for gene: RTN2 were set to 22232211; 27165006
Mendeliome v1.1704 RTN2 Zornitza Stark Mode of inheritance for gene: RTN2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Systemic Autoinflammatory Disease_Periodic Fever v1.38 PTCRA Zornitza Stark Marked gene: PTCRA as ready
Systemic Autoinflammatory Disease_Periodic Fever v1.38 PTCRA Zornitza Stark Gene: ptcra has been classified as Green List (High Evidence).
Systemic Autoinflammatory Disease_Periodic Fever v1.38 PTCRA Zornitza Stark Classified gene: PTCRA as Green List (high evidence)
Systemic Autoinflammatory Disease_Periodic Fever v1.38 PTCRA Zornitza Stark Gene: ptcra has been classified as Green List (High Evidence).
Systemic Autoinflammatory Disease_Periodic Fever v1.37 PTCRA Zornitza Stark gene: PTCRA was added
gene: PTCRA was added to Systemic Autoinflammatory Disease_Periodic Fever. Sources: Literature
Mode of inheritance for gene: PTCRA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PTCRA were set to 38422122
Phenotypes for gene: PTCRA were set to Autoinflammatory syndrome, MONDO:0019751, PTCRA-related
Review for gene: PTCRA was set to GREEN
Added comment: PMID:38422122 reported the identification of 10 individuals from seven kindreds from four different ethnicities with biallelic PTCRA variants (homozygous in five kindreds and compound heterozygous in two kindreds).

Six of these 10 patients were clinically asymptomatic at their most recent evaluation, while other four patients displayed infection, lymphoproliferation, and/or autoimmunity with an onset during their teens or in adulthood. One of these patients died from SARS-CoV-2 pneumonia at the age of 24 years. Patient 9 had a small thymus on MRI at the age of 2 years, whereas P5 and P6 had no visible thymus at the ages of 13 and 8 years, respectively. Three of the nine patients with pLOF PTCRA variants tested were found to produce autoantibodies, several of which were associated with clinical manifestations. Anti-thyroid autoantibodies and/or clinically overt thyroiditis were found in three of the nine patients. P7, who suffered from recurrent herpes infections, had autoantibodies against type I interferons.

Two of those identified variants are hypomorphic and are associated with autoimmunity. In addition, there is extensive functional and epidemiological data available.
Sources: Literature
Mendeliome v1.1703 PTCRA Zornitza Stark Marked gene: PTCRA as ready
Mendeliome v1.1703 PTCRA Zornitza Stark Gene: ptcra has been classified as Green List (High Evidence).
Mendeliome v1.1703 PTCRA Zornitza Stark Phenotypes for gene: PTCRA were changed from Autoimmunity, HP:0002960; lymphopenia, MONDO:0003783 to Autoinflammatory syndrome, MONDO:0019751, PTCRA-related
Mendeliome v1.1702 PTCRA Zornitza Stark Classified gene: PTCRA as Green List (high evidence)
Mendeliome v1.1702 PTCRA Zornitza Stark Gene: ptcra has been classified as Green List (High Evidence).
Mendeliome v1.1701 PTCRA Zornitza Stark reviewed gene: PTCRA: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Autoinflammatory syndrome, MONDO:0019751, PTCRA-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.136 SLC37A3 Zornitza Stark Marked gene: SLC37A3 as ready
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.136 SLC37A3 Zornitza Stark Gene: slc37a3 has been classified as Green List (High Evidence).
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.136 SLC37A3 Zornitza Stark Classified gene: SLC37A3 as Green List (high evidence)
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.136 SLC37A3 Zornitza Stark Gene: slc37a3 has been classified as Green List (High Evidence).
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.135 SLC37A3 Zornitza Stark gene: SLC37A3 was added
gene: SLC37A3 was added to Retinitis pigmentosa_Autosomal Recessive/X-linked. Sources: Literature
Mode of inheritance for gene: SLC37A3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC37A3 were set to 28041643; 35486108
Phenotypes for gene: SLC37A3 were set to Retinitis pigmentosa, MONDO:0019200, SLC37A3-related
Review for gene: SLC37A3 was set to GREEN
Added comment: Three unrelated cases reported with biallelic variants in SLC37A3 gene (One case in PMID:28041643 and two cases in PMID:35486108) and with autosomal recessive retinitis pigmentosa.
Sources: Literature
Mendeliome v1.1701 SLC37A3 Zornitza Stark Marked gene: SLC37A3 as ready
Mendeliome v1.1701 SLC37A3 Zornitza Stark Gene: slc37a3 has been classified as Green List (High Evidence).
Mendeliome v1.1701 SLC37A3 Zornitza Stark Classified gene: SLC37A3 as Green List (high evidence)
Mendeliome v1.1701 SLC37A3 Zornitza Stark Gene: slc37a3 has been classified as Green List (High Evidence).
Mendeliome v1.1700 CADM3 Zornitza Stark Publications for gene: CADM3 were set to PMID: 33889941
Mendeliome v1.1699 CADM3 Zornitza Stark Classified gene: CADM3 as Green List (high evidence)
Mendeliome v1.1699 CADM3 Zornitza Stark Gene: cadm3 has been classified as Green List (High Evidence).
Mendeliome v1.1698 CADM3 Zornitza Stark edited their review of gene: CADM3: Added comment: Two additional families reported with a different variant, de novo in one family.; Changed rating: GREEN; Changed publications: 38074074
Hereditary Neuropathy_CMT - isolated v1.41 CADM3 Zornitza Stark Publications for gene: CADM3 were set to PMID: 33889941
Hereditary Neuropathy_CMT - isolated v1.40 CADM3 Zornitza Stark Classified gene: CADM3 as Green List (high evidence)
Hereditary Neuropathy_CMT - isolated v1.40 CADM3 Zornitza Stark Gene: cadm3 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2599 CLCN2 Zornitza Stark Tag disputed was removed from gene: CLCN2.
Tag refuted tag was added to gene: CLCN2.
Mendeliome v1.1698 EMILIN1 Chern Lim reviewed gene: EMILIN1: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Neuronopathy, distal hereditary motor, autosomal dominant 10, MIM#620080, Aortic aneurysm, MONDO:0005160, EMILIN1-related, AR.; Mode of inheritance: None
Aortopathy_Connective Tissue Disorders v1.84 EMILIN1 Chern Lim reviewed gene: EMILIN1: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Neuronopathy, distal hereditary motor, autosomal dominant 10, MIM#620080, Aortic aneurysm, MONDO:0005160, EMILIN1-related, AR.; Mode of inheritance: None
Genetic Epilepsy v0.2599 CLCN2 Sangavi Sivagnanasundram reviewed gene: CLCN2: Rating: RED; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:004463; Phenotypes: epilepsy (MONDO:0005027); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Severe early-onset obesity v1.10 ACBD6 Zornitza Stark Phenotypes for gene: ACBD6 were changed from Neurodevelopmental disorder (MONDO#0700092), ACBD6-related to Neurodevelopmental disorder with progressive movement abnormalities, MIM# 620785
Severe early-onset obesity v1.9 ACBD6 Zornitza Stark reviewed gene: ACBD6: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with progressive movement abnormalities, MIM# 620785; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Dystonia - complex v0.235 ACBD6 Zornitza Stark Phenotypes for gene: ACBD6 were changed from Neurodevelopmental disorder (MONDO#0700092), ACBD6-related to Neurodevelopmental disorder with progressive movement abnormalities, MIM# 620785
Dystonia - complex v0.234 ACBD6 Zornitza Stark reviewed gene: ACBD6: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with progressive movement abnormalities, MIM# 620785; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia - paediatric v1.19 ACBD6 Zornitza Stark Phenotypes for gene: ACBD6 were changed from Neurodevelopmental disorder (MONDO#0700092), ACBD6-related to Neurodevelopmental disorder with progressive movement abnormalities, MIM# 620785
Ataxia - paediatric v1.18 ACBD6 Zornitza Stark reviewed gene: ACBD6: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with progressive movement abnormalities, MIM# 620785; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5779 ACBD6 Zornitza Stark Phenotypes for gene: ACBD6 were changed from Neurodevelopmental disorder (MONDO#0700092), ACBD6-related to Neurodevelopmental disorder with progressive movement abnormalities, MIM# 620785
Intellectual disability syndromic and non-syndromic v0.5778 ACBD6 Zornitza Stark reviewed gene: ACBD6: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with progressive movement abnormalities, MIM# 620785; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1698 ACBD6 Zornitza Stark Phenotypes for gene: ACBD6 were changed from Neurodevelopmental disorder (MONDO#0700092), ACBD6-related to Neurodevelopmental disorder with progressive movement abnormalities, MIM# 620785
Mendeliome v1.1697 ACBD6 Zornitza Stark reviewed gene: ACBD6: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with progressive movement abnormalities, MIM# 620785; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Neuropathy_CMT - isolated v1.39 CADM3 Achchuthan Shanmugasundram reviewed gene: CADM3: Rating: GREEN; Mode of pathogenicity: None; Publications: 38074074; Phenotypes: Charcot-Marie-Tooth disease, axonal, type 2FF, OMIM:619519; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Angelman Rett like syndromes v1.10 IQSEC2 Ain Roesley Phenotypes for gene: IQSEC2 were changed from Mental retardation, X-linked 1/78, MIM# 309530, MONDO:0010656; Severe intellectual disability-progressive postnatal microcephaly- midline stereotypic hand movements syndrome MONDO:0018347 to Intellectual developmental disorder, X-linked 1 MIM#309530, MONDO:0010656; Severe intellectual disability-progressive postnatal microcephaly- midline stereotypic hand movements syndrome MONDO:0018347
Intellectual disability syndromic and non-syndromic v0.5778 IQSEC2 Ain Roesley Phenotypes for gene: IQSEC2 were changed from Intellectual developmental disorder, X-linked 1 MIM#309530, MONDO:0010656; Severe intellectual disability-progressive postnatal microcephaly- midline stereotypic hand movements syndrome MONDO:0018347 to Intellectual developmental disorder, X-linked 1 MIM#309530, MONDO:0010656; Severe intellectual disability-progressive postnatal microcephaly- midline stereotypic hand movements syndrome MONDO:0018347
Intellectual disability syndromic and non-syndromic v0.5778 IQSEC2 Ain Roesley Phenotypes for gene: IQSEC2 were changed from Mental retardation, X-linked 1/78, MIM# 309530, MONDO:0010656; Severe intellectual disability-progressive postnatal microcephaly- midline stereotypic hand movements syndrome MONDO:0018347 to Intellectual developmental disorder, X-linked 1 MIM#309530, MONDO:0010656; Severe intellectual disability-progressive postnatal microcephaly- midline stereotypic hand movements syndrome MONDO:0018347
Genetic Epilepsy v0.2599 IQSEC2 Ain Roesley Phenotypes for gene: IQSEC2 were changed from Mental retardation, X-linked 1/78, MIM# 309530, MONDO:0010656; Severe intellectual disability-progressive postnatal microcephaly- midline stereotypic hand movements syndrome MONDO:0018347 to Intellectual developmental disorder, X-linked 1 MIM#309530, MONDO:0010656; Severe intellectual disability-progressive postnatal microcephaly- midline stereotypic hand movements syndrome MONDO:0018347
Autism v0.198 IQSEC2 Ain Roesley Phenotypes for gene: IQSEC2 were changed from Intellectual developmental disorder, X-linked 1 MIM#309530, MONDO:0010656; Severe intellectual disability-progressive postnatal microcephaly- midline stereotypic hand movements syndrome MONDO:0018347 to Intellectual developmental disorder, X-linked 1 MIM#309530, MONDO:0010656; Severe intellectual disability-progressive postnatal microcephaly- midline stereotypic hand movements syndrome MONDO:0018347
Autism v0.198 IQSEC2 Ain Roesley Phenotypes for gene: IQSEC2 were changed from Mental retardation, X-linked 1/78, MIM# 309530, MONDO:0010656; Severe intellectual disability-progressive postnatal microcephaly- midline stereotypic hand movements syndrome MONDO:0018347 to Intellectual developmental disorder, X-linked 1 MIM#309530, MONDO:0010656; Severe intellectual disability-progressive postnatal microcephaly- midline stereotypic hand movements syndrome MONDO:0018347
Mendeliome v1.1697 IQSEC2 Ain Roesley Phenotypes for gene: IQSEC2 were changed from Mental retardation, X-linked 1/78, MIM# 309530, MONDO:0010656; Severe intellectual disability-progressive postnatal microcephaly- midline stereotypic hand movements syndrome MONDO:0018347 to Intellectual developmental disorder, X-linked 1 MIM#309530, MONDO:0010656; Severe intellectual disability-progressive postnatal microcephaly- midline stereotypic hand movements syndrome MONDO:0018347
Mendeliome v1.1696 SLC37A3 Achchuthan Shanmugasundram gene: SLC37A3 was added
gene: SLC37A3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SLC37A3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC37A3 were set to 28041643; 35486108
Phenotypes for gene: SLC37A3 were set to retinitis pigmentosa, MONDO:0019200
Review for gene: SLC37A3 was set to GREEN
Added comment: Three unrelated cases reported with biallelic variants in SLC37A3 gene (One case in PMID:28041643 and two cases in PMID:35486108) and with autosomal recessive retinitis pigmentosa.
Sources: Literature
Mendeliome v1.1696 PTCRA Achchuthan Shanmugasundram gene: PTCRA was added
gene: PTCRA was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PTCRA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PTCRA were set to 38422122
Phenotypes for gene: PTCRA were set to Autoimmunity, HP:0002960; lymphopenia, MONDO:0003783
Review for gene: PTCRA was set to GREEN
Added comment: PMID:38422122 reported the identification of 10 individuals from seven kindreds from four different ethnicities with biallelic PTCRA variants (homozygous in five kindreds and compound heterozygous in two kindreds).

Six of these 10 patients were clinically asymptomatic at their most recent evaluation, while other four patients displayed infection, lymphoproliferation, and/or autoimmunity with an onset during their teens or in adulthood. One of these patients died from SARS-CoV-2 pneumonia at the age of 24 years. Patient 9 had a small thymus on MRI at the age of 2 years, whereas P5 and P6 had no visible thymus at the ages of 13 and 8 years, respectively. Three of the nine patients with pLOF PTCRA variants tested were found to produce autoantibodies, several of which were associated with clinical manifestations. Anti-thyroid autoantibodies and/or clinically overt thyroiditis were found in three of the nine patients. P7, who suffered from recurrent herpes infections, had autoantibodies against type I interferons.

Two of those identified variants are hypomorphic and are associated with autoimmunity. In addition, there is extensive functional and epidemiological data available.
Sources: Literature
Regression v0.548 NAA60 Zornitza Stark Phenotypes for gene: NAA60 were changed from Basal ganglia calcification, MONDO:0008947, NAA60-related to Basal ganglia calcification, idiopathic, 9, autosomal recessive, MIM# 620786
Regression v0.547 NAA60 Zornitza Stark edited their review of gene: NAA60: Changed phenotypes: Basal ganglia calcification, idiopathic, 9, autosomal recessive, MIM# 620786
Mendeliome v1.1696 NAA60 Zornitza Stark Phenotypes for gene: NAA60 were changed from Basal ganglia calcification, MONDO:0008947, NAA60-related to Basal ganglia calcification, idiopathic, 9, autosomal recessive, MIM# 620786
Mendeliome v1.1695 NAA60 Zornitza Stark reviewed gene: NAA60: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Basal ganglia calcification, idiopathic, 9, autosomal recessive, MIM# 620786; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Brain Calcification v1.95 NAA60 Zornitza Stark Phenotypes for gene: NAA60 were changed from Basal ganglia calcification, MONDO:0008947, NAA60-related to Basal ganglia calcification, idiopathic, 9, autosomal recessive, MIM# 620786
Brain Calcification v1.94 NAA60 Zornitza Stark reviewed gene: NAA60: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Basal ganglia calcification, idiopathic, 9, autosomal recessive, MIM# 620786; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1695 RTN2 Achchuthan Shanmugasundram changed review comment from: PMID:38527963 reported the identification of seven novel or ultra-rare homozygous loss-of-function RTN2 variants in 14 individuals from seven unrelated families with distal hereditary motor neuropathy.

All affected individuals exhibited weakness in the distal upper and lower limbs, lower limb spasticity, hyperreflexia, with an onset in the first decade of life. Nerve conduction studies revealed axonal motor neuropathy with neurogenic changes in the electromyography.

Characterisation of C. elegans RTN2 homolog loss-of-function variants demonstrated morphological and behavioural differences compared to the parental strain and treatment with an endoplasmic/sarcoplasmic reticulum Ca(2+) re-uptake inhibitor (2,5-di-tert-butylhydroquinone) rescued key phenotypic differences.

Biallelic variants in RTN2 gene have not yet been associated with any phenotypes in OMIM or Gene2Phenotype, while monoallelic variants have been associated with spastic paraplegia (MIM #604805) in OMIM.; to: PMID:38527963 reported the identification of seven novel or ultra-rare homozygous loss-of-function RTN2 variants in 14 individuals from seven unrelated families with distal hereditary motor neuropathy.

All affected individuals exhibited weakness in the distal upper and lower limbs, lower limb spasticity, hyperreflexia, with an onset in the first decade of life. Nerve conduction studies revealed axonal motor neuropathy with neurogenic changes in the electromyography.

Characterisation of C. elegans RTN2 homolog loss-of-function variants demonstrated morphological and behavioural differences compared to the parental strain, and treatment with an endoplasmic/sarcoplasmic reticulum Ca(2+) re-uptake inhibitor (2,5-di-tert-butylhydroquinone) rescued key phenotypic differences.

Biallelic variants in RTN2 gene have not yet been associated with any phenotypes in OMIM or Gene2Phenotype, while monoallelic variants have been associated with spastic paraplegia (MIM #604805) in OMIM.
Mendeliome v1.1695 RTN2 Achchuthan Shanmugasundram changed review comment from: PMID:38527963 reported the identification of seven novel or ultra-rare homozygous loss-of-function RTN2 variants in 14 individuals from seven unrelated families with distal hereditary motor neuropathy.

All affected individuals (seven males and seven females, aged 9-50 years) exhibited weakness in the distal upper and lower limbs, lower limb spasticity, hyperreflexia, with an onset in the first decade of life. Nerve conduction studies revealed axonal motor neuropathy with neurogenic changes in the electromyography.

Characterisation of C. elegans RTN2 homolog loss-of-function variants demonstrated morphological and behavioural differences compared to the parental strain and treatment with an endoplasmic/sarcoplasmic reticulum Ca(2+) re-uptake inhibitor (2,5-di-tert-butylhydroquinone) rescued key phenotypic differences.

Biallelic variants in RTN2 gene have not yet been associated with any phenotypes in OMIM or Gene2Phenotype, while monoallelic variants have been associated with spastic paraplegia (MIM #604805) in OMIM.; to: PMID:38527963 reported the identification of seven novel or ultra-rare homozygous loss-of-function RTN2 variants in 14 individuals from seven unrelated families with distal hereditary motor neuropathy.

All affected individuals exhibited weakness in the distal upper and lower limbs, lower limb spasticity, hyperreflexia, with an onset in the first decade of life. Nerve conduction studies revealed axonal motor neuropathy with neurogenic changes in the electromyography.

Characterisation of C. elegans RTN2 homolog loss-of-function variants demonstrated morphological and behavioural differences compared to the parental strain and treatment with an endoplasmic/sarcoplasmic reticulum Ca(2+) re-uptake inhibitor (2,5-di-tert-butylhydroquinone) rescued key phenotypic differences.

Biallelic variants in RTN2 gene have not yet been associated with any phenotypes in OMIM or Gene2Phenotype, while monoallelic variants have been associated with spastic paraplegia (MIM #604805) in OMIM.
Mendeliome v1.1695 RTN2 Achchuthan Shanmugasundram reviewed gene: RTN2: Rating: GREEN; Mode of pathogenicity: None; Publications: 38527963; Phenotypes: distal hereditary motor neuropathy, MONDO:0018894; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2598 PEX19 Zornitza Stark Marked gene: PEX19 as ready
Genetic Epilepsy v0.2598 PEX19 Zornitza Stark Gene: pex19 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2598 PEX19 Zornitza Stark Phenotypes for gene: PEX19 were changed from to Peroxisome biogenesis disorder 12A (Zellweger) - MIM#614886
Genetic Epilepsy v0.2597 PEX19 Zornitza Stark Publications for gene: PEX19 were set to
Genetic Epilepsy v0.2596 PEX19 Zornitza Stark Mode of inheritance for gene: PEX19 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2595 PEX19 Zornitza Stark reviewed gene: PEX19: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Peroxisome biogenesis disorder 12A (Zellweger) - MIM#614886; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2595 PEX12 Zornitza Stark Marked gene: PEX12 as ready
Genetic Epilepsy v0.2595 PEX12 Zornitza Stark Gene: pex12 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2595 PEX12 Zornitza Stark Phenotypes for gene: PEX12 were changed from to Peroxisome biogenesis disorder 3A (Zellweger) - MIM#614859; Peroxisome biogenesis disorder 3B - MIM#266510
Genetic Epilepsy v0.2594 PEX12 Zornitza Stark Mode of inheritance for gene: PEX12 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2593 PEX12 Zornitza Stark reviewed gene: PEX12: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Peroxisome biogenesis disorder 3A (Zellweger) - MIM#614859, Peroxisome biogenesis disorder 3B - MIM#266510; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2593 PEX1 Zornitza Stark Marked gene: PEX1 as ready
Genetic Epilepsy v0.2593 PEX1 Zornitza Stark Gene: pex1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2593 PEX1 Zornitza Stark Phenotypes for gene: PEX1 were changed from to Peroxisome biogenesis disorder 1A (Zellweger) 214100
Genetic Epilepsy v0.2592 PEX1 Zornitza Stark Publications for gene: PEX1 were set to
Genetic Epilepsy v0.2591 PEX1 Zornitza Stark Mode of inheritance for gene: PEX1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2590 PEX1 Zornitza Stark reviewed gene: PEX1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Peroxisome biogenesis disorder 1A (Zellweger) 214100; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2590 PDHX Zornitza Stark Marked gene: PDHX as ready
Genetic Epilepsy v0.2590 PDHX Zornitza Stark Gene: pdhx has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2590 PDHX Zornitza Stark Phenotypes for gene: PDHX were changed from to Lactic acidaemia due to PDX1 deficiency MIM#245349
Genetic Epilepsy v0.2589 PDHX Zornitza Stark Publications for gene: PDHX were set to
Genetic Epilepsy v0.2588 PDHX Zornitza Stark Mode of inheritance for gene: PDHX was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2587 PDHX Zornitza Stark reviewed gene: PDHX: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Lactic acidaemia due to PDX1 deficiency MIM#245349; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2587 PDHA1 Zornitza Stark Marked gene: PDHA1 as ready
Genetic Epilepsy v0.2587 PDHA1 Zornitza Stark Gene: pdha1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2587 PDHA1 Zornitza Stark Phenotypes for gene: PDHA1 were changed from to Pyruvate dehydrogenase E1-alpha deficiency - MIM#312170
Genetic Epilepsy v0.2586 PDHA1 Zornitza Stark Publications for gene: PDHA1 were set to
Genetic Epilepsy v0.2585 PDHA1 Zornitza Stark Mode of inheritance for gene: PDHA1 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 v0.2584 PDHA1 Zornitza Stark reviewed gene: PDHA1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Pyruvate dehydrogenase E1-alpha deficiency - MIM#312170; 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 v0.2584 PCDH12 Zornitza Stark Marked gene: PCDH12 as ready
Genetic Epilepsy v0.2584 PCDH12 Zornitza Stark Gene: pcdh12 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2584 PCDH12 Zornitza Stark Phenotypes for gene: PCDH12 were changed from to Diencephalic-mesencephalic junction dysplasia syndrome 1, MIM# 251280
Genetic Epilepsy v0.2583 PCDH12 Zornitza Stark Publications for gene: PCDH12 were set to
Genetic Epilepsy v0.2582 PCDH12 Zornitza Stark Mode of inheritance for gene: PCDH12 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2581 PCCB Zornitza Stark Marked gene: PCCB as ready
Genetic Epilepsy v0.2581 PCCB Zornitza Stark Gene: pccb has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2581 PCCB Zornitza Stark Phenotypes for gene: PCCB were changed from to Propionicacidemia - MIM#606054
Genetic Epilepsy v0.2580 PCCB Zornitza Stark Publications for gene: PCCB were set to
Genetic Epilepsy v0.2579 PCCB Zornitza Stark Mode of inheritance for gene: PCCB was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2578 PCCB Zornitza Stark reviewed gene: PCCB: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Propionicacidemia - MIM#606054; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2578 PCCA Zornitza Stark Marked gene: PCCA as ready
Genetic Epilepsy v0.2578 PCCA Zornitza Stark Gene: pcca has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2578 PCCA Zornitza Stark Phenotypes for gene: PCCA were changed from to Propionicacidemia - MIM#606054
Genetic Epilepsy v0.2577 PCCA Zornitza Stark Publications for gene: PCCA were set to
Genetic Epilepsy v0.2576 PCCA Zornitza Stark Mode of inheritance for gene: PCCA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2575 PCCA Zornitza Stark reviewed gene: PCCA: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Propionicacidemia - MIM#606054; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2575 OTUD6B Zornitza Stark Marked gene: OTUD6B as ready
Genetic Epilepsy v0.2575 OTUD6B Zornitza Stark Gene: otud6b has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2575 OTUD6B Zornitza Stark Phenotypes for gene: OTUD6B were changed from to Intellectual developmental disorder with dysmorphic facies, seizures, and distal limb anomalies, OMIM #617452
Genetic Epilepsy v0.2574 OTUD6B Zornitza Stark Publications for gene: OTUD6B were set to
Genetic Epilepsy v0.2573 OTUD6B Zornitza Stark Mode of inheritance for gene: OTUD6B was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2572 OPHN1 Zornitza Stark Marked gene: OPHN1 as ready
Genetic Epilepsy v0.2572 OPHN1 Zornitza Stark Gene: ophn1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2572 OPHN1 Zornitza Stark Phenotypes for gene: OPHN1 were changed from to Mental retardation, X-linked, with cerebellar hypoplasia and distinctive facial appearance, MIM#300486
Genetic Epilepsy v0.2571 OPHN1 Zornitza Stark Publications for gene: OPHN1 were set to
Genetic Epilepsy v0.2570 OPHN1 Zornitza Stark Mode of inheritance for gene: OPHN1 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Genetic Epilepsy v0.2569 OPHN1 Zornitza Stark changed review comment from: OPHN1 variants cause cerebellar hypoplasia and distinctive facial appearance, macrocephaly is a feature. At least 8 families reported.; to: OPHN1 variants cause cerebellar hypoplasia and distinctive facial appearance, macrocephaly is a feature. At least 8 families reported.

Seizures are a feature.
Genetic Epilepsy v0.2569 OCLN Zornitza Stark Marked gene: OCLN as ready
Genetic Epilepsy v0.2569 OCLN Zornitza Stark Gene: ocln has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2569 OCLN Zornitza Stark Phenotypes for gene: OCLN were changed from to Pseudo-TORCH syndrome 1, MIM#251290
Genetic Epilepsy v0.2568 OCLN Zornitza Stark Publications for gene: OCLN were set to
Genetic Epilepsy v0.2567 OCLN Zornitza Stark Mode of inheritance for gene: OCLN was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2566 NSD1 Zornitza Stark Marked gene: NSD1 as ready
Genetic Epilepsy v0.2566 NSD1 Zornitza Stark Gene: nsd1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2566 NSD1 Zornitza Stark Phenotypes for gene: NSD1 were changed from to Sotos syndrome 1 (MIM#117550), AD
Genetic Epilepsy v0.2565 NSD1 Zornitza Stark Publications for gene: NSD1 were set to
Genetic Epilepsy v0.2564 NSD1 Zornitza Stark Mode of inheritance for gene: NSD1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2563 NSD1 Zornitza Stark reviewed gene: NSD1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Sotos syndrome 1 (MIM#117550), AD; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2563 NGLY1 Zornitza Stark Marked gene: NGLY1 as ready
Genetic Epilepsy v0.2563 NGLY1 Zornitza Stark Gene: ngly1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2563 NGLY1 Zornitza Stark Phenotypes for gene: NGLY1 were changed from to Congenital disorder of deglycosylation, MIM# 615273
Genetic Epilepsy v0.2562 NGLY1 Zornitza Stark Publications for gene: NGLY1 were set to
Genetic Epilepsy v0.2561 NGLY1 Zornitza Stark Mode of inheritance for gene: NGLY1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2560 NDUFV1 Zornitza Stark Marked gene: NDUFV1 as ready
Genetic Epilepsy v0.2560 NDUFV1 Zornitza Stark Gene: ndufv1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2560 NDUFV1 Zornitza Stark Phenotypes for gene: NDUFV1 were changed from to Mitochondrial complex I deficiency, nuclear type 4 MIM#618225
Genetic Epilepsy v0.2559 NDUFV1 Zornitza Stark Publications for gene: NDUFV1 were set to
Genetic Epilepsy v0.2558 NDUFV1 Zornitza Stark Mode of inheritance for gene: NDUFV1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2557 NDUFV1 Zornitza Stark reviewed gene: NDUFV1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Mitochondrial complex I deficiency, nuclear type 4 MIM#618225; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2557 NDUFS8 Zornitza Stark Marked gene: NDUFS8 as ready
Genetic Epilepsy v0.2557 NDUFS8 Zornitza Stark Gene: ndufs8 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2557 NDUFS8 Zornitza Stark Phenotypes for gene: NDUFS8 were changed from to Mitochondrial complex I deficiency, nuclear type 2 MIM#618222
Genetic Epilepsy v0.2556 NDUFS8 Zornitza Stark Publications for gene: NDUFS8 were set to
Genetic Epilepsy v0.2555 NDUFS8 Zornitza Stark Mode of inheritance for gene: NDUFS8 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2554 NDUFS8 Zornitza Stark reviewed gene: NDUFS8: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Mitochondrial complex I deficiency, nuclear type 2 MIM#618222; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2554 NDUFS4 Zornitza Stark Marked gene: NDUFS4 as ready
Genetic Epilepsy v0.2554 NDUFS4 Zornitza Stark Gene: ndufs4 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2554 NDUFS4 Zornitza Stark Phenotypes for gene: NDUFS4 were changed from to Mitochondrial complex I deficiency, nuclear type 1 - MIM#252010
Genetic Epilepsy v0.2553 NDUFS4 Zornitza Stark Publications for gene: NDUFS4 were set to
Genetic Epilepsy v0.2552 NDUFS4 Zornitza Stark Mode of inheritance for gene: NDUFS4 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2551 NDUFS4 Zornitza Stark Mode of inheritance for gene: NDUFS4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5777 SOX2 Zornitza Stark Marked gene: SOX2 as ready
Intellectual disability syndromic and non-syndromic v0.5777 SOX2 Zornitza Stark Gene: sox2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5777 STRA6 Zornitza Stark Marked gene: STRA6 as ready
Intellectual disability syndromic and non-syndromic v0.5777 STRA6 Zornitza Stark Gene: stra6 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5777 STRA6 Zornitza Stark Phenotypes for gene: STRA6 were changed from to Matthew-Wood syndrome MONDO:0011010
Intellectual disability syndromic and non-syndromic v0.5776 STRA6 Zornitza Stark Publications for gene: STRA6 were set to
Intellectual disability syndromic and non-syndromic v0.5775 STRA6 Zornitza Stark Mode of inheritance for gene: STRA6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5774 UFC1 Zornitza Stark Marked gene: UFC1 as ready
Intellectual disability syndromic and non-syndromic v0.5774 UFC1 Zornitza Stark Gene: ufc1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5774 WARS2 Zornitza Stark Marked gene: WARS2 as ready
Intellectual disability syndromic and non-syndromic v0.5774 WARS2 Zornitza Stark Gene: wars2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5774 WDPCP Zornitza Stark Marked gene: WDPCP as ready
Intellectual disability syndromic and non-syndromic v0.5774 WDPCP Zornitza Stark Gene: wdpcp has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5774 WDPCP Zornitza Stark Phenotypes for gene: WDPCP were changed from to Bardet-Biedl syndrome 15, MIM# 615992; OFD; Congenital heart defects, hamartomas of tongue, and polysyndactyly, 217085
Intellectual disability syndromic and non-syndromic v0.5773 ZIC1 Zornitza Stark Marked gene: ZIC1 as ready
Intellectual disability syndromic and non-syndromic v0.5773 ZIC1 Zornitza Stark Gene: zic1 has been classified as Green List (High Evidence).
Mendeliome v1.1695 FAM58A Zornitza Stark Mode of inheritance for gene: FAM58A was changed from Other to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Mendeliome v1.1694 FAM58A Zornitza Stark reviewed gene: FAM58A: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Mendeliome v1.1694 TUBA8 Sangavi Sivagnanasundram reviewed gene: TUBA8: Rating: RED; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:006476; Phenotypes: polymicrogyria with optic nerve hypoplasia (MONDO:0013172); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1694 KIF1BP Sangavi Sivagnanasundram reviewed gene: KIF1BP: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Systemic Autoinflammatory Disease_Periodic Fever v1.36 SHARPIN Peter McNaughton gene: SHARPIN was added
gene: SHARPIN was added to Systemic Autoinflammatory Disease_Periodic Fever. Sources: Literature
Mode of inheritance for gene: SHARPIN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SHARPIN were set to PMID: 38609546
Phenotypes for gene: SHARPIN were set to recurrent fever
Review for gene: SHARPIN was set to GREEN
Added comment: Two unrelated patients with homozygous frameshift variants presenting with:
P1 - recurrent fever, parotitis, joint inflammation, colitis and chronic otitis media necessitating tympanoplasty
P2 - recurrent fever episodes with lymphadenopathy and vomiting every 2–3 weeks.

Extensive functional data and mouse model.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5773 SNF8 Zornitza Stark Phenotypes for gene: SNF8 were changed from Developmental and epileptic encephalopathy 115, MIM#620783 to Developmental and epileptic encephalopathy 115, MIM#620783; Neurodevelopmental disorder plus optic atrophy, MIM# 620784
Intellectual disability syndromic and non-syndromic v0.5772 SNF8 Zornitza Stark commented on gene: SNF8: Four individuals from 3 families with NDD plus OA, rather than DEE.
Intellectual disability syndromic and non-syndromic v0.5772 SNF8 Zornitza Stark edited their review of gene: SNF8: Changed phenotypes: Developmental and epileptic encephalopathy 115, MIM#620783, Neurodevelopmental disorder plus optic atrophy, MIM# 620784
Optic Atrophy v1.32 SNF8 Zornitza Stark Phenotypes for gene: SNF8 were changed from Developmental and epileptic encephalopathy 115, MIM#620783 to Neurodevelopmental disorder plus optic atrophy, MIM# 620784
Optic Atrophy v1.31 SNF8 Zornitza Stark edited their review of gene: SNF8: Changed phenotypes: Neurodevelopmental disorder plus optic atrophy, MIM# 620784
Mendeliome v1.1694 SNF8 Zornitza Stark Phenotypes for gene: SNF8 were changed from Developmental and epileptic encephalopathy 115, MIM#620783 to Developmental and epileptic encephalopathy 115, MIM#620783; Neurodevelopmental disorder plus optic atrophy, MIM# 620784
Mendeliome v1.1693 SNF8 Zornitza Stark edited their review of gene: SNF8: Added comment: Four individuals from 3 families with NDD plus OA, rather than DEE.; Changed phenotypes: Developmental and epileptic encephalopathy 115, MIM#620783, Neurodevelopmental disorder plus optic atrophy, MIM# 620784
Intellectual disability syndromic and non-syndromic v0.5772 NSUN6 Zornitza Stark Phenotypes for gene: NSUN6 were changed from neurodevelopmental disorder MONDO:0700092, NSUN6-related to Intellectual developmental disorder, autosomal recessive 82, MIM# 620779
Intellectual disability syndromic and non-syndromic v0.5771 NSUN6 Zornitza Stark reviewed gene: NSUN6: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Intellectual developmental disorder, autosomal recessive 82, MIM# 620779; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1693 NSUN6 Zornitza Stark Phenotypes for gene: NSUN6 were changed from neurodevelopmental disorder MONDO:0700092, NSUN6-related to Intellectual developmental disorder, autosomal recessive 82, MIM# 620779
Mendeliome v1.1692 NSUN6 Zornitza Stark reviewed gene: NSUN6: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Intellectual developmental disorder, autosomal recessive 82, MIM# 620779; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1692 CANVAS_ACAGG Bryony Thompson Classified STR: CANVAS_ACAGG as Green List (high evidence)
Mendeliome v1.1692 CANVAS_ACAGG Bryony Thompson Str: canvas_acagg has been classified as Green List (High Evidence).
Mendeliome v1.1691 CANVAS_ACAGG Bryony Thompson edited their review of STR: CANVAS_ACAGG: Added comment: Additional 4 unrelated cases homozygous for the (ACAGG)exp and one compound het with AAGGG/ACAGG expansion in a Japanese neuropathy cohort.; Changed rating: GREEN; Changed publications: 33103729, 36061987; Changed phenotypes: cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome MONDO:0044720; Set clinically relevant: yes
Intellectual disability syndromic and non-syndromic v0.5771 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 with language impairment, autism, and attention deficit-hyperactivity disorder, MIM# 620782; Neurodegeneration, childhood-onset, with cerebellar ataxia and cognitive decline, MIM# 620636
Genetic Epilepsy v0.2550 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 with language impairment, autism, and attention deficit-hyperactivity disorder, MIM# 620782; Neurodegeneration, childhood-onset, with cerebellar ataxia and cognitive decline, MIM# 620636
Mendeliome v1.1691 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 with language impairment, autism, and attention deficit-hyperactivity disorder, MIM# 620782; Neurodegeneration, childhood-onset, with cerebellar ataxia and cognitive decline, MIM# 620636
Congenital Heart Defect v0.418 BMP2 Ain Roesley Marked gene: BMP2 as ready
Congenital Heart Defect v0.418 BMP2 Ain Roesley Gene: bmp2 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.418 BMP2 Ain Roesley reviewed gene: BMP2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 37572998, 29198724; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Congenital Heart Defect v0.418 BMP2 Ain Roesley Deleted their review
Congenital Heart Defect v0.418 BMP2 Ain Roesley Deleted their comment
Congenital Heart Defect v0.418 BMP2 Ain Roesley Classified gene: BMP2 as Green List (high evidence)
Congenital Heart Defect v0.418 BMP2 Ain Roesley Gene: bmp2 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.417 BMP2 Ain Roesley gene: BMP2 was added
gene: BMP2 was added to Congenital Heart Defect. Sources: Literature
Mode of inheritance for gene: BMP2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: BMP2 were set to 29198724
Phenotypes for gene: BMP2 were set to Short stature, facial dysmorphism, and skeletal anomalies with or without cardiac anomalies 1, MIM# 617877
Review for gene: BMP2 was set to GREEN
gene: BMP2 was marked as current diagnostic
Added comment: 8 families with 12 affecteds

4 with CHD
Transposition of the great arteries HP:0001669
Mild pulmonary valve stenosis HP:0001642
Ebstein's anomaly HP:0010316
Wolff-Parkinson-White syndrome HP:0001716, perimembranous VSD HP:0011682
Sources: Literature
Muscular dystrophy and myopathy_Paediatric v1.29 COMP Ain Roesley Marked gene: COMP as ready
Muscular dystrophy and myopathy_Paediatric v1.29 COMP Ain Roesley Gene: comp has been classified as Amber List (Moderate Evidence).
Muscular dystrophy and myopathy_Paediatric v1.29 COMP Ain Roesley Classified gene: COMP as Amber List (moderate evidence)
Muscular dystrophy and myopathy_Paediatric v1.29 COMP Ain Roesley Gene: comp has been classified as Amber List (Moderate Evidence).
Muscular dystrophy and myopathy_Paediatric v1.28 COMP Ain Roesley gene: COMP was added
gene: COMP was added to Muscular dystrophy and myopathy_Paediatric. Sources: Literature
Mode of inheritance for gene: COMP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: COMP were set to 20508815; 14684695; 15880723
Phenotypes for gene: COMP were set to Epiphyseal dysplasia, multiple, 1 MIM#132400
Review for gene: COMP was set to AMBER
gene: COMP was marked as current diagnostic
Added comment: Not a common feature of MED.
Amber so as not to miss a diagnosis

PMID: 14684695
2 families only 1 with mild myopathy
Fam1: 1 father + 3 sibs, only 1 reported muscle weakness
Fam2: no muscle weakness reported

PMID: 15880723
10 families but only 1 reported mild myopathy

PMID: 20508815
additional 2 unrelated individuals from European Skeletal Dysplasia Network
Sources: Literature
Muscular dystrophy and myopathy_Paediatric v1.27 COL9A2 Ain Roesley Marked gene: COL9A2 as ready
Muscular dystrophy and myopathy_Paediatric v1.27 COL9A2 Ain Roesley Gene: col9a2 has been classified as Amber List (Moderate Evidence).
Muscular dystrophy and myopathy_Paediatric v1.27 COL9A2 Ain Roesley Classified gene: COL9A2 as Amber List (moderate evidence)
Muscular dystrophy and myopathy_Paediatric v1.27 COL9A2 Ain Roesley Gene: col9a2 has been classified as Amber List (Moderate Evidence).
Muscular dystrophy and myopathy_Paediatric v1.26 COL9A2 Ain Roesley gene: COL9A2 was added
gene: COL9A2 was added to Muscular dystrophy and myopathy_Paediatric. Sources: Literature
Mode of inheritance for gene: COL9A2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: COL9A2 were set to 20508815; 20358595
Phenotypes for gene: COL9A2 were set to Epiphyseal dysplasia, multiple, 2 MIM#600204
Review for gene: COL9A2 was set to AMBER
gene: COL9A2 was marked as current diagnostic
Added comment: not a common feature. only 1 paper found in pubmed and google (search terms COL9A2 AND myopathy)
Amber so as not to miss a diagnosis

PMID: 20358595
2 families with multiple affecteds but only 1 from each reporting muscle weakness

PMID: 20508815
additional individual from European Skeletal Dysplasia Network
Sources: Literature
Muscular dystrophy and myopathy_Paediatric v1.25 COL9A3 Ain Roesley Marked gene: COL9A3 as ready
Muscular dystrophy and myopathy_Paediatric v1.25 COL9A3 Ain Roesley Gene: col9a3 has been classified as Amber List (Moderate Evidence).
Muscular dystrophy and myopathy_Paediatric v1.25 COL9A3 Ain Roesley Classified gene: COL9A3 as Amber List (moderate evidence)
Muscular dystrophy and myopathy_Paediatric v1.25 COL9A3 Ain Roesley Gene: col9a3 has been classified as Amber List (Moderate Evidence).
Muscular dystrophy and myopathy_Paediatric v1.24 COL9A3 Ain Roesley gene: COL9A3 was added
gene: COL9A3 was added to Muscular dystrophy and myopathy_Paediatric. Sources: Literature
Mode of inheritance for gene: COL9A3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: COL9A3 were set to 10655510
Phenotypes for gene: COL9A3 were set to Epiphyseal dysplasia, multiple, 3, with or without myopathy MIM#600969
Review for gene: COL9A3 was set to AMBER
gene: COL9A3 was marked as current diagnostic
Added comment: Not a common feature of MED, only one paper found in pubmed (search terms COL9A3 AND myopathy).
Amber so as not to miss a diagnosis

PMID: 10655510
1x male with proximal muscle weakness
Sources: Literature
Genetic Epilepsy v0.2549 KDM5C Ain Roesley Phenotypes for gene: KDM5C were changed from Intellectual developmental disorder, X-linked syndromic, Claes-Jensen type MIM# 300534; MONDO:0010355 to Intellectual developmental disorder, X-linked syndromic, Claes-Jensen type MIM# 300534; MONDO:0010355
Mendeliome v1.1690 KDM5C Ain Roesley Phenotypes for gene: KDM5C were changed from Mental retardation, X-linked, syndromic, Claes-Jensen type, MIM# 300534; MONDO:0010355 to Intellectual developmental disorder, X-linked syndromic, Claes-Jensen type MIM# 300534; MONDO:0010355
Genetic Epilepsy v0.2549 KDM5C Ain Roesley Phenotypes for gene: KDM5C were changed from Epilepsy; Intellectual Disability; microcephaly; Spasticity; hypothyroidism; Mental retardation, X-linked, syndromic, Claes-Jensen type, MIM# 300534; MONDO:0010355 to Intellectual developmental disorder, X-linked syndromic, Claes-Jensen type MIM# 300534; MONDO:0010355
Hereditary Spastic Paraplegia - paediatric v1.73 KDM5C Ain Roesley Phenotypes for gene: KDM5C were changed from Mental retardation, X-linked, syndromic, Claes-Jensen type, MIM# 300534; MONDO:0010355; progressive spasticity; hypothyroidism; developmental delay; epilepsy to Intellectual developmental disorder, X-linked syndromic, Claes-Jensen type MIM# 300534; MONDO:0010355
Cerebral Palsy v1.192 KDM5C Ain Roesley Phenotypes for gene: KDM5C were changed from Mental retardation, X-linked, syndromic, Claes-Jensen type, MIM# 300534; MONDO:0010355 to Intellectual developmental disorder, X-linked syndromic, Claes-Jensen type MIM# 300534; MONDO:0010355
Intellectual disability syndromic and non-syndromic v0.5770 KDM5C Ain Roesley Phenotypes for gene: KDM5C were changed from Mental retardation, X-linked, syndromic, Claes-Jensen type, MIM# 300534; MONDO:0010355 to Intellectual developmental disorder, X-linked syndromic, Claes-Jensen type MIM# 300534; MONDO:0010355
Fetal anomalies v1.234 KDM5C Ain Roesley Phenotypes for gene: KDM5C were changed from Mental retardation, X-linked, syndromic, Claes-Jensen type, MIM# 300534; MONDO:0010355 to Intellectual developmental disorder, X-linked syndromic, Claes-Jensen type MIM# 300534; MONDO:0010355
Mendeliome v1.1689 PSMA5 Zornitza Stark Marked gene: PSMA5 as ready
Mendeliome v1.1689 PSMA5 Zornitza Stark Gene: psma5 has been classified as Red List (Low Evidence).
Mendeliome v1.1689 PSMA5 Zornitza Stark gene: PSMA5 was added
gene: PSMA5 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PSMA5 was set to Other
Publications for gene: PSMA5 were set to 37600812
Phenotypes for gene: PSMA5 were set to Inborn error of immunity, MONDO:0003778, PSMA5-related; PRAAS/CANDLE
Review for gene: PSMA5 was set to RED
Added comment: Single patient with heterozygous PSMB8 variant and de-novo PSMA5 truncating variant (p.Arg168*) with clinical features of CANDLE. Patient also had splice site variant in PSMC5. In silico modelling showing interaction of PSMB8 and PSMA5. PSMA5/a5 is a constitutive component of the 20S core proteasome, ? digenic model of disease.
Sources: Literature
Systemic Autoinflammatory Disease_Periodic Fever v1.36 PSMA5 Zornitza Stark Marked gene: PSMA5 as ready
Systemic Autoinflammatory Disease_Periodic Fever v1.36 PSMA5 Zornitza Stark Gene: psma5 has been classified as Red List (Low Evidence).
Systemic Autoinflammatory Disease_Periodic Fever v1.36 PSMA5 Zornitza Stark Phenotypes for gene: PSMA5 were changed from PRAAS/CANDLE to Inborn error of immunity, MONDO:0003778, PSMA5-related; PRAAS/CANDLE
Systemic Autoinflammatory Disease_Periodic Fever v1.35 PSMA5 Zornitza Stark Classified gene: PSMA5 as Red List (low evidence)
Systemic Autoinflammatory Disease_Periodic Fever v1.35 PSMA5 Zornitza Stark Gene: psma5 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.5769 SNF8 Zornitza Stark Phenotypes for gene: SNF8 were changed from Neurodevelopmental disorder (MONDO:0700092), SNF8-related to Developmental and epileptic encephalopathy 115, MIM#620783
Intellectual disability syndromic and non-syndromic v0.5768 SNF8 Zornitza Stark reviewed gene: SNF8: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Developmental and epileptic encephalopathy 115, MIM#620783; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Callosome v0.522 SNF8 Zornitza Stark Phenotypes for gene: SNF8 were changed from Neurodevelopmental disorder (MONDO:0700092), SNF8-related to Developmental and epileptic encephalopathy 115, MIM#620783
Callosome v0.521 SNF8 Zornitza Stark reviewed gene: SNF8: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Developmental and epileptic encephalopathy 115, MIM#620783; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2548 SNF8 Zornitza Stark Phenotypes for gene: SNF8 were changed from Developmental and epileptic encephalopathy 115, MIM#620783 to Developmental and epileptic encephalopathy 115, MIM#620783
Genetic Epilepsy v0.2547 SNF8 Zornitza Stark Phenotypes for gene: SNF8 were changed from Neurodevelopmental disorder (MONDO:0700092), SNF8-related to Developmental and epileptic encephalopathy 115, MIM#620783
Genetic Epilepsy v0.2546 SNF8 Zornitza Stark Classified gene: SNF8 as Green List (high evidence)
Genetic Epilepsy v0.2546 SNF8 Zornitza Stark Gene: snf8 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2545 SNF8 Zornitza Stark reviewed gene: SNF8: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Developmental and epileptic encephalopathy 115, MIM#620783; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Optic Atrophy v1.31 SNF8 Zornitza Stark Phenotypes for gene: SNF8 were changed from Neurodevelopmental disorder (MONDO:0700092), SNF8-related to Developmental and epileptic encephalopathy 115, MIM#620783
Optic Atrophy v1.30 SNF8 Zornitza Stark edited their review of gene: SNF8: Changed rating: AMBER
Optic Atrophy v1.30 SNF8 Zornitza Stark reviewed gene: SNF8: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Developmental and epileptic encephalopathy 115, MIM#620783; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1688 SNF8 Zornitza Stark Phenotypes for gene: SNF8 were changed from Neurodevelopmental disorder (MONDO:0700092), SNF8-related to Developmental and epileptic encephalopathy 115, MIM#620783
Mendeliome v1.1687 SNF8 Zornitza Stark reviewed gene: SNF8: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Developmental and epileptic encephalopathy 115, MIM#620783; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1687 CNOT1 Sangavi Sivagnanasundram reviewed gene: CNOT1: Rating: AMBER; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:004485; Phenotypes: holoprosencephaly 12 with or without pancreatic agenesis MONDO:0032787; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.1687 CENPE Sangavi Sivagnanasundram reviewed gene: CENPE: Rating: RED; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:004413; Phenotypes: autosomal recessive primary microcephaly MONDO:0016660; Mode of inheritance: None
Peroxisomal Disorders v0.47 ABCD1 Sangavi Sivagnanasundram reviewed gene: ABCD1: Rating: GREEN; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:004013c; Phenotypes: adrenoleukodystrophy (MONDO:0018544); Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Early-onset Parkinson disease v0.295 LRRK2 Sangavi Sivagnanasundram reviewed gene: LRRK2: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: PMID: 1626954, https://search.clinicalgenome.org/CCID:005305; Phenotypes: Parkinson disease (MONDO:0005180); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2545 PURA Ain Roesley Phenotypes for gene: PURA were changed from Neurodevelopmental disorder with neonatal respiratory insufficiency, hypotonia, and feeding difficulties (OMIM 616158) to Neurodevelopmental disorder with neonatal respiratory insufficiency, hypotonia, and feeding difficulties (OMIM 616158)
Intellectual disability syndromic and non-syndromic v0.5768 PURA Ain Roesley Phenotypes for gene: PURA were changed from Neurodevelopmental disorder with neonatal respiratory insufficiency, hypotonia, and feeding difficulties (OMIM 616158) to Neurodevelopmental disorder with neonatal respiratory insufficiency, hypotonia, and feeding difficulties (OMIM 616158)
Intellectual disability syndromic and non-syndromic v0.5768 PURA Ain Roesley Phenotypes for gene: PURA were changed from Mental retardation, autosomal dominant 31, MIM# 616158 to Neurodevelopmental disorder with neonatal respiratory insufficiency, hypotonia, and feeding difficulties (OMIM 616158)
Genetic Epilepsy v0.2545 PURA Ain Roesley Phenotypes for gene: PURA were changed from Mental retardation, autosomal dominant 31, MIM# 616158 to Neurodevelopmental disorder with neonatal respiratory insufficiency, hypotonia, and feeding difficulties (OMIM 616158)
Fetal anomalies v1.233 PURA Ain Roesley Phenotypes for gene: PURA were changed from Neurodevelopmental disorder with neonatal respiratory insufficiency, hypotonia, and feeding difficulties (OMIM 616158) to Neurodevelopmental disorder with neonatal respiratory insufficiency, hypotonia, and feeding difficulties (OMIM 616158)
Fetal anomalies v1.232 PURA Ain Roesley Phenotypes for gene: PURA were changed from Mental retardation, autosomal dominant 31, MIM# 616158 to Neurodevelopmental disorder with neonatal respiratory insufficiency, hypotonia, and feeding difficulties (OMIM 616158)
Mendeliome v1.1687 PURA Ain Roesley Phenotypes for gene: PURA were changed from Mental retardation, autosomal dominant 31, MIM# 616158 to Neurodevelopmental disorder with neonatal respiratory insufficiency, hypotonia, and feeding difficulties (OMIM 616158)
Hereditary Neuropathy_CMT - isolated v1.39 WARS Sangavi Sivagnanasundram reviewed gene: WARS: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: distal hereditary motor neuropathy MONDO:0018894; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary Neuropathy_CMT - isolated v1.39 SORD Sangavi Sivagnanasundram reviewed gene: SORD: Rating: GREEN; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:006246; Phenotypes: Charcot-Marie-Tooth disease (MONDO:0015626); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Neuropathy_CMT - isolated v1.39 PMP2 Sangavi Sivagnanasundram reviewed gene: PMP2: Rating: AMBER; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: PMID: 28747762, https://search.clinicalgenome.org/CCID:005836; Phenotypes: Charcot-Marie-Tooth disease MONDO:0015626; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary Neuropathy_CMT - isolated v1.39 MED25 Sangavi Sivagnanasundram reviewed gene: MED25: Rating: RED; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:005366; Phenotypes: Charcot-Marie-Tooth disease type 2B2 MONDO:0011570; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Neuropathy_CMT - isolated v1.39 MARS Sangavi Sivagnanasundram reviewed gene: MARS: Rating: RED; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:005337; Phenotypes: Charcot-Marie-Tooth disease MONDO:0015626; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary Neuropathy_CMT - isolated v1.39 HINT1 Sangavi Sivagnanasundram reviewed gene: HINT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 33404983; Phenotypes: Charcot-Marie-Tooth disease MONDO:0015626; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Neuropathy_CMT - isolated v1.39 BSCL2 Sangavi Sivagnanasundram edited their review of gene: BSCL2: Changed mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Hereditary Neuropathy_CMT - isolated v1.39 DYNC1H1 Sangavi Sivagnanasundram Deleted their review
Hereditary Neuropathy_CMT - isolated v1.39 DYNC1H1 Sangavi Sivagnanasundram Deleted their comment
Hereditary Neuropathy_CMT - isolated v1.39 DYNC1H1 Sangavi Sivagnanasundram reviewed gene: DYNC1H1: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: obsolete neuronopathy, distal hereditary motor (MONDO:0000075); Mode of inheritance: None
Hereditary Neuropathy_CMT - isolated v1.39 BSCL2 Sangavi Sivagnanasundram reviewed gene: BSCL2: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 25832430, 23470542, https://search.clinicalgenome.org/CCID:004292; Phenotypes: distal hereditary motor neuropathy MONDO:0018894; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary Neuropathy_CMT - isolated v1.39 ATP7A Sangavi Sivagnanasundram reviewed gene: ATP7A: Rating: ; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:004216; Phenotypes: X-linked distal spinal muscular atrophy type 3 (MONDO:0010338); Mode of inheritance: None
Hereditary Neuropathy_CMT - isolated v1.39 ATP1A1 Sangavi Sivagnanasundram commented on gene: ATP1A1
Hereditary Neuropathy_CMT - isolated v1.39 ATL3 Sangavi Sivagnanasundram reviewed gene: ATL3: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: neuropathy, hereditary sensory, type 1F (MONDO:0014286); Mode of inheritance: None
Motor Neurone Disease v1.8 SS18L1 Sangavi Sivagnanasundram reviewed gene: SS18L1: Rating: AMBER; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:006276; Phenotypes: amyotrophic lateral sclerosis (MONDO:0004976); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Motor Neurone Disease v1.8 CYLD Sangavi Sivagnanasundram reviewed gene: CYLD: Rating: RED; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:004615; Phenotypes: frontotemporal dementia and/or amyotrophic lateral sclerosis 8 (MONDO:0030872); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Motor Neurone Disease v1.8 CHMP2B Sangavi Sivagnanasundram reviewed gene: CHMP2B: Rating: GREEN; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:004450; Phenotypes: frontotemporal dementia and/or amyotrophic lateral sclerosis 7 (MONDO:0010936); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Repeat Disorders v0.167 DMD Bryony Thompson Publications for STR: DMD were set to 27417533
Repeat Disorders v0.166 FAME7 Bryony Thompson Publications for STR: FAME7 were set to 29507423
Repeat Disorders v0.165 FAME7 Bryony Thompson Classified STR: FAME7 as Amber List (moderate evidence)
Repeat Disorders v0.165 FAME7 Bryony Thompson Str: fame7 has been classified as Amber List (Moderate Evidence).
Repeat Disorders v0.164 FAME7 Bryony Thompson edited their review of STR: FAME7: Added comment: TTTCA expansion (without TTTTA expansion) identified in 3 affected individuals in a Chinese FAME family and another unrelated Japanese proband. Now 3 families reported.; Changed rating: AMBER; Changed publications: 29507423, 30351492, 33791773
Mendeliome v1.1686 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 Doyne honeycomb degeneration of retina, MIM# 126600; Cutis laxa, autosomal recessive, type ID, MIM# 620780; Glaucoma 1, open angle, H, MIM# 611276
Mendeliome v1.1685 EFEMP1 Zornitza Stark edited their review of gene: EFEMP1: Changed phenotypes: Doyne honeycomb degeneration of retina, MIM# 126600, Cutis laxa, autosomal recessive, type ID, MIM# 620780, Glaucoma 1, open angle, H, MIM# 611276
Aortopathy_Connective Tissue Disorders v1.84 EFEMP1 Zornitza Stark Phenotypes for gene: EFEMP1 were changed from EFEMP1-related connective tissue disorder; cutis laxa to Cutis laxa, autosomal recessive, type ID, MIM# 620780
Aortopathy_Connective Tissue Disorders v1.83 EFEMP1 Zornitza Stark edited their review of gene: EFEMP1: Changed phenotypes: Cutis laxa, autosomal recessive, type ID, MIM# 620780
Bone Marrow Failure v1.88 GALE Zornitza Stark Marked gene: GALE as ready
Bone Marrow Failure v1.88 GALE Zornitza Stark Gene: gale has been classified as Green List (High Evidence).
Bone Marrow Failure v1.88 GALE Zornitza Stark Classified gene: GALE as Green List (high evidence)
Bone Marrow Failure v1.88 GALE Zornitza Stark Gene: gale has been classified as Green List (High Evidence).
Bone Marrow Failure v1.87 GALE Zornitza Stark gene: GALE was added
gene: GALE was added to Bone Marrow Failure. Sources: Expert Review
Mode of inheritance for gene: GALE was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GALE were set to 30247636; 34159722; 36395340
Phenotypes for gene: GALE were set to Thrombocytopenia 12, syndromic, MIM#620776
Review for gene: GALE was set to GREEN
Added comment: 10 individuals from 5 families reported with bi-allelic variants in this gene and congenital thrombocytopenia resulting in increased bleeding. Platelets were enlarged (macrothrombocytopenia) and/or gray and had functional defects. Some individuals have infection-induced leukopenia or anaemia and pancytopenia. Additional more variable features have also been reported, including mitral valve malformations, pyloric stenosis, and impaired intellectual development.
Sources: Expert Review
Mendeliome v1.1685 GALE Zornitza Stark Phenotypes for gene: GALE were changed from Galactose epimerase deficiency MIM#230350; Disorders of galactose metabolism to Galactose epimerase deficiency MIM#230350; Thrombocytopenia 12, syndromic, MIM#620776
Mendeliome v1.1684 GALE Zornitza Stark Publications for gene: GALE were set to 27604308; 9700591
Mendeliome v1.1683 GALE Zornitza Stark reviewed gene: GALE: Rating: GREEN; Mode of pathogenicity: None; Publications: 30247636, 34159722, 36395340; Phenotypes: Thrombocytopenia 12, syndromic, MIM#620776; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Bleeding and Platelet Disorders v1.31 GALE Zornitza Stark Marked gene: GALE as ready
Bleeding and Platelet Disorders v1.31 GALE Zornitza Stark Gene: gale has been classified as Green List (High Evidence).
Bleeding and Platelet Disorders v1.31 GALE Zornitza Stark Classified gene: GALE as Green List (high evidence)
Bleeding and Platelet Disorders v1.31 GALE Zornitza Stark Gene: gale has been classified as Green List (High Evidence).
Bleeding and Platelet Disorders v1.30 GALE Zornitza Stark gene: GALE was added
gene: GALE was added to Bleeding and Platelet Disorders. Sources: Expert list
Mode of inheritance for gene: GALE was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GALE were set to 30247636; 34159722; 36395340
Phenotypes for gene: GALE were set to Thrombocytopenia 12, syndromic, MIM#620776
Review for gene: GALE was set to GREEN
Added comment: 10 individuals from 5 families reported with bi-allelic variants in this gene and congenital thrombocytopenia resulting in increased bleeding. Platelets were enlarged (macrothrombocytopenia) and/or gray and had functional defects. Some individuals have infection-induced leukopenia or anaemia and pancytopenia. Additional more variable features have also been reported, including mitral valve malformations, pyloric stenosis, and impaired intellectual development.
Sources: Expert list
Repeat Disorders v0.164 DMD Bryony Thompson changed review comment from: Another case with BMD (patient 18) form a Japanese registry was reported with an expansion of 1381–1502 repeats in intron 62.; to: Another case with BMD (patient 18) form a Japanese registry was reported with an expansion of 1381–1502 repeats in intron 62. Repeat expansion causes a splicing aberration
Repeat Disorders v0.164 DMD Bryony Thompson Classified STR: DMD as Amber List (moderate evidence)
Repeat Disorders v0.164 DMD Bryony Thompson Str: dmd has been classified as Amber List (Moderate Evidence).
Repeat Disorders v0.163 DMD Bryony Thompson edited their review of STR: DMD: Added comment: Another case with BMD (patient 18) form a Japanese registry was reported with an expansion of 1381–1502 repeats in intron 62.; Changed rating: AMBER; Changed publications: 27417533, 36048237
Repeat Disorders v0.163 HFGS_tract2 Bryony Thompson Marked STR: HFGS_tract2 as ready
Repeat Disorders v0.163 HFGS_tract2 Bryony Thompson Str: hfgs_tract2 has been classified as Green List (High Evidence).
Repeat Disorders v0.163 SCA_THAP11_CAG Bryony Thompson Marked STR: SCA_THAP11_CAG as ready
Repeat Disorders v0.163 SCA_THAP11_CAG Bryony Thompson Str: sca_thap11_cag has been classified as Amber List (Moderate Evidence).
Repeat Disorders v0.163 SCA_THAP11_CAG Bryony Thompson Classified STR: SCA_THAP11_CAG as Amber List (moderate evidence)
Repeat Disorders v0.163 SCA_THAP11_CAG Bryony Thompson Str: sca_thap11_cag has been classified as Amber List (Moderate Evidence).
Repeat Disorders v0.162 SCA_THAP11_CAG Bryony Thompson STR: SCA_THAP11_CAG was added
STR: SCA_THAP11_CAG was added to Repeat Disorders. Sources: Other
Mode of inheritance for STR: SCA_THAP11_CAG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: SCA_THAP11_CAG were set to 15368101; 24677642; 34165550; 38113319
Phenotypes for STR: SCA_THAP11_CAG were set to autosomal dominant cerebellar ataxia MONDO:0020380
Review for STR: SCA_THAP11_CAG was set to AMBER
Added comment: 7 individuals from 2 Chinese families with SCA (1 was pre-ataxic) and a THAP11 CAG (polyQ) expansion. 45 repeats was the lowest number of repeats in an affected individual. A 46/29 CAG THAP11 genotype has also been identified in an individual with ataxia of European ancestry, that also had a CACNA1A pathogenic expansion which causes SCA6. Analysis of the 1000 genomes cohort (n=2504), suggests a normal range between 19-39. Also, a supporting mouse model and functional assays support a toxic aggregation mechanism of disease.
Further probands/families are required to confirm the gene-disease association.
Sources: Other
Mendeliome v1.1683 BANF1 Zornitza Stark Phenotypes for gene: BANF1 were changed from Nestor-Guillermo progeria syndrome, MIM# 614008 to Nestor-Guillermo progeria syndrome, MIM# 614008; Neurodevelopmental disorder, MONDO:0700092, BANF1-related; Hereditary peripheral neuropathy, MONDO:0020127, BANF1-related
Mendeliome v1.1682 BANF1 Zornitza Stark Publications for gene: BANF1 were set to 32783369; 21549337
Mendeliome v1.1681 BANF1 Zornitza Stark Mode of inheritance for gene: BANF1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.1680 BANF1 Zornitza Stark changed review comment from: Two Spanish families reported but likely founder effect. One additional family. Lipoatrophy reported.; to: Bi-allelic disease: Two Spanish families reported with progeria but likely founder effect. One additional family. Lipoatrophy reported.
Mendeliome v1.1680 BANF1 Zornitza Stark edited their review of gene: BANF1: Added comment: PMID 35982159: Single individual reported with a de novo variant, p.Ala87Thr, and a neurodevelopmental disorder.

PMID 36980188: Hereditary peripheral neuropathy, MONDO:0020127, BANF1-related; Changed publications: 32783369, 21549337, 35982159, 36980188; Changed phenotypes: Nestor-Guillermo progeria syndrome, MIM# 614008, Neurodevelopmental disorder, MONDO:0700092, BANF1-related, Hereditary peripheral neuropathy, MONDO:0020127, BANF1-related; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5767 BANF1 Zornitza Stark Marked gene: BANF1 as ready
Intellectual disability syndromic and non-syndromic v0.5767 BANF1 Zornitza Stark Gene: banf1 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.5767 BANF1 Zornitza Stark gene: BANF1 was added
gene: BANF1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: BANF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: BANF1 were set to 35982159
Phenotypes for gene: BANF1 were set to Neurodevelopmental disorder, MONDO:0700092, BANF1-related
Review for gene: BANF1 was set to RED
Added comment: Single individual reported with a de novo variant, p.Ala87Thr, and a neurodevelopmental disorder.
Sources: Literature
Hereditary Neuropathy_CMT - isolated v1.39 BANF1 Zornitza Stark Marked gene: BANF1 as ready
Hereditary Neuropathy_CMT - isolated v1.39 BANF1 Zornitza Stark Gene: banf1 has been classified as Red List (Low Evidence).
Hereditary Neuropathy_CMT - isolated v1.39 BANF1 Zornitza Stark gene: BANF1 was added
gene: BANF1 was added to Hereditary Neuropathy_CMT - isolated. Sources: Literature
Mode of inheritance for gene: BANF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: BANF1 were set to 36980188
Phenotypes for gene: BANF1 were set to Hereditary peripheral neuropathy, MONDO:0020127, BANF1-related
Review for gene: BANF1 was set to RED
Added comment: Single individual reported with de novo variant, Gly16Arg, and a neuropathy.
Sources: Literature
Repeat Disorders v0.161 OPDM_ABCD3_GCC Bryony Thompson Marked STR: OPDM_ABCD3_GCC as ready
Repeat Disorders v0.161 OPDM_ABCD3_GCC Bryony Thompson Str: opdm_abcd3_gcc has been classified as Green List (High Evidence).
Repeat Disorders v0.161 OPDM_ABCD3_GCC Bryony Thompson Classified STR: OPDM_ABCD3_GCC as Green List (high evidence)
Repeat Disorders v0.161 OPDM_ABCD3_GCC Bryony Thompson Str: opdm_abcd3_gcc has been classified as Green List (High Evidence).
Repeat Disorders v0.160 OPDM_ABCD3_GCC Bryony Thompson STR: OPDM_ABCD3_GCC was added
STR: OPDM_ABCD3_GCC was added to Repeat Disorders. Sources: Other
Mode of inheritance for STR: OPDM_ABCD3_GCC was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: OPDM_ABCD3_GCC were set to https://doi.org/10.1101/2023.10.09.23296582
Phenotypes for STR: OPDM_ABCD3_GCC were set to Oculopharyngodistal myopathy MONDO:0025193
Review for STR: OPDM_ABCD3_GCC was set to GREEN
STR: OPDM_ABCD3_GCC was marked as clinically relevant
Added comment: 35 OPDM individuals from 8 unrelated families from Australia, the UK, and France with an ABCD3 5’UTR CGG repeat. Affected individuals had repeat expansions ranging from 118-694 (n=19). 7 repeats is the median repeat size in non-neurological controls from the GE 100,000 Genome Project. 10 controls had estimated repeats >50, up to ~93. 50 repeats would be a safe cut-off for normal
Sources: Other
Muscular dystrophy and myopathy_Paediatric v1.23 FILIP1 Zornitza Stark Marked gene: FILIP1 as ready
Muscular dystrophy and myopathy_Paediatric v1.23 FILIP1 Zornitza Stark Gene: filip1 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v1.23 FILIP1 Zornitza Stark Classified gene: FILIP1 as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v1.23 FILIP1 Zornitza Stark Gene: filip1 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v1.22 FILIP1 Zornitza Stark gene: FILIP1 was added
gene: FILIP1 was added to Muscular dystrophy and myopathy_Paediatric. Sources: Expert Review
Mode of inheritance for gene: FILIP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FILIP1 were set to 36943452; 37163662
Phenotypes for gene: FILIP1 were set to Neuromuscular disorder, congenital, with dysmorphic facies, MIM# 620775
Review for gene: FILIP1 was set to GREEN
Added comment: Congenital neuromuscular disorder with dysmorphic facies (NMDF) is an autosomal recessive disorder characterized by impaired skeletal muscle development, usually resulting in hypotonia and secondary joint contractures, and dysmorphic facial features. Features are apparent from birth. Affected individuals may show motor delay, speech delay, and impaired intellectual development.

Seven families reported.
Sources: Expert Review
Fetal anomalies v1.231 FILIP1 Zornitza Stark Phenotypes for gene: FILIP1 were changed from Arthrogryposis multiplex congenita MONDO:0015168, FILIP1 related to ANeuromuscular disorder, congenital, with dysmorphic facies, MIM# 620775
Fetal anomalies v1.230 FILIP1 Zornitza Stark reviewed gene: FILIP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neuromuscular disorder, congenital, with dysmorphic facies, MIM# 620775; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v1.258 FILIP1 Zornitza Stark Phenotypes for gene: FILIP1 were changed from Arthrogryposis multiplex congenita MONDO:0015168, FILIP1 related to Neuromuscular disorder, congenital, with dysmorphic facies, MIM# 620775
Microcephaly v1.257 FILIP1 Zornitza Stark reviewed gene: FILIP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neuromuscular disorder, congenital, with dysmorphic facies, MIM# 620775; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1680 FILIP1 Zornitza Stark Phenotypes for gene: FILIP1 were changed from Arthrogryposis multiplex congenita MONDO:0015168, FILIP1 related to Neuromuscular disorder, congenital, with dysmorphic facies, MIM# 620775
Mendeliome v1.1679 FILIP1 Zornitza Stark reviewed gene: FILIP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neuromuscular disorder, congenital, with dysmorphic facies, MIM# 620775; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.406 FILIP1 Zornitza Stark Phenotypes for gene: FILIP1 were changed from Arthrogryposis multiplex congenita MONDO:0015168, FILIP1-related to Neuromuscular disorder, congenital, with dysmorphic facies, MIM# 620775
Arthrogryposis v0.405 FILIP1 Zornitza Stark reviewed gene: FILIP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neuromuscular disorder, congenital, with dysmorphic facies, MIM# 620775; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1679 RNU4-2 Zornitza Stark Marked gene: RNU4-2 as ready
Mendeliome v1.1679 RNU4-2 Zornitza Stark Gene: rnu4-2 has been classified as Green List (High Evidence).
Mendeliome v1.1679 RNU4-2 Zornitza Stark Classified gene: RNU4-2 as Green List (high evidence)
Mendeliome v1.1679 RNU4-2 Zornitza Stark Gene: rnu4-2 has been classified as Green List (High Evidence).
Mendeliome v1.1678 RNU4-2 Zornitza Stark gene: RNU4-2 was added
gene: RNU4-2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RNU4-2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: RNU4-2 were set to Neurodevelopmental disorder, MONDO:0700092, RNU4-2 related
Review for gene: RNU4-2 was set to GREEN
Added comment: Emerging evidence that de novo variants in this gene cause ID.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5766 RNU4-2 Zornitza Stark Marked gene: RNU4-2 as ready
Intellectual disability syndromic and non-syndromic v0.5766 RNU4-2 Zornitza Stark Gene: rnu4-2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5766 RNU4-2 Zornitza Stark Classified gene: RNU4-2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5766 RNU4-2 Zornitza Stark Gene: rnu4-2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5765 RNU4-2 Zornitza Stark gene: RNU4-2 was added
gene: RNU4-2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: RNU4-2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: RNU4-2 were set to Neurodevelopmental disorder, MONDO:0700092, RNU4-2 related
Review for gene: RNU4-2 was set to GREEN
Added comment: Emerging evidence that de novo variants in this gene cause ID.
Sources: Literature
Liver Failure_Paediatric v1.24 YKT6 Zornitza Stark Marked gene: YKT6 as ready
Liver Failure_Paediatric v1.24 YKT6 Zornitza Stark Gene: ykt6 has been classified as Amber List (Moderate Evidence).
Liver Failure_Paediatric v1.24 YKT6 Zornitza Stark Classified gene: YKT6 as Amber List (moderate evidence)
Liver Failure_Paediatric v1.24 YKT6 Zornitza Stark Gene: ykt6 has been classified as Amber List (Moderate Evidence).
Liver Failure_Paediatric v1.23 YKT6 Zornitza Stark gene: YKT6 was added
gene: YKT6 was added to Liver Failure_Paediatric. Sources: Literature
Mode of inheritance for gene: YKT6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: YKT6 were set to 38522068
Phenotypes for gene: YKT6 were set to Syndromic disease, MONDO:0002254, YKT6-related
Review for gene: YKT6 was set to AMBER
Added comment: Two individuals homozygous for YKT6 [NM_006555.3:c.554A>G p.(Tyr185Cys)] exhibited normal prenatal course followed by failure to thrive, developmental delay and progressive liver disease. Haplotype analysis identified a shared homozygous region flanking the variant, suggesting a common ancestry. The third individual homozygous for YKT6 [NM_006555.3:c.191A>G p.(Tyr64Cys)] exhibited neurodevelopmental disorders and optic atrophy. Supportive functional data in Drosophila. Amber rating due to homozygous missense variants and founder effect in two of the families.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5764 YKT6 Zornitza Stark Marked gene: YKT6 as ready
Intellectual disability syndromic and non-syndromic v0.5764 YKT6 Zornitza Stark Gene: ykt6 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5764 YKT6 Zornitza Stark Classified gene: YKT6 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.5764 YKT6 Zornitza Stark Gene: ykt6 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5763 YKT6 Zornitza Stark gene: YKT6 was added
gene: YKT6 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: YKT6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: YKT6 were set to 38522068
Phenotypes for gene: YKT6 were set to Syndromic disease, MONDO:0002254, YKT6-related
Review for gene: YKT6 was set to AMBER
Added comment: Two individuals homozygous for YKT6 [NM_006555.3:c.554A>G p.(Tyr185Cys)] exhibited normal prenatal course followed by failure to thrive, developmental delay and progressive liver disease. Haplotype analysis identified a shared homozygous region flanking the variant, suggesting a common ancestry. The third individual homozygous for YKT6 [NM_006555.3:c.191A>G p.(Tyr64Cys)] exhibited neurodevelopmental disorders and optic atrophy. Supportive functional data in Drosophila. Amber rating due to homozygous missense variants and founder effect in two of the families.
Sources: Literature
Mendeliome v1.1677 YKT6 Zornitza Stark Marked gene: YKT6 as ready
Mendeliome v1.1677 YKT6 Zornitza Stark Gene: ykt6 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1677 YKT6 Zornitza Stark Classified gene: YKT6 as Amber List (moderate evidence)
Mendeliome v1.1677 YKT6 Zornitza Stark Gene: ykt6 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1676 YKT6 Zornitza Stark gene: YKT6 was added
gene: YKT6 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: YKT6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: YKT6 were set to 38522068
Phenotypes for gene: YKT6 were set to Syndromic disease, MONDO:0002254, YKT6-related
Review for gene: YKT6 was set to AMBER
Added comment: Two individuals homozygous for YKT6 [NM_006555.3:c.554A>G p.(Tyr185Cys)] exhibited normal prenatal course followed by failure to thrive, developmental delay and progressive liver disease. Haplotype analysis identified a shared homozygous region flanking the variant, suggesting a common ancestry. The third individual homozygous for YKT6 [NM_006555.3:c.191A>G p.(Tyr64Cys)] exhibited neurodevelopmental disorders and optic atrophy. Supportive functional data in Drosophila.

Amber rating due to homozygous missense variants and founder effect in two of the families.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5762 SEPHS1 Zornitza Stark Marked gene: SEPHS1 as ready
Intellectual disability syndromic and non-syndromic v0.5762 SEPHS1 Zornitza Stark Gene: sephs1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5762 SEPHS1 Zornitza Stark Classified gene: SEPHS1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5762 SEPHS1 Zornitza Stark Gene: sephs1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5761 SEPHS1 Zornitza Stark gene: SEPHS1 was added
gene: SEPHS1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: SEPHS1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SEPHS1 were set to 38531365
Phenotypes for gene: SEPHS1 were set to Neurodevelopmental disorder, MONDO:0700092, SEPHS1-related
Review for gene: SEPHS1 was set to GREEN
Added comment: Nine individuals from eight families with developmental delay, growth and feeding problems, hypotonia, and dysmorphic features, all with heterozygous missense variants in SEPHS1. Eight of these individuals had a recurrent variant at amino acid position 371 of SEPHS1 (p.Arg371Trp, p.Arg371Gln, and p.Arg371Gly); seven of these variants were known to be de novo.
Sources: Literature
Mendeliome v1.1675 SEPHS1 Zornitza Stark Marked gene: SEPHS1 as ready
Mendeliome v1.1675 SEPHS1 Zornitza Stark Gene: sephs1 has been classified as Green List (High Evidence).
Mendeliome v1.1675 SEPHS1 Zornitza Stark Classified gene: SEPHS1 as Green List (high evidence)
Mendeliome v1.1675 SEPHS1 Zornitza Stark Gene: sephs1 has been classified as Green List (High Evidence).
Mendeliome v1.1674 SEPHS1 Zornitza Stark gene: SEPHS1 was added
gene: SEPHS1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SEPHS1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SEPHS1 were set to 38531365
Phenotypes for gene: SEPHS1 were set to Neurodevelopmental disorder, MONDO:0700092, SEPHS1-related
Review for gene: SEPHS1 was set to GREEN
Added comment: Nine individuals from eight families with developmental delay, growth and feeding problems, hypotonia, and dysmorphic features, all with heterozygous missense variants in SEPHS1. Eight of these individuals had a recurrent variant at amino acid position 371 of SEPHS1 (p.Arg371Trp, p.Arg371Gln, and p.Arg371Gly); seven of these variants were known to be de novo.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5760 GLUL Zornitza Stark Marked gene: GLUL as ready
Intellectual disability syndromic and non-syndromic v0.5760 GLUL Zornitza Stark Gene: glul has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5760 GLUL Zornitza Stark Phenotypes for gene: GLUL were changed from to Developmental and epileptic encephalopathy, MONDO:0100062, GLUL-related; Glutamine deficiency, congenital MIM#610015
Intellectual disability syndromic and non-syndromic v0.5759 GLUL Zornitza Stark Publications for gene: GLUL were set to
Intellectual disability syndromic and non-syndromic v0.5758 GLUL Zornitza Stark Mode of inheritance for gene: GLUL was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5757 GLUL Zornitza Stark reviewed gene: GLUL: Rating: GREEN; Mode of pathogenicity: None; Publications: 16267323, 21353613, 33150193; Phenotypes: Developmental and epileptic encephalopathy, MONDO:0100062, GLUL-related, Glutamine deficiency, congenital MIM#610015, disorder of amino acid metabolism; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genetic Epilepsy v0.2544 GLUL Zornitza Stark Phenotypes for gene: GLUL were changed from Glutamine deficiency, congenital MIM#610015 to Glutamine deficiency, congenital MIM#610015; Developmental and epileptic encephalopathy, MONDO:0100062, GLUL-related
Genetic Epilepsy v0.2543 GLUL Zornitza Stark Mode of inheritance for gene: GLUL was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genetic Epilepsy v0.2542 GLUL Zornitza Stark edited their review of gene: GLUL: Added comment: Nine individuals with de novo variants in this gene and DEE. Seven out of nine were start-loss variants and two out of nine disrupted 5′ UTR splicing resulting in splice exclusion of the initiation codon.; Changed phenotypes: Glutamine deficiency, congenital MIM#610015, Developmental and epileptic encephalopathy, MONDO:0100062, GLUL-related; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.1673 GLUL Zornitza Stark Phenotypes for gene: GLUL were changed from Glutamine deficiency, congenital MIM#610015; disorder of amino acid metabolism to Developmental and epileptic encephalopathy, MONDO:0100062, GLUL-related; Glutamine deficiency, congenital MIM#610015; disorder of amino acid metabolism
Mendeliome v1.1672 GLUL Zornitza Stark Mode of inheritance for gene: GLUL was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.1671 GLUL Zornitza Stark reviewed gene: GLUL: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Developmental and epileptic encephalopathy, MONDO:0100062, GLUL-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary Neuropathy - complex v1.12 SCA4_ZFHX3_GGC Bryony Thompson Marked STR: SCA4_ZFHX3_GGC as ready
Hereditary Neuropathy - complex v1.12 SCA4_ZFHX3_GGC Bryony Thompson Str: sca4_zfhx3_ggc has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v1.12 SCA4_ZFHX3_GGC Bryony Thompson Classified STR: SCA4_ZFHX3_GGC as Green List (high evidence)
Hereditary Neuropathy - complex v1.12 SCA4_ZFHX3_GGC Bryony Thompson Str: sca4_zfhx3_ggc has been classified as Green List (High Evidence).
Ataxia - adult onset v1.8 SCA4_ZFHX3_GGC Bryony Thompson Marked STR: SCA4_ZFHX3_GGC as ready
Ataxia - adult onset v1.8 SCA4_ZFHX3_GGC Bryony Thompson Str: sca4_zfhx3_ggc has been classified as Green List (High Evidence).
Ataxia - adult onset v1.8 SCA4_ZFHX3_GGC Bryony Thompson Classified STR: SCA4_ZFHX3_GGC as Green List (high evidence)
Ataxia - adult onset v1.8 SCA4_ZFHX3_GGC Bryony Thompson Str: sca4_zfhx3_ggc has been classified as Green List (High Evidence).
Mendeliome v1.1671 SCA4_ZFHX3_GGC Bryony Thompson Marked STR: SCA4_ZFHX3_GGC as ready
Mendeliome v1.1671 SCA4_ZFHX3_GGC Bryony Thompson Str: sca4_zfhx3_ggc has been classified as Green List (High Evidence).
Mendeliome v1.1671 SCA4_ZFHX3_GGC Bryony Thompson Classified STR: SCA4_ZFHX3_GGC as Green List (high evidence)
Mendeliome v1.1671 SCA4_ZFHX3_GGC Bryony Thompson Str: sca4_zfhx3_ggc has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v1.11 SCA4_ZFHX3_GGC Bryony Thompson STR: SCA4_ZFHX3_GGC was added
STR: SCA4_ZFHX3_GGC was added to Hereditary Neuropathy - complex. Sources: Literature
Mode of inheritance for STR: SCA4_ZFHX3_GGC was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: SCA4_ZFHX3_GGC were set to 38035881; 38197134
Phenotypes for STR: SCA4_ZFHX3_GGC were set to spinocerebellar ataxia type 4 MONDO:0010847
Review for STR: SCA4_ZFHX3_GGC was set to GREEN
STR: SCA4_ZFHX3_GGC was marked as clinically relevant
Added comment: PMID: 38035881 - repeat expansion is identified in 5 Swedish ataxia families that developed balance and gait disturbances at 15 to 60 years of age and had sensory neuropathy and slow saccades.
PMID: 38197134 - Poly-glycine GGC expansion in the last coding exon of ZFHX3 was identified in the original SCA4 Utah pedigree (Swedish origin) in the region of high linkage identified on 16q22. The expansion was also identified in an Iowa ataxia pedigree of Swedish ancestry. The expansion wasn’t identified in 11,258 exomes, 7,650 WGS probands without neurological phenotype, or 803 individuals with ataxia. Grch38 chr16:72787695–72787758
Normal allele <30 repeats, 21 repeats is the most common (derived from 33,094 individuals)
Undefined pathogenic 30-48 repeats
Definitive pathogenicity 48+ repeats
Sources: Literature
Ataxia - adult onset v1.7 SCA4_ZFHX3_GGC Bryony Thompson STR: SCA4_ZFHX3_GGC was added
STR: SCA4_ZFHX3_GGC was added to Ataxia - adult onset. Sources: Literature
Mode of inheritance for STR: SCA4_ZFHX3_GGC was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: SCA4_ZFHX3_GGC were set to 38035881; 38197134
Phenotypes for STR: SCA4_ZFHX3_GGC were set to spinocerebellar ataxia type 4 MONDO:0010847
Review for STR: SCA4_ZFHX3_GGC was set to GREEN
STR: SCA4_ZFHX3_GGC was marked as clinically relevant
Added comment: PMID: 38035881 - repeat expansion is identified in 5 Swedish ataxia families that developed balance and gait disturbances at 15 to 60 years of age and had sensory neuropathy and slow saccades.
PMID: 38197134 - Poly-glycine GGC expansion in the last coding exon of ZFHX3 was identified in the original SCA4 Utah pedigree (Swedish origin) in the region of high linkage identified on 16q22. The expansion was also identified in an Iowa ataxia pedigree of Swedish ancestry. The expansion wasn’t identified in 11,258 exomes, 7,650 WGS probands without neurological phenotype, or 803 individuals with ataxia. Grch38 chr16:72787695–72787758
Normal allele <30 repeats, 21 repeats is the most common (derived from 33,094 individuals)
Undefined pathogenic 30-48 repeats
Definitive pathogenicity 48+ repeats
Sources: Literature
Mendeliome v1.1670 SCA4_ZFHX3_GGC Bryony Thompson STR: SCA4_ZFHX3_GGC was added
STR: SCA4_ZFHX3_GGC was added to Mendeliome. Sources: Literature
Mode of inheritance for STR: SCA4_ZFHX3_GGC was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: SCA4_ZFHX3_GGC were set to 38035881; 38197134
Phenotypes for STR: SCA4_ZFHX3_GGC were set to spinocerebellar ataxia type 4 MONDO:0010847
Review for STR: SCA4_ZFHX3_GGC was set to GREEN
STR: SCA4_ZFHX3_GGC was marked as clinically relevant
Added comment: PMID: 38035881 - repeat expansion is identified in 5 Swedish ataxia families that developed balance and gait disturbances at 15 to 60 years of age and had sensory neuropathy and slow saccades.
PMID: 38197134 - Poly-glycine GGC expansion in the last coding exon of ZFHX3 was identified in the original SCA4 Utah pedigree (Swedish origin) in the region of high linkage identified on 16q22. The expansion was also identified in an Iowa ataxia pedigree of Swedish ancestry. The expansion wasn’t identified in 11,258 exomes, 7,650 WGS probands without neurological phenotype, or 803 individuals with ataxia. Grch38 chr16:72787695–72787758
Normal allele <30 repeats, 21 repeats is the most common (derived from 33,094 individuals)
Undefined pathogenic 30-48 repeats
Definitive pathogenicity 48+ repeats
Sources: Literature
Repeat Disorders v0.159 SCA4_ZFHX3_GGC Bryony Thompson Marked STR: SCA4_ZFHX3_GGC as ready
Repeat Disorders v0.159 SCA4_ZFHX3_GGC Bryony Thompson Str: sca4_zfhx3_ggc has been classified as Green List (High Evidence).
Repeat Disorders v0.159 SCA4_ZFHX3_GGC Bryony Thompson Classified STR: SCA4_ZFHX3_GGC as Green List (high evidence)
Repeat Disorders v0.159 SCA4_ZFHX3_GGC Bryony Thompson Str: sca4_zfhx3_ggc has been classified as Green List (High Evidence).
Repeat Disorders v0.158 SCA4_ZFHX3_GGC Bryony Thompson STR: SCA4_ZFHX3_GGC was added
STR: SCA4_ZFHX3_GGC was added to Repeat Disorders. Sources: Literature
Mode of inheritance for STR: SCA4_ZFHX3_GGC was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: SCA4_ZFHX3_GGC were set to 38035881; 38197134
Phenotypes for STR: SCA4_ZFHX3_GGC were set to spinocerebellar ataxia type 4 MONDO:0010847
Review for STR: SCA4_ZFHX3_GGC was set to GREEN
STR: SCA4_ZFHX3_GGC was marked as clinically relevant
Added comment: PMID: 38035881 - repeat expansion is identified in 5 Swedish ataxia families that developed balance and gait disturbances at 15 to 60 years of age and had sensory neuropathy and slow saccades.
PMID: 38197134 - Poly-glycine GGC expansion in the last coding exon of ZFHX3 was identified in the original SCA4 Utah pedigree (Swedish origin) in the region of high linkage identified on 16q22. The expansion was also identified in an Iowa ataxia pedigree of Swedish ancestry. The expansion wasn’t identified in 11,258 exomes, 7,650 WGS probands without neurological phenotype, or 803 individuals with ataxia. Grch38 chr16:72787695–72787758
Normal allele <30 repeats, 21 repeats is the most common (derived from 33,094 individuals)
Undefined pathogenic 30-48 repeats
Definitive pathogenicity 48+ repeats
Sources: Literature
Genetic Epilepsy v0.2542 ZFHX3 Bryony Thompson Marked gene: ZFHX3 as ready
Genetic Epilepsy v0.2542 ZFHX3 Bryony Thompson Gene: zfhx3 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2542 ZFHX3 Bryony Thompson Classified gene: ZFHX3 as Green List (high evidence)
Genetic Epilepsy v0.2542 ZFHX3 Bryony Thompson Gene: zfhx3 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2541 ZFHX3 Bryony Thompson gene: ZFHX3 was added
gene: ZFHX3 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: ZFHX3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZFHX3 were set to 38508705
Phenotypes for gene: ZFHX3 were set to developmental and epileptic encephalopathy MONDO:0100062
Review for gene: ZFHX3 was set to GREEN
gene: ZFHX3 was marked as current diagnostic
Added comment: 8 unrelated probands with biallelic variants and a phenotype consistent with DEE and childhood partial epilepsy. Also a supporting Drosophila Zfh2 knockdown model with seizure-like behaviour.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5757 GTF3C5 Bryony Thompson Marked gene: GTF3C5 as ready
Intellectual disability syndromic and non-syndromic v0.5757 GTF3C5 Bryony Thompson Gene: gtf3c5 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5757 GTF3C5 Bryony Thompson Classified gene: GTF3C5 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5757 GTF3C5 Bryony Thompson Gene: gtf3c5 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5756 GTF3C5 Bryony Thompson gene: GTF3C5 was added
gene: GTF3C5 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: GTF3C5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GTF3C5 were set to 38520561; 35503477
Phenotypes for gene: GTF3C5 were set to neurodevelopmental disorder MONDO:0700092, GTF3C5-related
Review for gene: GTF3C5 was set to GREEN
gene: GTF3C5 was marked as current diagnostic
Added comment: 4 families/probands with syndromic ID. Loss of function is the expected
PMID: 38520561 - Biallelic variants identified (3 missense & 1 stopgain) in 4 individuals from 3 families presenting with multisystem developmental syndrome including the features: growth retardation, developmental delay, intellectual disability, dental anomalies, cerebellar malformations, delayed bone age, skeletal anomalies, and facial dysmorphism. Gene-disease relationship supported by: reduced protein expression in patient cells, yeast assays, and a zebrafish model
PMID: 35503477 - 1 proband with biallelic missense variants and hypomelanosis of Ito, seizures, growth retardation, abnormal brain MRI, developmental delay, and facial dysmorphism
Sources: Literature
Mendeliome v1.1669 GTF3C5 Bryony Thompson Marked gene: GTF3C5 as ready
Mendeliome v1.1669 GTF3C5 Bryony Thompson Gene: gtf3c5 has been classified as Green List (High Evidence).
Mendeliome v1.1669 GTF3C5 Bryony Thompson Classified gene: GTF3C5 as Green List (high evidence)
Mendeliome v1.1669 GTF3C5 Bryony Thompson Gene: gtf3c5 has been classified as Green List (High Evidence).
Mendeliome v1.1668 GTF3C5 Bryony Thompson gene: GTF3C5 was added
gene: GTF3C5 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GTF3C5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GTF3C5 were set to 38520561; 35503477
Phenotypes for gene: GTF3C5 were set to neurodevelopmental disorder MONDO:0700092, GTF3C5-related
Review for gene: GTF3C5 was set to GREEN
Added comment: 4 families/probands with syndromic ID. Loss of function is the expected
PMID: 38520561 - Biallelic variants identified (3 missense & 1 stopgain) in 4 individuals from 3 families presenting with multisystem developmental syndrome including the features: growth retardation, developmental delay, intellectual disability, dental anomalies, cerebellar malformations, delayed bone age, skeletal anomalies, and facial dysmorphism. Gene-disease relationship supported by: reduced protein expression in patient cells, yeast assays, and a zebrafish model
PMID: 35503477 - 1 proband with biallelic missense variants and hypomelanosis of Ito, seizures, growth retardation, abnormal brain MRI, developmental delay, and facial dysmorphism
Sources: Literature
Mendeliome v1.1667 MCOLN1 Zornitza Stark Phenotypes for gene: MCOLN1 were changed from Mucolipidosis IV, MIM# 252650; MONDO:0009653 to Mucolipidosis IV, MIM# 252650; MONDO:0009653; Lisch epithelial corneal dystrophy, OMIM# 620763
Mendeliome v1.1666 MCOLN1 Zornitza Stark Publications for gene: MCOLN1 were set to
Mendeliome v1.1665 MCOLN1 Zornitza Stark Mode of inheritance for gene: MCOLN1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.1664 MCOLN1 Zornitza Stark edited their review of gene: MCOLN1: Added comment: PMID 37972748: 23 affected individuals from 13 families with Lisch epithelial corneal dystrophy. WGS in 2 families and then targeted Sanger sequencing in the other families identified 9 rare heterozygous loss of function variants in MCOLN1. Homozygous and compound-heterozygous state of 4 of 9 LECD-associated variants cause Mucolipidosis IV (MLIV), which comprises neurodegeneration as well as corneal opacity of infantile-onset with epithelial autofluorescent lysosomal inclusions. Six parents of 3 patients with MLIV confirmed to carry pathogenic MCOLN1 variants did not have the LECD phenotype. Heterozygous MCOLN1 variants can be associated with incomplete penetrance and variable expressivity of LECD with an estimated penetrance of 0.2% for MCOLN1 loss-of-function variants based on gnomAD.; Changed publications: 37972748; Changed phenotypes: Mucolipidosis IV, MIM# 252650, MONDO:0009653, Lisch epithelial corneal dystrophy, OMIM# 620763; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Corneal Dystrophy v1.10 MCOLN1 Zornitza Stark Marked gene: MCOLN1 as ready
Corneal Dystrophy v1.10 MCOLN1 Zornitza Stark Gene: mcoln1 has been classified as Green List (High Evidence).
Growth failure v1.75 CEP295 Zornitza Stark Marked gene: CEP295 as ready
Growth failure v1.75 CEP295 Zornitza Stark Gene: cep295 has been classified as Green List (High Evidence).
Microcephalic Primordial Dwarfism and Slender bone dysplasias v0.29 CEP295 Zornitza Stark Marked gene: CEP295 as ready
Microcephalic Primordial Dwarfism and Slender bone dysplasias v0.29 CEP295 Zornitza Stark Gene: cep295 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5755 CEP295 Zornitza Stark Marked gene: CEP295 as ready
Intellectual disability syndromic and non-syndromic v0.5755 CEP295 Zornitza Stark Gene: cep295 has been classified as Green List (High Evidence).
Microcephaly v1.257 CEP295 Zornitza Stark Marked gene: CEP295 as ready
Microcephaly v1.257 CEP295 Zornitza Stark Gene: cep295 has been classified as Green List (High Evidence).
Mendeliome v1.1664 CEP295 Zornitza Stark Marked gene: CEP295 as ready
Mendeliome v1.1664 CEP295 Zornitza Stark Gene: cep295 has been classified as Green List (High Evidence).
Amelogenesis imperfecta v1.10 PLXNB2 Zornitza Stark Phenotypes for gene: PLXNB2 were changed from Amelogenesis imperfecta MONDO:0019507, PLXNB2 -related; Sensorineural hearing loss disorder MONDO:0020678, PLXNB2 -related to Syndromic disease MONDO:0002254, PLXNB2 -related
Deafness_IsolatedAndComplex v1.178 PLXNB2 Zornitza Stark Phenotypes for gene: PLXNB2 were changed from Amelogenesis imperfecta MONDO:0019507, PLXNB2 -related; Sensorineural hearing loss disorder MONDO:0020678, PLXNB2 -related to Syndromic disease MONDO:0002254, PLXNB2 -related
Mendeliome v1.1664 PLXNB2 Zornitza Stark Phenotypes for gene: PLXNB2 were changed from Amelogenesis imperfecta MONDO:0019507, PLXNB2 -related; Sensorineural hearing loss disorder MONDO:0020678, PLXNB2 -related to Syndromic disease MONDO:0002254, PLXNB2 -related
Intellectual disability syndromic and non-syndromic v0.5755 PLXNB2 Zornitza Stark Phenotypes for gene: PLXNB2 were changed from Amelogenesis imperfecta MONDO:0019507, PLXNB2 -related; Sensorineural hearing loss disorder MONDO:0020678, PLXNB2 -related to Syndromic disease MONDO:0002254, PLXNB2 -related
Intellectual disability syndromic and non-syndromic v0.5754 PLXNB2 Zornitza Stark Marked gene: PLXNB2 as ready
Intellectual disability syndromic and non-syndromic v0.5754 PLXNB2 Zornitza Stark Gene: plxnb2 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.177 PLXNB2 Zornitza Stark Marked gene: PLXNB2 as ready
Deafness_IsolatedAndComplex v1.177 PLXNB2 Zornitza Stark Gene: plxnb2 has been classified as Green List (High Evidence).
Amelogenesis imperfecta v1.9 PLXNB2 Zornitza Stark Marked gene: PLXNB2 as ready
Amelogenesis imperfecta v1.9 PLXNB2 Zornitza Stark Gene: plxnb2 has been classified as Green List (High Evidence).
Mendeliome v1.1663 PLXNB2 Zornitza Stark Marked gene: PLXNB2 as ready
Mendeliome v1.1663 PLXNB2 Zornitza Stark Gene: plxnb2 has been classified as Green List (High Evidence).
Catecholaminergic Polymorphic Ventricular Tachycardia v0.35 KCNJ2 Zornitza Stark Phenotypes for gene: KCNJ2 were changed from Andersen Tawil syndrome, LQTS to catecholaminergic polymorphic ventricular tachycardia MONDO:0017990
Catecholaminergic Polymorphic Ventricular Tachycardia v0.34 KCNJ2 Zornitza Stark Classified gene: KCNJ2 as Red List (low evidence)
Catecholaminergic Polymorphic Ventricular Tachycardia v0.34 KCNJ2 Zornitza Stark Gene: kcnj2 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.2540 KCNB2 Zornitza Stark Marked gene: KCNB2 as ready
Genetic Epilepsy v0.2540 KCNB2 Zornitza Stark Gene: kcnb2 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2540 KCNB2 Zornitza Stark Classified gene: KCNB2 as Amber List (moderate evidence)
Genetic Epilepsy v0.2540 KCNB2 Zornitza Stark Gene: kcnb2 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2539 KCNB2 Zornitza Stark gene: KCNB2 was added
gene: KCNB2 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: KCNB2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KCNB2 were set to 38503299
Phenotypes for gene: KCNB2 were set to neurodevelopmental disorder MONDO:0700092, KCNB2-related
Review for gene: KCNB2 was set to AMBER
Added comment: 7 individuals, all missense
5 de novo + 1x inherited from father who has hypotonia + 1x from asymptomatic father

2/5 MRI anomalies
2/5 cardiac anomalies
2/7 urogenital anomalies
7/7 with ID
2/7 epilepsy
2/7 hypotonia
Sources: Literature
Fetal anomalies v1.230 FRYL Zornitza Stark Classified gene: FRYL as Green List (high evidence)
Fetal anomalies v1.230 FRYL Zornitza Stark Gene: fryl has been classified as Green List (High Evidence).
Fetal anomalies v1.229 FRYL Zornitza Stark reviewed gene: FRYL: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: neurodevelopmental disorder MONDO:0700092, FRYL-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Renal Tubulopathies and related disorders v1.12 TRPV5 Zornitza Stark Marked gene: TRPV5 as ready
Renal Tubulopathies and related disorders v1.12 TRPV5 Zornitza Stark Gene: trpv5 has been classified as Red List (Low Evidence).
Renal Tubulopathies and related disorders v1.12 TRPV5 Zornitza Stark gene: TRPV5 was added
gene: TRPV5 was added to Renal Tubulopathies and related disorders. Sources: Literature
Mode of inheritance for gene: TRPV5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRPV5 were set to 38528055; 14679186
Phenotypes for gene: TRPV5 were set to TRPV5-related hypercalciuria (MONDO:0009550)
Review for gene: TRPV5 was set to RED
Added comment: Not a well-established gene-disease association. Has only been reported in one consanguineous family.

PMID: 38528055
3 individuals from the same family affected with hypercalciuria.
Biallelic Met598Val variant was identified in the proband and his two affect sibs

Functional assay using WT and mutant plasmid vectors were transfected into HEK293T cells. The assay showed that the mutant vector had a non-functional TRPV5 channel as compared to the WT however no positive control was used.

PMID: 14679186
TRPV5 knockout mice model was used to assess whether the abolishment of TRPV5 led to a disruption in Ca2+ handling. The effects of the disruption in Ca2+ handling resulted in bone abnormalities in the mice and is likely the cause of idiopathic hypercalciuria.
Sources: Literature
Fetal anomalies v1.229 DISP1 Zornitza Stark Phenotypes for gene: DISP1 were changed from Holoprosencephaly, MONDO:0016296 to Holoprosencephaly (MONDO:0016296), DISP1-related
Fetal anomalies v1.228 DISP1 Zornitza Stark Publications for gene: DISP1 were set to 27363716; 19184110; 26748417; 23542665
Fetal anomalies v1.227 DISP1 Zornitza Stark Mode of inheritance for gene: DISP1 was changed from Other to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v1.226 DISP1 Zornitza Stark Classified gene: DISP1 as Green List (high evidence)
Fetal anomalies v1.226 DISP1 Zornitza Stark Gene: disp1 has been classified as Green List (High Evidence).
Fetal anomalies v1.225 DISP1 Zornitza Stark edited their review of gene: DISP1: Added comment: PMID: 38529886
25 individuals from 20 unrelated families with a phenotype associated with mild holoprosencephaly (HPE).
A total of 23 different variants were identified in DISP1 (missense, frameshift and nonsense).
14 heterozygous individuals , 5 compound heterozygous individuals, 6 homozygous individuals (5 of the individuals were from 3 unrelated consanguineous families).

HPE phenotype was also seen prenatally as one of the reported monoallelic individuals was a fetus at 20+6 GW prior to passing due to MTP.; Changed rating: GREEN; Changed publications: 19184110, 26748417, 23542665, 38529886; Changed phenotypes: Holoprosencephaly (MONDO:0016296), DISP1-related; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5754 DISP1 Zornitza Stark Phenotypes for gene: DISP1 were changed from Holoprosencephaly, MONDO:0016296 to Holoprosencephaly (MONDO:0016296), DISP1-related
Intellectual disability syndromic and non-syndromic v0.5753 DISP1 Zornitza Stark Publications for gene: DISP1 were set to 19184110; 26748417; 23542665
Intellectual disability syndromic and non-syndromic v0.5752 DISP1 Zornitza Stark Mode of inheritance for gene: DISP1 was changed from Other to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5751 DISP1 Zornitza Stark Classified gene: DISP1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5751 DISP1 Zornitza Stark Gene: disp1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5750 DISP1 Zornitza Stark edited their review of gene: DISP1: Changed rating: GREEN
Intellectual disability syndromic and non-syndromic v0.5750 DISP1 Zornitza Stark edited their review of gene: DISP1: Added comment: PMID: 38529886
25 individuals from 20 unrelated families with a phenotype associated with mild holoprosencephaly (HPE).
A total of 23 different variants were identified in DISP1 (missense, frameshift and nonsense).
14 heterozygous individuals , 5 compound heterozygous individuals, 6 homozygous individuals (5 of the individuals were from 3 unrelated consanguineous families).

HPE phenotype was also seen prenatally as one of the reported monoallelic individuals was a fetus at 20+6 GW prior to passing due to MTP.; Changed publications: 19184110, 26748417, 23542665, 38529886; Changed phenotypes: Holoprosencephaly (MONDO:0016296), DISP1-related; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.1663 DOCK4 Zornitza Stark Marked gene: DOCK4 as ready
Mendeliome v1.1663 DOCK4 Zornitza Stark Gene: dock4 has been classified as Green List (High Evidence).
Mendeliome v1.1663 DOCK4 Zornitza Stark Classified gene: DOCK4 as Green List (high evidence)
Mendeliome v1.1663 DOCK4 Zornitza Stark Gene: dock4 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5750 DOCK4 Bryony Thompson Phenotypes for gene: DOCK4 were changed from to DOCK4-related neurodevelopmental disorder (MONDO:0060490)
Intellectual disability syndromic and non-syndromic v0.5749 DOCK4 Bryony Thompson Publications for gene: DOCK4 were set to
Holoprosencephaly and septo-optic dysplasia v1.14 DISP1 Bryony Thompson Publications for gene: DISP1 were set to 19184110; 26748417; 23542665
Intellectual disability syndromic and non-syndromic v0.5748 DOCK4 Bryony Thompson Mode of inheritance for gene: DOCK4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Holoprosencephaly and septo-optic dysplasia v1.13 DISP1 Bryony Thompson Mode of inheritance for gene: DISP1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5747 DOCK4 Bryony Thompson Classified gene: DOCK4 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5747 DOCK4 Bryony Thompson Gene: dock4 has been classified as Green List (High Evidence).
Mendeliome v1.1662 TRPV5 Bryony Thompson Marked gene: TRPV5 as ready
Mendeliome v1.1662 TRPV5 Bryony Thompson Gene: trpv5 has been classified as Red List (Low Evidence).
Mendeliome v1.1662 TRPV5 Bryony Thompson Publications for gene: TRPV5 were set to PMID: 38528055
Holoprosencephaly and septo-optic dysplasia v1.12 DISP1 Bryony Thompson Classified gene: DISP1 as Green List (high evidence)
Holoprosencephaly and septo-optic dysplasia v1.12 DISP1 Bryony Thompson Gene: disp1 has been classified as Green List (High Evidence).
Mendeliome v1.1661 TRPV5 Bryony Thompson Classified gene: TRPV5 as Red List (low evidence)
Mendeliome v1.1661 TRPV5 Bryony Thompson Gene: trpv5 has been classified as Red List (Low Evidence).
Mendeliome v1.1660 TRPV5 Sangavi Sivagnanasundram edited their review of gene: TRPV5: Changed publications: PMID: 38528055, 14679186
Mendeliome v1.1660 TRPV5 Sangavi Sivagnanasundram changed review comment from: Not a well-established gene-disease association. Has only been reported in one consanguineous family.

PMID: 38528055
3 individuals from the same family affected with hypercalciuria.
Biallelic Met598Val variant was identified in the proband and his two affect sibs

Functional assay using WT and mutant plasmid vectors were transfected into HEK293T cells. The assay showed that the mutant vector had a non-functional TRPV5 channel as compared to the WT however no positive control was used.
Sources: Other; to: Not a well-established gene-disease association. Has only been reported in one consanguineous family.

PMID: 38528055
3 individuals from the same family affected with hypercalciuria.
Biallelic Met598Val variant was identified in the proband and his two affect sibs

Functional assay using WT and mutant plasmid vectors were transfected into HEK293T cells. The assay showed that the mutant vector had a non-functional TRPV5 channel as compared to the WT however no positive control was used.

PMID: 14679186
TRPV5 knockout mice model was used to assess whether the abolishment of TRPV5 led to a disruption in Ca2+ handling. The effects of the disruption in Ca2+ handling resulted in bone abnormalities in the mice and is likely the cause of idiopathic hypercalciuria.

Sources: Other
Mendeliome v1.1660 DOCK4 Sangavi Sivagnanasundram gene: DOCK4 was added
gene: DOCK4 was added to Mendeliome. Sources: Other
Mode of inheritance for gene: DOCK4 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: DOCK4 were set to PMID: 38526744
Phenotypes for gene: DOCK4 were set to DOCK4-related neurodevelopmental disorder (MONDO:0060490)
Review for gene: DOCK4 was set to GREEN
Added comment: 7 unrelated individuals reported with heterozygous variants (missense or null variants) in DOCK4. The individuals either had ID or DD between mild and moderate with brain abnormalities. Two of the individuals are reportedly compound heterozygous.

Functional assay neuro-2A Dock4 knockout cells by using the Alt-R CRISPR-Cas9 system utilizing two different guide RNAs (ko1 and ko2) and one nonspecific control guide RNA (C: control). The assay depicted the loss of function mechanism in the presence of either p.Arg853Leu and p.Asp946_Lys1966delinsValSer* (described as 945VS).
Sources: Other
Intellectual disability syndromic and non-syndromic v0.5746 DOCK4 Sangavi Sivagnanasundram changed review comment from: 7 unrelated individuals reported with heterozygous variants (missense or null variants) in DOCK4. The individuals either had ID or DD between mild and moderate with brain abnormalities.

Functional assay neuro-2A Dock4 knockout cells by using the Alt-R CRISPR-Cas9 system utilizing two different guide RNAs (ko1 and ko2) and one nonspecific control guide RNA (C: control). The assay depicted the loss of function mechanism in the presence of either p.Arg853Leu and p.Asp946_Lys1966delinsValSer* (described as 945VS).; to: 7 unrelated individuals reported with heterozygous variants (missense or null variants) in DOCK4. The individuals either had ID or DD between mild and moderate with brain abnormalities. Two of the individuals are reportedly compound heterozygous.

Functional assay neuro-2A Dock4 knockout cells by using the Alt-R CRISPR-Cas9 system utilizing two different guide RNAs (ko1 and ko2) and one nonspecific control guide RNA (C: control). The assay depicted the loss of function mechanism in the presence of either p.Arg853Leu and p.Asp946_Lys1966delinsValSer* (described as 945VS).
Intellectual disability syndromic and non-syndromic v0.5746 DOCK4 Sangavi Sivagnanasundram changed review comment from: Well-established gene-disease association

7 unrelated individuals reported with heterozygous variants (missense or null variants) in DOCK4. The individuals either had ID or DD between mild and moderate with brain abnormalities.

Functional assay neuro-2A Dock4 knockout cells by using the Alt-R CRISPR-Cas9 system utilizing two different guide RNAs (ko1 and ko2) and one nonspecific control guide RNA (C: control). The assay depicted the loss of function mechanism in the presence of either p.Arg853Leu and p.Asp946_Lys1966delinsValSer* (described as 945VS).; to: 7 unrelated individuals reported with heterozygous variants (missense or null variants) in DOCK4. The individuals either had ID or DD between mild and moderate with brain abnormalities.

Functional assay neuro-2A Dock4 knockout cells by using the Alt-R CRISPR-Cas9 system utilizing two different guide RNAs (ko1 and ko2) and one nonspecific control guide RNA (C: control). The assay depicted the loss of function mechanism in the presence of either p.Arg853Leu and p.Asp946_Lys1966delinsValSer* (described as 945VS).
Mendeliome v1.1660 DISP1 Bryony Thompson Publications for gene: DISP1 were set to 19184110; 26748417; 23542665
Mendeliome v1.1659 DISP1 Bryony Thompson Mode of inheritance for gene: DISP1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.1658 DISP1 Bryony Thompson Classified gene: DISP1 as Green List (high evidence)
Mendeliome v1.1658 DISP1 Bryony Thompson Gene: disp1 has been classified as Green List (High Evidence).
Mendeliome v1.1657 DISP1 Sangavi Sivagnanasundram changed review comment from: Well-establised gene disease association with differing mechanism of disease depending on the type of causative variant.
Monoallelic truncating variants that resulted in haploinsufficiency in DISP1 led to mild HPE. However biallelic missense variants that results in a partial loss of function of DISP1 cause HPE as well.

PMID: 38529886
25 individuals from 20 unrelated families with a phenotype associated with mild holoprosencephaly (HPE).
A total of 23 different variants were identified in DISP1 (missense, frameshift and nonsense).
14 heterozygous individuals , 5 compound heterozygous individuals, 6 homozygous individuals (5 of the individuals were from 3 unrelated consanguineous families).

HPE phenotype was also seen prenatally as one of the reported monoallelic individuals was a fetus at 20+6 GW prior to passing due to MTP.

; to: Gene disease association with differing mechanism of disease depending on the type of causative variant.
Monoallelic truncating variants that resulted in haploinsufficiency in DISP1 led to mild HPE. However biallelic missense variants that results in a partial loss of function of DISP1 cause HPE as well.

PMID: 38529886
25 individuals from 20 unrelated families with a phenotype associated with mild holoprosencephaly (HPE).
A total of 23 different variants were identified in DISP1 (missense, frameshift and nonsense).
14 heterozygous individuals , 5 compound heterozygous individuals, 6 homozygous individuals (5 of the individuals were from 3 unrelated consanguineous families).

HPE phenotype was also seen prenatally as one of the reported monoallelic individuals was a fetus at 20+6 GW prior to passing due to MTP.

Mendeliome v1.1657 DISP1 Sangavi Sivagnanasundram changed review comment from: Well-establised gene disease association with differing mechanism of disease depending on the type of causative variant.

PMID: 38529886
25 individuals from 20 unrelated families with a phenotype associated with mild holoprosencephaly (HPE).
A total of 23 different variants were identified in DISP1 (missense, frameshift and nonsense).

Monoallelic truncating variants that resulted in haploinsufficiency in DISP1 led to mild HPE. However biallelic missense variants that results in a partial loss of function f DISP1 cause HPE as well.; to: Well-establised gene disease association with differing mechanism of disease depending on the type of causative variant.
Monoallelic truncating variants that resulted in haploinsufficiency in DISP1 led to mild HPE. However biallelic missense variants that results in a partial loss of function of DISP1 cause HPE as well.

PMID: 38529886
25 individuals from 20 unrelated families with a phenotype associated with mild holoprosencephaly (HPE).
A total of 23 different variants were identified in DISP1 (missense, frameshift and nonsense).
14 heterozygous individuals , 5 compound heterozygous individuals, 6 homozygous individuals (5 of the individuals were from 3 unrelated consanguineous families).

HPE phenotype was also seen prenatally as one of the reported monoallelic individuals was a fetus at 20+6 GW prior to passing due to MTP.

Fetal anomalies v1.225 FRYL Ain Roesley Marked gene: FRYL as ready
Fetal anomalies v1.225 FRYL Ain Roesley Gene: fryl has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.225 FRYL Ain Roesley Classified gene: FRYL as Amber List (moderate evidence)
Fetal anomalies v1.225 FRYL Ain Roesley Gene: fryl has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.224 FRYL Ain Roesley gene: FRYL was added
gene: FRYL was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: FRYL was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FRYL were set to 38479391
Phenotypes for gene: FRYL were set to neurodevelopmental disorder MONDO:0700092, FRYL-related
Review for gene: FRYL was set to AMBER
gene: FRYL was marked as current diagnostic
Added comment: 14 individuals, all de novo except 1x duo testing (not present in tested father)
5x missense + 8x fs/stopgain + 1x canonical splice

7/14 with cardiac anomalies

Of interest to this panel: 1x tetralogy of fallot (TOF) with pulmonary atresia (PA), 2x dextrocardia, 1x hypoplastic left heart syndrome

Other reported features AVSD, VSD, PDA
Sources: Literature
Congenital Heart Defect v0.416 FRYL Ain Roesley Classified gene: FRYL as Green List (high evidence)
Congenital Heart Defect v0.416 FRYL Ain Roesley Gene: fryl has been classified as Green List (High Evidence).
Congenital Heart Defect v0.415 FRYL Ain Roesley gene: FRYL was added
gene: FRYL was added to Congenital Heart Defect. Sources: Literature
Mode of inheritance for gene: FRYL was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FRYL were set to 38479391
Phenotypes for gene: FRYL were set to neurodevelopmental disorder MONDO:0700092, FRYL-related
Review for gene: FRYL was set to GREEN
gene: FRYL was marked as current diagnostic
Added comment: 14 individuals, all de novo except 1x duo testing (not present in tested father)
5x missense + 8x fs/stopgain + 1x canonical splice

13/13 with ID/DD (1x deceased)
4/14 seizures
7/14 with cardiac anomalies such as PDA, TOF, VSD, dextrocardia

1x also has a de novo fs variant in SF3B4
1x also has a de novo stop gain variant in SDHA

functional studies using flies were performed
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5746 FRYL Ain Roesley Marked gene: FRYL as ready
Intellectual disability syndromic and non-syndromic v0.5746 FRYL Ain Roesley Gene: fryl has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5746 FRYL Ain Roesley Classified gene: FRYL as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5746 FRYL Ain Roesley Gene: fryl has been classified as Green List (High Evidence).
Mendeliome v1.1657 FRYL Ain Roesley Marked gene: FRYL as ready
Mendeliome v1.1657 FRYL Ain Roesley Gene: fryl has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5745 FRYL Ain Roesley gene: FRYL was added
gene: FRYL was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: FRYL was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FRYL were set to 38479391
Phenotypes for gene: FRYL were set to neurodevelopmental disorder MONDO:0700092, FRYL-related
Review for gene: FRYL was set to GREEN
gene: FRYL was marked as current diagnostic
Added comment: 14 individuals, all de novo except 1x duo testing (not present in tested father)
5x missense + 8x fs/stopgain + 1x canonical splice

13/13 with ID/DD (1x deceased)
4/14 seizures
7/14 with cardiac anomalies such as PDA, TOF, VSD, dextrocardia

1x also has a de novo fs variant in SF3B4
1x also has a de novo stop gain variant in SDHA

functional studies using flies were performed
Sources: Literature
Mendeliome v1.1657 FRYL Ain Roesley Classified gene: FRYL as Green List (high evidence)
Mendeliome v1.1657 FRYL Ain Roesley Gene: fryl has been classified as Green List (High Evidence).
Mendeliome v1.1656 FRYL Ain Roesley gene: FRYL was added
gene: FRYL was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: FRYL was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FRYL were set to 38479391
Phenotypes for gene: FRYL were set to neurodevelopmental disorder MONDO:0700092, FRYL-related
Review for gene: FRYL was set to GREEN
gene: FRYL was marked as current diagnostic
Added comment: 14 individuals, all de novo except 1x duo testing (not present in tested father)
5x missense + 8x fs/stopgain + 1x canonical splice

13/13 with ID/DD (1x deceased)
4/14 seizures
7/14 with cardiac anomalies such as PDA, TOF, VSD, dextrocardia

1x also has a de novo fs variant in SF3B4
1x also has a de novo stop gain variant in SDHA

functional studies using flies were performed
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5744 KCNB2 Ain Roesley Marked gene: KCNB2 as ready
Intellectual disability syndromic and non-syndromic v0.5744 KCNB2 Ain Roesley Gene: kcnb2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5744 KCNB2 Ain Roesley Classified gene: KCNB2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5744 KCNB2 Ain Roesley Gene: kcnb2 has been classified as Green List (High Evidence).
Mendeliome v1.1655 KCNB2 Ain Roesley Marked gene: KCNB2 as ready
Mendeliome v1.1655 KCNB2 Ain Roesley Gene: kcnb2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5743 KCNB2 Ain Roesley gene: KCNB2 was added
gene: KCNB2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: KCNB2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KCNB2 were set to 38503299
Phenotypes for gene: KCNB2 were set to neurodevelopmental disorder MONDO:0700092, KCNB2-related
Review for gene: KCNB2 was set to GREEN
gene: KCNB2 was marked as current diagnostic
Added comment: 7 individuals, all missense
5 de novo + 1x inherited from father who has hypotonia + 1x from asymptomatic father

2/5 MRI anomalies
2/5 cardiac anomalies
2/7 urogenital anomalies
7/7 with ID
2/7 epilepsy
2/7 hypotonia
Sources: Literature
Sources: Literature
Mendeliome v1.1655 KCNB2 Ain Roesley Classified gene: KCNB2 as Green List (high evidence)
Mendeliome v1.1655 KCNB2 Ain Roesley Gene: kcnb2 has been classified as Green List (High Evidence).
Mendeliome v1.1654 KCNB2 Ain Roesley changed review comment from: 7 individuals, all missense
1x from asymptomatic father

2/5 MRI anomalies
2/5 cardiac anomalies
2/7 urogenital anomalies
7/7 with ID
2/7 epilepsy
2/7 hypotonia
Sources: Literature; to: 7 individuals, all missense
5 de novo + 1x inherited from father who has hypotonia + 1x from asymptomatic father

2/5 MRI anomalies
2/5 cardiac anomalies
2/7 urogenital anomalies
7/7 with ID
2/7 epilepsy
2/7 hypotonia
Sources: Literature
Mendeliome v1.1654 KCNB2 Ain Roesley gene: KCNB2 was added
gene: KCNB2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: KCNB2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KCNB2 were set to 38503299
Phenotypes for gene: KCNB2 were set to neurodevelopmental disorder MONDO:0700092, KCNB2-related
Review for gene: KCNB2 was set to GREEN
gene: KCNB2 was marked as current diagnostic
Added comment: 7 individuals, all missense
1x from asymptomatic father

2/5 MRI anomalies
2/5 cardiac anomalies
2/7 urogenital anomalies
7/7 with ID
2/7 epilepsy
2/7 hypotonia
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5742 DOCK4 Sangavi Sivagnanasundram edited their review of gene: DOCK4: Changed rating: GREEN
Catecholaminergic Polymorphic Ventricular Tachycardia v0.33 KCNJ2 Sangavi Sivagnanasundram reviewed gene: KCNJ2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: catecholaminergic polymorphic ventricular tachycardia MONDO:0017990; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v1.223 MAP3K20 Zornitza Stark edited their review of gene: MAP3K20: Added comment: PMID 38451290: five individuals with diverse clinical features, including craniosynostosis, limb anomalies, sensorineural hearing loss, and ectodermal dysplasia-like phenotypes who have heterozygous de novo variants in the linker region between the kinase domain and leucine zipper domain of MAP3K20.; Changed publications: 38451290; Changed phenotypes: Syndromic disease, MONDO:0002254, MAP3K20-related, Centronuclear myopathy 6 with fiber-type disproportion MIM#617760, Split-foot malformation with mesoaxial polydactyly MIM#616890; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Ectodermal Dysplasia v0.85 MAP3K20 Zornitza Stark Marked gene: MAP3K20 as ready
Ectodermal Dysplasia v0.85 MAP3K20 Zornitza Stark Gene: map3k20 has been classified as Green List (High Evidence).
Ectodermal Dysplasia v0.85 MAP3K20 Zornitza Stark Classified gene: MAP3K20 as Green List (high evidence)
Ectodermal Dysplasia v0.85 MAP3K20 Zornitza Stark Gene: map3k20 has been classified as Green List (High Evidence).
Ectodermal Dysplasia v0.84 MAP3K20 Zornitza Stark gene: MAP3K20 was added
gene: MAP3K20 was added to Ectodermal Dysplasia. Sources: Literature
Mode of inheritance for gene: MAP3K20 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAP3K20 were set to 38451290
Phenotypes for gene: MAP3K20 were set to Syndromic disease, MONDO:0002254, MAP3K20-related
Review for gene: MAP3K20 was set to GREEN
Added comment: PMID 38451290: five individuals with diverse clinical features, including craniosynostosis, limb anomalies, sensorineural hearing loss, and ectodermal dysplasia-like phenotypes who have heterozygous de novo variants in the linker region between the kinase domain and leucine zipper domain of MAP3K20.
Sources: Literature
Deafness_IsolatedAndComplex v1.177 MAP3K20 Zornitza Stark Marked gene: MAP3K20 as ready
Deafness_IsolatedAndComplex v1.177 MAP3K20 Zornitza Stark Gene: map3k20 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.177 MAP3K20 Zornitza Stark Classified gene: MAP3K20 as Green List (high evidence)
Deafness_IsolatedAndComplex v1.177 MAP3K20 Zornitza Stark Gene: map3k20 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.176 MAP3K20 Zornitza Stark gene: MAP3K20 was added
gene: MAP3K20 was added to Deafness_IsolatedAndComplex. Sources: Literature
Mode of inheritance for gene: MAP3K20 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAP3K20 were set to 38451290
Phenotypes for gene: MAP3K20 were set to Syndromic disease, MONDO:0002254, MAP3K20-related
Review for gene: MAP3K20 was set to GREEN
Added comment: PMID 38451290: five individuals with diverse clinical features, including craniosynostosis, limb anomalies, sensorineural hearing loss, and ectodermal dysplasia-like phenotypes who have heterozygous de novo variants in the linker region between the kinase domain and leucine zipper domain of MAP3K20.
Sources: Literature
Craniosynostosis v1.68 MAP3K20 Zornitza Stark Marked gene: MAP3K20 as ready
Craniosynostosis v1.68 MAP3K20 Zornitza Stark Gene: map3k20 has been classified as Green List (High Evidence).
Craniosynostosis v1.68 MAP3K20 Zornitza Stark Classified gene: MAP3K20 as Green List (high evidence)
Craniosynostosis v1.68 MAP3K20 Zornitza Stark Gene: map3k20 has been classified as Green List (High Evidence).
Craniosynostosis v1.67 MAP3K20 Zornitza Stark gene: MAP3K20 was added
gene: MAP3K20 was added to Craniosynostosis. Sources: Literature
Mode of inheritance for gene: MAP3K20 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAP3K20 were set to 38451290
Phenotypes for gene: MAP3K20 were set to Syndromic disease, MONDO:0002254, MAP3K20-related
Review for gene: MAP3K20 was set to GREEN
Added comment: PMID 38451290: five individuals with diverse clinical features, including craniosynostosis, limb anomalies, sensorineural hearing loss, and ectodermal dysplasia-like phenotypes who have heterozygous de novo variants in the linker region between the kinase domain and leucine zipper domain of MAP3K20.
Sources: Literature
Mendeliome v1.1653 MAP3K20 Zornitza Stark Phenotypes for gene: MAP3K20 were changed from Centronuclear myopathy 6 with fiber-type disproportion MIM#617760; Split-foot malformation with mesoaxial polydactyly MIM#616890 to Syndromic disease, MONDO:0002254, MAP3K20-related; Centronuclear myopathy 6 with fiber-type disproportion MIM#617760; Split-foot malformation with mesoaxial polydactyly MIM#616890
Mendeliome v1.1652 MAP3K20 Zornitza Stark Publications for gene: MAP3K20 were set to 27816943; 26755636
Mendeliome v1.1651 MAP3K20 Zornitza Stark Mode of inheritance for gene: MAP3K20 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.1650 MAP3K20 Zornitza Stark reviewed gene: MAP3K20: Rating: GREEN; Mode of pathogenicity: None; Publications: 38451290; Phenotypes: Syndromic disease, MONDO:0002254, MAP3K20-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Microcephaly v1.257 SASS6 Ain Roesley Publications for gene: SASS6 were set to 24951542; 30639237; 38501757; 36739862
Microcephaly v1.256 SASS6 Ain Roesley Publications for gene: SASS6 were set to 24951542; 30639237
Mendeliome v1.1650 PLXNB2 Chirag Patel Classified gene: PLXNB2 as Green List (high evidence)
Mendeliome v1.1650 PLXNB2 Chirag Patel Gene: plxnb2 has been classified as Green List (High Evidence).
Microcephaly v1.256 SASS6 Ain Roesley Classified gene: SASS6 as Green List (high evidence)
Microcephaly v1.256 SASS6 Ain Roesley Gene: sass6 has been classified as Green List (High Evidence).
Mendeliome v1.1649 CEP295 Chirag Patel Classified gene: CEP295 as Green List (high evidence)
Mendeliome v1.1649 CEP295 Chirag Patel Gene: cep295 has been classified as Green List (High Evidence).
Fetal anomalies v1.223 SASS6 Ain Roesley Publications for gene: SASS6 were set to 24951542; 30639237
Mendeliome v1.1649 PLXNB2 Chirag Patel gene: PLXNB2 was added
gene: PLXNB2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PLXNB2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PLXNB2 were set to PMID: 38458752
Phenotypes for gene: PLXNB2 were set to Amelogenesis imperfecta MONDO:0019507, PLXNB2 -related; Sensorineural hearing loss disorder MONDO:0020678, PLXNB2 -related
Review for gene: PLXNB2 was set to GREEN
gene: PLXNB2 was marked as current diagnostic
Added comment: 8 individuals from 6 families with core features of amelogenesis imperfecta and sensorineural hearing loss. Intellectual disability, ocular disease, ear developmental abnormalities and lymphoedema were also present in multiple cases. WES and WGS identified biallelic pathogenic variants in PLXNB2 (missense, nonsense, splice and a multiexon deletion variants). Variants segregated with disease.

PLXNB2 is a large transmembrane semaphorin receptor protein, and semaphorin-plexin signalling controls cellular interactions that are critical during development as well as in adult life stages. Plxnb2 expression was detected in differentiating ameloblasts in mice. Human phenotype overlaps with that seen in Plxnb2 knockout mice.
Sources: Literature
Fetal anomalies v1.223 SASS6 Ain Roesley Classified gene: SASS6 as Green List (high evidence)
Fetal anomalies v1.223 SASS6 Ain Roesley Gene: sass6 has been classified as Green List (High Evidence).
Microcephaly v1.255 SASS6 Ain Roesley reviewed gene: SASS6: Rating: GREEN; Mode of pathogenicity: None; Publications: 38501757, 36739862; Phenotypes: Microcephaly 14, primary, autosomal recessive, MIM# 616402; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Fetal anomalies v1.222 SASS6 Ain Roesley reviewed gene: SASS6: Rating: GREEN; Mode of pathogenicity: None; Publications: 38501757, 36739862; Phenotypes: Microcephaly 14, primary, autosomal recessive, MIM# 616402; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v1.1648 CEP295 Chirag Patel gene: CEP295 was added
gene: CEP295 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CEP295 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CEP295 were set to PMID: 38154379
Phenotypes for gene: CEP295 were set to Seckel syndrome 11, OMIM # 620767
Review for gene: CEP295 was set to GREEN
gene: CEP295 was marked as current diagnostic
Added comment: 4 children from 2 unrelated families with Seckel-like syndrome - severe primary microcephaly, short stature, developmental delay, intellectual disability, facial deformities, and abnormalities of fingers and toes. WES identified biallelic pathogenic variants in CEP295 gene (p(Q544∗) and p(R1520∗); p(R55Efs∗49) and p(P562L)).

Patient-derived fibroblasts and CEP295-depleted U2OS and RPE1 cells were used to clarify the underlying mechanisms. Depletion of CEP295 resulted in a decrease in the numbers of centrioles and centrosomes and triggered p53-dependent G1 cell cycle arrest. Loss of CEP295 caused extensive primary ciliary defects in both patient-derived fibroblasts and RPE1 cells. The results from complementary experiments revealed that the wild-type CEP295, but not the mutant protein, can correct the developmental defects of the centrosome/centriole and cilia in the patient-derived skin fibroblasts.
Sources: Literature
Mendeliome v1.1647 SASS6 Ain Roesley Publications for gene: SASS6 were set to 24951542; 30639237
Mendeliome v1.1647 SASS6 Ain Roesley Classified gene: SASS6 as Green List (high evidence)
Mendeliome v1.1647 SASS6 Ain Roesley Gene: sass6 has been classified as Green List (High Evidence).
Mendeliome v1.1646 SASS6 Ain Roesley Deleted their comment
Mendeliome v1.1646 SASS6 Ain Roesley commented on gene: SASS6: PMID: 38501757
1x compound het for a fs and +3 splice variant.

Using cDNA RT-ed from mother's RNA, exons 13-15 were amplified and exon 14 was found to be skipped resulting in c.1546_1674del and p.516_558del

PMID: 36739862
1x family, compound het for 2 missense
Functional studies not performed
Mendeliome v1.1646 SASS6 Ain Roesley reviewed gene: SASS6: Rating: GREEN; Mode of pathogenicity: None; Publications: 38501757, 36739862; Phenotypes: Microcephaly 14, primary, autosomal recessive, MIM# 616402; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v1.1646 FANCI Ain Roesley Phenotypes for gene: FANCI were changed from Fanconi anemia, complementation group I, MIM# 609053; MONDO:0012186 to Fanconi anemia, complementation group I, MIM# 609053; MONDO:0012186; primary ovarian failure MONDO:0005387, FANCI-related
Mendeliome v1.1645 FANCI Ain Roesley reviewed gene: FANCI: Rating: AMBER; Mode of pathogenicity: None; Publications: 38483614; Phenotypes: primary ovarian failure MONDO:0005387, FANCI-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.325 FANCI Ain Roesley edited their review of gene: FANCI: Changed phenotypes: primary ovarian failure MONDO:0005387, FANCI-related
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.325 FANCI Ain Roesley Marked gene: FANCI as ready
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.325 FANCI Ain Roesley Gene: fanci has been classified as Amber List (Moderate Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.325 FANCI Ain Roesley Classified gene: FANCI as Amber List (moderate evidence)
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.325 FANCI Ain Roesley Gene: fanci has been classified as Amber List (Moderate Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.324 FANCI Ain Roesley gene: FANCI was added
gene: FANCI was added to Primary Ovarian Insufficiency_Premature Ovarian Failure. Sources: Literature
Mode of inheritance for gene: FANCI was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FANCI were set to 38483614
Review for gene: FANCI was set to AMBER
gene: FANCI was marked as current diagnostic
Added comment: WES however FANCI was specifically looked at based on KO mouse model which had premature exhaustion of primordial follicles leading to complete sterility.

2x compound hets: 2x missense + 1x canonical splice+1x missense

Minigene performed on the splice variant
Functional assays using KO cells + expression of variant demonstrated reduced ubiquitination of FANCI and increased DNA damage under replication stress
Sources: Literature
Corneal Dystrophy v1.10 MCOLN1 Chirag Patel Classified gene: MCOLN1 as Green List (high evidence)
Corneal Dystrophy v1.10 MCOLN1 Chirag Patel Gene: mcoln1 has been classified as Green List (High Evidence).
Corneal Dystrophy v1.10 MCOLN1 Chirag Patel Classified gene: MCOLN1 as Green List (high evidence)
Corneal Dystrophy v1.10 MCOLN1 Chirag Patel Gene: mcoln1 has been classified as Green List (High Evidence).
Corneal Dystrophy v1.9 MCOLN1 Chirag Patel gene: MCOLN1 was added
gene: MCOLN1 was added to Corneal Dystrophy. Sources: Literature
Mode of inheritance for gene: MCOLN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MCOLN1 were set to PMID: 37972748,
Phenotypes for gene: MCOLN1 were set to Lisch epithelial corneal dystrophy, OMIM# 620763
Review for gene: MCOLN1 was set to GREEN
gene: MCOLN1 was marked as current diagnostic
Added comment: 23 affected individuals from 13 families with Lisch epithelial corneal dystrophy. WGS in 2 families and then targeted Sanger sequencing in the other families identified 9 rare heterozygous loss of function variants in MCOLN1.

Homozygous and compound-heterozygous state of 4 of 9 LECD-associated variants cause Mucolipidosis IV (MLIV), which comprises neurodegeneration as well as corneal opacity of infantile-onset with epithelial autofluorescent lysosomal inclusions. Six parents of 3 patients with MLIV confirmed to carry pathogenic MCOLN1 variants did not have the LECD phenotype.

Heterozygous MCOLN1 variants can be associated with incomplete penetrance and variable expressivity of LECD with an estimated penetrance of 0.2% for MCOLN1 loss-of-function variants based on gnomAD.
Sources: Literature
Deafness_IsolatedAndComplex v1.175 PLXNB2 Chirag Patel Classified gene: PLXNB2 as Green List (high evidence)
Deafness_IsolatedAndComplex v1.175 PLXNB2 Chirag Patel Gene: plxnb2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5742 PLXNB2 Chirag Patel Classified gene: PLXNB2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5742 PLXNB2 Chirag Patel Gene: plxnb2 has been classified as Green List (High Evidence).
Amelogenesis imperfecta v1.9 PLXNB2 Chirag Patel Classified gene: PLXNB2 as Green List (high evidence)
Amelogenesis imperfecta v1.9 PLXNB2 Chirag Patel Gene: plxnb2 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.174 PLXNB2 Chirag Patel gene: PLXNB2 was added
gene: PLXNB2 was added to Deafness_IsolatedAndComplex. Sources: Literature
Mode of inheritance for gene: PLXNB2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PLXNB2 were set to PMID: 38458752
Phenotypes for gene: PLXNB2 were set to Amelogenesis imperfecta MONDO:0019507, PLXNB2 -related; Sensorineural hearing loss disorder MONDO:0020678, PLXNB2 -related
Review for gene: PLXNB2 was set to GREEN
gene: PLXNB2 was marked as current diagnostic
Added comment: 8 individuals from 6 families with core features of amelogenesis imperfecta and sensorineural hearing loss. Intellectual disability, ocular disease, ear developmental abnormalities and lymphoedema were also present in multiple cases. WES and WGS identified biallelic pathogenic variants in PLXNB2 (missense, nonsense, splice and a multiexon deletion variants). Variants segregated with disease.

PLXNB2 is a large transmembrane semaphorin receptor protein, and semaphorin-plexin signalling controls cellular interactions that are critical during development as well as in adult life stages. Plxnb2 expression was detected in differentiating ameloblasts in mice. Human phenotype overlaps with that seen in Plxnb2 knockout mice.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5741 PLXNB2 Chirag Patel gene: PLXNB2 was added
gene: PLXNB2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: PLXNB2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PLXNB2 were set to PMID: 38458752
Phenotypes for gene: PLXNB2 were set to Amelogenesis imperfecta MONDO:0019507, PLXNB2 -related; Sensorineural hearing loss disorder MONDO:0020678, PLXNB2 -related
Review for gene: PLXNB2 was set to GREEN
gene: PLXNB2 was marked as current diagnostic
Added comment: 8 individuals from 6 families with core features of amelogenesis imperfecta and sensorineural hearing loss. Intellectual disability, ocular disease, ear developmental abnormalities and lymphoedema were also present in multiple cases. WES and WGS identified biallelic pathogenic variants in PLXNB2 (missense, nonsense, splice and a multiexon deletion variants). Variants segregated with disease.

PLXNB2 is a large transmembrane semaphorin receptor protein, and semaphorin-plexin signalling controls cellular interactions that are critical during development as well as in adult life stages. Plxnb2 expression was detected in differentiating ameloblasts in mice. Human phenotype overlaps with that seen in Plxnb2 knockout mice.
Sources: Literature
Amelogenesis imperfecta v1.8 PLXNB2 Chirag Patel gene: PLXNB2 was added
gene: PLXNB2 was added to Amelogenesis imperfecta. Sources: Literature
Mode of inheritance for gene: PLXNB2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PLXNB2 were set to PMID: 38458752
Phenotypes for gene: PLXNB2 were set to Amelogenesis imperfecta MONDO:0019507, PLXNB2 -related; Sensorineural hearing loss disorder MONDO:0020678, PLXNB2 -related
Review for gene: PLXNB2 was set to GREEN
gene: PLXNB2 was marked as current diagnostic
Added comment: 8 individuals from 6 families with core features of amelogenesis imperfecta and sensorineural hearing loss. Intellectual disability, ocular disease, ear developmental abnormalities and lymphoedema were also present in multiple cases. WES and WGS identified biallelic pathogenic variants in PLXNB2 (missense, nonsense, splice and a multiexon deletion variants). Variants segregated with disease.

PLXNB2 is a large transmembrane semaphorin receptor protein, and semaphorin-plexin signalling controls cellular interactions that are critical during development as well as in adult life stages. Plxnb2 expression was detected in differentiating ameloblasts in mice. Human phenotype overlaps with that seen in Plxnb2 knockout mice.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5740 CEP295 Chirag Patel Classified gene: CEP295 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5740 CEP295 Chirag Patel Gene: cep295 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5740 CEP295 Chirag Patel Classified gene: CEP295 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5740 CEP295 Chirag Patel Gene: cep295 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5739 CEP295 Chirag Patel Classified gene: CEP295 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5739 CEP295 Chirag Patel Gene: cep295 has been classified as Green List (High Evidence).
Microcephaly v1.255 CEP295 Chirag Patel Classified gene: CEP295 as Green List (high evidence)
Microcephaly v1.255 CEP295 Chirag Patel Gene: cep295 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5739 CEP295 Chirag Patel Classified gene: CEP295 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5739 CEP295 Chirag Patel Gene: cep295 has been classified as Green List (High Evidence).
Microcephaly v1.254 CEP295 Chirag Patel Classified gene: CEP295 as Green List (high evidence)
Microcephaly v1.254 CEP295 Chirag Patel Gene: cep295 has been classified as Green List (High Evidence).
Microcephalic Primordial Dwarfism and Slender bone dysplasias v0.29 CEP295 Chirag Patel Classified gene: CEP295 as Green List (high evidence)
Microcephalic Primordial Dwarfism and Slender bone dysplasias v0.29 CEP295 Chirag Patel Gene: cep295 has been classified as Green List (High Evidence).
Growth failure v1.75 CEP295 Chirag Patel Classified gene: CEP295 as Green List (high evidence)
Growth failure v1.75 CEP295 Chirag Patel Gene: cep295 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5738 CEP295 Chirag Patel gene: CEP295 was added
gene: CEP295 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: CEP295 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CEP295 were set to PMID: 38154379
Phenotypes for gene: CEP295 were set to Seckel syndrome 11, OMIM # 620767
Review for gene: CEP295 was set to GREEN
gene: CEP295 was marked as current diagnostic
Added comment: 4 children from 2 unrelated families with Seckel-like syndrome - severe primary microcephaly, short stature, developmental delay, intellectual disability, facial deformities, and abnormalities of fingers and toes. WES identified biallelic pathogenic variants in CEP295 gene (p(Q544∗) and p(R1520∗); p(R55Efs∗49) and p(P562L)).

Patient-derived fibroblasts and CEP295-depleted U2OS and RPE1 cells were used to clarify the underlying mechanisms. Depletion of CEP295 resulted in a decrease in the numbers of centrioles and centrosomes and triggered p53-dependent G1 cell cycle arrest. Loss of CEP295 caused extensive primary ciliary defects in both patient-derived fibroblasts and RPE1 cells. The results from complementary experiments revealed that the wild-type CEP295, but not the mutant protein, can correct the developmental defects of the centrosome/centriole and cilia in the patient-derived skin fibroblasts.
Sources: Literature
Microcephaly v1.253 CEP295 Chirag Patel gene: CEP295 was added
gene: CEP295 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: CEP295 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CEP295 were set to PMID: 38154379
Phenotypes for gene: CEP295 were set to Seckel syndrome 11, OMIM # 620767
Review for gene: CEP295 was set to GREEN
gene: CEP295 was marked as current diagnostic
Added comment: 4 children from 2 unrelated families with Seckel-like syndrome - severe primary microcephaly, short stature, developmental delay, intellectual disability, facial deformities, and abnormalities of fingers and toes. WES identified biallelic pathogenic variants in CEP295 gene (p(Q544∗) and p(R1520∗); p(R55Efs∗49) and p(P562L)).

Patient-derived fibroblasts and CEP295-depleted U2OS and RPE1 cells were used to clarify the underlying mechanisms. Depletion of CEP295 resulted in a decrease in the numbers of centrioles and centrosomes and triggered p53-dependent G1 cell cycle arrest. Loss of CEP295 caused extensive primary ciliary defects in both patient-derived fibroblasts and RPE1 cells. The results from complementary experiments revealed that the wild-type CEP295, but not the mutant protein, can correct the developmental defects of the centrosome/centriole and cilia in the patient-derived skin fibroblasts.
Sources: Literature
Growth failure v1.74 CEP295 Chirag Patel gene: CEP295 was added
gene: CEP295 was added to Growth failure. Sources: Literature
Mode of inheritance for gene: CEP295 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CEP295 were set to PMID: 38154379
Phenotypes for gene: CEP295 were set to Seckel syndrome 11, OMIM # 620767
Review for gene: CEP295 was set to GREEN
gene: CEP295 was marked as current diagnostic
Added comment: 4 children from 2 unrelated families with Seckel-like syndrome - severe primary microcephaly, short stature, developmental delay, intellectual disability, facial deformities, and abnormalities of fingers and toes. WES identified biallelic pathogenic variants in CEP295 gene (p(Q544∗) and p(R1520∗); p(R55Efs∗49) and p(P562L)).

Patient-derived fibroblasts and CEP295-depleted U2OS and RPE1 cells were used to clarify the underlying mechanisms. Depletion of CEP295 resulted in a decrease in the numbers of centrioles and centrosomes and triggered p53-dependent G1 cell cycle arrest. Loss of CEP295 caused extensive primary ciliary defects in both patient-derived fibroblasts and RPE1 cells. The results from complementary experiments revealed that the wild-type CEP295, but not the mutant protein, can correct the developmental defects of the centrosome/centriole and cilia in the patient-derived skin fibroblasts.
Sources: Literature
Microcephalic Primordial Dwarfism and Slender bone dysplasias v0.28 CEP295 Chirag Patel gene: CEP295 was added
gene: CEP295 was added to Microcephalic Primordial Dwarfism and Slender bone dysplasias. Sources: Literature
Mode of inheritance for gene: CEP295 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CEP295 were set to PMID: 38154379
Phenotypes for gene: CEP295 were set to Seckel syndrome 11, OMIM # 620767
Review for gene: CEP295 was set to GREEN
gene: CEP295 was marked as current diagnostic
Added comment: 4 children from 2 unrelated families with Seckel-like syndrome - severe primary microcephaly, short stature, developmental delay, intellectual disability, facial deformities, and abnormalities of fingers and toes. WES identified biallelic pathogenic variants in CEP295 gene (p(Q544∗) and p(R1520∗); p(R55Efs∗49) and p(P562L)).

Patient-derived fibroblasts and CEP295-depleted U2OS and RPE1 cells were used to clarify the underlying mechanisms. Depletion of CEP295 resulted in a decrease in the numbers of centrioles and centrosomes and triggered p53-dependent G1 cell cycle arrest. Loss of CEP295 caused extensive primary ciliary defects in both patient-derived fibroblasts and RPE1 cells. The results from complementary experiments revealed that the wild-type CEP295, but not the mutant protein, can correct the developmental defects of the centrosome/centriole and cilia in the patient-derived skin fibroblasts.
Sources: Literature
Mendeliome v1.1645 CAPNS1 Zornitza Stark Marked gene: CAPNS1 as ready
Mendeliome v1.1645 CAPNS1 Zornitza Stark Gene: capns1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1645 CAPNS1 Zornitza Stark Classified gene: CAPNS1 as Amber List (moderate evidence)
Mendeliome v1.1645 CAPNS1 Zornitza Stark Gene: capns1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1644 CAPNS1 Zornitza Stark gene: CAPNS1 was added
gene: CAPNS1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: CAPNS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CAPNS1 were set to 38230350
Phenotypes for gene: CAPNS1 were set to Hereditary pulmonary arterial hypertension MONDO:0017148, CAPNS1-related
Review for gene: CAPNS1 was set to AMBER
Added comment: Three individuals from two families reported with homozygous splice site variants.
Sources: Expert list
Pulmonary Arterial Hypertension v1.37 CAPNS1 Zornitza Stark Marked gene: CAPNS1 as ready
Pulmonary Arterial Hypertension v1.37 CAPNS1 Zornitza Stark Gene: capns1 has been classified as Amber List (Moderate Evidence).
Pulmonary Arterial Hypertension v1.37 CAPNS1 Zornitza Stark Classified gene: CAPNS1 as Amber List (moderate evidence)
Pulmonary Arterial Hypertension v1.37 CAPNS1 Zornitza Stark Gene: capns1 has been classified as Amber List (Moderate Evidence).
Pulmonary Arterial Hypertension v1.36 CAPNS1 Zornitza Stark gene: CAPNS1 was added
gene: CAPNS1 was added to Pulmonary Arterial Hypertension. Sources: Expert list
Mode of inheritance for gene: CAPNS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CAPNS1 were set to 38230350
Phenotypes for gene: CAPNS1 were set to Hereditary pulmonary arterial hypertension MONDO:0017148, CAPNS1-related
Review for gene: CAPNS1 was set to AMBER
Added comment: Three individuals from two families reported with homozygous splice site variants.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.5737 USP27X Zornitza Stark Phenotypes for gene: USP27X were changed from Mental retardation, X-linked 105, MIM#300984 to Intellectual disability, X-linked 105, MIM#300984
Intellectual disability syndromic and non-syndromic v0.5736 USP27X Zornitza Stark Publications for gene: USP27X were set to 25644381
Intellectual disability syndromic and non-syndromic v0.5735 USP27X Zornitza Stark Classified gene: USP27X as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5735 USP27X Zornitza Stark Gene: usp27x has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5734 USP27X Zornitza Stark edited their review of gene: USP27X: Added comment: Ten additional individuals and further experimental data reported.; Changed rating: GREEN; Changed publications: 25644381, 38182161; Changed phenotypes: Intellectual disability, X-linked 105, MIM#300984
Mendeliome v1.1643 USP27X Zornitza Stark Phenotypes for gene: USP27X were changed from Mental retardation, X-linked 105, MIM#300984 to Intellectual disability, X-linked 105, MIM#300984
Mendeliome v1.1642 USP27X Zornitza Stark Publications for gene: USP27X were set to 25644381
Mendeliome v1.1641 USP27X Zornitza Stark Classified gene: USP27X as Green List (high evidence)
Mendeliome v1.1641 USP27X Zornitza Stark Gene: usp27x has been classified as Green List (High Evidence).
Mendeliome v1.1640 USP27X Zornitza Stark edited their review of gene: USP27X: Added comment: Ten additional individuals and further experimental data reported.; Changed rating: GREEN; Changed publications: 25644381, 38182161; Changed phenotypes: Intellectual disability, X-linked 105, MIM#300984
Mendeliome v1.1640 ZNF143 Bryony Thompson Classified gene: ZNF143 as Amber List (moderate evidence)
Mendeliome v1.1640 ZNF143 Bryony Thompson Gene: znf143 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1639 ZNF143 Bryony Thompson reviewed gene: ZNF143: Rating: AMBER; Mode of pathogenicity: None; Publications: 27349184, 33845046, 9009278, 22268977, 27349184, 27349184; Phenotypes: methylmalonic aciduria and homocystinuria MONDO:0016826; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1639 TCN1 Bryony Thompson Marked gene: TCN1 as ready
Mendeliome v1.1639 TCN1 Bryony Thompson Gene: tcn1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1639 TCN1 Bryony Thompson Classified gene: TCN1 as Amber List (moderate evidence)
Mendeliome v1.1639 TCN1 Bryony Thompson Gene: tcn1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1638 TCN1 Bryony Thompson gene: TCN1 was added
gene: TCN1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TCN1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TCN1 were set to 29764838; 19686235
Phenotypes for gene: TCN1 were set to transcobalamin I deficiency MONDO:0008659
Review for gene: TCN1 was set to AMBER
Added comment: Unclear if TC1 deficiency is associated with a clinical phenotype and only found 2 families with genetic findings. 1 confirmed chet (2 truncating variants) with severe TC 1 deficiency (depression and anxiety only reported symptoms, had sickle cell trait) & another family with 2 siblings that are presumed homozygous for a truncating variant (no plasma or serum TC 1 levels but no DNA available for genetic testing) which was found heterozygous in multiple first-degree relatives. Unclear if there is a clinical phenotype. Heterozygous individuals displayed mildly low or low-normal TC 1 serum levels. Also, 4 homozygotes were identified in a study of a loss-of-function variant associated with lower vitamin B12 concentration in African Americans but there was limited ability to assess the clinical impact of the recessive disease
Sources: Literature
Mendeliome v1.1637 FEM1B Zornitza Stark Classified gene: FEM1B as Green List (high evidence)
Mendeliome v1.1637 FEM1B Zornitza Stark Gene: fem1b has been classified as Green List (High Evidence).
Mendeliome v1.1636 FEM1B Zornitza Stark Publications for gene: FEM1B were set to PMID: 31036916
Mendeliome v1.1635 FEM1B Zornitza Stark Phenotypes for gene: FEM1B were changed from Syndromic intellectual disability to Syndromic disease MONDO:0002254, FEM1B-related
Intellectual disability syndromic and non-syndromic v0.5734 FEM1B Zornitza Stark Phenotypes for gene: FEM1B were changed from Syndromic intellectual disability to Syndromic disease MONDO:0002254, FEM1B-related
Intellectual disability syndromic and non-syndromic v0.5733 FEM1B Zornitza Stark Publications for gene: FEM1B were set to 31036916
Mendeliome v1.1634 FEM1B Zornitza Stark edited their review of gene: FEM1B: Added comment: Five individuals reported now with same recurrent missense variant, NM_015322.5:c.377G>A NP_056137.1:p.(Arg126Gln). Affected individuals shared a severe neurodevelopmental disorder with behavioral phenotypes and a variable set of malformations, including brain anomalies, clubfeet, skeletal abnormalities, and facial dysmorphism. Overexpression of the the FEM1BR126Q variant but not FEM1B wild-type protein, during mouse brain development, resulted in delayed neuronal migration of the target cells.; Changed rating: GREEN; Changed publications: 31036916, 38465576; Changed phenotypes: Syndromic disease MONDO:0002254, FEM1B-related; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5732 FEM1B Zornitza Stark Classified gene: FEM1B as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5732 FEM1B Zornitza Stark Gene: fem1b has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5731 FEM1B Zornitza Stark edited their review of gene: FEM1B: Added comment: Five individuals reported now with same recurrent missense variant, NM_015322.5:c.377G>A NP_056137.1:p.(Arg126Gln). Affected individuals shared a severe neurodevelopmental disorder with behavioral phenotypes and a variable set of malformations, including brain anomalies, clubfeet, skeletal abnormalities, and facial dysmorphism. Overexpression of the the FEM1BR126Q variant but not FEM1B wild-type protein, during mouse brain development, resulted in delayed neuronal migration of the target cells.; Changed rating: GREEN; Changed publications: 31036916, 38465576; Changed phenotypes: Syndromic disease MONDO:0002254, FEM1B-related
Intellectual disability syndromic and non-syndromic v0.5731 USP14 Zornitza Stark Marked gene: USP14 as ready
Intellectual disability syndromic and non-syndromic v0.5731 USP14 Zornitza Stark Gene: usp14 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5731 USP14 Zornitza Stark Classified gene: USP14 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.5731 USP14 Zornitza Stark Gene: usp14 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5730 USP14 Zornitza Stark Classified gene: USP14 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.5730 USP14 Zornitza Stark Gene: usp14 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5729 USP14 Zornitza Stark gene: USP14 was added
gene: USP14 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: USP14 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: USP14 were set to 38469793; 35066879
Phenotypes for gene: USP14 were set to Syndromic disease MONDO:0002254, USP14-related
Review for gene: USP14 was set to AMBER
Added comment: AMBER rating as two of the families had affected fetuses, one had a severely affected newborn, and fourth had a progressive course: none fit well with ID, though there's likely to be a continuum.

PMID 35066879: 3 fetuses from 2 different branches of a consanguineous family, presenting with distal arthrogryposis, underdevelopment of the corpus callosum, and dysmorphic facial features. Exome sequencing identified a biallelic 4-bp deletion (c.233_236delTTCC; p.Leu78Glnfs*11) in USP14, and sequencing of family members showed segregation with the phenotype. Ubiquitin-specific protease 14 (USP14) encodes a major proteasome-associated deubiquitinating enzyme with an established dual role as an inhibitor and an activator of proteolysis, maintaining protein homeostasis. Usp14-deficient mice show a phenotype similar to lethal human multiple congenital contractures phenotypes, with callosal anomalies, muscle wasting, and early lethality, attributed to neuromuscular junction defects due to decreased monomeric ubiquitin pool. RT-qPCR experiment in an unaffected heterozygote revealed that mutant USP14 was expressed, indicating that abnormal transcript escapes nonsense-mediated mRNA decay.

PMID 38469793: biallelic USP14 variants in four individuals from three unrelated families: one fetus, a newborn with a syndromic NDD, and two siblings affected by a progressive neurological disease. Specifically, the two siblings from the latter family carried two compound heterozygous variants c.8T>C p.(Leu3Pro) and c.988C>T p.(Arg330*), while the fetus had a homozygous frameshift c.899_902del p.(Lys300Serfs*24) variant and the newborn patient harbored a homozygous frameshift c.233_236del p.(Leu78Glnfs*11) variant. The fetus and the newborn had extensive brain malformations.
Sources: Literature
Mendeliome v1.1634 DISP1 Sangavi Sivagnanasundram reviewed gene: DISP1: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 38529886; Phenotypes: Holoprosencephaly (MONDO:0016296); Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.1634 TRPV5 Sangavi Sivagnanasundram gene: TRPV5 was added
gene: TRPV5 was added to Mendeliome. Sources: Other
Mode of inheritance for gene: TRPV5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRPV5 were set to PMID: 38528055
Phenotypes for gene: TRPV5 were set to TRPV5-related hypercalciuria (MONDO:0009550)
Review for gene: TRPV5 was set to RED
Added comment: Not a well-established gene-disease association. Has only been reported in one consanguineous family.

PMID: 38528055
3 individuals from the same family affected with hypercalciuria.
Biallelic Met598Val variant was identified in the proband and his two affect sibs

Functional assay using WT and mutant plasmid vectors were transfected into HEK293T cells. The assay showed that the mutant vector had a non-functional TRPV5 channel as compared to the WT however no positive control was used.
Sources: Other
Intellectual disability syndromic and non-syndromic v0.5728 DOCK4 Sangavi Sivagnanasundram reviewed gene: DOCK4: Rating: ; Mode of pathogenicity: None; Publications: PMID: 38526744; Phenotypes: DOCK4-related neurodevelopmental disorder (MONDO:0060490); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Metabolic Disorders Superpanel v8.125 Bryony Thompson Changed child panels to: Congenital Disorders of Glycosylation; Miscellaneous Metabolic Disorders; Calcium and Phosphate disorders; Fatty Acid Oxidation Defects; Hypertension and Aldosterone disorders; Lysosomal Storage Disorder; Neurotransmitter Defects; Disorders of branched chain amino acid metabolism; Glycogen Storage Diseases; Rhabdomyolysis and Metabolic Myopathy; Inherited vitamin B12 or cobalamin deficiency; Mitochondrial disease; Peroxisomal Disorders; Iron metabolism disorders; Dyslipidaemia; Vitamin C Pathway Disorders; Porphyria; Hyperammonaemia
Miscellaneous Metabolic Disorders v1.44 DPYD Bryony Thompson Tag pharmacogenomic tag was added to gene: DPYD.
Callosome v0.521 USP14 Zornitza Stark Publications for gene: USP14 were set to PMID: 35066879
Callosome v0.520 USP14 Zornitza Stark Classified gene: USP14 as Green List (high evidence)
Callosome v0.520 USP14 Zornitza Stark Gene: usp14 has been classified as Green List (High Evidence).
Callosome v0.519 USP14 Zornitza Stark reviewed gene: USP14: Rating: GREEN; Mode of pathogenicity: None; Publications: 38469793; Phenotypes: Syndromic disease MONDO:0002254, USP14-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.222 USP14 Zornitza Stark Publications for gene: USP14 were set to PMID: 35066879
Fetal anomalies v1.221 USP14 Zornitza Stark Classified gene: USP14 as Green List (high evidence)
Fetal anomalies v1.221 USP14 Zornitza Stark Gene: usp14 has been classified as Green List (High Evidence).
Fetal anomalies v1.220 USP14 Zornitza Stark reviewed gene: USP14: Rating: GREEN; Mode of pathogenicity: None; Publications: 38469793; Phenotypes: Syndromic disease MONDO:0002254, USP14-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1634 USP14 Zornitza Stark Marked gene: USP14 as ready
Mendeliome v1.1634 USP14 Zornitza Stark Gene: usp14 has been classified as Green List (High Evidence).
Mendeliome v1.1634 USP14 Zornitza Stark Classified gene: USP14 as Green List (high evidence)
Mendeliome v1.1634 USP14 Zornitza Stark Gene: usp14 has been classified as Green List (High Evidence).
Mendeliome v1.1633 USP14 Zornitza Stark gene: USP14 was added
gene: USP14 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: USP14 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: USP14 were set to 38469793; 35066879
Phenotypes for gene: USP14 were set to Syndromic disease MONDO:0002254, USP14-related
Review for gene: USP14 was set to GREEN
Added comment: PMID 35066879: 3 fetuses from 2 different branches of a consanguineous family, presenting with distal arthrogryposis, underdevelopment of the corpus callosum, and dysmorphic facial features. Exome sequencing identified a biallelic 4-bp deletion (c.233_236delTTCC; p.Leu78Glnfs*11) in USP14, and sequencing of family members showed segregation with the phenotype. Ubiquitin-specific protease 14 (USP14) encodes a major proteasome-associated deubiquitinating enzyme with an established dual role as an inhibitor and an activator of proteolysis, maintaining protein homeostasis. Usp14-deficient mice show a phenotype similar to lethal human multiple congenital contractures phenotypes, with callosal anomalies, muscle wasting, and early lethality, attributed to neuromuscular junction defects due to decreased monomeric ubiquitin pool. RT-qPCR experiment in an unaffected heterozygote revealed that mutant USP14 was expressed, indicating that abnormal transcript escapes nonsense-mediated mRNA decay.

PMID 38469793: biallelic USP14 variants in four individuals from three unrelated families: one fetus, a newborn with a syndromic NDD, and two siblings affected by a progressive neurological disease. Specifically, the two siblings from the latter family carried two compound heterozygous variants c.8T>C p.(Leu3Pro) and c.988C>T p.(Arg330*), while the fetus had a homozygous frameshift c.899_902del p.(Lys300Serfs*24) variant and the newborn patient harbored a homozygous frameshift c.233_236del p.(Leu78Glnfs*11) variant. The fetus and the newborn had extensive brain malformations.
Sources: Literature
Vitamin metabolism disorders v1.0 Bryony Thompson promoted panel to version 1.0
Miscellaneous Metabolic Disorders v1.44 Bryony Thompson removed gene:THAP11 from the panel
Miscellaneous Metabolic Disorders v1.43 Bryony Thompson removed gene:ZNF143 from the panel
Miscellaneous Metabolic Disorders v1.42 Bryony Thompson removed gene:TCN2 from the panel
Miscellaneous Metabolic Disorders v1.41 Bryony Thompson removed gene:MTR from the panel
Miscellaneous Metabolic Disorders v1.40 Bryony Thompson removed gene:MMADHC from the panel
Vitamin metabolism disorders v0.36 MMADHC Bryony Thompson Tag treatable tag was added to gene: MMADHC.
Miscellaneous Metabolic Disorders v1.39 Bryony Thompson removed gene:MMACHC from the panel
Vitamin metabolism disorders v0.36 MMACHC Bryony Thompson Tag treatable tag was added to gene: MMACHC.
Miscellaneous Metabolic Disorders v1.38 Bryony Thompson removed gene:LMBRD1 from the panel
Vitamin metabolism disorders v0.36 LMBRD1 Bryony Thompson Tag treatable tag was added to gene: LMBRD1.
Miscellaneous Metabolic Disorders v1.37 Bryony Thompson removed gene:HCFC1 from the panel
Miscellaneous Metabolic Disorders v1.36 Bryony Thompson removed gene:GIF from the panel
Miscellaneous Metabolic Disorders v1.35 Bryony Thompson removed gene:CUBN from the panel
Vitamin metabolism disorders v0.36 CUBN Bryony Thompson Tag treatable tag was added to gene: CUBN.
Miscellaneous Metabolic Disorders v1.34 CBS Bryony Thompson Phenotypes for gene: CBS were changed from Homocystinuria, B6-responsive and nonresponsive types MIM#236200; disorder of intracellular cobalamin metabolism to Homocystinuria, B6-responsive and nonresponsive types MIM#236200; disorder of intracellular cobalamin metabolism; metabolic disorder of sulfur metabolism
Miscellaneous Metabolic Disorders v1.33 Bryony Thompson removed gene:AMN from the panel
Miscellaneous Metabolic Disorders v1.32 Bryony Thompson removed gene:ABCD4 from the panel
Vitamin metabolism disorders v0.36 ABCD4 Bryony Thompson Phenotypes for gene: ABCD4 were changed from Methylmalonic aciduria and homocystinuria, cblJ type MIM#614857 to Methylmalonic aciduria and homocystinuria, cblJ type MIM#614857; disorder of vitamin B12 metabolism
Vitamin metabolism disorders v0.35 Bryony Thompson Panel status changed from internal to public
Vitamin metabolism disorders v0.34 TCN1 Bryony Thompson Marked gene: TCN1 as ready
Vitamin metabolism disorders v0.34 TCN1 Bryony Thompson Gene: tcn1 has been classified as Amber List (Moderate Evidence).
Vitamin metabolism disorders v0.34 TCN1 Bryony Thompson changed review comment from: Unclear if TC1 deficiency is associated with a clinical phenotype and only found 2 families with genetic findings. 1 confirmed chet (2 truncating variants) with severe TC 1 deficiency (depression and anxiety only reported symptoms, had sickle cell trait) & another family with 2 siblings that are presumed homozygous for a truncating variant (no plasma or serum TC 1 levels but no DNA available for genetic testing) which was found heterozygous in multiple first degree relatives. Unclear if there is a clinical phenotype. Heterozygous individuals displayed mildly low or low-normal TC 1 serum levels
Sources: Literature; to: Unclear if TC1 deficiency is associated with a clinical phenotype and only found 2 families with genetic findings. 1 confirmed chet (2 truncating variants) with severe TC 1 deficiency (depression and anxiety only reported symptoms, had sickle cell trait) & another family with 2 siblings that are presumed homozygous for a truncating variant (no plasma or serum TC 1 levels but no DNA available for genetic testing) which was found heterozygous in multiple first-degree relatives. Unclear if there is a clinical phenotype. Heterozygous individuals displayed mildly low or low-normal TC 1 serum levels. Also, 4 homozygotes were identified in a study of a loss-of-function variant associated with lower vitamin B12 concentration in African Americans but there was limited ability to assess the clinical impact of the recessive disease
Sources: Literature
Vitamin metabolism disorders v0.34 TCN1 Bryony Thompson edited their review of gene: TCN1: Changed publications: 29764838, 19686235
Vitamin metabolism disorders v0.34 TCN1 Bryony Thompson Classified gene: TCN1 as Amber List (moderate evidence)
Vitamin metabolism disorders v0.34 TCN1 Bryony Thompson Gene: tcn1 has been classified as Amber List (Moderate Evidence).
Vitamin metabolism disorders v0.33 TCN1 Bryony Thompson gene: TCN1 was added
gene: TCN1 was added to Inherited vitamin B12 or cobalamin deficiency. Sources: Literature
Mode of inheritance for gene: TCN1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TCN1 were set to 19686235
Phenotypes for gene: TCN1 were set to transcobalamin I deficiency MONDO:0008659
Review for gene: TCN1 was set to AMBER
Added comment: Unclear if TC1 deficiency is associated with a clinical phenotype and only found 2 families with genetic findings. 1 confirmed chet (2 truncating variants) with severe TC 1 deficiency (depression and anxiety only reported symptoms, had sickle cell trait) & another family with 2 siblings that are presumed homozygous for a truncating variant (no plasma or serum TC 1 levels but no DNA available for genetic testing) which was found heterozygous in multiple first degree relatives. Unclear if there is a clinical phenotype. Heterozygous individuals displayed mildly low or low-normal TC 1 serum levels
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5728 ZFX Zornitza Stark Phenotypes for gene: ZFX were changed from Neurodevelopmental disorder, MONDO:0700092, ZFX-related to Intellectual developmental disorder, X-linked syndromic 37, MIM# 301118
Mendeliome v1.1632 ZFX Zornitza Stark Phenotypes for gene: ZFX were changed from Neurodevelopmental disorder, MONDO:0700092, ZFX-related to Intellectual developmental disorder, X-linked syndromic 37, MIM# 301118
Mendeliome v1.1631 ZFX Zornitza Stark edited their review of gene: ZFX: Changed phenotypes: Intellectual developmental disorder, X-linked syndromic 37, MIM# 301118
Vitamin metabolism disorders v0.32 MTRR Bryony Thompson Marked gene: MTRR as ready
Vitamin metabolism disorders v0.32 MTRR Bryony Thompson Gene: mtrr has been classified as Green List (High Evidence).
Vitamin metabolism disorders v0.32 MTRR Bryony Thompson Classified gene: MTRR as Green List (high evidence)
Vitamin metabolism disorders v0.32 MTRR Bryony Thompson Gene: mtrr has been classified as Green List (High Evidence).
Vitamin metabolism disorders v0.31 MTR Bryony Thompson Marked gene: MTR as ready
Vitamin metabolism disorders v0.31 MTR Bryony Thompson Gene: mtr has been classified as Green List (High Evidence).
Vitamin metabolism disorders v0.31 MTR Bryony Thompson Classified gene: MTR as Green List (high evidence)
Vitamin metabolism disorders v0.31 MTR Bryony Thompson Gene: mtr has been classified as Green List (High Evidence).
Vitamin metabolism disorders v0.30 MMADHC Bryony Thompson Marked gene: MMADHC as ready
Vitamin metabolism disorders v0.30 MMADHC Bryony Thompson Gene: mmadhc has been classified as Green List (High Evidence).
Vitamin metabolism disorders v0.30 MMADHC Bryony Thompson Classified gene: MMADHC as Green List (high evidence)
Vitamin metabolism disorders v0.30 MMADHC Bryony Thompson Gene: mmadhc has been classified as Green List (High Evidence).
Vitamin metabolism disorders v0.29 MMACHC Bryony Thompson Marked gene: MMACHC as ready
Vitamin metabolism disorders v0.29 MMACHC Bryony Thompson Gene: mmachc has been classified as Green List (High Evidence).
Vitamin metabolism disorders v0.29 MMACHC Bryony Thompson Classified gene: MMACHC as Green List (high evidence)
Vitamin metabolism disorders v0.29 MMACHC Bryony Thompson Gene: mmachc has been classified as Green List (High Evidence).
Vitamin metabolism disorders v0.28 LMBRD1 Bryony Thompson Marked gene: LMBRD1 as ready
Vitamin metabolism disorders v0.28 LMBRD1 Bryony Thompson Gene: lmbrd1 has been classified as Green List (High Evidence).
Vitamin metabolism disorders v0.28 LMBRD1 Bryony Thompson Classified gene: LMBRD1 as Green List (high evidence)
Vitamin metabolism disorders v0.28 LMBRD1 Bryony Thompson Gene: lmbrd1 has been classified as Green List (High Evidence).
Vitamin metabolism disorders v0.27 HCFC1 Bryony Thompson Marked gene: HCFC1 as ready
Vitamin metabolism disorders v0.27 HCFC1 Bryony Thompson Gene: hcfc1 has been classified as Green List (High Evidence).
Vitamin metabolism disorders v0.27 HCFC1 Bryony Thompson Classified gene: HCFC1 as Green List (high evidence)
Vitamin metabolism disorders v0.27 HCFC1 Bryony Thompson Gene: hcfc1 has been classified as Green List (High Evidence).
Vitamin metabolism disorders v0.26 GIF Bryony Thompson Marked gene: GIF as ready
Vitamin metabolism disorders v0.26 GIF Bryony Thompson Gene: gif has been classified as Green List (High Evidence).
Vitamin metabolism disorders v0.26 GIF Bryony Thompson Classified gene: GIF as Green List (high evidence)
Vitamin metabolism disorders v0.26 GIF Bryony Thompson Gene: gif has been classified as Green List (High Evidence).
Vitamin metabolism disorders v0.25 CUBN Bryony Thompson Marked gene: CUBN as ready
Vitamin metabolism disorders v0.25 CUBN Bryony Thompson Gene: cubn has been classified as Green List (High Evidence).
Vitamin metabolism disorders v0.25 CUBN Bryony Thompson Classified gene: CUBN as Green List (high evidence)
Vitamin metabolism disorders v0.25 CUBN Bryony Thompson Gene: cubn has been classified as Green List (High Evidence).
Vitamin metabolism disorders v0.24 AMN Bryony Thompson Marked gene: AMN as ready
Vitamin metabolism disorders v0.24 AMN Bryony Thompson Gene: amn has been classified as Green List (High Evidence).
Vitamin metabolism disorders v0.24 AMN Bryony Thompson Classified gene: AMN as Green List (high evidence)
Vitamin metabolism disorders v0.24 AMN Bryony Thompson Gene: amn has been classified as Green List (High Evidence).
Vitamin metabolism disorders v0.23 ABCD4 Bryony Thompson Marked gene: ABCD4 as ready
Vitamin metabolism disorders v0.23 ABCD4 Bryony Thompson Gene: abcd4 has been classified as Green List (High Evidence).
Vitamin metabolism disorders v0.23 ABCD4 Bryony Thompson Classified gene: ABCD4 as Green List (high evidence)
Vitamin metabolism disorders v0.23 ABCD4 Bryony Thompson Gene: abcd4 has been classified as Green List (High Evidence).
Vitamin metabolism disorders v0.21 THAP11 Bryony Thompson Marked gene: THAP11 as ready
Vitamin metabolism disorders v0.21 THAP11 Bryony Thompson Gene: thap11 has been classified as Red List (Low Evidence).
Vitamin metabolism disorders v0.21 TCN2 Bryony Thompson Marked gene: TCN2 as ready
Vitamin metabolism disorders v0.21 TCN2 Bryony Thompson Gene: tcn2 has been classified as Green List (High Evidence).
Vitamin metabolism disorders v0.21 TCN2 Bryony Thompson Classified gene: TCN2 as Green List (high evidence)
Vitamin metabolism disorders v0.21 TCN2 Bryony Thompson Gene: tcn2 has been classified as Green List (High Evidence).
Vitamin metabolism disorders v0.20 MTRR Bryony Thompson Deleted their review
Vitamin metabolism disorders v0.20 MTR Bryony Thompson Deleted their review
Vitamin metabolism disorders v0.20 MMADHC Bryony Thompson Deleted their review
Vitamin metabolism disorders v0.20 MMACHC Bryony Thompson Deleted their review
Vitamin metabolism disorders v0.20 LMBRD1 Bryony Thompson Deleted their review
Vitamin metabolism disorders v0.20 HCFC1 Bryony Thompson Deleted their review
Vitamin metabolism disorders v0.20 GIF Bryony Thompson Deleted their review
Vitamin metabolism disorders v0.20 CUBN Bryony Thompson Deleted their review
Vitamin metabolism disorders v0.20 AMN Bryony Thompson Deleted their review
Vitamin metabolism disorders v0.20 ABCD4 Bryony Thompson Deleted their review
Vitamin metabolism disorders v0.19 TCN2 Bryony Thompson gene: TCN2 was added
gene: TCN2 was added to Inherited vitamin B12 or cobalamin deficiency. Sources: Literature
Mode of inheritance for gene: TCN2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TCN2 were set to 19373259
Phenotypes for gene: TCN2 were set to Transcobalamin II deficiency, 275350
Vitamin metabolism disorders v0.18 ZNF143 Bryony Thompson Marked gene: ZNF143 as ready
Vitamin metabolism disorders v0.18 ZNF143 Bryony Thompson Gene: znf143 has been classified as Amber List (Moderate Evidence).
Vitamin metabolism disorders v0.18 ZNF143 Bryony Thompson Classified gene: ZNF143 as Amber List (moderate evidence)
Vitamin metabolism disorders v0.18 ZNF143 Bryony Thompson Gene: znf143 has been classified as Amber List (Moderate Evidence).
Vitamin metabolism disorders v0.17 ZNF143 Bryony Thompson gene: ZNF143 was added
gene: ZNF143 was added to Inherited vitamin B12 or cobalamin deficiency. Sources: Literature
Mode of inheritance for gene: ZNF143 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZNF143 were set to 27349184; 33845046; 9009278; 22268977; 27349184; 27349184
Phenotypes for gene: ZNF143 were set to methylmalonic aciduria and homocystinuria MONDO:0016826
Review for gene: ZNF143 was set to AMBER
Added comment: Only a single case with biallelic variants reported. However, given a Moderate gene-disease validity classification by the General Inborn Errors of Metabolism GCEP (assessed 05/03/2024). The gene-disease relationship is also supported by biochemical evidence, functional alteration assays, model systems, and rescue experiments
Sources: Literature
Vitamin metabolism disorders v0.16 THAP11 Bryony Thompson Classified gene: THAP11 as Red List (low evidence)
Vitamin metabolism disorders v0.16 THAP11 Bryony Thompson Added comment: Comment on list classification: Limited gene-disease validity classification on 09/02/2024 by General Inborn Errors of Metabolism GCEP
Vitamin metabolism disorders v0.16 THAP11 Bryony Thompson Gene: thap11 has been classified as Red List (Low Evidence).
Vitamin metabolism disorders v0.15 THAP11 Bryony Thompson Deleted their review
Vitamin metabolism disorders v0.15 THAP11 Bryony Thompson gene: THAP11 was added
gene: THAP11 was added to Inherited vitamin B12 or cobalamin deficiency. Sources: Literature
Mode of inheritance for gene: THAP11 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: THAP11 were set to 28449119
Phenotypes for gene: THAP11 were set to Methylmalonic aciduria and homocystinuria MONDO:0016826
Review for gene: THAP11 was set to RED
Added comment: Sources: Literature
Vitamin metabolism disorders v0.14 HCFC1 Bryony Thompson gene: HCFC1 was added
gene: HCFC1 was added to Inherited vitamin B12 or cobalamin deficiency. Sources: Literature
Mode of inheritance for gene: HCFC1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: HCFC1 were set to 24011988
Phenotypes for gene: HCFC1 were set to methylmalonic acidemia with homocystinuria, type cblX MONDO:0010657; disorder of cobalamin metabolism
Review for gene: HCFC1 was set to GREEN
gene: HCFC1 was marked as current diagnostic
Added comment: Sources: Literature
Vitamin metabolism disorders v0.13 ABCD4 Bryony Thompson gene: ABCD4 was added
gene: ABCD4 was added to Inherited vitamin B12 or cobalamin deficiency. Sources: Literature
Mode of inheritance for gene: ABCD4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ABCD4 were set to 22922874; 31113616; 30651581; 28572511
Phenotypes for gene: ABCD4 were set to Methylmalonic aciduria and homocystinuria, cblJ type MIM#614857
Review for gene: ABCD4 was set to GREEN
gene: ABCD4 was marked as current diagnostic
Added comment: Sources: Literature
Vitamin metabolism disorders v0.12 MTR Bryony Thompson gene: MTR was added
gene: MTR was added to Inherited vitamin B12 or cobalamin deficiency. Sources: Literature
Mode of inheritance for gene: MTR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MTR were set to 8968735; 27604308
Phenotypes for gene: MTR were set to Homocystinuria-megaloblastic anemia, cblG complementation type MIM#250940; Organic aciduria
Review for gene: MTR was set to GREEN
gene: MTR was marked as current diagnostic
Added comment: Sources: Literature
Vitamin metabolism disorders v0.11 LMBRD1 Bryony Thompson gene: LMBRD1 was added
gene: LMBRD1 was added to Inherited vitamin B12 or cobalamin deficiency. Sources: Literature
Mode of inheritance for gene: LMBRD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LMBRD1 were set to 19136951; 27604308
Phenotypes for gene: LMBRD1 were set to Methylmalonic aciduria and homocystinuria, cblF type MIM#277380; Disorders of cobalamin absorption, transport and metabolism
Review for gene: LMBRD1 was set to GREEN
gene: LMBRD1 was marked as current diagnostic
Added comment: Sources: Literature
Vitamin metabolism disorders v0.10 MTRR Bryony Thompson gene: MTRR was added
gene: MTRR was added to Inherited vitamin B12 or cobalamin deficiency. Sources: Literature
Mode of inheritance for gene: MTRR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MTRR were set to 27604308; 9501215
Phenotypes for gene: MTRR were set to Homocystinuria-megaloblastic anemia, cbl E type MIM#236270; Disorders of the metabolism of sulphur amino acids
Review for gene: MTRR was set to GREEN
gene: MTRR was marked as current diagnostic
Added comment: Sources: Literature
Vitamin metabolism disorders v0.9 MMADHC Bryony Thompson gene: MMADHC was added
gene: MMADHC was added to Inherited vitamin B12 or cobalamin deficiency. Sources: Literature
Mode of inheritance for gene: MMADHC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MMADHC were set to 27604308; 18385497
Phenotypes for gene: MMADHC were set to Homocystinuria, cblD type, variant 1 MIM#277410; Methylmalonic aciduria and homocystinuria, cblD type MIM#277410; Methylmalonic aciduria, cblD type, variant 2 MIM#277410; Disorders of cobalamin absorption, transport and metabolism
Review for gene: MMADHC was set to GREEN
gene: MMADHC was marked as current diagnostic
Added comment: Sources: Literature
Mendeliome v1.1631 PRDX1 Bryony Thompson Marked gene: PRDX1 as ready
Mendeliome v1.1631 PRDX1 Bryony Thompson Gene: prdx1 has been classified as Green List (High Evidence).
Mendeliome v1.1631 PRDX1 Bryony Thompson Classified gene: PRDX1 as Green List (high evidence)
Mendeliome v1.1631 PRDX1 Bryony Thompson Gene: prdx1 has been classified as Green List (High Evidence).
Mendeliome v1.1630 PRDX1 Bryony Thompson gene: PRDX1 was added
gene: PRDX1 was added to Mendeliome. Sources: Literature
digenic tags were added to gene: PRDX1.
Mode of inheritance for gene: PRDX1 was set to Other
Publications for gene: PRDX1 were set to 29302025; 35190856
Phenotypes for gene: PRDX1 were set to methylmalonic aciduria and homocystinuria type cblC MONDO:0010184
Mode of pathogenicity for gene: PRDX1 was set to Other
Review for gene: PRDX1 was set to GREEN
Added comment: Only variants affecting the canonical splice acceptor site of intron 5 (e.g. c.515-1G-T, c.515-2A-T) that cause skipping of exon 6 and the polyA termination signal of PRDX1 produce an MMACHC epimutation. The resulting read-through transcript extends through the adjacent MMACHC locus in the antisense orientation. These PRDX1 exon 6 acceptor splice site variants cause disease through digenic inheritance with a pathogenic MMACHC on the other allele.
Sources: Literature
Vitamin metabolism disorders v0.8 PRDX1 Bryony Thompson Marked gene: PRDX1 as ready
Vitamin metabolism disorders v0.8 PRDX1 Bryony Thompson Gene: prdx1 has been classified as Green List (High Evidence).
Vitamin metabolism disorders v0.8 PRDX1 Bryony Thompson Classified gene: PRDX1 as Green List (high evidence)
Vitamin metabolism disorders v0.8 PRDX1 Bryony Thompson Gene: prdx1 has been classified as Green List (High Evidence).
Vitamin metabolism disorders v0.7 PRDX1 Bryony Thompson Tag digenic tag was added to gene: PRDX1.
Vitamin metabolism disorders v0.7 PRDX1 Bryony Thompson gene: PRDX1 was added
gene: PRDX1 was added to Inherited vitamin B12 or cobalamin deficiency. Sources: Literature
Mode of inheritance for gene: PRDX1 was set to Other
Publications for gene: PRDX1 were set to 29302025; 35190856
Phenotypes for gene: PRDX1 were set to methylmalonic aciduria and homocystinuria type cblC MONDO:0010184
Mode of pathogenicity for gene: PRDX1 was set to Other
Review for gene: PRDX1 was set to GREEN
Added comment: Only variants affecting the canonical splice acceptor site of intron 5 (e.g. c.515-1G-T, c.515-2A-T) that cause skipping of exon 6 and the polyA termination signal of PRDX1 produce an MMACHC epimutation. The resulting read-through transcript extends through the adjacent MMACHC locus in the antisense orientation. These PRDX1 exon 6 acceptor splice site variants cause disease through digenic inheritance with a pathogenic MMACHC on the other allele.
Sources: Literature
Vitamin metabolism disorders v0.6 MMACHC Bryony Thompson gene: MMACHC was added
gene: MMACHC was added to Inherited vitamin B12 or cobalamin deficiency. Sources: Literature
Mode of inheritance for gene: MMACHC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MMACHC were set to 27604308; 16311595
Phenotypes for gene: MMACHC were set to Methylmalonic aciduria and homocystinuria, cblC type MIM#277400; Disorders of cobalamin absorption, transport and metabolism
Review for gene: MMACHC was set to GREEN
gene: MMACHC was marked as current diagnostic
Added comment: Sources: Literature
Vitamin metabolism disorders v0.5 MMAB Bryony Thompson Marked gene: MMAB as ready
Vitamin metabolism disorders v0.5 MMAB Bryony Thompson Gene: mmab has been classified as Green List (High Evidence).
Vitamin metabolism disorders v0.5 MMAB Bryony Thompson Classified gene: MMAB as Green List (high evidence)
Vitamin metabolism disorders v0.5 MMAB Bryony Thompson Gene: mmab has been classified as Green List (High Evidence).
Vitamin metabolism disorders v0.4 MMAB Bryony Thompson gene: MMAB was added
gene: MMAB was added to Inherited vitamin B12 or cobalamin deficiency. Sources: Literature
Mode of inheritance for gene: MMAB was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MMAB were set to 12471062; 20556797; 35712814; 24813872
Phenotypes for gene: MMAB were set to methylmalonic aciduria, cblB type MONDO:0009614
Review for gene: MMAB was set to GREEN
gene: MMAB was marked as current diagnostic
Added comment: Well-established gene-disease association. Inborn error of cobalamin metabolism.
Sources: Literature
Vitamin metabolism disorders v0.3 AMN Bryony Thompson gene: AMN was added
gene: AMN was added to Inherited vitamin B12 or cobalamin deficiency. Sources: Literature
Mode of inheritance for gene: AMN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AMN were set to 12590260; 27604308
Phenotypes for gene: AMN were set to Imerslund-Grasbeck syndrome 2 MIM#618882; Disorders of cobalamin absorption, transport and metabolism
Review for gene: AMN was set to GREEN
gene: AMN was marked as current diagnostic
Added comment: Sources: Literature
Vitamin metabolism disorders v0.2 CUBN Bryony Thompson gene: CUBN was added
gene: CUBN was added to Inherited vitamin B12 or cobalamin deficiency. Sources: Literature
Mode of inheritance for gene: CUBN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CUBN were set to 10080186; 31613795
Phenotypes for gene: CUBN were set to Proteinuria, chronic benign MIM#618884; Imerslund-Grasbeck syndrome 1 MIM#261100; Intrinsic factor receptor deficiency due to CUBN mutations (Disorders of cobalamin absorption, transport and metabolism)
Review for gene: CUBN was set to GREEN
Added comment: Sources: Literature
Mendeliome v1.1629 PSMB10 Zornitza Stark Phenotypes for gene: PSMB10 were changed from Proteasome-associated autoinflammatory syndrome 5, MIM# 619175 to Proteasome-associated autoinflammatory syndrome 5, MIM# 619175; Severe combined immunodeficiency, MONDO:0015974, PSMB10-related
Mendeliome v1.1628 PSMB10 Zornitza Stark Publications for gene: PSMB10 were set to 31783057; 37600812
Mendeliome v1.1627 PSMB10 Zornitza Stark Mode of inheritance for gene: PSMB10 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.1626 PSMB10 Zornitza Stark edited their review of gene: PSMB10: Added comment: PMID 38503300: Six individuals with three de novo missense variants. Individuals presented with T-B-NK± severe combined immunodeficiency (SCID) and clinical features suggestive of Omenn syndrome, including diarrhea, alopecia, and desquamating erythematous rash.; Changed publications: 31783057, 37600812, 38503300; Changed phenotypes: Proteasome-associated autoinflammatory syndrome 5, MIM# 619175, Severe combined immunodeficiency, MONDO:0015974, PSMB10-related; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Severe Combined Immunodeficiency (absent T absent B cells) v1.7 PSMB10 Zornitza Stark Marked gene: PSMB10 as ready
Severe Combined Immunodeficiency (absent T absent B cells) v1.7 PSMB10 Zornitza Stark Gene: psmb10 has been classified as Green List (High Evidence).
Severe Combined Immunodeficiency (absent T absent B cells) v1.7 PSMB10 Zornitza Stark Classified gene: PSMB10 as Green List (high evidence)
Severe Combined Immunodeficiency (absent T absent B cells) v1.7 PSMB10 Zornitza Stark Gene: psmb10 has been classified as Green List (High Evidence).
Severe Combined Immunodeficiency (absent T absent B cells) v1.6 PSMB10 Zornitza Stark gene: PSMB10 was added
gene: PSMB10 was added to Severe Combined Immunodeficiency (absent T absent B cells). Sources: Literature
Mode of inheritance for gene: PSMB10 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PSMB10 were set to 38503300
Phenotypes for gene: PSMB10 were set to Severe combined immunodeficiency, MONDO:0015974, PSMB10-related
Review for gene: PSMB10 was set to GREEN
Added comment: Six individuals with three de novo missense variants. Individuals presented with T-B-NK± severe combined immunodeficiency (SCID) and clinical features suggestive of Omenn syndrome, including diarrhea, alopecia, and desquamating erythematous rash.
Sources: Literature
Vitamin metabolism disorders v0.1 GIF Bryony Thompson gene: GIF was added
gene: GIF was added to Inherited vitamin B12 or cobalamin deficiency. Sources: Literature
new gene name tags were added to gene: GIF.
Mode of inheritance for gene: GIF was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GIF were set to 27604308; 14695536; 14576042
Phenotypes for gene: GIF were set to Intrinsic factor deficiency MIM#261000; Disorders of cobalamin absorption, transport and metabolism
Review for gene: GIF was set to GREEN
gene: GIF was marked as current diagnostic
Added comment: Sources: Literature
Vitamin metabolism disorders v0.0 Bryony Thompson Added Panel Inherited vitamin B12 or cobalamin deficiency
Set list of related panels to Abnormality of vitamin B12 metabolism; HP:0004341
Set panel types to: Royal Melbourne Hospital; Rare Disease
Transplant Co-Morbidity Superpanel v0.18 Bryony Thompson removed gene:IFNL3 from the panel
Leukodystrophy - adult onset v0.137 PRNP Bryony Thompson Marked gene: PRNP as ready
Leukodystrophy - adult onset v0.137 PRNP Bryony Thompson Gene: prnp has been classified as Green List (High Evidence).
Leukodystrophy - adult onset v0.137 PRNP Bryony Thompson Classified gene: PRNP as Green List (high evidence)
Leukodystrophy - adult onset v0.137 PRNP Bryony Thompson Gene: prnp has been classified as Green List (High Evidence).
Leukodystrophy - adult onset v0.136 PRNP Bryony Thompson gene: PRNP was added
gene: PRNP was added to Leukodystrophy - adult onset. Sources: Other
Mode of inheritance for gene: PRNP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PRNP were set to 25220284; 24252267
Phenotypes for gene: PRNP were set to fatal familial insomnia MONDO:0010808
Mode of pathogenicity for gene: PRNP was set to Other
Review for gene: PRNP was set to GREEN
gene: PRNP was marked as current diagnostic
Added comment: White-matter abnormalities have been reported in inherited prion diseases
Sources: Other
Leukodystrophy - adult onset v0.135 ITM2B Bryony Thompson Marked gene: ITM2B as ready
Leukodystrophy - adult onset v0.135 ITM2B Bryony Thompson Gene: itm2b has been classified as Amber List (Moderate Evidence).
Leukodystrophy - adult onset v0.135 ITM2B Bryony Thompson Classified gene: ITM2B as Amber List (moderate evidence)
Leukodystrophy - adult onset v0.135 ITM2B Bryony Thompson Gene: itm2b has been classified as Amber List (Moderate Evidence).
Leukodystrophy - adult onset v0.134 ITM2B Bryony Thompson gene: ITM2B was added
gene: ITM2B was added to Leukodystrophy - adult onset. Sources: Other
Mode of inheritance for gene: ITM2B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ITM2B were set to 10775542
Phenotypes for gene: ITM2B were set to ABri amyloidosis MONDO:0008306
Mode of pathogenicity for gene: ITM2B was set to Other
Review for gene: ITM2B was set to AMBER
Added comment: White matter abnormalities have been reported in 11 at-risk individuals from the original large family reported.
Sources: Other
Mendeliome v1.1626 CST3 Bryony Thompson Classified gene: CST3 as Green List (high evidence)
Mendeliome v1.1626 CST3 Bryony Thompson Gene: cst3 has been classified as Green List (High Evidence).
Mendeliome v1.1625 CST3 Bryony Thompson reviewed gene: CST3: Rating: GREEN; Mode of pathogenicity: Other; Publications: 38489591; Phenotypes: leukodystrophy MONDO:0019046, CST3-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Alternating Hemiplegia and Hemiplegic Migraine v0.57 CST3 Bryony Thompson Marked gene: CST3 as ready
Alternating Hemiplegia and Hemiplegic Migraine v0.57 CST3 Bryony Thompson Gene: cst3 has been classified as Green List (High Evidence).
Alternating Hemiplegia and Hemiplegic Migraine v0.57 CST3 Bryony Thompson Classified gene: CST3 as Green List (high evidence)
Alternating Hemiplegia and Hemiplegic Migraine v0.57 CST3 Bryony Thompson Gene: cst3 has been classified as Green List (High Evidence).
Alternating Hemiplegia and Hemiplegic Migraine v0.56 CST3 Bryony Thompson gene: CST3 was added
gene: CST3 was added to Alternating Hemiplegia and Hemiplegic Migraine. Sources: Literature
Mode of inheritance for gene: CST3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CST3 were set to 38489591
Phenotypes for gene: CST3 were set to leukodystrophy MONDO:0019046, CST3-related
Mode of pathogenicity for gene: CST3 was set to Other
Review for gene: CST3 was set to GREEN
Added comment: 16 patients from 8 leukodystrophy families carrying one of four different stop-gain or frameshift dominant variants in the C-terminal (in the NMD-exclusion zone) of the CST3 gene. Suggested mechanism of disease by rendering the protein more prone to aggregation. The clinical phenotype consists of recurrent episodes of hemiplegic migraine associated with transient unilateral focal deficits and slowly progressing motor symptoms and cognitive decline in mid-old adult ages. Clinical & radiological features differ from Cerebral Amyloid Angiopathy.
Sources: Literature
Early-onset Dementia v1.12 CST3 Bryony Thompson Phenotypes for gene: CST3 were changed from Cerebral amyloid angiopathy MIM#105150 to Cerebral amyloid angiopathy MIM#105150; leukodystrophy MONDO:0019046
Early-onset Dementia v1.11 CST3 Bryony Thompson Publications for gene: CST3 were set to 22435454; 8866434; 2602413; 8108423
Early-onset Dementia v1.10 CST3 Bryony Thompson Classified gene: CST3 as Green List (high evidence)
Early-onset Dementia v1.10 CST3 Bryony Thompson Added comment: Comment on list classification: Cognitive decline is a feature of CST3-leukodystrophy
Early-onset Dementia v1.10 CST3 Bryony Thompson Gene: cst3 has been classified as Green List (High Evidence).
Early-onset Dementia v1.9 CST3 Bryony Thompson edited their review of gene: CST3: Added comment: New gene-disease association: 16 patients from 8 leukodystrophy families carrying one of four different stop-gain or frameshift dominant variants in the C-terminal (in the NMD-exclusion zone) of the CST3 gene. Suggested mechanism of disease by rendering the protein more prone to aggregation. The clinical phenotype consists of recurrent episodes of hemiplegic migraine associated with transient unilateral focal deficits and slowly progressing motor symptoms and cognitive decline in mid-old adult ages. Clinical & radiological features differ from Cerebral Amyloid Angiopathy.; Changed publications: 22435454, 8866434, 2602413, 8108423, 38489591; Changed phenotypes: Cerebral amyloid angiopathy MIM#105150, leukodystrophy MONDO:0019046
Leukodystrophy - adult onset v0.133 CST3 Bryony Thompson Marked gene: CST3 as ready
Leukodystrophy - adult onset v0.133 CST3 Bryony Thompson Gene: cst3 has been classified as Green List (High Evidence).
Leukodystrophy - adult onset v0.133 CST3 Bryony Thompson Classified gene: CST3 as Green List (high evidence)
Leukodystrophy - adult onset v0.133 CST3 Bryony Thompson Gene: cst3 has been classified as Green List (High Evidence).
Leukodystrophy - adult onset v0.132 CST3 Bryony Thompson gene: CST3 was added
gene: CST3 was added to Leukodystrophy - adult onset. Sources: Literature
Mode of inheritance for gene: CST3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CST3 were set to 38489591
Phenotypes for gene: CST3 were set to leukodystrophy MONDO:0019046
Review for gene: CST3 was set to GREEN
Added comment: 16 patients from 8 leukodystrophy families carrying one of four different stop-gain or frameshift dominant variants in the C-terminal (in the NMD-exclusion zone) of the CST3 gene. The suggested mechanism of disease by rendering the protein more prone to aggregation. The clinical phenotype consists of recurrent episodes of hemiplegic migraine associated with transient unilateral focal deficits and slowly progressing motor symptoms and cognitive decline in mid-old adult ages. Clinical & radiological features differ from Cerebral Amyloid Angiopathy.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5727 SLC32A1 Zornitza Stark Phenotypes for gene: SLC32A1 were changed from Generalized epilepsy with febrile seizures plus, type 12, MIM# 620755 to Generalized epilepsy with febrile seizures plus, type 12, MIM# 620755; Developmental and epileptic encephalopathy 114, MIM# 620774
Intellectual disability syndromic and non-syndromic v0.5726 SLC32A1 Zornitza Stark reviewed gene: SLC32A1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Developmental and epileptic encephalopathy 114, MIM# 620774; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2538 SLC32A1 Zornitza Stark Phenotypes for gene: SLC32A1 were changed from Generalized epilepsy with febrile seizures plus, type 12, MIM# 620755 to Generalized epilepsy with febrile seizures plus, type 12, MIM# 620755; Developmental and epileptic encephalopathy 114, MIM# 620774
Genetic Epilepsy v0.2537 SLC32A1 Zornitza Stark edited their review of gene: SLC32A1: Changed phenotypes: Generalized epilepsy with febrile seizures plus, type 12, MIM# 620755, Developmental and epileptic encephalopathy 114, MIM# 620774
Mendeliome v1.1625 SLC32A1 Zornitza Stark Phenotypes for gene: SLC32A1 were changed from Generalized epilepsy with febrile seizures plus, type 12, MIM# 620755 to Generalized epilepsy with febrile seizures plus, type 12, MIM# 620755; Developmental and epileptic encephalopathy 114, MIM# 620774
Mendeliome v1.1624 SLC32A1 Zornitza Stark edited their review of gene: SLC32A1: Changed phenotypes: Generalized epilepsy with febrile seizures plus, type 12, MIM# 620755, Developmental and epileptic encephalopathy 114, MIM# 620774
Intellectual disability syndromic and non-syndromic v0.5726 CRELD1 Zornitza Stark Phenotypes for gene: CRELD1 were changed from Neurodevelopmental disorder (MONDO:0700092), CRELD1-related to Jeffries-Lakhani neurodevelopmental syndrome, MIM# 620771
Intellectual disability syndromic and non-syndromic v0.5725 CRELD1 Zornitza Stark reviewed gene: CRELD1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Jeffries-Lakhani neurodevelopmental syndrome, MIM# 620771; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2537 CRELD1 Zornitza Stark Phenotypes for gene: CRELD1 were changed from Developmental and epileptic encephalopathy, MONDO:0100062, CRELD1-related to Jeffries-Lakhani neurodevelopmental syndrome, MIM# 620771
Genetic Epilepsy v0.2536 CRELD1 Zornitza Stark edited their review of gene: CRELD1: Changed phenotypes: Jeffries-Lakhani neurodevelopmental syndrome, MIM# 620771
Mendeliome v1.1624 CRELD1 Zornitza Stark Phenotypes for gene: CRELD1 were changed from Developmental and epileptic encephalopathy, MONDO:0100062, CRELD1-related; Atrioventricular septal defect, partial, with heterotaxy syndrome, MIM# 606217 to Jeffries-Lakhani neurodevelopmental syndrome, MIM# 620771; Atrioventricular septal defect, partial, with heterotaxy syndrome, MIM# 606217
Mendeliome v1.1623 CRELD1 Zornitza Stark edited their review of gene: CRELD1: Changed phenotypes: Jeffries-Lakhani neurodevelopmental syndrome, MIM# 620771, Atrioventricular septal defect, partial, with heterotaxy syndrome, MIM# 606217
Leukodystrophy - adult onset v0.131 FTDALS Bryony Thompson Classified STR: FTDALS as Green List (high evidence)
Leukodystrophy - adult onset v0.131 FTDALS Bryony Thompson Str: ftdals has been classified as Green List (High Evidence).
Leukodystrophy - adult onset v0.130 FTDALS Bryony Thompson STR: FTDALS was added
STR: FTDALS was added to Leukodystrophy - adult onset. Sources: Literature
Mode of inheritance for STR: FTDALS was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: FTDALS were set to 36970046; 36632182
Phenotypes for STR: FTDALS were set to frontotemporal dementia and/or amyotrophic lateral sclerosis 1 MONDO:0007105
Penetrance for STR: FTDALS were set to Incomplete
Review for STR: FTDALS was set to GREEN
STR: FTDALS was marked as clinically relevant
STR: FTDALS was marked as current diagnostic
Added comment: Expansion carriers showed widespread white-matter abnormalities in the brain
Sources: Literature
Leukodystrophy - adult onset v0.129 MAPT Bryony Thompson Marked gene: MAPT as ready
Leukodystrophy - adult onset v0.129 MAPT Bryony Thompson Gene: mapt has been classified as Green List (High Evidence).
Leukodystrophy - adult onset v0.129 MAPT Bryony Thompson Classified gene: MAPT as Green List (high evidence)
Leukodystrophy - adult onset v0.129 MAPT Bryony Thompson Gene: mapt has been classified as Green List (High Evidence).
Leukodystrophy - adult onset v0.128 MAPT Bryony Thompson gene: MAPT was added
gene: MAPT was added to Leukodystrophy - adult onset. Sources: Literature
Mode of inheritance for gene: MAPT was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAPT were set to 33802612; 36970046
Phenotypes for gene: MAPT were set to semantic dementia MONDO:0010857
Mode of pathogenicity for gene: MAPT was set to Other
Review for gene: MAPT was set to GREEN
gene: MAPT was marked as current diagnostic
Added comment: White-matter abnormalities have been reported in symptomatic and pre-symptomatic carriers of MAPT pathogenic variants.
Sources: Literature
Leukodystrophy - adult onset v0.127 GRN Bryony Thompson Marked gene: GRN as ready
Leukodystrophy - adult onset v0.127 GRN Bryony Thompson Gene: grn has been classified as Green List (High Evidence).
Leukodystrophy - adult onset v0.127 GRN Bryony Thompson Classified gene: GRN as Green List (high evidence)
Leukodystrophy - adult onset v0.127 GRN Bryony Thompson Gene: grn has been classified as Green List (High Evidence).
Leukodystrophy - adult onset v0.126 GRN Bryony Thompson gene: GRN was added
gene: GRN was added to Leukodystrophy - adult onset. Sources: Other
Mode of inheritance for gene: GRN was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GRN were set to 36970046; 36632182
Phenotypes for gene: GRN were set to GRN-related frontotemporal lobar degeneration with Tdp43 inclusions MONDO:0011842
Review for gene: GRN was set to GREEN
gene: GRN was marked as current diagnostic
Added comment: White matter abnormalities have been reported in presymptomatic carriers and affected carriers.
Sources: Other
Calcium and Phosphate disorders v1.23 EHHADH Zornitza Stark Marked gene: EHHADH as ready
Calcium and Phosphate disorders v1.23 EHHADH Zornitza Stark Gene: ehhadh has been classified as Green List (High Evidence).
Calcium and Phosphate disorders v1.23 EHHADH Zornitza Stark Classified gene: EHHADH as Green List (high evidence)
Calcium and Phosphate disorders v1.23 EHHADH Zornitza Stark Gene: ehhadh has been classified as Green List (High Evidence).
Leukodystrophy - adult onset v0.125 PSEN2 Bryony Thompson Marked gene: PSEN2 as ready
Leukodystrophy - adult onset v0.125 PSEN2 Bryony Thompson Gene: psen2 has been classified as Green List (High Evidence).
Leukodystrophy - adult onset v0.125 PSEN2 Bryony Thompson Classified gene: PSEN2 as Green List (high evidence)
Leukodystrophy - adult onset v0.125 PSEN2 Bryony Thompson Gene: psen2 has been classified as Green List (High Evidence).
Leukodystrophy - adult onset v0.124 PSEN2 Bryony Thompson gene: PSEN2 was added
gene: PSEN2 was added to Leukodystrophy - adult onset. Sources: Other
Mode of inheritance for gene: PSEN2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PSEN2 were set to 36845656
Phenotypes for gene: PSEN2 were set to early-onset autosomal dominant Alzheimer disease MONDO:0015140
Mode of pathogenicity for gene: PSEN2 was set to Other
Review for gene: PSEN2 was set to GREEN
gene: PSEN2 was marked as current diagnostic
Added comment: White matter abnormalities are a common feature of Alzheimer's disease
Sources: Other
Early-onset Dementia v1.9 APP Bryony Thompson Marked gene: APP as ready
Early-onset Dementia v1.9 APP Bryony Thompson Gene: app has been classified as Green List (High Evidence).
Early-onset Dementia v1.9 APP Bryony Thompson Mode of pathogenicity for gene: APP was changed from to Other
Leukodystrophy - adult onset v0.123 PSEN1 Bryony Thompson Marked gene: PSEN1 as ready
Leukodystrophy - adult onset v0.123 PSEN1 Bryony Thompson Gene: psen1 has been classified as Green List (High Evidence).
Leukodystrophy - adult onset v0.123 PSEN1 Bryony Thompson Classified gene: PSEN1 as Green List (high evidence)
Leukodystrophy - adult onset v0.123 PSEN1 Bryony Thompson Gene: psen1 has been classified as Green List (High Evidence).
Early-onset Dementia v1.8 APP Bryony Thompson Publications for gene: APP were set to
Leukodystrophy - adult onset v0.122 PSEN1 Bryony Thompson gene: PSEN1 was added
gene: PSEN1 was added to Leukodystrophy - adult onset. Sources: Other
Mode of inheritance for gene: PSEN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PSEN1 were set to 36845656
Phenotypes for gene: PSEN1 were set to early-onset autosomal dominant Alzheimer disease MONDO:0015140
Mode of pathogenicity for gene: PSEN1 was set to Other
Review for gene: PSEN1 was set to GREEN
gene: PSEN1 was marked as current diagnostic
Added comment: White matter abnormalities are a common feature of Alzheimer's disease
Sources: Other
Leukodystrophy - adult onset v0.121 APP Bryony Thompson Marked gene: APP as ready
Leukodystrophy - adult onset v0.121 APP Bryony Thompson Gene: app has been classified as Green List (High Evidence).
Leukodystrophy - adult onset v0.121 APP Bryony Thompson Classified gene: APP as Green List (high evidence)
Leukodystrophy - adult onset v0.121 APP Bryony Thompson Gene: app has been classified as Green List (High Evidence).
Leukodystrophy - adult onset v0.120 APP Bryony Thompson gene: APP was added
gene: APP was added to Leukodystrophy - adult onset. Sources: Other
Mode of inheritance for gene: APP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: APP were set to 36845656
Phenotypes for gene: APP were set to early-onset autosomal dominant Alzheimer disease MONDO:0015140
Review for gene: APP was set to GREEN
gene: APP was marked as current diagnostic
Added comment: White matter abnormalities are a common feature of Alzheimer's disease
Sources: Other
Early-onset Dementia v1.7 APP Bryony Thompson Phenotypes for gene: APP were changed from to Alzheimer disease MONDO:0007088
Early-onset Dementia v1.6 APP Bryony Thompson Mode of inheritance for gene: APP was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Calcium and Phosphate disorders v1.22 NRAS Bryony Thompson Marked gene: NRAS as ready
Calcium and Phosphate disorders v1.22 NRAS Bryony Thompson Gene: nras has been classified as Green List (High Evidence).
Calcium and Phosphate disorders v1.22 NRAS Bryony Thompson Classified gene: NRAS as Green List (high evidence)
Calcium and Phosphate disorders v1.22 NRAS Bryony Thompson Gene: nras has been classified as Green List (High Evidence).
Calcium and Phosphate disorders v1.21 NRAS Bryony Thompson gene: NRAS was added
gene: NRAS was added to Calcium and Phosphate disorders. Sources: Literature
Mode of inheritance for gene: NRAS was set to Other
Publications for gene: NRAS were set to 24006476; 35999193; 32157705; 27900779
Phenotypes for gene: NRAS were set to Costello syndrome MONDO:0009026
Mode of pathogenicity for gene: NRAS was set to Other
Review for gene: NRAS was set to GREEN
gene: NRAS was marked as current diagnostic
Added comment: 5 cases with cutaneous skeletal hypophosphatemia syndrome and all with somatic mosaic activating NRAS Q61R
Sources: Literature
Calcium and Phosphate disorders v1.20 HRAS Bryony Thompson Marked gene: HRAS as ready
Calcium and Phosphate disorders v1.20 HRAS Bryony Thompson Gene: hras has been classified as Green List (High Evidence).
Calcium and Phosphate disorders v1.20 HRAS Bryony Thompson Classified gene: HRAS as Green List (high evidence)
Calcium and Phosphate disorders v1.20 HRAS Bryony Thompson Gene: hras has been classified as Green List (High Evidence).
Calcium and Phosphate disorders v1.19 HRAS Bryony Thompson gene: HRAS was added
gene: HRAS was added to Calcium and Phosphate disorders. Sources: Literature
Mode of inheritance for gene: HRAS was set to Other
Publications for gene: HRAS were set to 35738466; 36943390; 30373874; 27444071
Phenotypes for gene: HRAS were set to Costello syndrome MONDO:0009026
Mode of pathogenicity for gene: HRAS was set to Other
Review for gene: HRAS was set to GREEN
gene: HRAS was marked as current diagnostic
Added comment: Gain of function is the mechanism of disease and only somatic mosaic variants have been reported in association with hypophosphataemia
PMID: 35738466 - 1 case with a VUS & vitamin dependent rickets as a feature of the phenotype
PMID: 36943390 - mouse model with hypophosphataemia
PMID: 30373874 - 1 somatic mosaic HRAS c.182A>G (p.Gln61Arg) case with cutaneous skeletal hypophosphatemia syndrome (CSHS)
PMID: 27444071 - review with 4 cases of CSHS with somatic mosaic variants (G13R or Q61R)
Sources: Literature
Calcium and Phosphate disorders v1.18 ATP6V0A4 Bryony Thompson Marked gene: ATP6V0A4 as ready
Calcium and Phosphate disorders v1.18 ATP6V0A4 Bryony Thompson Gene: atp6v0a4 has been classified as Red List (Low Evidence).
Calcium and Phosphate disorders v1.18 ATP6V0A4 Bryony Thompson gene: ATP6V0A4 was added
gene: ATP6V0A4 was added to Calcium and Phosphate disorders. Sources: Literature
Mode of inheritance for gene: ATP6V0A4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATP6V0A4 were set to 35738466
Phenotypes for gene: ATP6V0A4 were set to renal tubular acidosis, distal, 3, with or without sensorineural hearing loss MONDO:0011268
Review for gene: ATP6V0A4 was set to RED
Added comment: 1 homozygous case with hypophosphataemic rickets and renal tubular dysfunction
Sources: Literature
Calcium and Phosphate disorders v1.17 ATP6V1B1 Bryony Thompson Marked gene: ATP6V1B1 as ready
Calcium and Phosphate disorders v1.17 ATP6V1B1 Bryony Thompson Gene: atp6v1b1 has been classified as Green List (High Evidence).
Calcium and Phosphate disorders v1.17 ATP6V1B1 Bryony Thompson Classified gene: ATP6V1B1 as Green List (high evidence)
Calcium and Phosphate disorders v1.17 ATP6V1B1 Bryony Thompson Gene: atp6v1b1 has been classified as Green List (High Evidence).
Calcium and Phosphate disorders v1.16 ATP6V1B1 Bryony Thompson gene: ATP6V1B1 was added
gene: ATP6V1B1 was added to Calcium and Phosphate disorders. Sources: Literature
Mode of inheritance for gene: ATP6V1B1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATP6V1B1 were set to 35738466; 18386070
Phenotypes for gene: ATP6V1B1 were set to renal tubular acidosis, distal, 2, with progressive sensorineural hearing loss MONDO:0009968
Review for gene: ATP6V1B1 was set to GREEN
gene: ATP6V1B1 was marked as current diagnostic
Added comment: Hypophosphataemic rickets can be a feature of the condition
PMID: 35738466 - 2 homozygous & 1 Chet case with hypophosphataemic rickets and renal tubular dysfunction
PMID: 18386070 - 2 siblings with distal renal tubular acidosis and hypophosphataemic rickets homozygous for a missense variant (c.242T>C p.Leu81Pro)
Sources: Literature
Calcium and Phosphate disorders v1.10 EHHADH Bryony Thompson gene: EHHADH was added
gene: EHHADH was added to Calcium and Phosphate disorders. Sources: Literature
Mode of inheritance for gene: EHHADH was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: EHHADH were set to 24401050; 35738466; 38310177
Phenotypes for gene: EHHADH were set to Fanconi renotubular syndrome 3 MONDO:0014275
Review for gene: EHHADH was set to GREEN
Added comment: Now 3 different variants from 4 families/cases were reported with consistent phenotypes. Assessed as Limited by ClinGen in March 2023. However, this assessment doesn't include: PMID: 35738466, 38310177; https://clinmedjournals.org/articles/jcnrc/journal-of-clinical-nephrology-and-renal-care-jcnrc-3-027.pdf
Additional info:
PMID: 35738466 - 1 family (proband and mother) with missense (c.385C>G, p.Leu129Val) with hypophosphataemic rickets and renal tubular dysfunction
PMID: 38310177 - case with a diagnosis of Fanconi renotubular syndrome with a whole gene deletion. Hypophosphataemic rickets was part of the clinical presentation
Sources: Literature
Calcium and Phosphate disorders v1.10 EHHADH Bryony Thompson gene: EHHADH was added
gene: EHHADH was added to Calcium and Phosphate disorders. Sources: Literature
Mode of inheritance for gene: EHHADH was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: EHHADH were set to 24401050; 35738466; 38310177
Phenotypes for gene: EHHADH were set to Fanconi renotubular syndrome 3 MONDO:0014275
Review for gene: EHHADH was set to GREEN
Added comment: Now 3 different variants from 4 families/cases were reported with consistent phenotypes. Assessed as Limited by ClinGen in March 2023. However, this assessment doesn't include: PMID: 35738466, 38310177; https://clinmedjournals.org/articles/jcnrc/journal-of-clinical-nephrology-and-renal-care-jcnrc-3-027.pdf
Additional info:
PMID: 35738466 - 1 family (proband and mother) with missense (c.385C>G, p.Leu129Val) with hypophosphataemic rickets and renal tubular dysfunction
PMID: 38310177 - case with a diagnosis of Fanconi renotubular syndrome with a whole gene deletion. Hypophosphataemic rickets was part of the clinical presentation
Sources: Literature
Renal Tubulopathies and related disorders v1.11 EHHADH Bryony Thompson Marked gene: EHHADH as ready
Renal Tubulopathies and related disorders v1.11 EHHADH Bryony Thompson Gene: ehhadh has been classified as Green List (High Evidence).
Renal Tubulopathies and related disorders v1.11 EHHADH Bryony Thompson Publications for gene: EHHADH were set to 24401050
Renal Tubulopathies and related disorders v1.10 EHHADH Bryony Thompson Classified gene: EHHADH as Green List (high evidence)
Renal Tubulopathies and related disorders v1.10 EHHADH Bryony Thompson Gene: ehhadh has been classified as Green List (High Evidence).
Renal Tubulopathies and related disorders v1.9 EHHADH Bryony Thompson reviewed gene: EHHADH: Rating: GREEN; Mode of pathogenicity: None; Publications: 24401050, 35738466, 38310177; Phenotypes: Fanconi renotubular syndrome 3 MONDO:0014275; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.1623 EHHADH Bryony Thompson Publications for gene: EHHADH were set to 24401050
Mendeliome v1.1622 EHHADH Bryony Thompson Classified gene: EHHADH as Green List (high evidence)
Mendeliome v1.1622 EHHADH Bryony Thompson Gene: ehhadh has been classified as Green List (High Evidence).
Mendeliome v1.1621 EHHADH Bryony Thompson reviewed gene: EHHADH: Rating: GREEN; Mode of pathogenicity: None; Publications: 35738466, 38310177, 24401050; Phenotypes: Fanconi renotubular syndrome 3 MONDO:0014275; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Calcium and Phosphate disorders v1.9 FGFR1 Bryony Thompson Marked gene: FGFR1 as ready
Calcium and Phosphate disorders v1.9 FGFR1 Bryony Thompson Gene: fgfr1 has been classified as Amber List (Moderate Evidence).
Calcium and Phosphate disorders v1.9 FGFR1 Bryony Thompson Classified gene: FGFR1 as Amber List (moderate evidence)
Calcium and Phosphate disorders v1.9 FGFR1 Bryony Thompson Gene: fgfr1 has been classified as Amber List (Moderate Evidence).
Calcium and Phosphate disorders v1.8 FGFR1 Bryony Thompson gene: FGFR1 was added
gene: FGFR1 was added to Calcium and Phosphate disorders. Sources: Other
Mode of inheritance for gene: FGFR1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FGFR1 were set to 35738466; 36999651; 29147600; 26839958
Phenotypes for gene: FGFR1 were set to osteoglophonic dwarfism MONDO:0008150
Review for gene: FGFR1 was set to AMBER
gene: FGFR1 was marked as current diagnostic
Added comment: PMID: 35738466 - 1 case with vitamin dependent rickets & osteoglophonic dysplasia
PMID: 36999651 - 1 missense (VUS) in a case with hypophosphataemia
PMID: 29147600 - 1 case with Osteoglophonic dysplasia including hypophosphataemia, with c.1115G > A [p.(Cys372Tyr)]
PMID: 26839958 - mouse model demonstrates role for Fgrf1 in phosphate transport
Sources: Other
Calcium and Phosphate disorders v1.7 INPPL1 Bryony Thompson Marked gene: INPPL1 as ready
Calcium and Phosphate disorders v1.7 INPPL1 Bryony Thompson Gene: inppl1 has been classified as Green List (High Evidence).
Calcium and Phosphate disorders v1.7 INPPL1 Bryony Thompson Classified gene: INPPL1 as Green List (high evidence)
Calcium and Phosphate disorders v1.7 INPPL1 Bryony Thompson Gene: inppl1 has been classified as Green List (High Evidence).
Calcium and Phosphate disorders v1.6 INPPL1 Bryony Thompson gene: INPPL1 was added
gene: INPPL1 was added to Calcium and Phosphate disorders. Sources: Other
Mode of inheritance for gene: INPPL1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: INPPL1 were set to 23273567
Phenotypes for gene: INPPL1 were set to opsismodysplasia MONDO:0009785
Review for gene: INPPL1 was set to GREEN
gene: INPPL1 was marked as current diagnostic
Added comment: Hypophosphataemia can be a feature of the condition and has been reported in at least 5 individuals with chet/homozygous variants from 4 families.
Sources: Other
Calcium and Phosphate disorders v1.5 SLC4A1 Bryony Thompson Marked gene: SLC4A1 as ready
Calcium and Phosphate disorders v1.5 SLC4A1 Bryony Thompson Gene: slc4a1 has been classified as Green List (High Evidence).
Calcium and Phosphate disorders v1.5 SLC4A1 Bryony Thompson changed review comment from: Hypophosphataemic rickets can be a feature of condition
PMID: 35738466 - 5 monoallelic & 2 biallelic cases with hypophosphataemic rickets and renal tubular dysfunction
Sources: Literature; to: Hypophosphataemic rickets can be a feature of the condition
PMID: 35738466 - 5 monoallelic & 2 biallelic cases with hypophosphataemic rickets and renal tubular dysfunction
Sources: Literature
Calcium and Phosphate disorders v1.5 SLC4A1 Bryony Thompson edited their review of gene: SLC4A1: Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Calcium and Phosphate disorders v1.5 SLC4A1 Bryony Thompson Mode of inheritance for gene: SLC4A1 was changed from BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Calcium and Phosphate disorders v1.4 SLC4A1 Bryony Thompson edited their review of gene: SLC4A1: Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Calcium and Phosphate disorders v1.4 SLC4A1 Bryony Thompson Classified gene: SLC4A1 as Green List (high evidence)
Calcium and Phosphate disorders v1.4 SLC4A1 Bryony Thompson Gene: slc4a1 has been classified as Green List (High Evidence).
Calcium and Phosphate disorders v1.3 SLC4A1 Bryony Thompson gene: SLC4A1 was added
gene: SLC4A1 was added to Calcium and Phosphate disorders. Sources: Literature
Mode of inheritance for gene: SLC4A1 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: SLC4A1 were set to 35738466
Phenotypes for gene: SLC4A1 were set to renal tubular acidosis, distal, 4, with hemolytic anemia MONDO:0012700
Review for gene: SLC4A1 was set to GREEN
gene: SLC4A1 was marked as current diagnostic
Added comment: Hypophosphataemic rickets can be a feature of condition
PMID: 35738466 - 5 monoallelic & 2 biallelic cases with hypophosphataemic rickets and renal tubular dysfunction
Sources: Literature
Calcium and Phosphate disorders v1.2 SLC2A2 Bryony Thompson Marked gene: SLC2A2 as ready
Calcium and Phosphate disorders v1.2 SLC2A2 Bryony Thompson Gene: slc2a2 has been classified as Green List (High Evidence).
Calcium and Phosphate disorders v1.2 SLC2A2 Bryony Thompson Classified gene: SLC2A2 as Green List (high evidence)
Calcium and Phosphate disorders v1.2 SLC2A2 Bryony Thompson Gene: slc2a2 has been classified as Green List (High Evidence).
Calcium and Phosphate disorders v1.1 SLC2A2 Bryony Thompson gene: SLC2A2 was added
gene: SLC2A2 was added to Calcium and Phosphate disorders. Sources: Literature
Mode of inheritance for gene: SLC2A2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC2A2 were set to 35738466
Phenotypes for gene: SLC2A2 were set to glycogen storage disease due to GLUT2 deficiency MONDO:0009216
Review for gene: SLC2A2 was set to GREEN
gene: SLC2A2 was marked as current diagnostic
Added comment: Hypophosphataemic rickets can be a feature of the condition.
PMID: 35738466 - 4 homozygous & 1 Chet case with hypophosphataemic rickets and renal tubular dysfunction
Sources: Literature
Mendeliome v1.1621 RXFP2 Katie Ayers reviewed gene: RXFP2: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: 37208861, 38430325; Phenotypes: Infertility, cryptorchidism, non-obstructive azoospermia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.293 RXFP2 Katie Ayers edited their review of gene: RXFP2: Added comment: One individual with bilateral cryptorchidism and infertility had homozygous c.1406delT in RXFP2 (NM_130806.5), leading to a frameshift p.(Phe469Serfs*8). From consanguinous family.

Two affected brothers with homozygous missense variant c.1015A>G in RXFP2 (NM_130806.5) resulting in an amino acid substitution p.(Asn339Asp) with bilateral cryptorchidism.; Changed publications: 37208861; Changed phenotypes: Infertility, cryptorchidism, non-obstructive azoospermia
Differences of Sex Development v0.293 RXFP2 Katie Ayers edited their review of gene: RXFP2: Added comment: Homozygous non-canonical splicing variant by whole-exome sequencing and Sanger sequencing . NM_130806: c.1376-12A > G; Changed rating: GREEN; Changed mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Changed publications: 38430325; Changed phenotypes: cryptorchidism and non-obstructive azoospermia; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.293 RXFP2 Katie Ayers commented on gene: RXFP2
Genetic Epilepsy v0.2536 NDUFAF5 Zornitza Stark Marked gene: NDUFAF5 as ready
Genetic Epilepsy v0.2536 NDUFAF5 Zornitza Stark Gene: ndufaf5 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2536 NDUFAF5 Zornitza Stark Phenotypes for gene: NDUFAF5 were changed from to Mitochondrial complex I deficiency, nuclear type 3 MIM#618224
Genetic Epilepsy v0.2535 NDUFAF5 Zornitza Stark Publications for gene: NDUFAF5 were set to
Genetic Epilepsy v0.2534 NDUFAF5 Zornitza Stark Mode of inheritance for gene: NDUFAF5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2533 NDUFAF5 Zornitza Stark reviewed gene: NDUFAF5: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Mitochondrial complex I deficiency, nuclear type 3 MIM#618224; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2533 NDUFA1 Zornitza Stark Marked gene: NDUFA1 as ready
Genetic Epilepsy v0.2533 NDUFA1 Zornitza Stark Gene: ndufa1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2533 NDUFA1 Zornitza Stark Phenotypes for gene: NDUFA1 were changed from to Mitochondrial complex I deficiency, nuclear type 12 MIM#301020
Genetic Epilepsy v0.2532 NDUFA1 Zornitza Stark Publications for gene: NDUFA1 were set to
Genetic Epilepsy v0.2531 NDUFA1 Zornitza Stark Mode of inheritance for gene: NDUFA1 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Genetic Epilepsy v0.2530 NDUFA1 Zornitza Stark reviewed gene: NDUFA1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Mitochondrial complex I deficiency, nuclear type 12 MIM#301020; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Genetic Epilepsy v0.2530 NDE1 Zornitza Stark Marked gene: NDE1 as ready
Genetic Epilepsy v0.2530 NDE1 Zornitza Stark Gene: nde1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2530 NDE1 Zornitza Stark Phenotypes for gene: NDE1 were changed from to Microhydranencephaly 605013; Lissencephaly 4 (with microcephaly) 614019
Genetic Epilepsy v0.2529 NDE1 Zornitza Stark Publications for gene: NDE1 were set to
Genetic Epilepsy v0.2528 NDE1 Zornitza Stark Mode of inheritance for gene: NDE1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2527 NAGA Zornitza Stark Marked gene: NAGA as ready
Genetic Epilepsy v0.2527 NAGA Zornitza Stark Gene: naga has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2527 NAGA Zornitza Stark Phenotypes for gene: NAGA were changed from to Schindler disease, type I and type II 609241
Genetic Epilepsy v0.2526 NAGA Zornitza Stark Publications for gene: NAGA were set to
Genetic Epilepsy v0.2525 NAGA Zornitza Stark Mode of inheritance for gene: NAGA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2524 NAGA Zornitza Stark Classified gene: NAGA as Amber List (moderate evidence)
Genetic Epilepsy v0.2524 NAGA Zornitza Stark Gene: naga has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.2523 NAGA Zornitza Stark edited their review of gene: NAGA: Changed rating: AMBER
Genetic Epilepsy v0.2523 MTOR Zornitza Stark Marked gene: MTOR as ready
Genetic Epilepsy v0.2523 MTOR Zornitza Stark Gene: mtor has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2523 MTOR Zornitza Stark Phenotypes for gene: MTOR were changed from to Smith-Kingsmore syndrome, MIM# 616638; Focal cortical dysplasia, type II, somatic, MIM# 607341; Overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes, MONDO:0100283
Genetic Epilepsy v0.2522 MTOR Zornitza Stark Mode of pathogenicity for gene: MTOR was changed from to Other
Genetic Epilepsy v0.2521 MTOR Zornitza Stark Publications for gene: MTOR were set to
Genetic Epilepsy v0.2520 MTOR Zornitza Stark Mode of inheritance for gene: MTOR was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2519 MTHFR Zornitza Stark Marked gene: MTHFR as ready
Genetic Epilepsy v0.2519 MTHFR Zornitza Stark Gene: mthfr has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2519 MTHFR Zornitza Stark Phenotypes for gene: MTHFR were changed from Homocystinuria due to MTHFR deficiency MIM#236250 to Homocystinuria due to MTHFR deficiency MIM#236250
Genetic Epilepsy v0.2518 MTHFR Zornitza Stark Phenotypes for gene: MTHFR were changed from to Homocystinuria due to MTHFR deficiency MIM#236250
Genetic Epilepsy v0.2517 MTHFR Zornitza Stark Publications for gene: MTHFR were set to
Genetic Epilepsy v0.2516 MTHFR Zornitza Stark Mode of inheritance for gene: MTHFR was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2515 MTHFR Zornitza Stark reviewed gene: MTHFR: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Homocystinuria due to MTHFR deficiency MIM#236250; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2515 MOCS2 Zornitza Stark Mode of inheritance for gene: MOCS2 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2514 MOCS2 Zornitza Stark Mode of inheritance for gene: MOCS2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2513 MOCS2 Zornitza Stark reviewed gene: MOCS2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Molybdenum cofactor deficiency B MIM#252160; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2513 MMADHC Zornitza Stark Marked gene: MMADHC as ready
Genetic Epilepsy v0.2513 MMADHC Zornitza Stark Gene: mmadhc has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2513 MMADHC Zornitza Stark Phenotypes for gene: MMADHC were changed from to Homocystinuria, cblD type, variant 1 MIM#277410; Methylmalonic aciduria and homocystinuria, cblD type MIM#277410; Methylmalonic aciduria, cblD type, variant 2 MIM#277410
Genetic Epilepsy v0.2513 MMADHC Zornitza Stark Publications for gene: MMADHC were set to
Genetic Epilepsy v0.2512 MMADHC Zornitza Stark Mode of inheritance for gene: MMADHC was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2511 MMACHC Zornitza Stark Marked gene: MMACHC as ready
Genetic Epilepsy v0.2511 MMACHC Zornitza Stark Gene: mmachc has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2511 MMACHC Zornitza Stark Phenotypes for gene: MMACHC were changed from to Methylmalonic aciduria and homocystinuria, cblC type MIM#277400
Genetic Epilepsy v0.2510 MMACHC Zornitza Stark Publications for gene: MMACHC were set to
Genetic Epilepsy v0.2509 MMACHC Zornitza Stark Mode of inheritance for gene: MMACHC was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2508 MLC1 Zornitza Stark Marked gene: MLC1 as ready
Genetic Epilepsy v0.2508 MLC1 Zornitza Stark Gene: mlc1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2508 MLC1 Zornitza Stark Phenotypes for gene: MLC1 were changed from to Megalencephalic leukoencephalopathy with subcortical cysts (MIM#604004)
Genetic Epilepsy v0.2507 MLC1 Zornitza Stark Publications for gene: MLC1 were set to
Genetic Epilepsy v0.2506 MLC1 Zornitza Stark Mode of inheritance for gene: MLC1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2505 MFF Zornitza Stark Marked gene: MFF as ready
Genetic Epilepsy v0.2505 MFF Zornitza Stark Gene: mff has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2505 MFF Zornitza Stark Phenotypes for gene: MFF were changed from to Encephalopathy due to defective mitochondrial and peroxisomal fission 2, MIM# 617086
Genetic Epilepsy v0.2504 MFF Zornitza Stark Publications for gene: MFF were set to
Genetic Epilepsy v0.2503 MFF Zornitza Stark Mode of inheritance for gene: MFF was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1621 KAT6B Ain Roesley Phenotypes for gene: KAT6B were changed from SBBYSS syndrome MIM#603736; Genitopatellar syndrome MIM#606170 to SBBYSS syndrome MIM#603736; Genitopatellar syndrome MIM#606170; KAT6B-related multiple congenital anomalies syndrome MONDO:0036042
Intellectual disability syndromic and non-syndromic v0.5725 SV2A Zornitza Stark Phenotypes for gene: SV2A were changed from Neurodevelopmental disorder, MONDO:0700092, SV2A-related to Neurodevelopmental disorder, MONDO:0700092, SV2A-related; Developmental and epileptic encephalopathy 113, MIM# 620772
Intellectual disability syndromic and non-syndromic v0.5724 SV2A Zornitza Stark reviewed gene: SV2A: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Developmental and epileptic encephalopathy 113, MIM# 620772; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2502 SV2A Zornitza Stark Phenotypes for gene: SV2A were changed from Neurodevelopmental disorder, MONDO:0700092, SV2A-related; Developmental and epileptic encephalopathy 113, MIM# 620772 to Neurodevelopmental disorder, MONDO:0700092, SV2A-related; Developmental and epileptic encephalopathy 113, MIM# 620772
Genetic Epilepsy v0.2501 SV2A Zornitza Stark Phenotypes for gene: SV2A were changed from Neurodevelopmental disorder, MONDO:0700092, SV2A-related to Neurodevelopmental disorder, MONDO:0700092, SV2A-related; Developmental and epileptic encephalopathy 113, MIM# 620772
Genetic Epilepsy v0.2500 SV2A Zornitza Stark reviewed gene: SV2A: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Developmental and epileptic encephalopathy 113, MIM# 620772; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v1.252 SV2A Zornitza Stark Phenotypes for gene: SV2A were changed from Neurodevelopmental disorder, MONDO:0700092, SV2A-related to Developmental and epileptic encephalopathy 113, MIM# 620772
Microcephaly v1.251 SV2A Zornitza Stark reviewed gene: SV2A: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Developmental and epileptic encephalopathy 113, MIM# 620772; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1620 SV2A Zornitza Stark Phenotypes for gene: SV2A were changed from Neurodevelopmental disorder, MONDO:0700092, SV2A-related to Neurodevelopmental disorder, MONDO:0700092, SV2A-related; Developmental and epileptic encephalopathy 113, MIM# 620772
Mendeliome v1.1619 SV2A Zornitza Stark edited their review of gene: SV2A: Changed phenotypes: Neurodevelopmental disorder, MONDO:0700092, SV2A-related, Developmental and epileptic encephalopathy 113, MIM# 620772
Fetal anomalies v1.220 PRDM6 Ain Roesley Classified gene: PRDM6 as Amber List (moderate evidence)
Fetal anomalies v1.220 PRDM6 Ain Roesley Gene: prdm6 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.219 PRDM6 Ain Roesley edited their review of gene: PRDM6: Changed rating: AMBER; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v1.219 WASHC5 Ain Roesley Classified gene: WASHC5 as Green List (high evidence)
Fetal anomalies v1.219 WASHC5 Ain Roesley Gene: washc5 has been classified as Green List (High Evidence).
Fetal anomalies v1.218 WASHC5 Ain Roesley reviewed gene: WASHC5: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Ritscher-Schinzel syndrome 1 MIM#220210; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Fetal anomalies v1.218 SLC37A4 Ain Roesley Classified gene: SLC37A4 as Amber List (moderate evidence)
Fetal anomalies v1.218 SLC37A4 Ain Roesley Gene: slc37a4 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.217 SLC37A4 Ain Roesley reviewed gene: SLC37A4: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Fetal anomalies v1.217 RBFOX2 Ain Roesley Marked gene: RBFOX2 as ready
Fetal anomalies v1.217 RBFOX2 Ain Roesley Gene: rbfox2 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.217 RBFOX2 Ain Roesley Classified gene: RBFOX2 as Amber List (moderate evidence)
Fetal anomalies v1.217 RBFOX2 Ain Roesley Gene: rbfox2 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.216 RBFOX2 Ain Roesley gene: RBFOX2 was added
gene: RBFOX2 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: RBFOX2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RBFOX2 were set to 26785492; 27670201; 27485310; 25205790; 35137168; 26785492; 37165897
Review for gene: RBFOX2 was set to AMBER
gene: RBFOX2 was marked as current diagnostic
Added comment: PMID: 37165897
1x 'splice altering' de novo in in an individual with HLSH + AVSD

- PMID: 26785492: Analysed CHD (1213 congenital heart disease trios) and control (autism spectrum disorder) trios for de novo mutations. Found RBFOX2 gene had significantly more damaging de novo variants than expected: 3 de novo LoF variants (eg. nonsense, frameshift, or canonical splice disruptions). All 3 probands have hypoplastic left heart syndrome (HLHS). No further patient-specific clinical or variant info were available. Same cohort later included in PMID: 32368696, listed 4 de novo variants in this gene, in patients with left ventricular outflow tract obstruction (LVOTO) or conotruncal defects (CTDs).

- PMID: 27670201: RNA expression study showed the silenced allele harbours a nonsense RBFOX2 variant (Arg287*), CHD patient heart tissue sample, same patient published in PMID: 26785492.
- PMID: 27485310: Functional studies using heart tissue sample from HLHS patient with NM_001031695.2:c.859C>T p.(Arg287*) showed subcellular mislocalisation, impacting its nuclear function in RNA splicing.

- PMID: 25205790: De novo 111.3kb del chr22:36038076-36149338 (hg19) which includes APOL5,APOL6,RBFOX2, in a patient with HLHS.

- PMID: 35137168: Rbfox2 conditional knockout mouse model recapitulated several molecular and phenotypic features of HLHS.
Sources: Literature
Fetal anomalies v1.215 PRDM6 Ain Roesley reviewed gene: PRDM6: Rating: ; Mode of pathogenicity: None; Publications: 38071433; Phenotypes: ; Mode of inheritance: None; Current diagnostic: yes
Congenital Heart Defect v0.414 RBFOX2 Ain Roesley Publications for gene: RBFOX2 were set to 26785492; 27670201; 27485310; 25205790; 35137168; 26785492
Congenital Heart Defect v0.413 RBFOX2 Ain Roesley commented on gene: RBFOX2
Congenital Heart Defect v0.413 KDR Ain Roesley Classified gene: KDR as Green List (high evidence)
Congenital Heart Defect v0.413 KDR Ain Roesley Gene: kdr has been classified as Green List (High Evidence).
Congenital Heart Defect v0.413 KDR Ain Roesley Classified gene: KDR as Green List (high evidence)
Congenital Heart Defect v0.413 KDR Ain Roesley Gene: kdr has been classified as Green List (High Evidence).
Congenital Heart Defect v0.413 KDR Ain Roesley Classified gene: KDR as Green List (high evidence)
Congenital Heart Defect v0.413 KDR Ain Roesley Gene: kdr has been classified as Green List (High Evidence).
Congenital Heart Defect v0.412 KDR Ain Roesley reviewed gene: KDR: Rating: GREEN; Mode of pathogenicity: None; Publications: 34113005, 30232381, 28991257, 30232381; Phenotypes: ; Mode of inheritance: None; Current diagnostic: yes
Fetal anomalies v1.215 KDR Ain Roesley Classified gene: KDR as Green List (high evidence)
Fetal anomalies v1.215 KDR Ain Roesley Gene: kdr has been classified as Green List (High Evidence).
Fetal anomalies v1.214 KDR Ain Roesley Marked gene: KDR as ready
Fetal anomalies v1.214 KDR Ain Roesley Gene: kdr has been classified as Red List (Low Evidence).
Fetal anomalies v1.214 KDR Ain Roesley Publications for gene: KDR were set to 34113005; 30232381
Fetal anomalies v1.213 KDR Ain Roesley Mode of inheritance for gene: KDR was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v1.212 KDR Ain Roesley edited their review of gene: KDR: Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v1.212 KDR Ain Roesley edited their review of gene: KDR: Changed rating: GREEN; Changed publications: 34113005, 30232381, 28991257, 30232381; Set current diagnostic: yes
Fetal anomalies v1.212 KDR Ain Roesley changed review comment from: PMID:30232381
5x families (6 affecteds) with ToF: 2x PTCs + 2x missense + 1x inframe del
noted that all individuals were adults at time of assessment but known to have ToF and/or other CHD

PMID:34113005;
1x family with 2 affecteds, Chet for 2x missense
Sources: Literature; to: GREEN for AD
RED for AR

PMID:30232381
5x families (6 affecteds) with ToF: 2x PTCs + 2x missense + 1x inframe del
noted that all individuals were adults at time of assessment but known to have ToF and/or other CHD

PMID: 34328347;
cohort of ToF, looking into LoF variants
4x identified + 1x classified as VUS (stop gain in penultimate exon)
1x stop gain citing PMID: 28991257

PMID:34113005;
1x family with 2 affecteds, Chet for 2x missense



Sources: Literature
Fetal anomalies v1.212 KDR Ain Roesley gene: KDR was added
gene: KDR was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: KDR was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: KDR were set to 34113005; 30232381
Phenotypes for gene: KDR were set to Tetralogy of Fallot
Added comment: PMID:30232381
5x families (6 affecteds) with ToF: 2x PTCs + 2x missense + 1x inframe del
noted that all individuals were adults at time of assessment but known to have ToF and/or other CHD

PMID:34113005;
1x family with 2 affecteds, Chet for 2x missense
Sources: Literature
Fetal anomalies v1.211 IRX4 Ain Roesley Marked gene: IRX4 as ready
Fetal anomalies v1.211 IRX4 Ain Roesley Gene: irx4 has been classified as Red List (Low Evidence).
Fetal anomalies v1.211 IRX4 Ain Roesley gene: IRX4 was added
gene: IRX4 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: IRX4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: IRX4 were set to 21544582
Phenotypes for gene: IRX4 were set to Ventricular septal defect
Review for gene: IRX4 was set to RED
gene: IRX4 was marked as current diagnostic
Added comment: Two individuals with novel missense variants identified in a large cohort in 2011.

nothing new in punned
Sources: Literature
Fetal anomalies v1.210 HEY2 Ain Roesley Marked gene: HEY2 as ready
Fetal anomalies v1.210 HEY2 Ain Roesley Gene: hey2 has been classified as Red List (Low Evidence).
Fetal anomalies v1.210 HEY2 Ain Roesley gene: HEY2 was added
gene: HEY2 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: HEY2 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: HEY2 were set to 32820247
Phenotypes for gene: HEY2 were set to congenital heart defects and thoracic aortic aneurysms
Review for gene: HEY2 was set to RED
gene: HEY2 was marked as current diagnostic
Added comment: A very large family affected by CHD and familial thoracic aortic aneurysms. Trio genome sequencing was carried out in an index patient with critical CHD, and family members had either exome or Sanger sequencing. Identified homozygous loss-of-function variant (c.318_319delAG, p.G108*) in HEY2 in 3 individuals in family with critical CHD, whereas the 20 heterozygous carriers show a spectrum of CVDs (CHD and FTAA, but varying expressivity and incomplete penetrance).

Other studies show that knockout of HEY2 in mice results in cardiovascular defects (CVDs), including septal defects, cardiomyopathy, a thin-walled aorta, and valve anomalies.
Sources: Literature
Fetal anomalies v1.209 DOHH Ain Roesley Marked gene: DOHH as ready
Fetal anomalies v1.209 DOHH Ain Roesley Gene: dohh has been classified as Green List (High Evidence).
Fetal anomalies v1.209 DOHH Ain Roesley Classified gene: DOHH as Green List (high evidence)
Fetal anomalies v1.209 DOHH Ain Roesley Gene: dohh has been classified as Green List (High Evidence).
Fetal anomalies v1.208 DOHH Ain Roesley changed review comment from: 4 families - 5 affecteds

1x cardiomyopathy at prenatal examination
4/5 presented with CHD post-natally - VSD, ASD, severe cardiomegaly, Shone syndrome with aortic coarctation; bicuspid aortic valve; tricuspid-valve insufficiency etc

microcephaly was post-natal
Sources: Literature; to: 4 families - 5 affecteds

prenatal examination:
1x cardiomyopathy
1x increased nuchal translucency; chylothorax

post-natal:
4/5 presented with CHD - VSD, ASD, severe cardiomegaly, Shone syndrome with aortic coarctation; bicuspid aortic valve; tricuspid-valve insufficiency etc

5/5 microcephaly
Fetal anomalies v1.208 DOHH Ain Roesley gene: DOHH was added
gene: DOHH was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: DOHH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DOHH were set to 35858628
Phenotypes for gene: DOHH were set to Neurodevelopmental disorder with microcephaly, cerebral atrophy, and visual impairment, MIM# 620066
Review for gene: DOHH was set to GREEN
gene: DOHH was marked as current diagnostic
Added comment: 4 families - 5 affecteds

1x cardiomyopathy at prenatal examination
4/5 presented with CHD post-natally - VSD, ASD, severe cardiomegaly, Shone syndrome with aortic coarctation; bicuspid aortic valve; tricuspid-valve insufficiency etc

microcephaly was post-natal
Sources: Literature
Fetal anomalies v1.207 AMOTL1 Ain Roesley Marked gene: AMOTL1 as ready
Fetal anomalies v1.207 AMOTL1 Ain Roesley Gene: amotl1 has been classified as Green List (High Evidence).
Fetal anomalies v1.207 AMOTL1 Ain Roesley Classified gene: AMOTL1 as Green List (high evidence)
Fetal anomalies v1.207 AMOTL1 Ain Roesley Gene: amotl1 has been classified as Green List (High Evidence).
Fetal anomalies v1.207 AMOTL1 Ain Roesley Classified gene: AMOTL1 as Green List (high evidence)
Fetal anomalies v1.207 AMOTL1 Ain Roesley Gene: amotl1 has been classified as Green List (High Evidence).
Fetal anomalies v1.206 AMOTL1 Ain Roesley gene: AMOTL1 was added
gene: AMOTL1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: AMOTL1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: AMOTL1 were set to 36751037
Phenotypes for gene: AMOTL1 were set to Orofacial clefting syndrome, MONDO:0015335, AMOTL1-related
Review for gene: AMOTL1 was set to GREEN
gene: AMOTL1 was marked as current diagnostic
Added comment: PMID: 36751037- 16 individuals from 12 families with orofacial clefting syndrome and het variants in AMOTL1. Many in 1 hotspot: 5 individuals from 3 families have R157C, 6 individuals from another 4 families have R157H, 1 has P160L, and another has Q161R. Out of this hostpaot- 1 with P368A, 1 with E507K, 1 with E579K. 7 are de novo. All but 2 have clefting, 7 are dysmorphic, 5 have hearing loss, 9 have CHD, 7 have tall stature, 6 have dev delay. Other features include liver disease, myopia, scoliosis and immune involvement.

Another 2 families have been previously reported (described in the panelapp review below) with variants in this hotspot 1 has 2 individuals with R157C, the other has 1 individual with P160L. All hotspot are absent from gnomad v2.
Sources: Literature
Fetal anomalies v1.205 AL117258.1 Ain Roesley Marked gene: AL117258.1 as ready
Fetal anomalies v1.205 AL117258.1 Ain Roesley Gene: al117258.1 has been classified as Green List (High Evidence).
Fetal anomalies v1.205 AL117258.1 Ain Roesley Classified gene: AL117258.1 as Green List (high evidence)
Fetal anomalies v1.205 AL117258.1 Ain Roesley Gene: al117258.1 has been classified as Green List (High Evidence).
Fetal anomalies v1.204 AL117258.1 Ain Roesley gene: AL117258.1 was added
gene: AL117258.1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: AL117258.1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AL117258.1 were set to 34903892
Phenotypes for gene: AL117258.1 were set to Heterotaxy; congenital heart defects
Review for gene: AL117258.1 was set to GREEN
gene: AL117258.1 was marked as current diagnostic
Added comment: Gene also known as CIROP and LMLN2

Homozygous or compound heterozygous CIROP variants identified in 12 families with congenital heart defects associated with heterotaxy.

Functional tests performed on Xenopus and zebrafish embryos showed that CIROP was essential for left side symmetry and is expressed in ciliated left–right organisers.
Sources: Literature
Sources: Literature
Genetic Epilepsy v0.2500 MED12 Zornitza Stark Marked gene: MED12 as ready
Genetic Epilepsy v0.2500 MED12 Zornitza Stark Gene: med12 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2500 MED12 Zornitza Stark Mode of inheritance for gene: MED12 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, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Genetic Epilepsy v0.2499 MED12 Zornitza Stark Phenotypes for gene: MED12 were changed from to Ohdo syndrome, X-linked MIM#300895; Lujan-Fryns syndrome MIM#309520; Opitz-Kaveggia syndrome MIM#305450
Genetic Epilepsy v0.2498 MED12 Zornitza Stark Publications for gene: MED12 were set to 33244166; 32174975; 30006928; 27312080; 33244166
Genetic Epilepsy v0.2497 MED12 Zornitza Stark Publications for gene: MED12 were set to
Genetic Epilepsy v0.2497 MED12 Zornitza Stark Mode of inheritance for gene: MED12 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 v0.2496 MECP2 Zornitza Stark Marked gene: MECP2 as ready
Genetic Epilepsy v0.2496 MECP2 Zornitza Stark Gene: mecp2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2496 MECP2 Zornitza Stark Phenotypes for gene: MECP2 were changed from to Rett syndrome, MIM# 312750; Intellectual developmental disorder, X-linked, syndromic 13, MIM# 300055; Encephalopathy, neonatal severe, MIM# 300673
Genetic Epilepsy v0.2495 MECP2 Zornitza Stark Publications for gene: MECP2 were set to
Genetic Epilepsy v0.2494 MECP2 Zornitza Stark Mode of inheritance for gene: MECP2 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 v0.2493 MBOAT7 Zornitza Stark Marked gene: MBOAT7 as ready
Genetic Epilepsy v0.2493 MBOAT7 Zornitza Stark Gene: mboat7 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2493 MBOAT7 Zornitza Stark Phenotypes for gene: MBOAT7 were changed from to intellectual disability MIM#617188
Genetic Epilepsy v0.2492 MBOAT7 Zornitza Stark Publications for gene: MBOAT7 were set to
Genetic Epilepsy v0.2491 MBOAT7 Zornitza Stark Mode of inheritance for gene: MBOAT7 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2490 KCNJ11 Zornitza Stark Marked gene: KCNJ11 as ready
Genetic Epilepsy v0.2490 KCNJ11 Zornitza Stark Gene: kcnj11 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2490 KCNJ11 Zornitza Stark Phenotypes for gene: KCNJ11 were changed from to Diabetes mellitus, transient neonatal, 3 610582; Diabetes, permanent neonatal, with or without neurologic features 606176; Hyperinsulinemic hypoglycemia, familial, 2 601820
Genetic Epilepsy v0.2489 KCNJ11 Zornitza Stark Publications for gene: KCNJ11 were set to
Genetic Epilepsy v0.2488 KCNJ11 Zornitza Stark Mode of inheritance for gene: KCNJ11 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genetic Epilepsy v0.2487 DYNC1H1 Zornitza Stark Marked gene: DYNC1H1 as ready
Genetic Epilepsy v0.2487 DYNC1H1 Zornitza Stark Gene: dync1h1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2487 DYNC1H1 Zornitza Stark Phenotypes for gene: DYNC1H1 were changed from to Cortical dysplasia, complex, with other brain malformations 13, MIM# 614563
Genetic Epilepsy v0.2486 DYNC1H1 Zornitza Stark Publications for gene: DYNC1H1 were set to
Genetic Epilepsy v0.2485 DYNC1H1 Zornitza Stark Mode of inheritance for gene: DYNC1H1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2484 DYNC1H1 Zornitza Stark edited their review of gene: DYNC1H1: Changed phenotypes: Cortical dysplasia, complex, with other brain malformations 13, MIM# 614563
Prepair 1000+ v1.6 ADPRHL2 Zornitza Stark Classified gene: ADPRHL2 as Amber List (moderate evidence)
Prepair 1000+ v1.6 ADPRHL2 Zornitza Stark Gene: adprhl2 has been classified as Amber List (Moderate Evidence).
Prepair 1000+ v1.5 ADPRHL2 Zornitza Stark changed review comment from: Fourteen unrelated families reported with stress-induced childhood-onset neurodegeneration with variable ataxia and seizures (CONDSIAS), an autosomal recessive neurodegenerative disorder with onset in the first years of life following normal early development. The disorder is characterised by cyclic episodic deterioration in response to stress, such as infection or febrile illness. The severity is highly variable: some individuals develop seizures early in life that are associated with loss of developmental milestones and early sudden death in childhood, whereas others present at a later age with muscle weakness, gait ataxia, impaired speech, more subtle clinical deterioration, and cognitive decline. Neurologic involvement includes gait ataxia, cerebellar signs associated with cerebellar atrophy, generalized brain atrophy, impaired intellectual development, hearing loss, and peripheral neuropathy.

New HGNC approved name is ADPRS.; to: Fourteen unrelated families reported with stress-induced childhood-onset neurodegeneration with variable ataxia and seizures (CONDSIAS), an autosomal recessive neurodegenerative disorder with onset in the first years of life following normal early development. The disorder is characterised by cyclic episodic deterioration in response to stress, such as infection or febrile illness. The severity is highly variable: some individuals develop seizures early in life that are associated with loss of developmental milestones and early sudden death in childhood, whereas others present at a later age with muscle weakness, gait ataxia, impaired speech, more subtle clinical deterioration, and cognitive decline. Neurologic involvement includes gait ataxia, cerebellar signs associated with cerebellar atrophy, generalized brain atrophy, impaired intellectual development, hearing loss, and peripheral neuropathy.

New HGNC approved name is ADPRS.

To be upgraded to GREEN in next version of panel.
Prepair 1000+ v1.5 ADPRHL2 Zornitza Stark edited their review of gene: ADPRHL2: Changed rating: AMBER
Genetic Epilepsy v0.2484 MAP2K2 Zornitza Stark Marked gene: MAP2K2 as ready
Genetic Epilepsy v0.2484 MAP2K2 Zornitza Stark Gene: map2k2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2484 MAP2K2 Zornitza Stark Phenotypes for gene: MAP2K2 were changed from to Cardiofaciocutaneous syndrome 4, MIM# 615280
Genetic Epilepsy v0.2483 MAP2K2 Zornitza Stark Publications for gene: MAP2K2 were set to
Genetic Epilepsy v0.2482 MAP2K2 Zornitza Stark Mode of pathogenicity for gene: MAP2K2 was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Genetic Epilepsy v0.2481 MAP2K2 Zornitza Stark Mode of inheritance for gene: MAP2K2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2480 MAP2K1 Zornitza Stark Marked gene: MAP2K1 as ready
Genetic Epilepsy v0.2480 MAP2K1 Zornitza Stark Gene: map2k1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2480 MAP2K1 Zornitza Stark Phenotypes for gene: MAP2K1 were changed from to Cardiofaciocutaneous syndrome 3, MIM# 615279
Genetic Epilepsy v0.2479 MAP2K1 Zornitza Stark Publications for gene: MAP2K1 were set to
Genetic Epilepsy v0.2478 MAP2K1 Zornitza Stark Mode of pathogenicity for gene: MAP2K1 was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Genetic Epilepsy v0.2477 MAP2K1 Zornitza Stark Mode of inheritance for gene: MAP2K1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2476 MAF Zornitza Stark Marked gene: MAF as ready
Genetic Epilepsy v0.2476 MAF Zornitza Stark Gene: maf has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2476 MAF Zornitza Stark Phenotypes for gene: MAF were changed from to Ayme-Gripp syndrome (MIM#601088)
Genetic Epilepsy v0.2475 MAF Zornitza Stark Publications for gene: MAF were set to
Genetic Epilepsy v0.2474 MAF Zornitza Stark Mode of inheritance for gene: MAF was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2473 KIF1A Zornitza Stark Marked gene: KIF1A as ready
Genetic Epilepsy v0.2473 KIF1A Zornitza Stark Gene: kif1a has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2473 KIF1A Zornitza Stark Phenotypes for gene: KIF1A were changed from to NESCAV syndrome, MIM# 614255
Genetic Epilepsy v0.2472 KIF1A Zornitza Stark Publications for gene: KIF1A were set to
Genetic Epilepsy v0.2471 KIF1A Zornitza Stark Mode of inheritance for gene: KIF1A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2470 KIF1A Zornitza Stark changed review comment from: HSN2C is an autosomal recessive disorder characterized by onset in the first decade of progressive distal sensory loss leading to ulceration and amputation of the fingers and toes. Affected individuals also develop distal muscle weakness, primarily affecting the lower limbs. At least 4 families reported, although 3 shared same founder variant.

De novo variants in this gene are also more commonly associated with spastic paraplegia, and a complex neurodevelopmental disorder, NESCAV syndrome.; to: De novo variants in this gene are also more commonly associated with spastic paraplegia, and a complex neurodevelopmental disorder, NESCAV syndrome, which can include seizures.
Genetic Epilepsy v0.2470 KIF1A Zornitza Stark edited their review of gene: KIF1A: Changed phenotypes: NESCAV syndrome, MIM# 614255; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2470 KIAA1109 Zornitza Stark Marked gene: KIAA1109 as ready
Genetic Epilepsy v0.2470 KIAA1109 Zornitza Stark Gene: kiaa1109 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2470 KIAA1109 Zornitza Stark Phenotypes for gene: KIAA1109 were changed from to lkuraya-Kucinskas syndrome, MIM# 617822
Genetic Epilepsy v0.2469 KIAA1109 Zornitza Stark Publications for gene: KIAA1109 were set to
Genetic Epilepsy v0.2468 KIAA1109 Zornitza Stark Mode of inheritance for gene: KIAA1109 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2467 KCTD7 Zornitza Stark Marked gene: KCTD7 as ready
Genetic Epilepsy v0.2467 KCTD7 Zornitza Stark Gene: kctd7 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2467 KCTD7 Zornitza Stark Phenotypes for gene: KCTD7 were changed from to Epilepsy, progressive myoclonic 3, with or without intracellular inclusions (MIM#611726), AR
Genetic Epilepsy v0.2466 KCTD7 Zornitza Stark Publications for gene: KCTD7 were set to
Genetic Epilepsy v0.2465 KCTD7 Zornitza Stark Mode of inheritance for gene: KCTD7 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2464 ITPA Zornitza Stark Marked gene: ITPA as ready
Genetic Epilepsy v0.2464 ITPA Zornitza Stark Gene: itpa has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2464 ITPA Zornitza Stark Phenotypes for gene: ITPA were changed from to Developmental and epileptic encephalopathy 35, MIM# 616647
Genetic Epilepsy v0.2463 ITPA Zornitza Stark Publications for gene: ITPA were set to
Genetic Epilepsy v0.2462 ITPA Zornitza Stark Mode of inheritance for gene: ITPA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2461 IKBKG Zornitza Stark Marked gene: IKBKG as ready
Genetic Epilepsy v0.2461 IKBKG Zornitza Stark Gene: ikbkg has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2461 IKBKG Zornitza Stark Phenotypes for gene: IKBKG were changed from to Incontinentia pigmenti, MIM# 308300
Genetic Epilepsy v0.2460 IKBKG Zornitza Stark Publications for gene: IKBKG were set to
Genetic Epilepsy v0.2459 IKBKG Zornitza Stark Mode of inheritance for gene: IKBKG 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 v0.2458 IKBKG Zornitza Stark changed review comment from: X-linked systemic autoinflammatory disease (SAIDX) is characterized by the onset of systemic autoinflammation in the first months of life. Features include lymphadenopathy, hepatosplenomegaly, fever, panniculitis, and nodular skin rash. Additional manifestations may include inflammation of the optic nerve, intracranial hemorrhage, and lipodystrophy. Laboratory studies show hypogammaglobulinemia, increased or decreased white blood cell count, autoimmune cytopenias, elevated serum inflammatory markers, and a type I interferon signature. 6 unrelated boys and a girl reported. All variants resulted in absence of the domain encoded by exon 5 (NEMOdelEx5).

Note variants in this gene are associated with immunodeficiency +/- ectodermal features and with IP.; to: X-linked systemic autoinflammatory disease (SAIDX) is characterized by the onset of systemic autoinflammation in the first months of life. Features include lymphadenopathy, hepatosplenomegaly, fever, panniculitis, and nodular skin rash. Additional manifestations may include inflammation of the optic nerve, intracranial hemorrhage, and lipodystrophy. Laboratory studies show hypogammaglobulinemia, increased or decreased white blood cell count, autoimmune cytopenias, elevated serum inflammatory markers, and a type I interferon signature. 6 unrelated boys and a girl reported. All variants resulted in absence of the domain encoded by exon 5 (NEMOdelEx5).

Note variants in this gene are associated with immunodeficiency +/- ectodermal features and with IP.

Seizures reported in the IP phenotype.
Genetic Epilepsy v0.2458 IFIH1 Zornitza Stark Marked gene: IFIH1 as ready
Genetic Epilepsy v0.2458 IFIH1 Zornitza Stark Gene: ifih1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2458 IFIH1 Zornitza Stark Phenotypes for gene: IFIH1 were changed from to Aicardi-Goutieres syndrome 7, MIM#615846
Genetic Epilepsy v0.2457 IFIH1 Zornitza Stark Publications for gene: IFIH1 were set to
Genetic Epilepsy v0.2456 IFIH1 Zornitza Stark Mode of pathogenicity for gene: IFIH1 was changed from to Other
Genetic Epilepsy v0.2455 IFIH1 Zornitza Stark Mode of inheritance for gene: IFIH1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2454 IDH2 Zornitza Stark Marked gene: IDH2 as ready
Genetic Epilepsy v0.2454 IDH2 Zornitza Stark Gene: idh2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2454 IDH2 Zornitza Stark Phenotypes for gene: IDH2 were changed from to D-2-hydroxyglutaric aciduria 2, MIM# 613657
Genetic Epilepsy v0.2453 IDH2 Zornitza Stark Publications for gene: IDH2 were set to
Genetic Epilepsy v0.2452 IDH2 Zornitza Stark Mode of inheritance for gene: IDH2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2451 HTRA2 Zornitza Stark Marked gene: HTRA2 as ready
Genetic Epilepsy v0.2451 HTRA2 Zornitza Stark Gene: htra2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2451 HTRA2 Zornitza Stark Phenotypes for gene: HTRA2 were changed from to 3-methylglutaconic aciduria, type VIII, MIM# 617248
Genetic Epilepsy v0.2450 HTRA2 Zornitza Stark Publications for gene: HTRA2 were set to
Genetic Epilepsy v0.2449 HTRA2 Zornitza Stark Mode of inheritance for gene: HTRA2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2448 HSPD1 Zornitza Stark changed review comment from: Multiple families reported with bi-allelic variants in HSPD1 and hypomyelinating leukodystrophy. Supportive mouse model. In addition, two unrelated individuals reported with same de novo missense p.Leu47Val and leukodystrophy.

In addition, mono-allelic variants found in families with SPG.; to: Multiple families reported with bi-allelic variants in HSPD1 and hypomyelinating leukodystrophy. Supportive mouse model. In addition, two unrelated individuals reported with same de novo missense p.Leu47Val and leukodystrophy.

In addition, mono-allelic variants found in families with SPG, not relevant to this panel.
Genetic Epilepsy v0.2448 HSPD1 Zornitza Stark edited their review of gene: HSPD1: Changed phenotypes: Leukodystrophy, hypomyelinating, 4, MIM# 612233; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2448 HSPD1 Zornitza Stark Marked gene: HSPD1 as ready
Genetic Epilepsy v0.2448 HSPD1 Zornitza Stark Gene: hspd1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2448 HSPD1 Zornitza Stark Phenotypes for gene: HSPD1 were changed from to Leukodystrophy, hypomyelinating, 4, MIM# 612233
Genetic Epilepsy v0.2447 HSPD1 Zornitza Stark Mode of inheritance for gene: HSPD1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2446 HSPD1 Zornitza Stark Publications for gene: HSPD1 were set to
Genetic Epilepsy v0.2445 HSPD1 Zornitza Stark Mode of inheritance for gene: HSPD1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genetic Epilepsy v0.2444 HSD17B4 Zornitza Stark Marked gene: HSD17B4 as ready
Genetic Epilepsy v0.2444 HSD17B4 Zornitza Stark Gene: hsd17b4 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2444 HSD17B4 Zornitza Stark Phenotypes for gene: HSD17B4 were changed from to D-bifunctional protein deficiency, AR (MIM#261515); Perrault syndrome 1, AR (MIM#233400)
Genetic Epilepsy v0.2443 HSD17B4 Zornitza Stark Publications for gene: HSD17B4 were set to
Genetic Epilepsy v0.2442 HSD17B4 Zornitza Stark Mode of inheritance for gene: HSD17B4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2441 HRAS Zornitza Stark Marked gene: HRAS as ready
Genetic Epilepsy v0.2441 HRAS Zornitza Stark Gene: hras has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2441 HRAS Zornitza Stark Phenotypes for gene: HRAS were changed from Costello syndrome, MIM# 218040 to Costello syndrome, MIM# 218040
Genetic Epilepsy v0.2440 HRAS Zornitza Stark Phenotypes for gene: HRAS were changed from to Costello syndrome, MIM# 218040
Genetic Epilepsy v0.2439 HRAS Zornitza Stark Publications for gene: HRAS were set to
Genetic Epilepsy v0.2438 HRAS Zornitza Stark Mode of pathogenicity for gene: HRAS was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Genetic Epilepsy v0.2437 HRAS Zornitza Stark Mode of inheritance for gene: HRAS was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2436 HMGCL Zornitza Stark Marked gene: HMGCL as ready
Genetic Epilepsy v0.2436 HMGCL Zornitza Stark Gene: hmgcl has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2436 HMGCL Zornitza Stark Phenotypes for gene: HMGCL were changed from to HMG-CoA lyase deficiency, MIM# 246450
Genetic Epilepsy v0.2435 HMGCL Zornitza Stark Publications for gene: HMGCL were set to
Genetic Epilepsy v0.2434 HMGCL Zornitza Stark Mode of inheritance for gene: HMGCL was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2433 HLCS Zornitza Stark Marked gene: HLCS as ready
Genetic Epilepsy v0.2433 HLCS Zornitza Stark Gene: hlcs has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2433 HLCS Zornitza Stark Phenotypes for gene: HLCS were changed from to Holocarboxylase synthetase deficiency, MIM# 253270
Genetic Epilepsy v0.2432 HLCS Zornitza Stark Publications for gene: HLCS were set to
Genetic Epilepsy v0.2431 HLCS Zornitza Stark Mode of inheritance for gene: HLCS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2430 HEXB Zornitza Stark Marked gene: HEXB as ready
Genetic Epilepsy v0.2430 HEXB Zornitza Stark Gene: hexb has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2430 HEXB Zornitza Stark Phenotypes for gene: HEXB were changed from to Sandhoff disease, infantile, juvenile, and adult forms, MIM# 268800; MONDO:0010006
Genetic Epilepsy v0.2429 HEXB Zornitza Stark Mode of inheritance for gene: HEXB was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2428 HEXA Zornitza Stark Marked gene: HEXA as ready
Genetic Epilepsy v0.2428 HEXA Zornitza Stark Gene: hexa has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2428 HEXA Zornitza Stark Phenotypes for gene: HEXA were changed from to GM2-gangliosidosis, several forms 272800; Tay-Sachs disease 272800
Genetic Epilepsy v0.2427 HEXA Zornitza Stark Publications for gene: HEXA were set to
Genetic Epilepsy v0.2426 HEXA Zornitza Stark Mode of inheritance for gene: HEXA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2425 HEPACAM Zornitza Stark Marked gene: HEPACAM as ready
Genetic Epilepsy v0.2425 HEPACAM Zornitza Stark Gene: hepacam has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2425 HEPACAM Zornitza Stark Phenotypes for gene: HEPACAM were changed from to Megalencephalic leukoencephalopathy with subcortical cysts 2A, MIM# 613925; Megalencephalic leukoencephalopathy with subcortical cysts 2B, remitting, with or without mental retardation, MIM# 613926
Genetic Epilepsy v0.2424 HEPACAM Zornitza Stark Publications for gene: HEPACAM were set to
Genetic Epilepsy v0.2423 HEPACAM Zornitza Stark Mode of inheritance for gene: HEPACAM was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Genetic Epilepsy v0.2422 HAX1 Zornitza Stark Marked gene: HAX1 as ready
Genetic Epilepsy v0.2422 HAX1 Zornitza Stark Gene: hax1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2422 HAX1 Zornitza Stark Phenotypes for gene: HAX1 were changed from to Neutropaenia, severe congenital 3, autosomal recessive, MIM# 610738; Kostmann syndrome MONDO:0012548
Genetic Epilepsy v0.2421 HAX1 Zornitza Stark Publications for gene: HAX1 were set to
Genetic Epilepsy v0.2420 HAX1 Zornitza Stark Mode of inheritance for gene: HAX1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2419 GOSR2 Zornitza Stark Marked gene: GOSR2 as ready
Genetic Epilepsy v0.2419 GOSR2 Zornitza Stark Gene: gosr2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2419 GOSR2 Zornitza Stark Phenotypes for gene: GOSR2 were changed from to Epilepsy, progressive myoclonic 6 , MIM#614018
Genetic Epilepsy v0.2418 GOSR2 Zornitza Stark Publications for gene: GOSR2 were set to
Genetic Epilepsy v0.2417 GOSR2 Zornitza Stark Mode of inheritance for gene: GOSR2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2416 GNAQ Zornitza Stark Marked gene: GNAQ as ready
Genetic Epilepsy v0.2416 GNAQ Zornitza Stark Gene: gnaq has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2416 GNAQ Zornitza Stark Phenotypes for gene: GNAQ were changed from to Sturge-Weber syndrome, somatic, mosaic 185300
Genetic Epilepsy v0.2415 GNAQ Zornitza Stark Publications for gene: GNAQ were set to
Genetic Epilepsy v0.2414 GNAQ Zornitza Stark Mode of pathogenicity for gene: GNAQ was changed from to Other
Genetic Epilepsy v0.2413 GNAQ Zornitza Stark Mode of inheritance for gene: GNAQ was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.2412 GNAQ Zornitza Stark Tag somatic tag was added to gene: GNAQ.
Genetic Epilepsy v0.2412 GM2A Zornitza Stark Marked gene: GM2A as ready
Genetic Epilepsy v0.2412 GM2A Zornitza Stark Gene: gm2a has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2412 GM2A Zornitza Stark Phenotypes for gene: GM2A were changed from to GM2-gangliosidosis, AB variant MIM#272750
Genetic Epilepsy v0.2411 GM2A Zornitza Stark Publications for gene: GM2A were set to
Genetic Epilepsy v0.2410 GM2A Zornitza Stark Mode of inheritance for gene: GM2A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2409 GLUL Zornitza Stark Marked gene: GLUL as ready
Genetic Epilepsy v0.2409 GLUL Zornitza Stark Gene: glul has been classified as Green List (High Evidence).
Genetic Epilepsy v0.2409 GLUL Zornitza Stark Phenotypes for gene: GLUL were changed from to Glutamine deficiency, congenital MIM#610015
Genetic Epilepsy v0.2408 GLUL Zornitza Stark Publications for gene: GLUL were set to
Genetic Epilepsy v0.2407 GLUL Zornitza Stark Mode of inheritance for gene: GLUL was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.2406 GLUL Zornitza Stark reviewed gene: GLUL: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Glutamine deficiency, congenital MIM#610015; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal