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Intellectual disability syndromic and non-syndromic v0.5569 ATP13A2 Zornitza Stark Mode of inheritance for gene: ATP13A2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5568 ATP13A2 Zornitza Stark Classified gene: ATP13A2 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.5568 ATP13A2 Zornitza Stark Gene: atp13a2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5567 ATP13A2 Zornitza Stark reviewed gene: ATP13A2: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Kufor-Rakeb syndrome, MIM# 606693; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5567 BRAF Zornitza Stark Marked gene: BRAF as ready
Intellectual disability syndromic and non-syndromic v0.5567 BRAF Zornitza Stark Gene: braf has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5567 BRAF Zornitza Stark Phenotypes for gene: BRAF were changed from to Cardiofaciocutaneous syndrome (MIM# 115150); Noonan syndrome (MIM# 613706); LEOPARD syndrome (MIM# 613707)
Intellectual disability syndromic and non-syndromic v0.5566 BRAF Zornitza Stark Publications for gene: BRAF were set to
Intellectual disability syndromic and non-syndromic v0.5565 BRAF Zornitza Stark Mode of pathogenicity for gene: BRAF 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
Intellectual disability syndromic and non-syndromic v0.5564 BRAF Zornitza Stark Mode of inheritance for gene: BRAF was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5563 SMARCA4 Zornitza Stark Marked gene: SMARCA4 as ready
Intellectual disability syndromic and non-syndromic v0.5563 SMARCA4 Zornitza Stark Gene: smarca4 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5563 SMARCA4 Zornitza Stark Phenotypes for gene: SMARCA4 were changed from to Coffin-Siris syndrome 4 (MIM# 614609)
Intellectual disability syndromic and non-syndromic v0.5562 SMARCA4 Zornitza Stark Publications for gene: SMARCA4 were set to
Intellectual disability syndromic and non-syndromic v0.5561 SMARCA4 Zornitza Stark Mode of pathogenicity for gene: SMARCA4 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
Intellectual disability syndromic and non-syndromic v0.5560 SMARCA4 Zornitza Stark Mode of inheritance for gene: SMARCA4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5559 SMC3 Zornitza Stark Marked gene: SMC3 as ready
Intellectual disability syndromic and non-syndromic v0.5559 SMC3 Zornitza Stark Gene: smc3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5559 SMC3 Zornitza Stark Phenotypes for gene: SMC3 were changed from to Cornelia de Lange syndrome 3 MONDO:0012555
Intellectual disability syndromic and non-syndromic v0.5558 SMC3 Zornitza Stark Publications for gene: SMC3 were set to
Intellectual disability syndromic and non-syndromic v0.5557 SMC3 Zornitza Stark Mode of inheritance for gene: SMC3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5556 SMC1A Zornitza Stark Marked gene: SMC1A as ready
Intellectual disability syndromic and non-syndromic v0.5556 SMC1A Zornitza Stark Gene: smc1a has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5556 SMC1A Zornitza Stark Phenotypes for gene: SMC1A were changed from to Cornelia de Lange syndrome 2 MONDO:0010370
Intellectual disability syndromic and non-syndromic v0.5555 SMC1A Zornitza Stark Publications for gene: SMC1A were set to
Intellectual disability syndromic and non-syndromic v0.5554 SMC1A Zornitza Stark Mode of inheritance for gene: SMC1A 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 v0.5553 SMARCB1 Zornitza Stark Marked gene: SMARCB1 as ready
Intellectual disability syndromic and non-syndromic v0.5553 SMARCB1 Zornitza Stark Gene: smarcb1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5553 SMARCB1 Zornitza Stark Phenotypes for gene: SMARCB1 were changed from to Coffin-Siris syndrome 3 (MIM# 614608); MONDO:0015452
Intellectual disability syndromic and non-syndromic v0.5552 SMARCB1 Zornitza Stark Publications for gene: SMARCB1 were set to
Intellectual disability syndromic and non-syndromic v0.5551 SMARCB1 Zornitza Stark Mode of pathogenicity for gene: SMARCB1 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
Intellectual disability syndromic and non-syndromic v0.5550 SMARCB1 Zornitza Stark Mode of inheritance for gene: SMARCB1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.1268 SRP68 Zornitza Stark Marked gene: SRP68 as ready
Mendeliome v1.1268 SRP68 Zornitza Stark Gene: srp68 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1268 SRP68 Zornitza Stark Classified gene: SRP68 as Amber List (moderate evidence)
Mendeliome v1.1268 SRP68 Zornitza Stark Gene: srp68 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1267 SRP68 Zornitza Stark gene: SRP68 was added
gene: SRP68 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: SRP68 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SRP68 were set to 32273475
Phenotypes for gene: SRP68 were set to Neutropenia, severe congenital, 10, autosomal recessive, MIM# 620534
Review for gene: SRP68 was set to AMBER
Added comment: Single individual reported with bi-allelic LoF variants and presenting with infantile-onset severe neutropenia and recurrent infections. Multiple lines of functional evidence provided.
Sources: Expert list
Phagocyte Defects v1.18 SRP68 Zornitza Stark Marked gene: SRP68 as ready
Phagocyte Defects v1.18 SRP68 Zornitza Stark Gene: srp68 has been classified as Amber List (Moderate Evidence).
Phagocyte Defects v1.18 SRP68 Zornitza Stark Classified gene: SRP68 as Amber List (moderate evidence)
Phagocyte Defects v1.18 SRP68 Zornitza Stark Gene: srp68 has been classified as Amber List (Moderate Evidence).
Phagocyte Defects v1.17 SRP68 Zornitza Stark gene: SRP68 was added
gene: SRP68 was added to Phagocyte Defects. Sources: Expert list
Mode of inheritance for gene: SRP68 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SRP68 were set to 32273475
Phenotypes for gene: SRP68 were set to Neutropenia, severe congenital, 10, autosomal recessive, MIM# 620534
Review for gene: SRP68 was set to AMBER
Added comment: Single individual reported with bi-allelic LoF variants and presenting with infantile-onset severe neutropenia and recurrent infections. Multiple lines of functional evidence provided.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.5549 SMARCB1 Kaitlyn Dianna Weldon reviewed gene: SMARCB1: Rating: GREEN; Mode of pathogenicity: None; Publications: 23556151; Phenotypes: Coffin-Siris syndrome MONDO:0015452; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5549 SMC1A Kaitlyn Dianna Weldon reviewed gene: SMC1A: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301283; Phenotypes: Cornelia de Lange syndrome 2 MONDO:0010370; 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 v0.5549 SMC3 Kaitlyn Dianna Weldon reviewed gene: SMC3: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301283; Phenotypes: Cornelia de Lange syndrome 3 MONDO:0012555; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5549 SMARCB1 Claire Fryer-Smith reviewed gene: SMARCB1: 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: 22426308, 29907796, 3175698; Phenotypes: Coffin-Siris syndrome 3 (MIM# 614608); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5549 SMARCA4 Claire Fryer-Smith changed review comment from: Coffin-Siris syndrome is a congenital malformation syndrome characterized by developmental delay, intellectual disability, coarse facial features, feeding difficulties, and hypoplastic or absent fifth fingernails and fifth distal phalanges.

Missense and an in-frame deletion in SCARCA4 have been observed across 15 CSS patients in the literature (22426308, 23637025, 23929686), suggesting a dominant negative GoF effect.

LoF variants in SMARCA4 result in Rhabdoid tumor predisposition syndrome, which does not exhibit ID.; to: Coffin-Siris syndrome is a congenital malformation syndrome characterized by developmental delay, intellectual disability, coarse facial features, feeding difficulties, and hypoplastic or absent fifth fingernails and fifth distal phalanges.

Missense and an in-frame deletion in SMARCA4 have been observed across 15 CSS patients in the literature (22426308, 23637025, 23929686), suggesting a dominant negative GoF effect.

LoF variants in SMARCA4 result in Rhabdoid tumor predisposition syndrome, which does not exhibit ID.
Intellectual disability syndromic and non-syndromic v0.5549 SMARCA4 Claire Fryer-Smith reviewed gene: SMARCA4: 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: 22426308, 23929686, 23637025; Phenotypes: Coffin-Siris syndrome 4 (MIM# 614609); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5549 BRAF Claire Fryer-Smith reviewed gene: BRAF: 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: 10610177, 16474404, 19206169; Phenotypes: Cardiofaciocutaneous syndrome (MIM# 115150), Noonan syndrome (MIM# 613706), LEOPARD syndrome (MIM# 613707); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5549 STXBP1 Zornitza Stark Marked gene: STXBP1 as ready
Intellectual disability syndromic and non-syndromic v0.5549 STXBP1 Zornitza Stark Gene: stxbp1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5549 STXBP1 Zornitza Stark Phenotypes for gene: STXBP1 were changed from to developmental and epileptic encephalopathy, 4 MONDO:0012812
Intellectual disability syndromic and non-syndromic v0.5548 STXBP1 Zornitza Stark Publications for gene: STXBP1 were set to
Intellectual disability syndromic and non-syndromic v0.5547 STXBP1 Zornitza Stark Mode of inheritance for gene: STXBP1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5546 FH Zornitza Stark Marked gene: FH as ready
Intellectual disability syndromic and non-syndromic v0.5546 FH Zornitza Stark Gene: fh has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5546 FH Zornitza Stark Phenotypes for gene: FH were changed from to Fumarase deficiency (MIM# 606812)
Intellectual disability syndromic and non-syndromic v0.5545 FH Zornitza Stark Publications for gene: FH were set to
Intellectual disability syndromic and non-syndromic v0.5544 FH Zornitza Stark Mode of inheritance for gene: FH was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5543 TMEM70 Zornitza Stark Marked gene: TMEM70 as ready
Intellectual disability syndromic and non-syndromic v0.5543 TMEM70 Zornitza Stark Gene: tmem70 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5543 TMEM70 Zornitza Stark Phenotypes for gene: TMEM70 were changed from to Mitochondrial complex V (ATP synthase) deficiency, nuclear type 2, MIM# 614052
Intellectual disability syndromic and non-syndromic v0.5542 TMEM70 Zornitza Stark Publications for gene: TMEM70 were set to
Intellectual disability syndromic and non-syndromic v0.5541 FH Claire Fryer-Smith reviewed gene: FH: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31746132, 29052812, 21560188; Phenotypes: Fumarase deficiency (MIM# 606812); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5541 TMEM70 Zornitza Stark Mode of inheritance for gene: TMEM70 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5540 TMEM70 Zornitza Stark reviewed gene: TMEM70: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Mitochondrial complex V (ATP synthase) deficiency, nuclear type 2, MIM# 614052; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5540 TMEM240 Zornitza Stark Marked gene: TMEM240 as ready
Intellectual disability syndromic and non-syndromic v0.5540 TMEM240 Zornitza Stark Gene: tmem240 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5540 TMEM240 Zornitza Stark Publications for gene: TMEM240 were set to
Intellectual disability syndromic and non-syndromic v0.5539 TMEM240 Zornitza Stark Phenotypes for gene: TMEM240 were changed from to Spinocerebellar ataxia 21, MIM# 607454; spinocerebellar ataxia type 21 MONDO:0011833
Intellectual disability syndromic and non-syndromic v0.5538 TMEM240 Zornitza Stark Mode of inheritance for gene: TMEM240 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5537 TMEM216 Zornitza Stark Marked gene: TMEM216 as ready
Intellectual disability syndromic and non-syndromic v0.5537 TMEM216 Zornitza Stark Gene: tmem216 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5537 TMEM216 Zornitza Stark Phenotypes for gene: TMEM216 were changed from to Joubert syndrome 2 MONDO:0011963
Intellectual disability syndromic and non-syndromic v0.5536 TMEM216 Zornitza Stark Publications for gene: TMEM216 were set to
Intellectual disability syndromic and non-syndromic v0.5535 TMEM216 Zornitza Stark Mode of inheritance for gene: TMEM216 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5534 TMCO1 Zornitza Stark Marked gene: TMCO1 as ready
Intellectual disability syndromic and non-syndromic v0.5534 TMCO1 Zornitza Stark Gene: tmco1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5534 TMCO1 Zornitza Stark Phenotypes for gene: TMCO1 were changed from to Craniofacial dysmorphism, skeletal anomalies, and impaired intellectual development 1, MIM# 213980; cerebrofaciothoracic dysplasia MONDO:0008952
Intellectual disability syndromic and non-syndromic v0.5533 TMCO1 Zornitza Stark Publications for gene: TMCO1 were set to
Intellectual disability syndromic and non-syndromic v0.5532 TMCO1 Zornitza Stark Mode of inheritance for gene: TMCO1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5531 TCF4 Zornitza Stark Marked gene: TCF4 as ready
Intellectual disability syndromic and non-syndromic v0.5531 TCF4 Zornitza Stark Gene: tcf4 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5531 TCF4 Zornitza Stark Phenotypes for gene: TCF4 were changed from to Pitt-Hopkins syndrome MONDO:0012589
Intellectual disability syndromic and non-syndromic v0.5530 TCF4 Zornitza Stark Publications for gene: TCF4 were set to
Intellectual disability syndromic and non-syndromic v0.5529 TCF4 Zornitza Stark Mode of inheritance for gene: TCF4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5528 STRA6 Kaitlyn Dianna Weldon reviewed gene: STRA6: Rating: GREEN; Mode of pathogenicity: None; Publications: 17273977; Phenotypes: Matthew-Wood syndrome MONDO:0011010; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5528 TBC1D24 Zornitza Stark Marked gene: TBC1D24 as ready
Intellectual disability syndromic and non-syndromic v0.5528 TBC1D24 Zornitza Stark Gene: tbc1d24 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5528 TBC1D24 Zornitza Stark Phenotypes for gene: TBC1D24 were changed from to Developmental and epileptic encephalopathy 16, MIM# 615338; DOORS syndrome, MIM# 220500
Intellectual disability syndromic and non-syndromic v0.5527 TBC1D24 Zornitza Stark Publications for gene: TBC1D24 were set to
Intellectual disability syndromic and non-syndromic v0.5526 TBC1D24 Zornitza Stark Mode of inheritance for gene: TBC1D24 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5525 TAZ Zornitza Stark Marked gene: TAZ as ready
Intellectual disability syndromic and non-syndromic v0.5525 TAZ Zornitza Stark Gene: taz has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5525 TAZ Zornitza Stark Phenotypes for gene: TAZ were changed from to Barth syndrome MONDO:0010543
Intellectual disability syndromic and non-syndromic v0.5524 STXBP1 Kaitlyn Dianna Weldon reviewed gene: STXBP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 27905812; Phenotypes: developmental and epileptic encephalopathy, 4 MONDO:0012812; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5524 TAZ Zornitza Stark Publications for gene: TAZ were set to
Intellectual disability syndromic and non-syndromic v0.5523 TAZ Zornitza Stark Mode of inheritance for gene: TAZ was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.5522 TAT Zornitza Stark Marked gene: TAT as ready
Intellectual disability syndromic and non-syndromic v0.5522 TAT Zornitza Stark Gene: tat has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5522 TAT Zornitza Stark Phenotypes for gene: TAT were changed from to tyrosinemia type II MONDO:0010160
Intellectual disability syndromic and non-syndromic v0.5521 TAT Zornitza Stark Publications for gene: TAT were set to
Intellectual disability syndromic and non-syndromic v0.5520 TAT Zornitza Stark Mode of inheritance for gene: TAT was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5519 TANGO2 Zornitza Stark Marked gene: TANGO2 as ready
Intellectual disability syndromic and non-syndromic v0.5519 TANGO2 Zornitza Stark Gene: tango2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5519 TANGO2 Zornitza Stark Phenotypes for gene: TANGO2 were changed from to Metabolic encephalomyopathic crises, recurrent, with rhabdomyolysis, cardiac arrhythmias, and neurodegeneration, MIM# 616878; metabolic encephalomyopathic crises, recurrent, with rhabdomyolysis, cardiac arrhythmias, and neurodegeneration MONDO:0014812
Intellectual disability syndromic and non-syndromic v0.5518 TANGO2 Zornitza Stark Publications for gene: TANGO2 were set to
Intellectual disability syndromic and non-syndromic v0.5517 TANGO2 Zornitza Stark Mode of inheritance for gene: TANGO2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5516 NF1 Claire Fryer-Smith changed review comment from: NF1 shows a high degree of phenotypic variability. Intellectual disability has been shown to occur in 4%-8% of cases, typically appearing in childhood and persisting through life (PMID: 23931823, 10762507).; to: NF1 shows a high degree of phenotypic variability. Intellectual disability has been shown to occur in 4%-8% of cases, typically appearing in childhood and persisting through life (PMID: 23931823, 10762507).
Intellectual disability syndromic and non-syndromic v0.5516 NF1 Claire Fryer-Smith reviewed gene: NF1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 23931823, 10762507; Phenotypes: Neurofibromatosis, type 1 (MIM#162200); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5516 SUOX Kaitlyn Dianna Weldon reviewed gene: SUOX: Rating: GREEN; Mode of pathogenicity: None; Publications: 28933809; Phenotypes: isolated sulfite oxidase deficiency MONDO:0010089; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Liver Failure_Paediatric v1.22 MTM1 Zornitza Stark Marked gene: MTM1 as ready
Liver Failure_Paediatric v1.22 MTM1 Zornitza Stark Gene: mtm1 has been classified as Amber List (Moderate Evidence).
Liver Failure_Paediatric v1.22 MTM1 Zornitza Stark Phenotypes for gene: MTM1 were changed from X-linked myotubular myopathy to Myopathy, centronuclear, X-linked, MIM# 310400
Liver Failure_Paediatric v1.21 MTM1 Zornitza Stark Classified gene: MTM1 as Amber List (moderate evidence)
Liver Failure_Paediatric v1.21 MTM1 Zornitza Stark Gene: mtm1 has been classified as Amber List (Moderate Evidence).
Liver Failure_Paediatric v1.20 MTM1 Zornitza Stark reviewed gene: MTM1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Myopathy, centronuclear, X-linked, MIM# 310400; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.5516 SYN1 Zornitza Stark Marked gene: SYN1 as ready
Intellectual disability syndromic and non-syndromic v0.5516 SYN1 Zornitza Stark Gene: syn1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5516 SYN1 Zornitza Stark Phenotypes for gene: SYN1 were changed from to X-linked complex neurodevelopmental disorder MONDO:0100148; epilepsy, X-linked 1, with variable learning disabilities and behavior disorders MONDO:0010339
Intellectual disability syndromic and non-syndromic v0.5515 SYN1 Zornitza Stark Mode of inheritance for gene: SYN1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1266 PLS3 Zornitza Stark Phenotypes for gene: PLS3 were changed from Bone mineral density QTL18, osteoporosis - MIM#300910 to Bone mineral density QTL18, osteoporosis - MIM#300910; congenital diaphragmatic hernia MONDO:0005711, PLS3-related
Mendeliome v1.1265 PLS3 Zornitza Stark Publications for gene: PLS3 were set to 32655496; 25209159; 29736964; 29884797; 28777485; 24088043
Mendeliome v1.1264 PLS3 Zornitza Stark Mode of inheritance for gene: PLS3 was changed from X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.5514 SYN1 Kaitlyn Dianna Weldon reviewed gene: SYN1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: X-linked complex neurodevelopmental disorder MONDO:0100148, epilepsy, X-linked 1, with variable learning disabilities and behavior disorders MONDO:0010339; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1263 PLS3 Zornitza Stark edited their review of gene: PLS3: Added comment: PMID 37751738: 8 unrelated families with affected males with an X-linked condition characterised by diaphragm defects, variable anterior body-wall anomalies, and/or facial dysmorphism. All were missense variants. A mouse knock in model of a variant identified in one of the CDH-affected families, c.1497G>C (p.Trp499Cys), shows partial perinatal lethality and recapitulates the key findings of the human phenotype, including diaphragm and abdominal-wall defects. Gain-of-function is a suggested mechanism.; Changed publications: 32655496, 25209159, 29736964, 29884797, 28777485, 24088043, 37751738; Changed phenotypes: Bone mineral density QTL18, osteoporosis - MIM#300910, congenital diaphragmatic hernia MONDO:0005711, PLS3-related; Changed mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Liver Failure_Paediatric v1.20 MTM1 Rylee Peters changed review comment from: Functional studies using a zebrafish model of X-linked myotubular myopathy showed that loss-of-function mutations in the MTM1 gene led to severe liver abnormalities including impaired bile flux, structural abnormalities of the bile canaliculus, and improper endosome-mediated trafficking of canalicular transporters.
Sources: Literature; to: Functional studies using a zebrafish model of X-linked myotubular myopathy showed that loss-of-function mutations in the MTM1 gene led to severe liver abnormalities including impaired bile flux, structural abnormalities of the bile canaliculus, and improper endosome-mediated trafficking of canalicular transporters.
Sources: Literature
Mendeliome v1.1263 EFCAB7 Zornitza Stark Marked gene: EFCAB7 as ready
Mendeliome v1.1263 EFCAB7 Zornitza Stark Gene: efcab7 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.155 PLS3 Ain Roesley Phenotypes for gene: PLS3 were changed from Bone mineral density QTL18, osteoporosis - MIM#300910 to Bone mineral density QTL18, osteoporosis - MIM#300910; congenital diaphragmatic hernia MONDO:0005711, PLS3-related
Fetal anomalies v1.154 PLS3 Ain Roesley Publications for gene: PLS3 were set to 32655496; 25209159; 29736964; 29884797; 28777485; 24088043
Fetal anomalies v1.153 PLS3 Ain Roesley Classified gene: PLS3 as Green List (high evidence)
Fetal anomalies v1.153 PLS3 Ain Roesley Gene: pls3 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v1.20 MTM1 Rylee Peters edited their review of gene: MTM1: Changed rating: AMBER; Changed phenotypes: Myopathy, centronuclear, X-linked, MIM# 310400
Fetal anomalies v1.152 PLS3 Lauren Rogers reviewed gene: PLS3: Rating: GREEN; Mode of pathogenicity: None; Publications: 37751738; Phenotypes: congenital diaphragmatic hernia MONDO:0005711, PLS3-related; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Liver Failure_Paediatric v1.20 MTM1 Rylee Peters changed review comment from: Functional studies using a zebrafish model of X-linked myotubular myopathy showed that loss-of-function mutations in the MTM1 gene led to severe liver abnormalities including impaired bile flux, structural abnormalities of the bile canaliculus, and improper endosome-mediated trafficking of canalicular transporters.
Sources: Literature; to: Functional studies using a zebrafish model of X-linked myotubular myopathy showed that loss-of-function mutations in the MTM1 gene led to severe liver abnormalities including impaired bile flux, structural abnormalities of the bile canaliculus, and improper endosome-mediated trafficking of canalicular transporters.
Sources: Literature
Fetal anomalies v1.152 MYCN Elena Savva Phenotypes for gene: MYCN were changed from Feingold syndrome 1 (MIM#164280); eurodevelopmental disorder (MONDO:0700092), MYCN-related to Feingold syndrome 1 (MIM#164280); Neurodevelopmental disorder (MONDO:0700092), MYCN-related
Fetal anomalies v1.151 MYCN Elena Savva Added comment: Comment on phenotypes: Three individuals now reported with gain-of-function missense variants (identical variant in two individuals). Clinical presentation includes megalencephaly, hypoplastic corpus callosum, postaxial polydactyly, intellectual disability and motor delay. Knock-in mouse model showed morphological manifestations in multiple tissues including digits, female reproductive system and kidney.
Fetal anomalies v1.151 MYCN Elena Savva Phenotypes for gene: MYCN were changed from Feingold syndrome 1 (MIM#164280) to Feingold syndrome 1 (MIM#164280); eurodevelopmental disorder (MONDO:0700092), MYCN-related
Liver Failure_Paediatric v1.20 MTM1 Rylee Peters gene: MTM1 was added
gene: MTM1 was added to Liver Failure_Paediatric. Sources: Literature
Mode of inheritance for gene: MTM1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: MTM1 were set to PMID: 37490339
Phenotypes for gene: MTM1 were set to X-linked myotubular myopathy
Added comment: Functional studies using a zebrafish model of X-linked myotubular myopathy showed that loss-of-function mutations in the MTM1 gene led to severe liver abnormalities including impaired bile flux, structural abnormalities of the bile canaliculus, and improper endosome-mediated trafficking of canalicular transporters.
Sources: Literature
Fetal anomalies v1.150 MYCN Elena Savva Publications for gene: MYCN were set to 18470948
Congenital diaphragmatic hernia v1.13 PLS3 Ain Roesley Marked gene: PLS3 as ready
Congenital diaphragmatic hernia v1.13 PLS3 Ain Roesley Gene: pls3 has been classified as Green List (High Evidence).
Congenital diaphragmatic hernia v1.13 PLS3 Ain Roesley Classified gene: PLS3 as Green List (high evidence)
Congenital diaphragmatic hernia v1.13 PLS3 Ain Roesley Gene: pls3 has been classified as Green List (High Evidence).
Mendeliome v1.1263 EFCAB7 Zornitza Stark Classified gene: EFCAB7 as Amber List (moderate evidence)
Mendeliome v1.1263 EFCAB7 Zornitza Stark Gene: efcab7 has been classified as Amber List (Moderate Evidence).
Polydactyly v0.268 EFCAB7 Zornitza Stark Marked gene: EFCAB7 as ready
Polydactyly v0.268 EFCAB7 Zornitza Stark Gene: efcab7 has been classified as Amber List (Moderate Evidence).
Polydactyly v0.268 EFCAB7 Zornitza Stark Classified gene: EFCAB7 as Amber List (moderate evidence)
Polydactyly v0.268 EFCAB7 Zornitza Stark Gene: efcab7 has been classified as Amber List (Moderate Evidence).
Polydactyly v0.268 MYCN Elena Savva Classified gene: MYCN as Green List (high evidence)
Polydactyly v0.268 MYCN Elena Savva Gene: mycn has been classified as Green List (High Evidence).
Mendeliome v1.1262 MYCN Elena Savva Phenotypes for gene: MYCN were changed from Feingold syndrome 1; megalencephaly; ventriculomegaly; hypoplastic corpus callosum; intellectual disability; polydactyly; neuroblastoma to Neurodevelopmental disorder (MONDO:0700092), MYCN-related; Feingold syndrome 1 MIM#164280
Mendeliome v1.1261 CDC23 Zornitza Stark Marked gene: CDC23 as ready
Mendeliome v1.1261 CDC23 Zornitza Stark Gene: cdc23 has been classified as Green List (High Evidence).
Mendeliome v1.1261 MYCN Elena Savva Publications for gene: MYCN were set to 21224895; 8470948; 30573562
Polydactyly v0.267 MYCN Elena Savva Classified gene: MYCN as Green List (high evidence)
Polydactyly v0.267 MYCN Elena Savva Gene: mycn has been classified as Green List (High Evidence).
Mendeliome v1.1260 CDC23 Zornitza Stark Classified gene: CDC23 as Green List (high evidence)
Mendeliome v1.1260 CDC23 Zornitza Stark Gene: cdc23 has been classified as Green List (High Evidence).
Polydactyly v0.266 MYCN Elena Savva Marked gene: MYCN as ready
Polydactyly v0.266 MYCN Elena Savva Gene: mycn has been removed from the panel.
Macrocephaly_Megalencephaly v0.134 MYCN Elena Savva Phenotypes for gene: MYCN were changed from Neurodevelopmental disorder with megalencephaly to Neurodevelopmental disorder (MONDO:0700092), MYCN-related
Genetic Epilepsy v0.1931 COG3 Elena Savva Classified gene: COG3 as Amber List (moderate evidence)
Genetic Epilepsy v0.1931 COG3 Elena Savva Gene: cog3 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1259 CFAP20 Ain Roesley Marked gene: CFAP20 as ready
Mendeliome v1.1259 CFAP20 Ain Roesley Gene: cfap20 has been classified as Green List (High Evidence).
Clefting disorders v0.243 SEC24D Zornitza Stark Marked gene: SEC24D as ready
Clefting disorders v0.243 SEC24D Zornitza Stark Gene: sec24d has been classified as Red List (Low Evidence).
Macrocephaly_Megalencephaly v0.133 MYCN Elena Savva Publications for gene: MYCN were set to 30573562
Clefting disorders v0.243 SEC24D Zornitza Stark Classified gene: SEC24D as Red List (low evidence)
Clefting disorders v0.243 SEC24D Zornitza Stark Gene: sec24d has been classified as Red List (Low Evidence).
Mendeliome v1.1259 CFAP20 Ain Roesley Phenotypes for gene: CFAP20 were changed from Retinitis pigmentosa (MONDO:0019200) to Retinitis pigmentosa (MONDO:0019200), CFAP20-related
Macrocephaly_Megalencephaly v0.133 MYCN Elena Savva Classified gene: MYCN as Green List (high evidence)
Macrocephaly_Megalencephaly v0.133 MYCN Elena Savva Gene: mycn has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1931 COG3 Elena Savva Classified gene: COG3 as Amber List (moderate evidence)
Genetic Epilepsy v0.1931 COG3 Elena Savva Gene: cog3 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1258 CFAP20 Ain Roesley Classified gene: CFAP20 as Green List (high evidence)
Mendeliome v1.1258 CFAP20 Ain Roesley Gene: cfap20 has been classified as Green List (High Evidence).
Mendeliome v1.1257 COG3 Elena Savva Classified gene: COG3 as Amber List (moderate evidence)
Mendeliome v1.1257 COG3 Elena Savva Gene: cog3 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.1931 COG3 Elena Savva Classified gene: COG3 as Amber List (moderate evidence)
Genetic Epilepsy v0.1931 COG3 Elena Savva Gene: cog3 has been classified as Amber List (Moderate Evidence).
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.134 CFAP20 Ain Roesley Marked gene: CFAP20 as ready
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.134 CFAP20 Ain Roesley Gene: cfap20 has been classified as Green List (High Evidence).
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.134 CFAP20 Ain Roesley Phenotypes for gene: CFAP20 were changed from Retinitis pigmentosa (MONDO:0019200) to Retinitis pigmentosa (MONDO:0019200), CFAP20-related
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.133 CFAP20 Ain Roesley Classified gene: CFAP20 as Green List (high evidence)
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.133 CFAP20 Ain Roesley Gene: cfap20 has been classified as Green List (High Evidence).
Mendeliome v1.1256 COG3 Elena Savva Classified gene: COG3 as Amber List (moderate evidence)
Mendeliome v1.1256 COG3 Elena Savva Gene: cog3 has been classified as Amber List (Moderate Evidence).
Microcephaly v1.235 COG3 Elena Savva Classified gene: COG3 as Amber List (moderate evidence)
Microcephaly v1.235 COG3 Elena Savva Gene: cog3 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1255 COG3 Elena Savva Marked gene: COG3 as ready
Mendeliome v1.1255 COG3 Elena Savva Gene: cog3 has been removed from the panel.
Genetic Epilepsy v0.1930 MAST4 Ain Roesley Classified gene: MAST4 as Green List (high evidence)
Genetic Epilepsy v0.1930 MAST4 Ain Roesley Gene: mast4 has been classified as Green List (High Evidence).
Dystonia - complex v0.232 ATP2B2 Zornitza Stark Marked gene: ATP2B2 as ready
Dystonia - complex v0.232 ATP2B2 Zornitza Stark Gene: atp2b2 has been classified as Green List (High Evidence).
Dystonia - complex v0.232 ATP2B2 Zornitza Stark Classified gene: ATP2B2 as Green List (high evidence)
Dystonia - complex v0.232 ATP2B2 Zornitza Stark Gene: atp2b2 has been classified as Green List (High Evidence).
Dystonia - complex v0.232 ATP2B2 Zornitza Stark Classified gene: ATP2B2 as Green List (high evidence)
Dystonia - complex v0.232 ATP2B2 Zornitza Stark Gene: atp2b2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5514 MYCN Naomi Baker commented on gene: MYCN: Three individuals now reported with gain-of-function missense variants (identical variant in two individuals). Clinical presentation includes megalencephaly, hypoplastic corpus callosum, postaxial polydactyly, intellectual disability and motor delay. Knock-in mouse model showed morphological manifestations in multiple tissues including digits, female reproductive system and kidney.
Microcephaly v1.235 COG3 Elena Savva Classified gene: COG3 as Amber List (moderate evidence)
Microcephaly v1.235 COG3 Elena Savva Gene: cog3 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1255 EFCAB7 Melanie Marty gene: EFCAB7 was added
gene: EFCAB7 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: EFCAB7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EFCAB7 were set to PMID: 37684519
Phenotypes for gene: EFCAB7 were set to Polydactyly (MONDO:0021003), EFCAB7-related
Review for gene: EFCAB7 was set to AMBER
Added comment: PMID: 37684519: two homozygous frameshift variants were identified by exome sequencing in four consanguinous Pakistani families, 3 families with p.(Gly277Valfs*5) and 1 family with p.(Asn451Phefs*2). Variants segregated with disease and het carriers were unaffected. Counting as 2 families to be conservative.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5514 MAST4 Ain Roesley Classified gene: MAST4 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5514 MAST4 Ain Roesley Gene: mast4 has been classified as Green List (High Evidence).
Polydactyly v0.266 MYCN Naomi Baker gene: MYCN was added
gene: MYCN was added to Polydactyly. Sources: Literature
Mode of inheritance for gene: MYCN was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MYCN were set to PMID:37710961
Phenotypes for gene: MYCN were set to Neurodevelopmental disorder (MONDO:0700092), MYCN-related
Mode of pathogenicity for gene: MYCN was set to Other
Review for gene: MYCN was set to GREEN
Added comment: Three individuals now reported with gain-of-function missense variants (identical variant in two individuals). Clinical presentation includes megalencephaly, hypoplastic corpus callosum, postaxial polydactyly, intellectual disability and motor delay. Knock-in mouse model showed morphological manifestations in multiple tissues including digits, female reproductive system and kidney.
Sources: Literature
Microcephaly v1.234 COG3 Elena Savva Marked gene: COG3 as ready
Microcephaly v1.234 COG3 Elena Savva Gene: cog3 has been removed from the panel.
Genetic Epilepsy v0.1930 COG3 Elena Savva Marked gene: COG3 as ready
Genetic Epilepsy v0.1930 COG3 Elena Savva Gene: cog3 has been removed from the panel.
Congenital diaphragmatic hernia v1.12 PLS3 Lauren Rogers changed review comment from: 8 unrelated families with affected males with X-linked condition characterised by diaphragm defects, variable anterior body-wall anomalies, and/or facial dysmorphism. All were missense variants. A mouse knock in model of a variant identified in one of the CDH-affected families, c.1497G>C (p.Trp499Cys), shows partial perinatal lethality and recapitulates the key findings of the human phenotype, including diaphragm and abdominal-wall defects. Gain-of-function is a suggested mechanism.
Sources: Literature; to: 8 unrelated families with affected males with an X-linked condition characterised by diaphragm defects, variable anterior body-wall anomalies, and/or facial dysmorphism. All were missense variants. A mouse knock in model of a variant identified in one of the CDH-affected families, c.1497G>C (p.Trp499Cys), shows partial perinatal lethality and recapitulates the key findings of the human phenotype, including diaphragm and abdominal-wall defects. Gain-of-function is a suggested mechanism.
Sources: Literature
Genetic Epilepsy v0.1930 MAST4 Ain Roesley Classified gene: MAST4 as Green List (high evidence)
Genetic Epilepsy v0.1930 MAST4 Ain Roesley Gene: mast4 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5514 MAST4 Ain Roesley Classified gene: MAST4 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5514 MAST4 Ain Roesley Gene: mast4 has been classified as Green List (High Evidence).
Ataxia - paediatric v1.12 ATP2B2 Zornitza Stark Marked gene: ATP2B2 as ready
Ataxia - paediatric v1.12 ATP2B2 Zornitza Stark Gene: atp2b2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5513 MYCN Naomi Baker reviewed gene: MYCN: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID:37710961; Phenotypes: Neurodevelopmental disorder (MONDO:0700092), MYCN-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Ataxia - paediatric v1.12 ATP2B2 Zornitza Stark Classified gene: ATP2B2 as Green List (high evidence)
Ataxia - paediatric v1.12 ATP2B2 Zornitza Stark Gene: atp2b2 has been classified as Green List (High Evidence).
Congenital diaphragmatic hernia v1.12 PLS3 Lauren Rogers gene: PLS3 was added
gene: PLS3 was added to Congenital diaphragmatic hernia. Sources: Literature
Mode of inheritance for gene: PLS3 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: PLS3 were set to 37751738
Phenotypes for gene: PLS3 were set to congenital diaphragmatic hernia MONDO:0005711, PLS3-related
Review for gene: PLS3 was set to GREEN
Added comment: 8 unrelated families with affected males with X-linked condition characterised by diaphragm defects, variable anterior body-wall anomalies, and/or facial dysmorphism. All were missense variants. A mouse knock in model of a variant identified in one of the CDH-affected families, c.1497G>C (p.Trp499Cys), shows partial perinatal lethality and recapitulates the key findings of the human phenotype, including diaphragm and abdominal-wall defects. Gain-of-function is a suggested mechanism.
Sources: Literature
Mendeliome v1.1254 CFAP20 Sarah Pantaleo gene: CFAP20 was added
gene: CFAP20 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CFAP20 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CFAP20 were set to PMID:36329026
Phenotypes for gene: CFAP20 were set to Retinitis pigmentosa (MONDO:0019200)
Review for gene: CFAP20 was set to GREEN
Added comment: CFAP20 is a ciliopathy candidate. Demonstrate in zebrafish that cfap20 is required for motile cilia function, and in C. elegans, CFAP-20 maintains the structural integrity of non-motile cilia inner junctions, influencing sensory-dependent signalling and development.

Human patients and zebrafish with CFAP20 mutations both exhibit retinal dystrophy (retinitis pigments). Hence, CFAP20 functions within a structural./functional hub centred on the inner junction that is shared between motile and non-motile cilia, and is distinct from other ciliopathy-associaetd domains or macromolecular complexes.

Describe 8 individuals from 4 independent families with damaging biallelic variants (homozygous or compound heterozygous) in CFAP20 that segregate with retinal dystrophy. All variants cluster to one side of the protein, with two of the residues directly contacting alpha-tubullin.

Family 1 - consanguineous set of 3 siblings from Sudan, homozygous for CFAP20 c.305G>A; p.Arg102His (they also had a homozygous variant in DYNC1LI2 however CFAP20 was considered the better candidate.
Family 2 - 3 siblings from Spain, 2 with retinal dystrophy, 1 genetically tested and has c.337C>T; p.(Arg113Trp) and c.397delC; p.(Gln133Serfs*5)
Family 3 - single affected family member compound het for c.164+1G>A and c.457A>G; p.(Arg153Gly).
Family 4 - 3 affected siblings with generalised retinopathy and variable neurological deficits with c.164+1G>A and c.257G>A; p.(Tyr86Cys)

For all families, no individuals had signs of polycystic kidney disease; however, not all individuals had kidney imaging. Visual defecit phenotype presented between adolescence and adulthood (17-56 years old).

Used HEK293T cell expression studies to demonstrate a statistically significant decline of mutated CFAP20 protein levels (with the exception of p.Arg102His). To test the specific variants, they used the C.elegans orthologues.
Sources: Literature
Mendeliome v1.1255 GPRASP1 Elena Savva Classified gene: GPRASP1 as Amber List (moderate evidence)
Mendeliome v1.1255 GPRASP1 Elena Savva Gene: gprasp1 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.1929 MAST4 Ain Roesley Marked gene: MAST4 as ready
Genetic Epilepsy v0.1929 MAST4 Ain Roesley Gene: mast4 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.5513 MAST4 Ain Roesley Marked gene: MAST4 as ready
Intellectual disability syndromic and non-syndromic v0.5513 MAST4 Ain Roesley Gene: mast4 has been classified as Red List (Low Evidence).
Mendeliome v1.1254 GPRASP1 Elena Savva Classified gene: GPRASP1 as Amber List (moderate evidence)
Mendeliome v1.1254 GPRASP1 Elena Savva Gene: gprasp1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1253 GPRASP1 Elena Savva Classified gene: GPRASP1 as Amber List (moderate evidence)
Mendeliome v1.1253 GPRASP1 Elena Savva Gene: gprasp1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1252 GPRASP1 Elena Savva Marked gene: GPRASP1 as ready
Mendeliome v1.1252 GPRASP1 Elena Savva Gene: gprasp1 has been removed from the panel.
Mendeliome v1.1252 MYCN Naomi Baker reviewed gene: MYCN: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID:37710961; Phenotypes: Neurodevelopmental disorder (MONDO:0700092), MYCN-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Polydactyly v0.266 EFCAB7 Melanie Marty gene: EFCAB7 was added
gene: EFCAB7 was added to Polydactyly. Sources: Literature
Mode of inheritance for gene: EFCAB7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EFCAB7 were set to PMID: 37684519
Phenotypes for gene: EFCAB7 were set to Polydactyly (MONDO:0021003), EFCAB7-related
Review for gene: EFCAB7 was set to AMBER
Added comment: PMID: 37684519: two homozygous frameshift variants were identified by exome sequencing in four consanguinous Pakistani families, 3 families with p.(Gly277Valfs*5) and 1 family with p.(Asn451Phefs*2). Variants segregated with disease and het carriers were unaffected. Counting as 2 families to be conservative.
Sources: Literature
Mendeliome v1.1252 MAST4 Ain Roesley Marked gene: MAST4 as ready
Mendeliome v1.1252 MAST4 Ain Roesley Gene: mast4 has been classified as Green List (High Evidence).
Vascular Malformations_Germline v1.11 GPRASP1 Elena Savva Marked gene: GPRASP1 as ready
Vascular Malformations_Germline v1.11 GPRASP1 Elena Savva Gene: gprasp1 has been classified as Amber List (Moderate Evidence).
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.132 CFAP20 Sarah Pantaleo gene: CFAP20 was added
gene: CFAP20 was added to Retinitis pigmentosa_Autosomal Recessive/X-linked. Sources: Literature
Mode of inheritance for gene: CFAP20 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CFAP20 were set to PMID:36329026
Phenotypes for gene: CFAP20 were set to Retinitis pigmentosa (MONDO:0019200)
Review for gene: CFAP20 was set to GREEN
Added comment: CFAP20 is a ciliopathy candidate. Demonstrate in zebrafish that cfap20 is required for motile cilia function, and in C. elegans, CFAP-20 maintains the structural integrity of non-motile cilia inner junctions, influencing sensory-dependent signalling and development.

Human patients and zebrafish with CFAP20 mutations both exhibit retinal dystrophy (retinitis pigments). Hence, CFAP20 functions within a structural./functional hub centred on the inner junction that is shared between motile and non-motile cilia, and is distinct from other ciliopathy-associaetd domains or macromolecular complexes.

Describe 8 individuals from 4 independent families with damaging biallelic variants (homozygous or compound heterozygous) in CFAP20 that segregate with retinal dystrophy. All variants cluster to one side of the protein, with two of the residues directly contacting alpha-tubullin.

Family 1 - consanguineous set of 3 siblings from Sudan, homozygous for CFAP20 c.305G>A; p.Arg102His (they also had a homozygous variant in DYNC1LI2 however CFAP20 was considered the better candidate.
Family 2 - 3 siblings from Spain, 2 with retinal dystrophy, 1 genetically tested and has c.337C>T; p.(Arg113Trp) and c.397delC; p.(Gln133Serfs*5)
Family 3 - single affected family member compound het for c.164+1G>A and c.457A>G; p.(Arg153Gly).
Family 4 - 3 affected siblings with generalised retinopathy and variable neurological deficits with c.164+1G>A and c.257G>A; p.(Tyr86Cys)

For all families, no individuals had signs of polycystic kidney disease; however, not all individuals had kidney imaging. Visual defecit phenotype presented between adolescence and adulthood (17-56 years old).

Used HEK293T cell expression studies to demonstrate a statistically significant decline of mutated CFAP20 protein levels (with the exception of p.Arg102His). To test the specific variants, they used the C.elegans orthologues.
Sources: Literature
Vascular Malformations_Germline v1.11 GPRASP1 Elena Savva Classified gene: GPRASP1 as Amber List (moderate evidence)
Vascular Malformations_Germline v1.11 GPRASP1 Elena Savva Gene: gprasp1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5513 ATP2B2 Zornitza Stark Marked gene: ATP2B2 as ready
Intellectual disability syndromic and non-syndromic v0.5513 ATP2B2 Zornitza Stark Gene: atp2b2 has been classified as Green List (High Evidence).
Mendeliome v1.1252 MAST4 Ain Roesley Classified gene: MAST4 as Green List (high evidence)
Mendeliome v1.1252 MAST4 Ain Roesley Gene: mast4 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1929 MAST4 Ain Roesley gene: MAST4 was added
gene: MAST4 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: MAST4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAST4 were set to 36910266; 33057194
Phenotypes for gene: MAST4 were set to neurodevelopmental disorder MONDO:0700092, MAST4-related
Penetrance for gene: MAST4 were set to Complete
Review for gene: MAST4 was set to GREEN
gene: MAST4 was marked as current diagnostic
Added comment: PMID: 36910266 - 4 families with 4 affecteds, all de novo missense

2x borderline microcephaly (-2SD)
2x gross motor delay
2x dysmorphism
4x ID + seizures
3x abnormal brain MRI findings

PMID: 33057194 - 5x de novos, 4x missense + 1x PTC
Cohort of individuals with severe developmental disorder
individual phenotypic information not provided


Recurrent variants are Thr1471Ile (3x) and Ser1181Phe)
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5513 ATP2B2 Zornitza Stark Classified gene: ATP2B2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5513 ATP2B2 Zornitza Stark Gene: atp2b2 has been classified as Green List (High Evidence).
Mendeliome v1.1251 CDC23 Michelle Torres gene: CDC23 was added
gene: CDC23 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CDC23 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CDC23 were set to 37768355
Phenotypes for gene: CDC23 were set to inherited oocyte maturation defect MONDO#0014769, CDC23-related
Review for gene: CDC23 was set to GREEN
Added comment: Two missense variants, p.(Y329C) and p.(R330C), detected in three unrelated homozygous infertile females characterised by oocyte maturation defects.

In vitro studies using HeLa cells showed either decreased protein levels (Y329C) or impaired localisation (R330C). In vivo studies in mice homozygous for Y329C reproduced patient’s phenotype.
Sources: Literature
Macrocephaly_Megalencephaly v0.132 MYCN Naomi Baker reviewed gene: MYCN: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID:37710961; Phenotypes: Neurodevelopmental disorder (MONDO:0700092), MYCN-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5512 MAST4 Ain Roesley gene: MAST4 was added
gene: MAST4 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: MAST4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAST4 were set to 36910266; 33057194
Phenotypes for gene: MAST4 were set to neurodevelopmental disorder MONDO:0700092, MAST4-related
Penetrance for gene: MAST4 were set to Complete
Review for gene: MAST4 was set to GREEN
gene: MAST4 was marked as current diagnostic
Added comment: PMID: 36910266 - 4 families with 4 affecteds, all de novo missense

2x borderline microcephaly (-2SD)
2x gross motor delay
2x dysmorphism
4x ID + seizures
3x abnormal brain MRI findings

PMID: 33057194 - 5x de novos, 4x missense + 1x PTC
Cohort of individuals with severe developmental disorder
individual phenotypic information not provided


Recurrent variants are Thr1471Ile (3x) and Ser1181Phe)
Sources: Literature
Clefting disorders v0.242 SEC24D Ee Ming Wong gene: SEC24D was added
gene: SEC24D was added to Clefting disorders. Sources: Literature
Mode of inheritance for gene: SEC24D was set to Unknown
Publications for gene: SEC24D were set to PMID:37676273
Phenotypes for gene: SEC24D were set to Cleft lip with or without cleft palate, MONDO:0016034, SEC24D-related
Review for gene: SEC24D was set to RED
gene: SEC24D was marked as current diagnostic
Added comment: - Subtype-specific genome-wide study to test for genetic modifiers of cleft lip VS cleft lip and palate
- SEC24D was genome-wide significant (p = 6.86 × 10-7), and having a burden of rare variants in cleft lip VS cleft lip and palate
Sources: Literature
Mendeliome v1.1251 GPRASP1 Paul De Fazio gene: GPRASP1 was added
gene: GPRASP1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GPRASP1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: GPRASP1 were set to 37787182
Phenotypes for gene: GPRASP1 were set to Arteriovenous hemangioma/malformation, GPRASP1-related, MONDO:0001256
Penetrance for gene: GPRASP1 were set to unknown
Review for gene: GPRASP1 was set to AMBER
gene: GPRASP1 was marked as current diagnostic
Added comment: Two hemizygous germline missense variants, p.Arg1167Trp and p.Trp553Cys, were identified in three male patients presenting with spinal AVM, Cobb syndrome, or scalp AVM. The variants were inherited from unaffected heterozygous mothers. Note that p.Arg1167Trp has hemizygous (>70) and homozygous individuals reported in gnomAD.

The variants were found to result in LoF in endothelial cells. Endothelial Gprasp1 knockout mice suffered a high probability of cerebral hemorrhage, AVMs, and exhibited vascular anomalies in multiple organs.
Sources: Literature
Genetic Epilepsy v0.1928 ATP2B2 Zornitza Stark Marked gene: ATP2B2 as ready
Genetic Epilepsy v0.1928 ATP2B2 Zornitza Stark Gene: atp2b2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1928 ATP2B2 Zornitza Stark Classified gene: ATP2B2 as Green List (high evidence)
Genetic Epilepsy v0.1928 ATP2B2 Zornitza Stark Gene: atp2b2 has been classified as Green List (High Evidence).
Vascular Malformations_Germline v1.10 GPRASP1 Paul De Fazio gene: GPRASP1 was added
gene: GPRASP1 was added to Vascular Malformations_Germline. Sources: Literature
Mode of inheritance for gene: GPRASP1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: GPRASP1 were set to 37787182
Phenotypes for gene: GPRASP1 were set to Arteriovenous hemangioma/malformation, GPRASP1-related, MONDO:0001256
Penetrance for gene: GPRASP1 were set to unknown
Review for gene: GPRASP1 was set to AMBER
gene: GPRASP1 was marked as current diagnostic
Added comment: Two hemizygous germline missense variants, p.Arg1167Trp and p.Trp553Cys, were identified in three male patients presenting with spinal AVM, Cobb syndrome, or scalp AVM. The variants were inherited from unaffected heterozygous mothers. Note that p.Arg1167Trp has hemizygous (>70) and homozygous individuals reported in gnomAD.

The variants were found to result in LoF in endothelial cells. Endothelial Gprasp1 knockout mice suffered a high probability of cerebral hemorrhage, AVMs, and exhibited vascular anomalies in multiple organs.
Sources: Literature
Mendeliome v1.1251 COG3 Daniel Flanagan gene: COG3 was added
gene: COG3 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: COG3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COG3 were set to PMID: 37711075
Phenotypes for gene: COG3 were set to Neurodevelopmental disorder (MONDO#0700092), COG3-related
Review for gene: COG3 was set to AMBER
Added comment: Two COG3 homozygous missense variants in four individuals from two unrelated consanguineous families. Clinical phenotypes of affected individuals include global developmental delay, severe intellectual disability, microcephaly, epilepsy, facial dysmorphism, and variable neurological findings.
Sources: Expert list
Mendeliome v1.1251 ATP2B2 Zornitza Stark Phenotypes for gene: ATP2B2 were changed from Deafness, autosomal dominant 82, MIM# 619804; {Deafness, autosomal recessive 12, modifier of}, MIM# 601386 to Deafness, autosomal dominant 82, MIM# 619804; Neurodevelopmental Disorder, MONDO:0700092, ATP2B2-related
Mendeliome v1.1250 ATP2B2 Zornitza Stark Publications for gene: ATP2B2 were set to 30535804; 15829536
Mendeliome v1.1249 MAST4 Ain Roesley gene: MAST4 was added
gene: MAST4 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MAST4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAST4 were set to 36910266; 33057194
Phenotypes for gene: MAST4 were set to neurodevelopmental disorder MONDO:0700092, MAST4-related
Penetrance for gene: MAST4 were set to Complete
Review for gene: MAST4 was set to GREEN
gene: MAST4 was marked as current diagnostic
Added comment: PMID: 36910266 - 4 families with 4 affecteds, all de novo missense

2x borderline microcephaly (-2SD)
2x gross motor delay
2x dysmorphism
4x ID + seizures
3x abnormal brain MRI findings

PMID: 33057194 - 5x de novos, 4x missense + 1x PTC
Cohort of individuals with severe developmental disorder
individual phenotypic information not provided


Recurrent variants are Thr1471Ile (3x) and Ser1181Phe)
Sources: Literature
Microcephaly v1.234 COG3 Daniel Flanagan gene: COG3 was added
gene: COG3 was added to Microcephaly. Sources: Expert list
Mode of inheritance for gene: COG3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COG3 were set to PMID: 37711075
Phenotypes for gene: COG3 were set to Neurodevelopmental disorder (MONDO#0700092), COG3-related
Review for gene: COG3 was set to AMBER
Added comment: Two COG3 homozygous missense variants in four individuals from two unrelated consanguineous families. Clinical phenotypes of affected individuals include global developmental delay, severe intellectual disability, microcephaly, epilepsy, facial dysmorphism, and variable neurological findings.
Sources: Expert list
Genetic Epilepsy v0.1927 COG3 Daniel Flanagan gene: COG3 was added
gene: COG3 was added to Genetic Epilepsy. Sources: Expert list
Mode of inheritance for gene: COG3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COG3 were set to PMID: 37711075
Phenotypes for gene: COG3 were set to Neurodevelopmental disorder (MONDO#0700092), COG3-related
Review for gene: COG3 was set to AMBER
Added comment: Two COG3 homozygous missense variants in four individuals from two unrelated consanguineous families. Clinical phenotypes of affected individuals include global developmental delay, severe intellectual disability, microcephaly, epilepsy, facial dysmorphism, and variable neurological findings.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.5511 COG3 Zornitza Stark Marked gene: COG3 as ready
Intellectual disability syndromic and non-syndromic v0.5511 COG3 Zornitza Stark Gene: cog3 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5511 COG3 Zornitza Stark Classified gene: COG3 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.5511 COG3 Zornitza Stark Gene: cog3 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.1927 ATP2B2 Andrew Fennell gene: ATP2B2 was added
gene: ATP2B2 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: ATP2B2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ATP2B2 were set to PMID: 37675773
Phenotypes for gene: ATP2B2 were set to Neurodevelopmental Disorder, MONDO:0700092, ATP2B2-related
Mode of pathogenicity for gene: ATP2B2 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Review for gene: ATP2B2 was set to GREEN
Added comment: 7 unrelated individuals reported with a variable phenotype including dystonia, ataxia, intellectual disability, behavioural symptoms, and seizures.

All patients have either missense variants or frameshift variants in the penultimate exon not expected to lead to NMD. This is in contrast to patients with isolated deafness previously reported to have nonsense, frameshift, or splice-site variants outside of this region.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5510 ZBTB47 Elena Savva Classified gene: ZBTB47 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5510 ZBTB47 Elena Savva Gene: zbtb47 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1927 ZBTB47 Elena Savva Classified gene: ZBTB47 as Green List (high evidence)
Genetic Epilepsy v0.1927 ZBTB47 Elena Savva Gene: zbtb47 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5510 ZBTB47 Elena Savva Classified gene: ZBTB47 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5510 ZBTB47 Elena Savva Gene: zbtb47 has been classified as Green List (High Evidence).
Ataxia - paediatric v1.11 ATP2B2 Andrew Fennell gene: ATP2B2 was added
gene: ATP2B2 was added to Ataxia - paediatric. Sources: Literature
Mode of inheritance for gene: ATP2B2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ATP2B2 were set to PMID: 37675773
Phenotypes for gene: ATP2B2 were set to Neurodevelopmental Disorder, MONDO:0700092, ATP2B2-related
Mode of pathogenicity for gene: ATP2B2 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Review for gene: ATP2B2 was set to GREEN
Added comment: 7 unrelated individuals reported with a variable phenotype including dystonia, ataxia, intellectual disability, behavioural symptoms, and seizures.

All patients have either missense variants or frameshift variants in the penultimate exon not expected to lead to NMD. This is in contrast to patients with isolated deafness previously reported to have nonsense, frameshift, or splice-site variants outside of this region.
Sources: Literature
Genetic Epilepsy v0.1926 ZBTB47 Elena Savva Classified gene: ZBTB47 as Green List (high evidence)
Genetic Epilepsy v0.1926 ZBTB47 Elena Savva Gene: zbtb47 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5509 ZBTB47 Elena Savva Marked gene: ZBTB47 as ready
Intellectual disability syndromic and non-syndromic v0.5509 ZBTB47 Elena Savva Gene: zbtb47 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.1925 ZBTB47 Elena Savva Marked gene: ZBTB47 as ready
Genetic Epilepsy v0.1925 ZBTB47 Elena Savva Gene: zbtb47 has been classified as Red List (Low Evidence).
Mendeliome v1.1248 ZBTB47 Elena Savva Marked gene: ZBTB47 as ready
Mendeliome v1.1248 ZBTB47 Elena Savva Gene: zbtb47 has been classified as Green List (High Evidence).
Mendeliome v1.1248 ZBTB47 Elena Savva Classified gene: ZBTB47 as Green List (high evidence)
Mendeliome v1.1248 ZBTB47 Elena Savva Gene: zbtb47 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5509 ATP2B2 Andrew Fennell gene: ATP2B2 was added
gene: ATP2B2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: ATP2B2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ATP2B2 were set to PMID: 37675773
Phenotypes for gene: ATP2B2 were set to Neurodevelopmental Disorder, MONDO:0700092, ATP2B2-related
Mode of pathogenicity for gene: ATP2B2 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Review for gene: ATP2B2 was set to GREEN
Added comment: 7 unrelated individuals reported with a variable phenotype including dystonia, ataxia, intellectual disability, behavioural symptoms, and seizures.

All patients have either missense variants or frameshift variants in the penultimate exon not expected to lead to NMD. This is in contrast to patients with isolated deafness previously reported to have nonsense, frameshift, or splice-site variants outside of this region.
Sources: Literature
Dystonia - complex v0.231 ATP2B2 Andrew Fennell gene: ATP2B2 was added
gene: ATP2B2 was added to Dystonia - complex. Sources: Literature
Mode of inheritance for gene: ATP2B2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ATP2B2 were set to PMID: 37675773
Phenotypes for gene: ATP2B2 were set to Neurodevelopmental Disorder, MONDO:0700092, ATP2B2-related
Mode of pathogenicity for gene: ATP2B2 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Review for gene: ATP2B2 was set to GREEN
Added comment: 7 unrelated individuals reported with a variable phenotype including dystonia, ataxia, intellectual disability, behavioural symptoms, and seizures.

All patients have either missense variants or frameshift variants in the penultimate exon not expected to lead to NMD. This is in contrast to patients with isolated deafness previously reported to have nonsense, frameshift, or splice-site variants outside of this region.
Sources: Literature
Mendeliome v1.1247 ZBTB47 Elena Savva gene: ZBTB47 was added
gene: ZBTB47 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ZBTB47 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ZBTB47 were set to 37743782
Phenotypes for gene: ZBTB47 were set to Neurodevelopmental disorder (MONDO#0700092), ZBTB47-related
Review for gene: ZBTB47 was set to GREEN
Added comment: PMID 37743782:
- 5 patients with de novo missense, 4/5 have a recurring p.Gly477Lys. Probands have intellectual disability (5/5), seizures (5/5), hypotonia (5/5), gait abnormalities, and variable movement abnormalities (5/5).
- Missense variants are positioned close to His and Cys residues involved in forming C2H2 zinc fingers.
- No functional studies performed
- Minimal PTCs in gnomAD
Sources: Literature
Mendeliome v1.1246 KIF4A Zornitza Stark Phenotypes for gene: KIF4A were changed from Mental retardation, X-linked 100, MIM# 300923 to Mental retardation, X-linked 100, MIM# 300923; Taurodontism, microdontia, and dens invaginatus (MIM#313490)
Genetic Epilepsy v0.1925 ZBTB47 Elena Savva gene: ZBTB47 was added
gene: ZBTB47 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: ZBTB47 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ZBTB47 were set to 37743782
Phenotypes for gene: ZBTB47 were set to Neurodevelopmental disorder (MONDO#0700092), ZBTB47-related
Review for gene: ZBTB47 was set to GREEN
Added comment: PMID 37743782:
- 5 patients with de novo missense, 4/5 have a recurring p.Gly477Lys. Probands have intellectual disability (5/5), seizures (5/5), hypotonia (5/5), gait abnormalities, and variable movement abnormalities (5/5).
- Missense variants are positioned close to His and Cys residues involved in forming C2H2 zinc fingers.
- No functional studies performed
- Minimal PTCs in gnomAD
Sources: Literature
Mendeliome v1.1245 ATP2B2 Andrew Fennell reviewed gene: ATP2B2: 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: 37675773; Phenotypes: Neurodevelopmental Disorder, MONDO:0700092, ATP2B2-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5509 COG3 Daniel Flanagan gene: COG3 was added
gene: COG3 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list
Mode of inheritance for gene: COG3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COG3 were set to PMID: 37711075
Phenotypes for gene: COG3 were set to Neurodevelopmental disorder (MONDO#0700092), COG3-related
Review for gene: COG3 was set to AMBER
Added comment: Two COG3 homozygous missense variants in four individuals from two unrelated consanguineous families. Clinical phenotypes of affected individuals include global developmental delay, severe intellectual disability, microcephaly, epilepsy, facial dysmorphism, and variable neurological findings.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.5509 ZBTB47 Elena Savva gene: ZBTB47 was added
gene: ZBTB47 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: ZBTB47 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ZBTB47 were set to 37743782
Phenotypes for gene: ZBTB47 were set to Neurodevelopmental disorder (MONDO#0700092), ZBTB47-related
Review for gene: ZBTB47 was set to GREEN
Added comment: PMID 37743782:
- 5 patients with de novo missense, 4/5 have a recurring p.Gly477Lys. Probands have intellectual disability (5/5), seizures (5/5), hypotonia (5/5), gait abnormalities, and variable movement abnormalities (5/5).
- Missense variants are positioned close to His and Cys residues involved in forming C2H2 zinc fingers.
- No functional studies performed
- Minimal PTCs in gnomAD
Sources: Literature
Mendeliome v1.1245 KIF4A Lucy Spencer reviewed gene: KIF4A: Rating: AMBER; Mode of pathogenicity: None; Publications: 31616463; Phenotypes: Taurodontism, microdontia, and dens invaginatus (MIM#313490); Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.5508 TANGO2 Kaitlyn Dianna Weldon reviewed gene: TANGO2: Rating: GREEN; Mode of pathogenicity: None; Publications: 29369572; Phenotypes: obsolete metabolic encephalomyopathic crises, recurrent, with rhabdomyolysis, cardiac arrhythmias, and neurodegeneration MONDO:0014812; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5508 TAT Kaitlyn Dianna Weldon reviewed gene: TAT: Rating: GREEN; Mode of pathogenicity: None; Publications: 28255985; Phenotypes: tyrosinemia type II MONDO:0010160; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5508 TAZ Kaitlyn Dianna Weldon reviewed gene: TAZ: Rating: GREEN; Mode of pathogenicity: None; Publications: 25299040; Phenotypes: Barth syndrome MONDO:0010543; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.5508 TBC1D24 Kaitlyn Dianna Weldon reviewed gene: TBC1D24: Rating: GREEN; Mode of pathogenicity: None; Publications: 25719194; Phenotypes: familial infantile myoclonic epilepsy MONDO:0011506, DOORS syndrome MONDO:0009079; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5508 TCF4 Kaitlyn Dianna Weldon reviewed gene: TCF4: Rating: GREEN; Mode of pathogenicity: None; Publications: 22934316; Phenotypes: Pitt-Hopkins syndrome MONDO:0012589; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5508 TMCO1 Kaitlyn Dianna Weldon reviewed gene: TMCO1: Rating: GREEN; Mode of pathogenicity: None; Publications: 1204988, 1640432, 15326640, 20018682; Phenotypes: obsolete cerebrofaciothoracic dysplasia MONDO:0008952; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5508 TMEM216 Kaitlyn Dianna Weldon reviewed gene: TMEM216: Rating: GREEN; Mode of pathogenicity: None; Publications: 20036350; Phenotypes: Joubert syndrome 2 MONDO:0011963; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5508 TMEM240 Kaitlyn Dianna Weldon reviewed gene: TMEM240: Rating: GREEN; Mode of pathogenicity: None; Publications: 25070513; Phenotypes: spinocerebellar ataxia type 21 MONDO:0011833; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5508 TMEM70 Kaitlyn Dianna Weldon reviewed gene: TMEM70: Rating: GREEN; Mode of pathogenicity: None; Publications: 18953340; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v1.107 WNK1 Zornitza Stark Marked gene: WNK1 as ready
BabyScreen+ newborn screening v1.107 WNK1 Zornitza Stark Gene: wnk1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.107 WNK1 Zornitza Stark Phenotypes for gene: WNK1 were changed from Neuropathy, hereditary sensory and autonomic, type I to Pseudohypoaldosteronism 2C (PHA2C), MIM#614492
BabyScreen+ newborn screening v1.106 WNK1 Zornitza Stark Mode of inheritance for gene: WNK1 was changed from BIALLELIC, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v1.105 WNK1 Zornitza Stark Classified gene: WNK1 as Green List (high evidence)
BabyScreen+ newborn screening v1.105 WNK1 Zornitza Stark Gene: wnk1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.104 WNK1 Zornitza Stark Tag treatable tag was added to gene: WNK1.
Tag endocrine tag was added to gene: WNK1.
BabyScreen+ newborn screening v1.104 WNK1 Zornitza Stark reviewed gene: WNK1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Pseudohypoaldosteronism 2C (PHA2C), MIM#614492; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v1.104 TRIM28 Zornitza Stark Marked gene: TRIM28 as ready
BabyScreen+ newborn screening v1.104 TRIM28 Zornitza Stark Gene: trim28 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.104 TRIM28 Zornitza Stark Classified gene: TRIM28 as Green List (high evidence)
BabyScreen+ newborn screening v1.104 TRIM28 Zornitza Stark Gene: trim28 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.103 TRIM28 Zornitza Stark Tag cancer tag was added to gene: TRIM28.
Tag treatable tag was added to gene: TRIM28.
BabyScreen+ newborn screening v1.103 TRIM28 Zornitza Stark gene: TRIM28 was added
gene: TRIM28 was added to BabyScreen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: TRIM28 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TRIM28 were set to 30694527
Phenotypes for gene: TRIM28 were set to Wilms tumour, MONDO:0006058, TRIM28-related
Review for gene: TRIM28 was set to GREEN
Added comment: Established gene-disease association, more than 10 individuals reported.

Onset in childhood.

Included for completeness as managed similarly to WT1.
Sources: Expert list
BabyScreen+ newborn screening v1.102 TRHR Zornitza Stark Marked gene: TRHR as ready
BabyScreen+ newborn screening v1.102 TRHR Zornitza Stark Gene: trhr has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.102 TRHR Zornitza Stark Phenotypes for gene: TRHR were changed from Thyrotropin-releasing hormone resistance, generalized to Hypothyroidism, congenital, nongoitrous, 7, MIM# 618573
BabyScreen+ newborn screening v1.101 TRHR Zornitza Stark Publications for gene: TRHR were set to
BabyScreen+ newborn screening v1.100 TRHR Zornitza Stark Classified gene: TRHR as Green List (high evidence)
BabyScreen+ newborn screening v1.100 TRHR Zornitza Stark Gene: trhr has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.99 TRHR Zornitza Stark Tag treatable tag was added to gene: TRHR.
Tag endocrine tag was added to gene: TRHR.
BabyScreen+ newborn screening v1.99 TRHR Zornitza Stark reviewed gene: TRHR: Rating: GREEN; Mode of pathogenicity: None; Publications: 9141550, 19213692, 26735259, 28419241, 32319661; Phenotypes: Hypothyroidism, congenital, nongoitrous, 7, MIM# 618573; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v1.99 SGPL1 Zornitza Stark Classified gene: SGPL1 as Green List (high evidence)
BabyScreen+ newborn screening v1.99 SGPL1 Zornitza Stark Gene: sgpl1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.98 SGPL1 Zornitza Stark Tag renal was removed from gene: SGPL1.
Tag treatable tag was added to gene: SGPL1.
Tag endocrine tag was added to gene: SGPL1.
BabyScreen+ newborn screening v1.98 SGPL1 Zornitza Stark reviewed gene: SGPL1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Nephrotic syndrome, type 14 MIM#617575; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v1.98 SCNN1G Zornitza Stark Marked gene: SCNN1G as ready
BabyScreen+ newborn screening v1.98 SCNN1G Zornitza Stark Gene: scnn1g has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.98 SCNN1G Zornitza Stark Phenotypes for gene: SCNN1G were changed from Pseudohypoaldosteronism, type I, MIM# 264350; Pseudohypoaldosteronism to Pseudohypoaldosteronism, type I, MIM# 264350
BabyScreen+ newborn screening v1.97 SCNN1G Zornitza Stark Classified gene: SCNN1G as Green List (high evidence)
BabyScreen+ newborn screening v1.97 SCNN1G Zornitza Stark Gene: scnn1g has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.96 SCNN1G Zornitza Stark Tag treatable tag was added to gene: SCNN1G.
Tag endocrine tag was added to gene: SCNN1G.
BabyScreen+ newborn screening v1.96 SCNN1G Zornitza Stark reviewed gene: SCNN1G: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Pseudohypoaldosteronism, type I, MIM# 264350; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v1.96 RPS7 Zornitza Stark Marked gene: RPS7 as ready
BabyScreen+ newborn screening v1.96 RPS7 Zornitza Stark Gene: rps7 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.96 RPS7 Zornitza Stark Phenotypes for gene: RPS7 were changed from Diamond-Blackfan anaemia 8, MIM# 612563; Diamond-Blackfan anemia to Diamond-Blackfan anaemia 8, MIM# 612563
BabyScreen+ newborn screening v1.95 RPS7 Zornitza Stark Publications for gene: RPS7 were set to
BabyScreen+ newborn screening v1.94 RPS7 Zornitza Stark Classified gene: RPS7 as Green List (high evidence)
BabyScreen+ newborn screening v1.94 RPS7 Zornitza Stark Gene: rps7 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.93 RPS7 Zornitza Stark Tag treatable tag was added to gene: RPS7.
Tag haematological tag was added to gene: RPS7.
BabyScreen+ newborn screening v1.93 RPS7 Zornitza Stark reviewed gene: RPS7: Rating: GREEN; Mode of pathogenicity: None; Publications: 19061985, 23718193, 27882484, 32772263; Phenotypes: Diamond-Blackfan anemia 8, MIM# 612563; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Microcephaly v1.234 DDX3X Ain Roesley Marked gene: DDX3X as ready
Microcephaly v1.234 DDX3X Ain Roesley Gene: ddx3x has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.93 RPL35A Zornitza Stark Marked gene: RPL35A as ready
BabyScreen+ newborn screening v1.93 RPL35A Zornitza Stark Gene: rpl35a has been classified as Green List (High Evidence).
Microcephaly v1.234 DDX3X Ain Roesley Classified gene: DDX3X as Green List (high evidence)
Microcephaly v1.234 DDX3X Ain Roesley Gene: ddx3x has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.93 RPL35A Zornitza Stark Phenotypes for gene: RPL35A were changed from Diamond-Blackfan anaemia 5, MIM# 612528; Diamond-Blackfan anemia to Diamond-Blackfan anaemia 5, MIM# 612528
BabyScreen+ newborn screening v1.92 RPL35A Zornitza Stark Publications for gene: RPL35A were set to
BabyScreen+ newborn screening v1.91 RPL35A Zornitza Stark Classified gene: RPL35A as Green List (high evidence)
BabyScreen+ newborn screening v1.91 RPL35A Zornitza Stark Gene: rpl35a has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.90 RPL35A Zornitza Stark Tag treatable tag was added to gene: RPL35A.
Tag haematological tag was added to gene: RPL35A.
BabyScreen+ newborn screening v1.90 RPL35A Zornitza Stark reviewed gene: RPL35A: Rating: GREEN; Mode of pathogenicity: None; Publications: 18535205, 32241839; Phenotypes: Diamond-Blackfan anemia 5, MIM# 612528; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v1.90 REST Zornitza Stark Marked gene: REST as ready
BabyScreen+ newborn screening v1.90 REST Zornitza Stark Gene: rest has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.90 REST Zornitza Stark Classified gene: REST as Green List (high evidence)
BabyScreen+ newborn screening v1.90 REST Zornitza Stark Gene: rest has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.89 REST Zornitza Stark gene: REST was added
gene: REST was added to BabyScreen+ newborn screening. Sources: Expert list
cancer, treatable tags were added to gene: REST.
Mode of inheritance for gene: REST was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: REST were set to 26551668; 34308104
Phenotypes for gene: REST were set to {Wilms tumor 6, susceptibility to}, MIM# 616806
Review for gene: REST was set to GREEN
Added comment: Established association, more than 10 families reported.

Childhood onset.

Included for completeness as managed similarly to WT1.
Sources: Expert list
BabyScreen+ newborn screening v1.88 PSTPIP1 Zornitza Stark Marked gene: PSTPIP1 as ready
BabyScreen+ newborn screening v1.88 PSTPIP1 Zornitza Stark Gene: pstpip1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.88 PSTPIP1 Zornitza Stark Classified gene: PSTPIP1 as Green List (high evidence)
BabyScreen+ newborn screening v1.88 PSTPIP1 Zornitza Stark Gene: pstpip1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.87 PSTPIP1 Zornitza Stark gene: PSTPIP1 was added
gene: PSTPIP1 was added to BabyScreen+ newborn screening. Sources: Expert list
treatable, immunological tags were added to gene: PSTPIP1.
Mode of inheritance for gene: PSTPIP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: PSTPIP1 were set to Pyogenic sterile arthritis, pyoderma gangrenosum, and acne, MIM# 604416
Review for gene: PSTPIP1 was set to GREEN
Added comment: Established gene-disease association.

Onset in childhood.

Treatment: adalimumab and tacrolimus, NSAIDs, corticosteroids, BMT

non-genetic confirmatory testing: no
Sources: Expert list
BabyScreen+ newborn screening v1.86 PPOX Zornitza Stark Marked gene: PPOX as ready
BabyScreen+ newborn screening v1.86 PPOX Zornitza Stark Gene: ppox has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.86 PPOX Zornitza Stark Phenotypes for gene: PPOX were changed from Porphyria variegata to Variegate porphyria, childhood-onset, MIM# 620483
BabyScreen+ newborn screening v1.85 PPOX Zornitza Stark Tag treatable tag was added to gene: PPOX.
Tag haematological tag was added to gene: PPOX.
BabyScreen+ newborn screening v1.85 PPOX Zornitza Stark Mode of inheritance for gene: PPOX was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v1.84 PPOX Zornitza Stark Classified gene: PPOX as Green List (high evidence)
BabyScreen+ newborn screening v1.84 PPOX Zornitza Stark Gene: ppox has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.83 PPOX Zornitza Stark reviewed gene: PPOX: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Variegate porphyria, childhood-onset, MIM# 620483; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v1.83 POMC Zornitza Stark Marked gene: POMC as ready
BabyScreen+ newborn screening v1.83 POMC Zornitza Stark Gene: pomc has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.83 POMC Zornitza Stark Phenotypes for gene: POMC were changed from Proopiomelanocortin deficiency to Obesity, adrenal insufficiency, and red hair due to POMC deficiency MIM#609734
BabyScreen+ newborn screening v1.82 POMC Zornitza Stark Classified gene: POMC as Green List (high evidence)
BabyScreen+ newborn screening v1.82 POMC Zornitza Stark Gene: pomc has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.81 POMC Zornitza Stark reviewed gene: POMC: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Obesity, adrenal insufficiency, and red hair due to POMC deficiency MIM#609734; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v1.81 POLE Zornitza Stark Marked gene: POLE as ready
BabyScreen+ newborn screening v1.81 POLE Zornitza Stark Gene: pole has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.81 POLE Zornitza Stark Classified gene: POLE as Green List (high evidence)
BabyScreen+ newborn screening v1.81 POLE Zornitza Stark Gene: pole has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.80 POLE Zornitza Stark gene: POLE was added
gene: POLE was added to BabyScreen+ newborn screening. Sources: Expert list
treatable, endocrine tags were added to gene: POLE.
Mode of inheritance for gene: POLE was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: POLE were set to IMAGE-I syndrome, MIM# 618336
Review for gene: POLE was set to GREEN
Added comment: Established gene-disease association.

Multi-system disorder comprising GH and adrenal hypoplasia.

Treatment: hydrocortisone

non-genetic confirmatory testing: hormone levels
Sources: Expert list
BabyScreen+ newborn screening v1.79 NCF4 Zornitza Stark Marked gene: NCF4 as ready
BabyScreen+ newborn screening v1.79 NCF4 Zornitza Stark Gene: ncf4 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.79 NCF4 Zornitza Stark Phenotypes for gene: NCF4 were changed from Chronic granulomatous disease 3, autosomal recessive, MIM# 613960; Chronic granulomatous disease to Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type III MIM#613960
BabyScreen+ newborn screening v1.78 NCF4 Zornitza Stark Classified gene: NCF4 as Green List (high evidence)
BabyScreen+ newborn screening v1.78 NCF4 Zornitza Stark Gene: ncf4 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.77 NCF4 Zornitza Stark Tag treatable tag was added to gene: NCF4.
Tag immunological tag was added to gene: NCF4.
BabyScreen+ newborn screening v1.77 NCF4 Zornitza Stark reviewed gene: NCF4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type III MIM#613960; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v1.77 LPL Zornitza Stark Marked gene: LPL as ready
BabyScreen+ newborn screening v1.77 LPL Zornitza Stark Gene: lpl has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.77 LPL Zornitza Stark Classified gene: LPL as Green List (high evidence)
BabyScreen+ newborn screening v1.77 LPL Zornitza Stark Gene: lpl has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.76 LPL Zornitza Stark gene: LPL was added
gene: LPL was added to BabyScreen+ newborn screening. Sources: Expert list
treatable, metabolic tags were added to gene: LPL.
Mode of inheritance for gene: LPL was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: LPL were set to Lipoprotein lipase deficiency, MIM# 238600
Review for gene: LPL was set to GREEN
Added comment: Established gene-disease association.

Bi-allelic disease is severe and presents in infancy.

Treatment: volanesorsen, dietary fat restriction, lomitapide

Non-genetic confirmatory testing: LPL activity
Sources: Expert list
BabyScreen+ newborn screening v1.75 LAT Zornitza Stark Marked gene: LAT as ready
BabyScreen+ newborn screening v1.75 LAT Zornitza Stark Gene: lat has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.75 LAT Zornitza Stark Classified gene: LAT as Green List (high evidence)
BabyScreen+ newborn screening v1.75 LAT Zornitza Stark Gene: lat has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.74 LAT Zornitza Stark gene: LAT was added
gene: LAT was added to BabyScreen+ newborn screening. Sources: Expert list
treatable, immunological tags were added to gene: LAT.
Mode of inheritance for gene: LAT was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: LAT were set to Immunodeficiency 52, MIM# 617514
Review for gene: LAT was set to GREEN
Added comment: Established gene-disease association.

SCID-like presentation.

Treatment: BMT

Non-genetic confirmatory testing: yes
Sources: Expert list
BabyScreen+ newborn screening v1.73 KLHL3 Zornitza Stark Marked gene: KLHL3 as ready
BabyScreen+ newborn screening v1.73 KLHL3 Zornitza Stark Gene: klhl3 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.73 KLHL3 Zornitza Stark Classified gene: KLHL3 as Green List (high evidence)
BabyScreen+ newborn screening v1.73 KLHL3 Zornitza Stark Gene: klhl3 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.72 KLHL3 Zornitza Stark gene: KLHL3 was added
gene: KLHL3 was added to BabyScreen+ newborn screening. Sources: Expert list
treatable, endocrine tags were added to gene: KLHL3.
Mode of inheritance for gene: KLHL3 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: KLHL3 were set to Pseudohypoaldosteronism, type IID, MIM# 614495
Review for gene: KLHL3 was set to GREEN
Added comment: Established gene disease association.

Results in hyperkalaemia and later, the development of hypertension.

Treatment: thiazide diuretics normalise electrolytes

Non-genetic confirmatory testing: electrolytes
Sources: Expert list
BabyScreen+ newborn screening v1.71 IRF8 Zornitza Stark Marked gene: IRF8 as ready
BabyScreen+ newborn screening v1.71 IRF8 Zornitza Stark Gene: irf8 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.71 IRF8 Zornitza Stark Classified gene: IRF8 as Green List (high evidence)
BabyScreen+ newborn screening v1.71 IRF8 Zornitza Stark Gene: irf8 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.70 IRF8 Zornitza Stark gene: IRF8 was added
gene: IRF8 was added to BabyScreen+ newborn screening. Sources: Expert list
treatable, immunological tags were added to gene: IRF8.
Mode of inheritance for gene: IRF8 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: IRF8 were set to Immunodeficiency 32B, monocyte and dendritic cell deficiency, autosomal recessive, MIM# 226990
Review for gene: IRF8 was set to GREEN
Added comment: At least 4 families reported with bi-allelic variants. Gene-disease association also proposed for mono-allelic variants but only two individuals reported.

Recurrent infections presenting in infancy.

Treatment: BMT

Non-genetic confirmatory testing available
Sources: Expert list
BabyScreen+ newborn screening v1.69 IL10RB Zornitza Stark Marked gene: IL10RB as ready
BabyScreen+ newborn screening v1.69 IL10RB Zornitza Stark Gene: il10rb has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.69 IL10RB Zornitza Stark Phenotypes for gene: IL10RB were changed from Inflammatory bowel disease; Inflammatory bowel disease 25, early onset, autosomal recessive, MIM# 612567 to Inflammatory bowel disease 25, early onset, autosomal recessive, MIM# 612567
BabyScreen+ newborn screening v1.68 IL10RB Zornitza Stark Classified gene: IL10RB as Green List (high evidence)
BabyScreen+ newborn screening v1.68 IL10RB Zornitza Stark Gene: il10rb has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.67 IL10RB Zornitza Stark Tag treatable tag was added to gene: IL10RB.
Tag immunological tag was added to gene: IL10RB.
BabyScreen+ newborn screening v1.67 IL10RB Zornitza Stark reviewed gene: IL10RB: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Inflammatory bowel disease 25, early onset, autosomal recessive, MIM# 612567; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v1.67 IL10 Zornitza Stark Marked gene: IL10 as ready
BabyScreen+ newborn screening v1.67 IL10 Zornitza Stark Gene: il10 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.67 IL10 Zornitza Stark Classified gene: IL10 as Green List (high evidence)
BabyScreen+ newborn screening v1.67 IL10 Zornitza Stark Gene: il10 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.66 IL10 Zornitza Stark Tag treatable tag was added to gene: IL10.
Tag immunological tag was added to gene: IL10.
BabyScreen+ newborn screening v1.66 IL10 Zornitza Stark gene: IL10 was added
gene: IL10 was added to BabyScreen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: IL10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IL10 were set to 22236434; 20951137; 19890111
Phenotypes for gene: IL10 were set to Autoinflammatory syndrome, MONDO:0019751, IL10-related
Review for gene: IL10 was set to GREEN
Added comment: Established gene-disease association.

Onset in infancy and childhood.

Treatment: BMT

Non-genetic confirmatory testing: flow cytometry
Sources: Expert list
BabyScreen+ newborn screening v1.65 IGF1 Zornitza Stark Marked gene: IGF1 as ready
BabyScreen+ newborn screening v1.65 IGF1 Zornitza Stark Gene: igf1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.65 IGF1 Zornitza Stark Phenotypes for gene: IGF1 were changed from Insulin-like growth factor deficiency to Insulin-like growth factor I deficiency, MIM# 608747
BabyScreen+ newborn screening v1.64 IGF1 Zornitza Stark Classified gene: IGF1 as Green List (high evidence)
BabyScreen+ newborn screening v1.64 IGF1 Zornitza Stark Gene: igf1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.63 IGF1 Zornitza Stark Tag treatable tag was added to gene: IGF1.
Tag endocrine tag was added to gene: IGF1.
BabyScreen+ newborn screening v1.63 IGF1 Zornitza Stark reviewed gene: IGF1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Insulin-like growth factor I deficiency, MIM# 608747; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v1.63 GALNT3 Zornitza Stark Marked gene: GALNT3 as ready
BabyScreen+ newborn screening v1.63 GALNT3 Zornitza Stark Gene: galnt3 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.63 GALNT3 Zornitza Stark Classified gene: GALNT3 as Green List (high evidence)
BabyScreen+ newborn screening v1.63 GALNT3 Zornitza Stark Gene: galnt3 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.62 GALNT3 Zornitza Stark gene: GALNT3 was added
gene: GALNT3 was added to BabyScreen+ newborn screening. Sources: Expert list
treatable, endocrine tags were added to gene: GALNT3.
Mode of inheritance for gene: GALNT3 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: GALNT3 were set to Tumoral calcinosis, hyperphosphatemic, familial, 1, MIM# 211900
Review for gene: GALNT3 was set to GREEN
Added comment: Established gene-disease association.

Onset in infancy/childhood.

Treatment: dietary restriction, phosphate binders, acetazolamide

Non-genetic confirmatory testing: serum phosphate, calcium, PTH, alkaline phosphatase, vitamin D serum levels, urine calcium, phosphate levels, plasma levels of the C-terminal portion of the phosphate-regulating hormone, fibroblast growth factor 23
Sources: Expert list
BabyScreen+ newborn screening v1.61 FECH Zornitza Stark Marked gene: FECH as ready
BabyScreen+ newborn screening v1.61 FECH Zornitza Stark Gene: fech has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.61 FECH Zornitza Stark Classified gene: FECH as Green List (high evidence)
BabyScreen+ newborn screening v1.61 FECH Zornitza Stark Gene: fech has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.60 FECH Zornitza Stark gene: FECH was added
gene: FECH was added to BabyScreen+ newborn screening. Sources: Expert list
treatable, haematological tags were added to gene: FECH.
Mode of inheritance for gene: FECH was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: FECH were set to Protoporphyria, erythropoietic, 1, MIM# 177000
Review for gene: FECH was set to GREEN
Added comment: Established gene-disease association.

Onset of photosensitivity is in infancy/childhood.

Treatment: Afamelanotide

Non-genetic confirmatory testing: free protoporphyrin
Sources: Expert list
BabyScreen+ newborn screening v1.59 F13B Zornitza Stark Marked gene: F13B as ready
BabyScreen+ newborn screening v1.59 F13B Zornitza Stark Gene: f13b has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.59 F13B Zornitza Stark Phenotypes for gene: F13B were changed from Factor XIIIB deficiency MIM# 613235; Factor XIIIB deficiency, MIM# 613235 to Factor XIIIB deficiency, MIM#613235
BabyScreen+ newborn screening v1.58 F13B Zornitza Stark Classified gene: F13B as Green List (high evidence)
BabyScreen+ newborn screening v1.58 F13B Zornitza Stark Gene: f13b has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.57 F13B Zornitza Stark Tag treatable tag was added to gene: F13B.
Tag haematological tag was added to gene: F13B.
BabyScreen+ newborn screening v1.57 F13B Zornitza Stark reviewed gene: F13B: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Factor XIIIB deficiency, MIM#613235; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v1.57 F10 Zornitza Stark Classified gene: F10 as Green List (high evidence)
BabyScreen+ newborn screening v1.57 F10 Zornitza Stark Gene: f10 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.56 F10 Zornitza Stark Tag for review was removed from gene: F10.
Tag treatable tag was added to gene: F10.
Tag haematological tag was added to gene: F10.
BabyScreen+ newborn screening v1.56 F10 Zornitza Stark changed review comment from: Well established gene-disease association.

Variable severity: for review. Affected individuals can manifest prolonged nasal and mucosal haemorrhage, menorrhagia, haematuria, and occasionally hemarthrosis.

Treatment: plasma-derived factor 10 concentrate (Coagadex); to: Well established gene-disease association.

Affected individuals can manifest prolonged nasal and mucosal haemorrhage, menorrhagia, haematuria, and occasionally hemarthrosis.

Treatment: plasma-derived factor 10 concentrate (Coagadex)
BabyScreen+ newborn screening v1.56 F10 Zornitza Stark edited their review of gene: F10: Changed rating: GREEN
BabyScreen+ newborn screening v1.56 ERCC4 Zornitza Stark Marked gene: ERCC4 as ready
BabyScreen+ newborn screening v1.56 ERCC4 Zornitza Stark Gene: ercc4 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.56 ERCC4 Zornitza Stark Phenotypes for gene: ERCC4 were changed from Xeroderma pigmentosum, group F, MIM# 278760; Xeroderma pigmentosum; Fanconi anaemia, complementation group Q, MIM# 615272 to Fanconi anemia, complementation group Q, MIM# 615272
BabyScreen+ newborn screening v1.55 ERCC4 Zornitza Stark Classified gene: ERCC4 as Green List (high evidence)
BabyScreen+ newborn screening v1.55 ERCC4 Zornitza Stark Gene: ercc4 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.54 ERCC4 Zornitza Stark Tag treatable tag was added to gene: ERCC4.
Tag haematological tag was added to gene: ERCC4.
BabyScreen+ newborn screening v1.54 ERCC4 Zornitza Stark reviewed gene: ERCC4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Fanconi anemia, complementation group Q, MIM# 615272; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v1.54 CYP7B1 Zornitza Stark Marked gene: CYP7B1 as ready
BabyScreen+ newborn screening v1.54 CYP7B1 Zornitza Stark Gene: cyp7b1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.54 CYP7B1 Zornitza Stark Phenotypes for gene: CYP7B1 were changed from Cholestasis, severe to Bile acid synthesis defect, congenital, 3, MIM# 613812
BabyScreen+ newborn screening v1.53 CYP7B1 Zornitza Stark Publications for gene: CYP7B1 were set to
BabyScreen+ newborn screening v1.52 CYP7B1 Zornitza Stark Classified gene: CYP7B1 as Green List (high evidence)
BabyScreen+ newborn screening v1.52 CYP7B1 Zornitza Stark Gene: cyp7b1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.51 CYP7B1 Zornitza Stark Tag treatable tag was added to gene: CYP7B1.
Tag liver tag was added to gene: CYP7B1.
BabyScreen+ newborn screening v1.51 CYP7B1 Zornitza Stark reviewed gene: CYP7B1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24658845, 31337596, 30366773, 9802883; Phenotypes: Bile acid synthesis defect, congenital, 3, MIM# 613812; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v1.51 CUL3 Zornitza Stark Marked gene: CUL3 as ready
BabyScreen+ newborn screening v1.51 CUL3 Zornitza Stark Gene: cul3 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.51 CUL3 Zornitza Stark Classified gene: CUL3 as Green List (high evidence)
BabyScreen+ newborn screening v1.51 CUL3 Zornitza Stark Gene: cul3 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.50 CUL3 Zornitza Stark gene: CUL3 was added
gene: CUL3 was added to BabyScreen+ newborn screening. Sources: Expert list
treatable, endocrine tags were added to gene: CUL3.
Mode of inheritance for gene: CUL3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: CUL3 were set to Pseudohypoaldosteronism, type IIE 614496
Review for gene: CUL3 was set to GREEN
Added comment: Established gene-disease association.

Variants in this gene also cause a neurodevelopmental disorder; however, there is some genotype-phenotype correlation literature to help distinguish the two.

Results in hyperkalaemia and development of hypertension. However, the onset of hypertension is generally later in life.

Treatment: thiazide diuretics normalise biochemical abnormalities
Sources: Expert list
BabyScreen+ newborn screening v1.48 COQ6 Zornitza Stark Marked gene: COQ6 as ready
BabyScreen+ newborn screening v1.48 COQ6 Zornitza Stark Gene: coq6 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.48 COQ6 Zornitza Stark Phenotypes for gene: COQ6 were changed from Nephrotic syndrome with sensorineural deafness; Coenzyme Q10 deficiency, primary, 6, MIM# 614650 to Coenzyme Q10 deficiency, primary, 6, MIM# 614650
BabyScreen+ newborn screening v1.47 COQ6 Zornitza Stark Classified gene: COQ6 as Green List (high evidence)
BabyScreen+ newborn screening v1.47 COQ6 Zornitza Stark Gene: coq6 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.46 COQ6 Zornitza Stark Tag treatable tag was added to gene: COQ6.
Tag metabolic tag was added to gene: COQ6.
BabyScreen+ newborn screening v1.46 COQ6 Zornitza Stark reviewed gene: COQ6: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Coenzyme Q10 deficiency, primary, 6 MIM#614650; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v1.46 COQ2 Zornitza Stark Marked gene: COQ2 as ready
BabyScreen+ newborn screening v1.46 COQ2 Zornitza Stark Gene: coq2 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.46 COQ2 Zornitza Stark Phenotypes for gene: COQ2 were changed from Coenzyme Q10 deficiency, primary, 1, MIM# 607426; Coenzyme Q10 deficiency, primary, 1 to Coenzyme Q10 deficiency, primary, 1, MIM# 607426
BabyScreen+ newborn screening v1.45 COQ2 Zornitza Stark Classified gene: COQ2 as Green List (high evidence)
BabyScreen+ newborn screening v1.45 COQ2 Zornitza Stark Gene: coq2 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.44 COQ2 Zornitza Stark Tag treatable tag was added to gene: COQ2.
Tag metabolic tag was added to gene: COQ2.
BabyScreen+ newborn screening v1.44 COQ2 Zornitza Stark reviewed gene: COQ2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Coenzyme Q10 deficiency, primary, 1, MIM# 607426; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v1.44 CHRNB1 Zornitza Stark Marked gene: CHRNB1 as ready
BabyScreen+ newborn screening v1.44 CHRNB1 Zornitza Stark Gene: chrnb1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.44 CHRNB1 Zornitza Stark Classified gene: CHRNB1 as Green List (high evidence)
BabyScreen+ newborn screening v1.44 CHRNB1 Zornitza Stark Gene: chrnb1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.43 CHRNB1 Zornitza Stark Tag treatable tag was added to gene: CHRNB1.
Tag neurological tag was added to gene: CHRNB1.
BabyScreen+ newborn screening v1.43 CHRNB1 Zornitza Stark reviewed gene: CHRNB1: Rating: GREEN; Mode of pathogenicity: None; Publications: 32895905; Phenotypes: Myasthenic syndrome, slow-channel congenital, 601462 Myasthenic syndrome, congenital, 2A, slow-channel, 616313, Myasthenic syndrome, congenital, 2C, associated with acetylcholine receptor deficiency, 616314; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
BabyScreen+ newborn screening v1.43 CFI Zornitza Stark Marked gene: CFI as ready
BabyScreen+ newborn screening v1.43 CFI Zornitza Stark Gene: cfi has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.43 CFI Zornitza Stark Phenotypes for gene: CFI were changed from Haemolytic uraemic syndrome to Complement factor I deficiency MIM#610984
BabyScreen+ newborn screening v1.42 CFI Zornitza Stark Classified gene: CFI as Green List (high evidence)
BabyScreen+ newborn screening v1.42 CFI Zornitza Stark Gene: cfi has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.41 CFI Zornitza Stark reviewed gene: CFI: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Complement factor I deficiency MIM#610984; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v1.41 CFH Zornitza Stark Marked gene: CFH as ready
BabyScreen+ newborn screening v1.41 CFH Zornitza Stark Gene: cfh has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.41 CFH Zornitza Stark Phenotypes for gene: CFH were changed from Haemolytic uraemic syndrome to Complement factor H deficiency, MIM# 609814
BabyScreen+ newborn screening v1.40 CFH Zornitza Stark Classified gene: CFH as Green List (high evidence)
BabyScreen+ newborn screening v1.40 CFH Zornitza Stark Gene: cfh has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.39 CFH Zornitza Stark Tag treatable tag was added to gene: CFH.
Tag immunological tag was added to gene: CFH.
BabyScreen+ newborn screening v1.39 CFH Zornitza Stark reviewed gene: CFH: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Complement factor H deficiency, MIM# 609814; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v1.39 CFD Zornitza Stark Marked gene: CFD as ready
BabyScreen+ newborn screening v1.39 CFD Zornitza Stark Gene: cfd has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.39 CFD Zornitza Stark Phenotypes for gene: CFD were changed from Complement factor D deficiency, MIM# 613912; Complement factor D deficiency to Complement factor D deficiency, MIM# 613912
BabyScreen+ newborn screening v1.38 CFD Zornitza Stark Publications for gene: CFD were set to
BabyScreen+ newborn screening v1.37 CFD Zornitza Stark Classified gene: CFD as Green List (high evidence)
BabyScreen+ newborn screening v1.37 CFD Zornitza Stark Gene: cfd has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.36 CFD Zornitza Stark Tag treatable tag was added to gene: CFD.
Tag immunological tag was added to gene: CFD.
BabyScreen+ newborn screening v1.36 CFD Zornitza Stark reviewed gene: CFD: Rating: GREEN; Mode of pathogenicity: None; Publications: 11457876, 16527897, 31440263; Phenotypes: Complement factor D deficiency, MIM# 613912; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v1.36 CEBPE Zornitza Stark Marked gene: CEBPE as ready
BabyScreen+ newborn screening v1.36 CEBPE Zornitza Stark Gene: cebpe has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.36 CEBPE Zornitza Stark Classified gene: CEBPE as Green List (high evidence)
BabyScreen+ newborn screening v1.36 CEBPE Zornitza Stark Gene: cebpe has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.35 CEBPE Zornitza Stark Tag treatable tag was added to gene: CEBPE.
Tag immunological tag was added to gene: CEBPE.
BabyScreen+ newborn screening v1.35 CEBPE Zornitza Stark gene: CEBPE was added
gene: CEBPE was added to BabyScreen+ newborn screening. Sources: Expert Review
Mode of inheritance for gene: CEBPE was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CEBPE were set to Specific granule deficiency, MIM# 245480
Review for gene: CEBPE was set to GREEN
Added comment: Established gene-disease association.

Recurrent infections in infancy and childhood.

Treatment: long term antimicrobial prophalaxis

Non-genetic confirmatory testing available
Sources: Expert Review
BabyScreen+ newborn screening v1.34 C3 Zornitza Stark Marked gene: C3 as ready
BabyScreen+ newborn screening v1.34 C3 Zornitza Stark Gene: c3 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.34 C3 Zornitza Stark Phenotypes for gene: C3 were changed from Haemolytic uraemic syndrome; C3 deficiency, MIM# 613779 to C3 deficiency, MIM# 613779
BabyScreen+ newborn screening v1.33 C3 Zornitza Stark Classified gene: C3 as Green List (high evidence)
BabyScreen+ newborn screening v1.33 C3 Zornitza Stark Gene: c3 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.32 C3 Zornitza Stark Tag treatable tag was added to gene: C3.
Tag immunological tag was added to gene: C3.
BabyScreen+ newborn screening v1.32 C3 Zornitza Stark reviewed gene: C3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: C3 deficiency, MIM# 613779; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v1.32 C2 Zornitza Stark Marked gene: C2 as ready
BabyScreen+ newborn screening v1.32 C2 Zornitza Stark Gene: c2 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.32 C2 Zornitza Stark Classified gene: C2 as Green List (high evidence)
BabyScreen+ newborn screening v1.32 C2 Zornitza Stark Gene: c2 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.31 C2 Zornitza Stark Tag treatable tag was added to gene: C2.
Tag immunological tag was added to gene: C2.
BabyScreen+ newborn screening v1.31 C2 Zornitza Stark gene: C2 was added
gene: C2 was added to BabyScreen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: C2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C2 were set to 31421540
Phenotypes for gene: C2 were set to C2 deficiency, MIM# 217000
Review for gene: C2 was set to GREEN
Added comment: Established gene-disease association.

Can present with severe early infections in infancy/childhood.

Later manifestations include autoimmune phenomena.

Treatment: pneumococcal, meningococcal, haemophilus influenzae vaccines

Non-genetic confirmatory tests: complement levels
Sources: Expert list
BabyScreen+ newborn screening v1.30 APOA5 Zornitza Stark Marked gene: APOA5 as ready
BabyScreen+ newborn screening v1.30 APOA5 Zornitza Stark Gene: apoa5 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v1.30 APOA5 Zornitza Stark gene: APOA5 was added
gene: APOA5 was added to BabyScreen+ newborn screening. Sources: Expert list
treatable tags were added to gene: APOA5.
Mode of inheritance for gene: APOA5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: APOA5 were set to 23307945; 31390500
Phenotypes for gene: APOA5 were set to Hyperchylomicronaemia, late-onset, MIM# 144650
Review for gene: APOA5 was set to RED
Added comment: Established gene-disease association.

Variable age of onset, many of the reported individuals are adults.

Treatment: Volanesorsen
Sources: Expert list
BabyScreen+ newborn screening v1.29 AP3D1 Zornitza Stark Marked gene: AP3D1 as ready
BabyScreen+ newborn screening v1.29 AP3D1 Zornitza Stark Gene: ap3d1 has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v1.29 AP3D1 Zornitza Stark Classified gene: AP3D1 as Amber List (moderate evidence)
BabyScreen+ newborn screening v1.29 AP3D1 Zornitza Stark Gene: ap3d1 has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v1.28 AP3D1 Zornitza Stark gene: AP3D1 was added
gene: AP3D1 was added to BabyScreen+ newborn screening. Sources: Expert list
treatable, haematological tags were added to gene: AP3D1.
Mode of inheritance for gene: AP3D1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AP3D1 were set to 26744459; 9697856; 30472485; 36445457
Phenotypes for gene: AP3D1 were set to Hermansky-Pudlak syndrome 10, MIM# 617050
Review for gene: AP3D1 was set to AMBER
Added comment: Four individuals from two unrelated families and a mouse model. Borderline gene-disease association.

New case report 36445457, proband presenting with SNHL and questionable other subtle features of HPS, homozygous missense variant (VOUS).

Onset in infancy.

Treatable: BMT for immunodeficiency.
Sources: Expert list
BabyScreen+ newborn screening v1.27 AMACR Zornitza Stark Marked gene: AMACR as ready
BabyScreen+ newborn screening v1.27 AMACR Zornitza Stark Gene: amacr has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.27 AMACR Zornitza Stark Phenotypes for gene: AMACR were changed from Alpha-methylacyl-CoA racemase deficiency; Bile acid synthesis defect, congenital, 4 to Bile acid synthesis defect, congenital, 4, MIM# 214950
BabyScreen+ newborn screening v1.26 AMACR Zornitza Stark Publications for gene: AMACR were set to
BabyScreen+ newborn screening v1.25 AMACR Zornitza Stark Classified gene: AMACR as Green List (high evidence)
BabyScreen+ newborn screening v1.25 AMACR Zornitza Stark Gene: amacr has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.24 AMACR Zornitza Stark Tag treatable tag was added to gene: AMACR.
Tag liver tag was added to gene: AMACR.
BabyScreen+ newborn screening v1.24 AMACR Zornitza Stark reviewed gene: AMACR: Rating: GREEN; Mode of pathogenicity: None; Publications: 12512044; Phenotypes: Bile acid synthesis defect, congenital, 4, MIM# 214950; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v1.24 ABCD4 Zornitza Stark Tag treatable tag was added to gene: ABCD4.
BabyScreen+ newborn screening v1.24 SLC9A3 Zornitza Stark edited their review of gene: SLC9A3: Changed rating: AMBER
BabyScreen+ newborn screening v1.24 SLC9A3 Zornitza Stark commented on gene: SLC9A3
Complement Deficiencies v0.73 CFB Zornitza Stark Marked gene: CFB as ready
Complement Deficiencies v0.73 CFB Zornitza Stark Gene: cfb has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v1.24 ATRX Zornitza Stark edited their review of gene: ATRX: Changed phenotypes: ATR-X-related syndrome MONDO:0016980
BabyScreen+ newborn screening v1.24 ATRX Zornitza Stark Phenotypes for gene: ATRX were changed from Alpha-thalassemia/mental retardation syndrome, MIM# 301040; Intellectual disability-hypotonic facies syndrome, X-linked, MIM# 309580 to ATR-X-related syndrome MONDO:0016980
Prepair 1000+ v1.2 ATRX Zornitza Stark Phenotypes for gene: ATRX were changed from Mental retardation-hypotonic facies syndrome, X-linked, 309580 (3) to ATR-X-related syndrome MONDO:0016980
Fetal anomalies v1.149 ATRX Zornitza Stark Phenotypes for gene: ATRX were changed from Alpha-thalassemia/mental retardation syndrome, MIM# 301040 to ATR-X-related syndrome MONDO:0016980
Growth failure v1.70 ATRX Zornitza Stark Phenotypes for gene: ATRX were changed from Alpha-thalassemia/mental retardation syndrome, MIM# 301040; Mental retardation-hypotonic facies syndrome, X-linked, MIM# 309580 to ATR-X-related syndrome MONDO:0016980
Growth failure v1.69 ATRX Zornitza Stark edited their review of gene: ATRX: Changed phenotypes: ATR-X-related syndrome MONDO:0016980
Intellectual disability syndromic and non-syndromic v0.5508 ATRX Zornitza Stark Marked gene: ATRX as ready
Intellectual disability syndromic and non-syndromic v0.5508 ATRX Zornitza Stark Gene: atrx has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5508 ATRX Zornitza Stark Phenotypes for gene: ATRX were changed from to ATR-X-related syndrome MONDO:0016980
Intellectual disability syndromic and non-syndromic v0.5507 ATRX Zornitza Stark Mode of inheritance for gene: ATRX 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 v0.5506 ATRX Zornitza Stark reviewed gene: ATRX: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ATR-X-related syndrome MONDO:0016980; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Red cell disorders v1.20 ATRX Zornitza Stark Phenotypes for gene: ATRX were changed from Alpha-thalassaemia/mental retardation syndrome, MIM# 301040 to ATR-X-related syndrome MONDO:0016980
Additional findings_Paediatric v0.278 ATRX Zornitza Stark Phenotypes for gene: ATRX were changed from Alpha-thalassemia/mental retardation syndrome to ATR-X-related syndrome MONDO:0016980
Mackenzie's Mission_Reproductive Carrier Screening v0.109 ATRX Zornitza Stark Phenotypes for gene: ATRX were changed from Mental retardation-hypotonic facies syndrome, X-linked, 309580 (3) to ATR-X-related syndrome MONDO:0016980
Gastrointestinal neuromuscular disease v1.22 ATRX Zornitza Stark Phenotypes for gene: ATRX were changed from Alpha-thalassemia/mental retardation syndrome MIM#301040 to ATR-X-related syndrome MONDO:0016980
Genetic Epilepsy v0.1924 ATRX Zornitza Stark Phenotypes for gene: ATRX were changed from Alpha-thalassemia/mental retardation syndrome, MIM# 301040; Intellectual disability-hypotonic facies syndrome, X-linked, MIM# 309580 to ATR-X-related syndrome MONDO:0016980
Genetic Epilepsy v0.1923 ATRX Zornitza Stark edited their review of gene: ATRX: Changed phenotypes: ATR-X-related syndrome MONDO:0016980
Cancer Predisposition_Paediatric v0.131 ATRX Zornitza Stark Phenotypes for gene: ATRX were changed from Intellectual disability-hypotonic facies syndrome, X-linked, MIM# 309580; Osteosarcoma, mild to severe intellectual disability, facial, skeletal, urogenital, and hematopoietic anomalies. to ATR-X-related syndrome MONDO:0016980; Osteosarcoma, mild to severe intellectual disability, facial, skeletal, urogenital, and hematopoietic anomalies.
Microcephaly v1.233 ATRX Zornitza Stark Phenotypes for gene: ATRX were changed from Mental retardation-hypotonic facies syndrome, X-linked, MIM# 309580; Alpha-thalassemia/mental retardation syndrome, MIM# 301040 to ATR-X-related syndrome MONDO:0016980
Microcephaly v1.232 ATRX Zornitza Stark edited their review of gene: ATRX: Changed phenotypes: ATR-X-related syndrome MONDO:0016980
Mendeliome v1.1245 ATRX Zornitza Stark Phenotypes for gene: ATRX were changed from Alpha-thalassemia/mental retardation syndrome, MIM# 301040; Intellectual disability-hypotonic facies syndrome, X-linked, MIM# 309580 to ATR-X-related syndrome MONDO:0016980
Cerebral Palsy v1.190 ATRX Zornitza Stark Phenotypes for gene: ATRX were changed from Alpha-thalassemia/mental retardation syndrome, MIM# 301040; Mental retardation-hypotonic facies syndrome, X-linked, MIM# 309580 to ATR-X-related syndrome MONDO:0016980
Cerebral Palsy v1.189 ATRX Zornitza Stark edited their review of gene: ATRX: Changed phenotypes: ATR-X-related syndrome MONDO:0016980
Angelman Rett like syndromes v1.9 ATRX Zornitza Stark edited their review of gene: ATRX: Changed phenotypes: ATR-X-related syndrome MONDO:0016980
Angelman Rett like syndromes v1.9 ATRX Zornitza Stark Phenotypes for gene: ATRX were changed from Alpha-thalassemia/mental retardation syndrome, MIM# 301040; Mental retardation-hypotonic facies syndrome, X-linked, MIM# 309580 to ATR-X-related syndrome MONDO:0016980
Microcephaly v1.232 DDX3X Lauren Rogers gene: DDX3X was added
gene: DDX3X was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: DDX3X 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: DDX3X were set to 26235985
Phenotypes for gene: DDX3X were set to Snijders Blok-type X-linked syndromic intellectual developmental disorder (MIM#300958)
Review for gene: DDX3X was set to GREEN
Added comment: PMID: 26235985 - microcephaly seen in 12/38 females with de novo DDX3X variants
Sources: Literature
Ciliopathies v1.46 DLG5 Zornitza Stark Phenotypes for gene: DLG5 were changed from Cystic kidneys, nephrotic syndrome, hydrocephalus, limb abnormalities, congenital heart disease and craniofacial malformations to Ciliopathy, MONDO:0016044, DLG5-related; Cystic kidneys, nephrotic syndrome, hydrocephalus, limb abnormalities, congenital heart disease and craniofacial malformations
Mendeliome v1.1244 DLG5 Zornitza Stark Phenotypes for gene: DLG5 were changed from Cystic kidneys, nephrotic syndrome, hydrocephalus, limb abnormalities, congenital heart disease and craniofacial malformations to Ciliopathy, MONDO:0016044, DLG5-related; Cystic kidneys, nephrotic syndrome, hydrocephalus, limb abnormalities, congenital heart disease and craniofacial malformations
Cerebral Palsy v1.189 DHX32 Zornitza Stark Phenotypes for gene: DHX32 were changed from Intellectual disability, spastic diplegia, dystonia, brain abnormalities to Neurodevelopmental disorder, MONDO:0700092, DHX32-related
Intellectual disability syndromic and non-syndromic v0.5506 DHX32 Zornitza Stark Phenotypes for gene: DHX32 were changed from Intellectual disability, spastic diplegia, dystonia, brain abnormalities to Neurodevelopmental disorder, MONDO:0700092, DHX32-related
Mendeliome v1.1243 DHX32 Zornitza Stark Phenotypes for gene: DHX32 were changed from Intellectual disability, spastic diplegia, dystonia, brain abnormalities to Neurodevelopmental disorder, MONDO:0700092, DHX32-related
Hereditary Neuropathy_CMT - isolated v1.33 DGAT2 Zornitza Stark Phenotypes for gene: DGAT2 were changed from HMSN; Autosomal dominant Charcot-Marie-Tooth disease type 2 to Charcot-Marie-Tooth disease, MONDO:0015626, DGAT2-related
Mendeliome v1.1242 DGAT2 Zornitza Stark Phenotypes for gene: DGAT2 were changed from axonal Charcot-Marie-Tooth disease to Charcot-Marie-Tooth disease, MONDO:0015626, DGAT2-related
Mendeliome v1.1241 DDX54 Zornitza Stark Phenotypes for gene: DDX54 were changed from Intellectual disability; congenital anomalies to Neurodevelopmental disorder, MONDO:0700092, DDX54-related
Mendeliome v1.1240 DDX54 Zornitza Stark edited their review of gene: DDX54: Changed phenotypes: Neurodevelopmental disorder, MONDO:0700092, DDX54-related
Mendeliome v1.1240 DDX23 Zornitza Stark Phenotypes for gene: DDX23 were changed from DDX23-associated neurodevelopmental disorder to Neurodevelopmental disorder, MONDO:0700092, DDX23-related
Mendeliome v1.1239 DDX23 Zornitza Stark edited their review of gene: DDX23: Changed phenotypes: Neurodevelopmental disorder, MONDO:0700092, DDX23-related
Intellectual disability syndromic and non-syndromic v0.5505 DDX23 Zornitza Stark Phenotypes for gene: DDX23 were changed from DDX23-associated neurodevelopmental disorder to Neurodevelopmental disorder, MONDO:0700092, DDX23-related
Intellectual disability syndromic and non-syndromic v0.5504 DDX23 Zornitza Stark edited their review of gene: DDX23: Changed phenotypes: Neurodevelopmental disorder, MONDO:0700092, DDX23-related
Mendeliome v1.1239 CSNK1G1 Zornitza Stark Phenotypes for gene: CSNK1G1 were changed from Global developmental delay; Intellectual disability; Autism; Seizures to Neurodevelopmental disorder, MONDO:0700092, CSNK1G-related
Mendeliome v1.1238 CSNK1G1 Zornitza Stark edited their review of gene: CSNK1G1: Changed phenotypes: Neurodevelopmental disorder, MONDO:0700092, CSNK1G-related
Intellectual disability syndromic and non-syndromic v0.5504 CSNK1G1 Zornitza Stark Phenotypes for gene: CSNK1G1 were changed from Global developmental delay; Intellectual disability; Autism; Seizures; Abnormality of the face; Abnromality of limbs to Neurodevelopmental disorder, MONDO:0700092, CSNK1G-related
Mendeliome v1.1238 SPTAN1 Zornitza Stark Phenotypes for gene: SPTAN1 were changed from Developmental and epileptic encephalopathy 5, MIM# 613477; Hereditary spastic paraplegia MONDO:0019064, SPTAN1-related; hereditary motor neuropathy to Developmental and epileptic encephalopathy 5, MIM# 613477; Hereditary spastic paraplegia MONDO:0019064, SPTAN1-related; Neuronopathy, distal hereditary motor, 11, autosomal dominant, MIM# 620528
Mendeliome v1.1237 SPTAN1 Zornitza Stark edited their review of gene: SPTAN1: Changed phenotypes: Developmental and epileptic encephalopathy 5, MIM# 613477, Hereditary spastic paraplegia MONDO:0019064, SPTAN1-related, Neuronopathy, distal hereditary motor, 11, autosomal dominant, MIM# 620528
Hereditary Neuropathy_CMT - isolated v1.32 SPTAN1 Zornitza Stark Phenotypes for gene: SPTAN1 were changed from Distal hereditary motor neuropathy to Neuronopathy, distal hereditary motor, 11, autosomal dominant, MIM# 620528
Hereditary Neuropathy_CMT - isolated v1.31 SPTAN1 Zornitza Stark edited their review of gene: SPTAN1: Changed phenotypes: Neuronopathy, distal hereditary motor, 11, autosomal dominant, MIM# 620528
Mendeliome v1.1237 DAZL Zornitza Stark Phenotypes for gene: DAZL were changed from Primary ovarian insufficiency to Primary ovarian failure, MONDO:0005387, DAZL-related
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.318 DAZL Zornitza Stark Phenotypes for gene: DAZL were changed from Primary ovarian insufficiency to Primary ovarian failure, MONDO:0005387, DAZL-related
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.317 DACH2 Zornitza Stark Phenotypes for gene: DACH2 were changed from Primary ovarian insufficiency to Primary ovarian failure, MONDO:0005387, DACH2-related
Mendeliome v1.1236 DACH2 Zornitza Stark Phenotypes for gene: DACH2 were changed from Primary ovarian insufficiency to Primary ovarian failure, MONDO:0005387, DACH2-related
Metal Metabolism Disorders v0.36 CYBRD1 Zornitza Stark Phenotypes for gene: CYBRD1 were changed from Iron overload to Iron metabolism disease, MONDO:0002279, CYBRD1-related
Metal Metabolism Disorders v0.35 CYBRD1 Zornitza Stark edited their review of gene: CYBRD1: Changed phenotypes: Iron metabolism disease, MONDO:0002279, CYBRD1-related
Mendeliome v1.1235 CYBRD1 Zornitza Stark Phenotypes for gene: CYBRD1 were changed from Iron overload to Iron metabolism disease, MONDO:0002279, CYBRD1-related
Mendeliome v1.1234 CYBRD1 Zornitza Stark edited their review of gene: CYBRD1: Changed phenotypes: Iron metabolism disease, MONDO:0002279, CYBRD1-related
Intellectual disability syndromic and non-syndromic v0.5503 CTNND2 Zornitza Stark Phenotypes for gene: CTNND2 were changed from Intellectual disability; Autism; Epilepsy to Neurodevelopmental disorder, MONDO:0700092, CTNND2-related
Mendeliome v1.1234 CTNND2 Zornitza Stark Phenotypes for gene: CTNND2 were changed from Intellectual disability; Autism; Epilepsy to Neurodevelopmental disorder, MONDO:0700092, CTNND2-related
Mendeliome v1.1233 CTNNBL1 Zornitza Stark Phenotypes for gene: CTNNBL1 were changed from Primary Immunodeficiency; Autoimmune Cytopenias; Common variable immunodeficiency to Immunodeficiency 99 with hypogammaglobulinemia and autoimmune cytopenias, MIM# 619846
Mendeliome v1.1232 CTNNBL1 Zornitza Stark edited their review of gene: CTNNBL1: Changed phenotypes: Immunodeficiency 99 with hypogammaglobulinemia and autoimmune cytopenias, MIM# 619846
Common Variable Immunodeficiency v1.6 CTNNBL1 Zornitza Stark Phenotypes for gene: CTNNBL1 were changed from Primary Immunodeficiency; Autoimmune Cytopenias; Common variable immunodeficiency to Immunodeficiency 99 with hypogammaglobulinemia and autoimmune cytopenias, MIM# 619846
Common Variable Immunodeficiency v1.5 CTNNBL1 Zornitza Stark edited their review of gene: CTNNBL1: Changed phenotypes: Immunodeficiency 99 with hypogammaglobulinemia and autoimmune cytopenias, MIM# 619846
Mendeliome v1.1232 CSNK1E Zornitza Stark Phenotypes for gene: CSNK1E were changed from Epileptic encephalopathy to Developmental and epileptic encephalopathy, MONDO:0100062, CSNK1E-related
Genetic Epilepsy v0.1923 CSNK1E Zornitza Stark Phenotypes for gene: CSNK1E were changed from Epileptic encephalopathy to Developmental and epileptic encephalopathy, MONDO:0100062, CSNK1E-related
Genetic Epilepsy v0.1922 CSNK1E Zornitza Stark edited their review of gene: CSNK1E: Changed phenotypes: Developmental and epileptic encephalopathy, MONDO:0100062, CSNK1E-related
Congenital Disorders of Glycosylation v1.37 CSGALNACT1 Zornitza Stark Phenotypes for gene: CSGALNACT1 were changed from Congenital disorder of glycosylation; skeletal dysplasia to Congenital disorder of glycosylation; Skeletal dysplasia, mild, with joint laxity and advanced bone age, MIM# 618870
Congenital Disorders of Glycosylation v1.36 CSGALNACT1 Zornitza Stark edited their review of gene: CSGALNACT1: Changed phenotypes: Congenital disorder of glycosylation, Skeletal dysplasia, mild, with joint laxity and advanced bone age, MIM# 618870
Skeletal dysplasia v0.255 CSGALNACT1 Zornitza Stark Marked gene: CSGALNACT1 as ready
Skeletal dysplasia v0.255 CSGALNACT1 Zornitza Stark Gene: csgalnact1 has been classified as Green List (High Evidence).
Skeletal dysplasia v0.255 CSGALNACT1 Zornitza Stark Classified gene: CSGALNACT1 as Green List (high evidence)
Skeletal dysplasia v0.255 CSGALNACT1 Zornitza Stark Gene: csgalnact1 has been classified as Green List (High Evidence).
Skeletal dysplasia v0.254 CSGALNACT1 Zornitza Stark gene: CSGALNACT1 was added
gene: CSGALNACT1 was added to Skeletal dysplasia. Sources: Expert Review
Mode of inheritance for gene: CSGALNACT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CSGALNACT1 were set to 31705726; 31325655
Phenotypes for gene: CSGALNACT1 were set to Skeletal dysplasia, mild, with joint laxity and advanced bone age, MIM# 618870
Review for gene: CSGALNACT1 was set to GREEN
Added comment: Four families reported.
Sources: Expert Review
Multiple joint dislocations and laxity v0.9 CSGALNACT1 Zornitza Stark Marked gene: CSGALNACT1 as ready
Multiple joint dislocations and laxity v0.9 CSGALNACT1 Zornitza Stark Gene: csgalnact1 has been classified as Green List (High Evidence).
Multiple joint dislocations and laxity v0.9 CSGALNACT1 Zornitza Stark Phenotypes for gene: CSGALNACT1 were changed from CHONDROITIN SULFATE N-ACETYLGALACTOSAMINYLTRANSFERASE 1 616615 to Skeletal dysplasia, mild, with joint laxity and advanced bone age, MIM# 618870
Mendeliome v1.1231 CSGALNACT1 Zornitza Stark Phenotypes for gene: CSGALNACT1 were changed from Congenital disorders of glycosylation; skeletal dysplasia; advanced bone age to Skeletal dysplasia, mild, with joint laxity and advanced bone age, MIM# 618870
Mendeliome v1.1230 CSGALNACT1 Zornitza Stark edited their review of gene: CSGALNACT1: Changed phenotypes: Skeletal dysplasia, mild, with joint laxity and advanced bone age, MIM# 618870
Autism v0.193 CSDE1 Zornitza Stark Phenotypes for gene: CSDE1 were changed from Autism; intellectual disability; seizures; macrocephaly to Neurodevelopmental disorder, MONDO:0700092, CSDE1-related
Autism v0.192 CSDE1 Zornitza Stark edited their review of gene: CSDE1: Changed phenotypes: Neurodevelopmental disorder, MONDO:0700092, CSDE1-related
Intellectual disability syndromic and non-syndromic v0.5502 CSDE1 Zornitza Stark Phenotypes for gene: CSDE1 were changed from Autism; intellectual disability; seizures; macrocephaly to Neurodevelopmental disorder, MONDO:0700092, CSDE1-related
Mendeliome v1.1230 CSDE1 Zornitza Stark Phenotypes for gene: CSDE1 were changed from Autism; intellectual disability; seizures; macrocephaly to Neurodevelopmental disorder, MONDO:0700092, CSDE1-related
Mendeliome v1.1229 CSDE1 Zornitza Stark edited their review of gene: CSDE1: Changed phenotypes: Neurodevelopmental disorder, MONDO:0700092, CSDE1-related
Susceptibility to Viral Infections v0.115 PLCG2 Zornitza Stark Marked gene: PLCG2 as ready
Susceptibility to Viral Infections v0.115 PLCG2 Zornitza Stark Gene: plcg2 has been classified as Green List (High Evidence).
Susceptibility to Viral Infections v0.115 PLCG2 Zornitza Stark Phenotypes for gene: PLCG2 were changed from Susceptibility to herpes virus to Hereditary susceptibility to infections, MONDO:0015979, PLCG2-related; Susceptibility to herpes virus
Susceptibility to Viral Infections v0.114 PLCG2 Zornitza Stark Classified gene: PLCG2 as Green List (high evidence)
Susceptibility to Viral Infections v0.114 PLCG2 Zornitza Stark Gene: plcg2 has been classified as Green List (High Evidence).
Mendeliome v1.1229 CASP4 Zornitza Stark Marked gene: CASP4 as ready
Mendeliome v1.1229 CASP4 Zornitza Stark Gene: casp4 has been classified as Red List (Low Evidence).
Holoprosencephaly and septo-optic dysplasia v1.9 STIL Chirag Patel Classified gene: STIL as Amber List (moderate evidence)
Holoprosencephaly and septo-optic dysplasia v1.9 STIL Chirag Patel Gene: stil has been classified as Amber List (Moderate Evidence).
Holoprosencephaly and septo-optic dysplasia v1.9 STIL Chirag Patel Classified gene: STIL as Amber List (moderate evidence)
Holoprosencephaly and septo-optic dysplasia v1.9 STIL Chirag Patel Gene: stil has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1229 CASP4 Zornitza Stark gene: CASP4 was added
gene: CASP4 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: CASP4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CASP4 were set to 37647624
Phenotypes for gene: CASP4 were set to Hereditary susceptibility to infection, MONDO:0015979, CASP4-related; Susceptibility to meliodiosis
Review for gene: CASP4 was set to RED
Added comment: Single patient with severe disease secondary to B. pseudomallei requiring ECMO. Adjunctive IFN-γ administration as replacement for its failed induction by IL-18 promptly led to clearance of B. pseudomallei and subsequent weaning of support. Novel homozygous missense mutation in CASP4, at exon 7 c.1030C > T. Peripheral blood mononuclear cells (PBMC) of the patient and her parents showed reduced IFN-γ production, notably to IL-12 stimulation, and decreased IL-18 in response to LPS and increased IL-1B. Cloned cells show impacts on CASP4 activation and pyroptosis.
Sources: Expert Review
Defects of innate immunity v0.130 CASP4 Zornitza Stark Marked gene: CASP4 as ready
Defects of innate immunity v0.130 CASP4 Zornitza Stark Gene: casp4 has been classified as Red List (Low Evidence).
Defects of innate immunity v0.130 CASP4 Zornitza Stark Phenotypes for gene: CASP4 were changed from Susceptibility to meliodiosis to Hereditary susceptibility to infection, MONDO:0015979, CASP4-related; Susceptibility to meliodiosis
Defects of innate immunity v0.129 CASP4 Zornitza Stark Classified gene: CASP4 as Red List (low evidence)
Defects of innate immunity v0.129 CASP4 Zornitza Stark Gene: casp4 has been classified as Red List (Low Evidence).
Mendeliome v1.1228 IL36RN Zornitza Stark Phenotypes for gene: IL36RN were changed from Psoriasis 14, pustular, MIM# 614204 to Psoriasis 14, pustular, MIM# 614204; Autoinflammatory syndrome, MONDO:0019751, IL36RN-related
Mendeliome v1.1227 IL36RN Zornitza Stark Mode of inheritance for gene: IL36RN was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.1226 IL36RN Zornitza Stark edited their review of gene: IL36RN: Added comment: Monoallelic disease: Multiple patients with systemic inflammation with monoallelic variants in IL36RN suggesting a gene dosage effect whereby GPP onset is significantly delayed in subjects with monoallelic mutations but still at high risk of systemic inflammation.; Changed publications: 21848462, 21839423, 22903787, 23648549, 25458002; Changed phenotypes: Psoriasis 14, pustular, MIM# 614204, Autoinflammatory syndrome, MONDO:0019751, IL36RN-related; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Systemic Autoinflammatory Disease_Periodic Fever v1.16 IL36RN Zornitza Stark Phenotypes for gene: IL36RN were changed from Psoriasis 14, pustular, MIM# 614204 to Psoriasis 14, pustular, MIM# 614204; Autoinflammatory syndrome, MONDO:0019751, IL36RN-related
Systemic Autoinflammatory Disease_Periodic Fever v1.15 IL36RN Zornitza Stark Mode of inheritance for gene: IL36RN was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5501 TSEN54 Zornitza Stark Marked gene: TSEN54 as ready
Intellectual disability syndromic and non-syndromic v0.5501 TSEN54 Zornitza Stark Gene: tsen54 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5501 TSEN54 Zornitza Stark Phenotypes for gene: TSEN54 were changed from to pontocerebellar hypoplasia type 2A MONDO:0010190
Intellectual disability syndromic and non-syndromic v0.5500 TSEN54 Zornitza Stark Publications for gene: TSEN54 were set to
Intellectual disability syndromic and non-syndromic v0.5499 TSEN54 Zornitza Stark Mode of inheritance for gene: TSEN54 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5498 TSFM Zornitza Stark Marked gene: TSFM as ready
Intellectual disability syndromic and non-syndromic v0.5498 TSFM Zornitza Stark Gene: tsfm has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5498 TSFM Zornitza Stark Phenotypes for gene: TSFM were changed from to Combined oxidative phosphorylation deficiency 3, MIM#610505
Intellectual disability syndromic and non-syndromic v0.5497 TSFM Zornitza Stark Publications for gene: TSFM were set to
Intellectual disability syndromic and non-syndromic v0.5496 TSFM Zornitza Stark Mode of inheritance for gene: TSFM was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5495 TSFM Zornitza Stark reviewed gene: TSFM: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Combined oxidative phosphorylation deficiency 3, MIM#610505; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5495 TSHB Zornitza Stark Marked gene: TSHB as ready
Intellectual disability syndromic and non-syndromic v0.5495 TSHB Zornitza Stark Gene: tshb has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5495 TSHB Zornitza Stark Phenotypes for gene: TSHB were changed from to Central congenital hypothyroidism Orphanet:226298
Intellectual disability syndromic and non-syndromic v0.5494 TSHB Zornitza Stark Publications for gene: TSHB were set to
Intellectual disability syndromic and non-syndromic v0.5493 TSHB Zornitza Stark Mode of inheritance for gene: TSHB was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5492 TSHB Zornitza Stark reviewed gene: TSHB: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Central congenital hypothyroidism Orphanet:226298; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v1.164 ATP6V1B2 Zornitza Stark Marked gene: ATP6V1B2 as ready
Deafness_IsolatedAndComplex v1.164 ATP6V1B2 Zornitza Stark Gene: atp6v1b2 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.164 ATP6V1B2 Zornitza Stark Classified gene: ATP6V1B2 as Green List (high evidence)
Deafness_IsolatedAndComplex v1.164 ATP6V1B2 Zornitza Stark Gene: atp6v1b2 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.163 LMX1B Zornitza Stark Marked gene: LMX1B as ready
Deafness_IsolatedAndComplex v1.163 LMX1B Zornitza Stark Gene: lmx1b has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.163 LMX1B Zornitza Stark Phenotypes for gene: LMX1B were changed from Nail-patella syndrome (MIM#161200), MONDO:0008061; LMX1B-related nephropathy; Focal segmental glomerulosclerosis-10 (FSGS10), MIM#256020 to Nail-patella syndrome (MIM#161200), MONDO:0008061
Deafness_IsolatedAndComplex v1.162 LMX1B Zornitza Stark Classified gene: LMX1B as Green List (high evidence)
Deafness_IsolatedAndComplex v1.162 LMX1B Zornitza Stark Gene: lmx1b has been classified as Green List (High Evidence).
Systemic Autoinflammatory Disease_Periodic Fever v1.14 IRAK4 Zornitza Stark Marked gene: IRAK4 as ready
Systemic Autoinflammatory Disease_Periodic Fever v1.14 IRAK4 Zornitza Stark Gene: irak4 has been classified as Green List (High Evidence).
Systemic Autoinflammatory Disease_Periodic Fever v1.14 IRAK4 Zornitza Stark Phenotypes for gene: IRAK4 were changed from neuroinflammation, systemic autoinflammation, splenomegaly, and anemia to Autoinflammatory syndrome, MONDO:0019751, IRAK4-related
Systemic Autoinflammatory Disease_Periodic Fever v1.13 IRAK4 Zornitza Stark Classified gene: IRAK4 as Green List (high evidence)
Systemic Autoinflammatory Disease_Periodic Fever v1.13 IRAK4 Zornitza Stark Gene: irak4 has been classified as Green List (High Evidence).
Systemic Autoinflammatory Disease_Periodic Fever v1.12 IRAK4 Zornitza Stark reviewed gene: IRAK4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Autoinflammatory syndrome, MONDO:0019751, IRAK4-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Spastic Paraplegia - paediatric v1.69 SNAPC4 Zornitza Stark Phenotypes for gene: SNAPC4 were changed from Neurodevelopmental disorder (MONDO#0700092), SNAPC4-related to Neurodevelopmental disorder with motor regression, progressive spastic paraplegia, and oromotor dysfunction, MIM# 620515
Intellectual disability syndromic and non-syndromic v0.5492 SNAPC4 Zornitza Stark Phenotypes for gene: SNAPC4 were changed from Neurodevelopmental disorder (MONDO#0700092), SNAPC4-related to Neurodevelopmental disorder with motor regression, progressive spastic paraplegia, and oromotor dysfunction, MIM# 620515
Microcephaly v1.232 SNAPC4 Zornitza Stark Phenotypes for gene: SNAPC4 were changed from Neurodevelopmental disorder (MONDO#0700092), SNAPC4-related to Neurodevelopmental disorder with motor regression, progressive spastic paraplegia, and oromotor dysfunction, MIM# 620515
Mendeliome v1.1226 SNAPC4 Zornitza Stark Phenotypes for gene: SNAPC4 were changed from Neurodevelopmental disorder (MONDO#0700092), SNAPC4-related to Neurodevelopmental disorder with motor regression, progressive spastic paraplegia, and oromotor dysfunction, MIM# 620515
Disorders of immune dysregulation v0.180 PLCG1 Zornitza Stark Phenotypes for gene: PLCG1 were changed from Autoinflammatory syndrome, MONDO:0019751, PLCG1-related; Immune dysregulation to Immune dysregulation, autoimmunity, and autoinflammation, MIM# 620514
Mendeliome v1.1225 PLCG1 Zornitza Stark Phenotypes for gene: PLCG1 were changed from Autoinflammatory syndrome, MONDO:0019751, PLCG1-related; Immune dysregulation to Immune dysregulation, autoimmunity, and autoinflammation, MIM# 620514
Mendeliome v1.1224 PLCG1 Zornitza Stark edited their review of gene: PLCG1: Changed phenotypes: Immune dysregulation, autoimmunity, and autoinflammation, MIM# 620514
Systemic Autoinflammatory Disease_Periodic Fever v1.12 IL36RN Peter McNaughton reviewed gene: IL36RN: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 25458002; Phenotypes: Autoinflammation; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5491 TSEN54 Kaitlyn Dianna Weldon reviewed gene: TSEN54: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301773; Phenotypes: pontocerebellar hypoplasia type 2A MONDO:0010190; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5491 TSFM Kaitlyn Dianna Weldon reviewed gene: TSFM: Rating: GREEN; Mode of pathogenicity: None; Publications: 25037205, 33816677, 31451716, 22499341; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5491 TSHB Kaitlyn Dianna Weldon reviewed gene: TSHB: Rating: GREEN; Mode of pathogenicity: None; Publications: 15292359, 27362444; Phenotypes: Central congenital hypothyroidism Orphanet:226298; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v1.161 ATP6V1B2 Manny Jacobs gene: ATP6V1B2 was added
gene: ATP6V1B2 was added to Deafness_IsolatedAndComplex. Sources: Literature
Mode of inheritance for gene: ATP6V1B2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: ATP6V1B2 were set to PMID: 24913193; 28396750; 34746137; 32873933; 25915598
Phenotypes for gene: ATP6V1B2 were set to Zimmermann-Laband syndrome 2, MIM# 616455; Deafness, congenital, with onychodystrophy, autosomal dominant, MIM# 124480; Epileptic encephalopathy
Review for gene: ATP6V1B2 was set to GREEN
Added comment: Pathogenic variation in this gene is associated with a group of syndromes with clinical overlap, though deafness is a common feature.

PMID: 32873933; 28396750 - recurrent truncating variant (NM_001693.4:c.1516C>T; p.Arg506*) with a supporting mouse model (PMID: 34746137).
Sources: Literature
Deafness_IsolatedAndComplex v1.161 LMX1B Manny Jacobs gene: LMX1B was added
gene: LMX1B was added to Deafness_IsolatedAndComplex. Sources: Literature
Mode of inheritance for gene: LMX1B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: LMX1B were set to PMID: 27450397, 32457516, 15928687
Phenotypes for gene: LMX1B were set to Nail-patella syndrome (MIM#161200), MONDO:0008061; LMX1B-related nephropathy; Focal segmental glomerulosclerosis-10 (FSGS10), MIM#256020
Review for gene: LMX1B was set to GREEN
Added comment: Nail-patella syndrome (NPS) is an autosomal-dominant disease characterized by dysplastic nails, absent or hypoplastic patellae, elbow dysplasia, and iliac horns. Varying degrees of proteinuria or hematuria are present, and can occasionally progress to chronic renal failure. Some variants in the homeodomain of LMX1B cause isolated nephropathy without nail, patellar or skeletal abnormality (LMX1B-associated nephropathy).

PMID 15928687 - reports 11 individuals across four families with sensorineural hearing impairment and NPS.
Sources: Literature
Systemic Autoinflammatory Disease_Periodic Fever v1.12 IRAK4 Peter McNaughton gene: IRAK4 was added
gene: IRAK4 was added to Systemic Autoinflammatory Disease_Periodic Fever. Sources: Literature
Mode of inheritance for gene: IRAK4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IRAK4 were set to PMID: 37744344
Phenotypes for gene: IRAK4 were set to neuroinflammation, systemic autoinflammation, splenomegaly, and anemia
Review for gene: IRAK4 was set to GREEN
Added comment: 5 patients from 2 unrelated kindreds with bi-allelic mutations in IRAK4, resulting in a severe autoinflammatory phenotype without overt immune deficiency, presenting with fever without infection, increased inflammatory markers, massive splenomegaly, transfusion dependent anemia; and severe neuroinflammation in 3/5 cases.
Sources: Literature
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.316 CPEB1 Zornitza Stark Phenotypes for gene: CPEB1 were changed from Primary ovarian insufficiency to Primary ovarian insufficiency, MONDO:0005387, CPEB1-related
Mendeliome v1.1224 CPEB1 Zornitza Stark Phenotypes for gene: CPEB1 were changed from Primary ovarian insufficiency to Primary ovarian insufficiency, MONDO:0005387, CPEB1-related
Pancreatitis v1.5 CPA1 Zornitza Stark Phenotypes for gene: CPA1 were changed from Susceptibility to chronic pancreatitis; Hereditary pancreatitis to Hereditary pancreatitis, MONDO:0008185, CPA1-related
Pancreatitis v1.4 CPA1 Zornitza Stark edited their review of gene: CPA1: Changed phenotypes: Hereditary pancreatitis, MONDO:0008185, CPA1-related
Mendeliome v1.1223 CPA1 Zornitza Stark Phenotypes for gene: CPA1 were changed from Susceptibility to chronic pancreatitis; Hereditary pancreatitis to Hereditary pancreatitis, MONDO:0008185, CPA1-related
Mendeliome v1.1222 CPA1 Zornitza Stark edited their review of gene: CPA1: Changed phenotypes: Hereditary pancreatitis, MONDO:0008185, CPA1-related
Palmoplantar Keratoderma and Erythrokeratoderma v0.129 COL14A1 Zornitza Stark Phenotypes for gene: COL14A1 were changed from Punctate palmoplantar keratoderma type 1B to Punctate palmoplantar keratoderma type 1B, MONDO:0017675, COL14A1-related
Intellectual disability syndromic and non-syndromic v0.5491 CNTN6 Zornitza Stark Phenotypes for gene: CNTN6 were changed from Intellectual disability; autism; Tourette syndrome; schizophrenia to Neurodevelopmental disorder, MONDO:0700092, CNTN6-related
Intellectual disability syndromic and non-syndromic v0.5490 CNTN6 Zornitza Stark edited their review of gene: CNTN6: Changed phenotypes: Neurodevelopmental disorder, MONDO:0700092, CNTN6-related
Mendeliome v1.1222 CNTN6 Zornitza Stark Phenotypes for gene: CNTN6 were changed from Intellectual disability; autism; Tourette syndrome; schizophrenia to Neurodevelopmental disorder, MONDO:0700092, CNTN6-related
Mendeliome v1.1221 CNTN6 Zornitza Stark edited their review of gene: CNTN6: Changed phenotypes: Neurodevelopmental disorder, MONDO:0700092, CNTN6-related
Intellectual disability syndromic and non-syndromic v0.5490 CNTN3 Zornitza Stark Phenotypes for gene: CNTN3 were changed from to Neurodevelopmental disorder, MONDO:0700092, CNTN3-related
Intellectual disability syndromic and non-syndromic v0.5489 CNTN3 Zornitza Stark edited their review of gene: CNTN3: Changed phenotypes: Neurodevelopmental disorder, MONDO:0700092, CNTN3-related
Mendeliome v1.1221 CNTN3 Zornitza Stark Phenotypes for gene: CNTN3 were changed from Intellectual disability to Neurodevelopmental disorder, MONDO:0700092, CNTN3-related
Mendeliome v1.1220 CNTN2 Zornitza Stark Phenotypes for gene: CNTN2 were changed from Epilepsy to Epilepsy, MONDO:0015653, CNTN2-related
Genetic Epilepsy v0.1922 CNTN2 Zornitza Stark Publications for gene: CNTN2 were set to 23518707
Genetic Epilepsy v0.1921 CNTN2 Zornitza Stark Phenotypes for gene: CNTN2 were changed from Epilepsy to Epilepsy, MONDO:0015653, CNTN2-related
Mendeliome v1.1219 CNKSR1 Zornitza Stark Phenotypes for gene: CNKSR1 were changed from Intellectual disability to Neurodevelopmental disorder, MONDO:0700092, CNKSR1-related
Intellectual disability syndromic and non-syndromic v0.5489 CNKSR1 Zornitza Stark Phenotypes for gene: CNKSR1 were changed from Intellectual disability to Neurodevelopmental disorder, MONDO:0700092, CNKSR1-related
Intellectual disability syndromic and non-syndromic v0.5488 CMAS Zornitza Stark Phenotypes for gene: CMAS were changed from Intellectual disability to Neurodevelopmental disorder, MONDO:0700092, CMAS-related
Intellectual disability syndromic and non-syndromic v0.5487 CMAS Zornitza Stark edited their review of gene: CMAS: Changed phenotypes: Neurodevelopmental disorder, MONDO:0700092, CMAS-related
Mendeliome v1.1218 CMAS Zornitza Stark Phenotypes for gene: CMAS were changed from Intellectual disability to Neurodevelopmental disorder, MONDO:0700092, CMAS-related
Mendeliome v1.1217 CHST8 Zornitza Stark Phenotypes for gene: CHST8 were changed from Peeling skin syndrome to Peeling skin syndrome, MONDO:0019347, CHST8-realted
Defects of innate immunity v0.128 CASP4 Peter McNaughton gene: CASP4 was added
gene: CASP4 was added to Defects of innate immunity. Sources: Literature
Mode of inheritance for gene: CASP4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CASP4 were set to PMID: 37647624
Phenotypes for gene: CASP4 were set to Susceptibility to meliodiosis
Review for gene: CASP4 was set to RED
Added comment: Single patient with severe disease secondary to B. pseudomallei requiring ECMO. Adjunctive IFN-γ administration as replacement for its failed induction by IL-18 promptly led to clearance of B. pseudomallei and subsequent weaning of support.
Novel homozygous missense mutation in CASP4, at exon 7 c.1030C > T. Peripheral blood mononuclear cells (PBMC) of the patient and her parents showed reduced IFN-γ production, notably to IL-12 stimulation, and decreased IL-18 in response to LPS and increased IL-1B. Cloned cells show impacts on CASP4 activation and pyroptosis.
Sources: Literature
Susceptibility to Viral Infections v0.113 PLCG2 Peter McNaughton gene: PLCG2 was added
gene: PLCG2 was added to Susceptibility to Viral Infections. Sources: Literature
Mode of inheritance for gene: PLCG2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PLCG2 were set to PMID: 37714437
Phenotypes for gene: PLCG2 were set to Susceptibility to herpes virus
Review for gene: PLCG2 was set to GREEN
Added comment: Patients from two unrelated nonconsanguineous families with PLCG2 haploinsufficiency, characterized by herpesvirus infections and reduced NK cell killing. A mouse model of haploinsufficiency was validated by comparing wildtype (Plcg2+/+) and Plcg2+/- mice, NK cell maturation was increased in Plcg2+/- mice, NK1.1-induced calcium flux was attenuated in Plcg2+/- NK cells, NK cell killing of RMA-S target cells was inhibited in Plcg2+/- mice
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5487 TTC37 Zornitza Stark Marked gene: TTC37 as ready
Intellectual disability syndromic and non-syndromic v0.5487 TTC37 Zornitza Stark Gene: ttc37 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5487 TTC37 Zornitza Stark Phenotypes for gene: TTC37 were changed from to trichohepatoenteric syndrome 1 MONDO:0024541
Intellectual disability syndromic and non-syndromic v0.5486 TTC37 Zornitza Stark Publications for gene: TTC37 were set to
Intellectual disability syndromic and non-syndromic v0.5485 TTC37 Zornitza Stark Mode of inheritance for gene: TTC37 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5484 TTC37 Zornitza Stark Mode of inheritance for gene: TTC37 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5484 NCKAP1 Ain Roesley Phenotypes for gene: NCKAP1 were changed from Neurodevelopmental disorder (MONDO#0700092)​​​​​​​, NCKAP1-related to Neurodevelopmental disorder (MONDO#0700092)​​​​​​​, NCKAP1-related
Intellectual disability syndromic and non-syndromic v0.5483 NCKAP1 Ain Roesley Phenotypes for gene: NCKAP1 were changed from Intellectual disability; autism to Neurodevelopmental disorder (MONDO#0700092)​​​​​​​, NCKAP1-related
Mendeliome v1.1216 NCKAP1 Ain Roesley Phenotypes for gene: NCKAP1 were changed from Intellectual disability; autism to Neurodevelopmental disorder (MONDO#0700092)​​​​​​​, NCKAP1-related
Autism v0.192 NCKAP1 Ain Roesley Phenotypes for gene: NCKAP1 were changed from Intellectual disability; autism to Neurodevelopmental disorder (MONDO#0700092)​​​​​​​, NCKAP1-related
Fetal anomalies v1.148 PPP1R13L Zornitza Stark Phenotypes for gene: PPP1R13L were changed from Multiple congenital anomalies/dysmorphic syndrome, MONDO:0019042 - PPP1R13L-related; Dilated cardiomyopathy, onset in infancy; Cleft lip and palate to Arrhythmogenic cardiomyopathy with or without ectodermal abnormalities, MIM#620519
Clefting disorders v0.242 PPP1R13L Zornitza Stark Phenotypes for gene: PPP1R13L were changed from Multiple congenital anomalies/dysmorphic syndrome, MONDO:0019042 - PPP1R13L-related; Dilated cardiomyopathy, onset in infancy; Cleft lip and palate to Arrhythmogenic cardiomyopathy with or without ectodermal abnormalities, MIM#620519
Clefting disorders v0.241 PPP1R13L Zornitza Stark edited their review of gene: PPP1R13L: Changed phenotypes: Arrhythmogenic cardiomyopathy with or without ectodermal abnormalities, MIM#620519
Cardiomyopathy_Paediatric v0.170 PPP1R13L Zornitza Stark Phenotypes for gene: PPP1R13L were changed from Multiple congenital anomalies/dysmorphic syndrome, MONDO:0019042 - PPP1R13L-related; Dilated cardiomyopathy, onset in infancy to Arrhythmogenic cardiomyopathy with or without ectodermal abnormalities, MIM#620519
Cardiomyopathy_Paediatric v0.169 PPP1R13L Zornitza Stark edited their review of gene: PPP1R13L: Changed phenotypes: Arrhythmogenic cardiomyopathy with or without ectodermal abnormalities, MIM#620519
Mendeliome v1.1215 PPP1R13L Zornitza Stark Phenotypes for gene: PPP1R13L were changed from Multiple congenital anomalies/dysmorphic syndrome, MONDO:0019042 - PPP1R13L-related; Dilated cardiomyopathy, onset in infancy to Arrhythmogenic cardiomyopathy with or without ectodermal abnormalities, MIM#620519
Mendeliome v1.1214 PPP1R13L Zornitza Stark edited their review of gene: PPP1R13L: Changed phenotypes: Arrhythmogenic cardiomyopathy with or without ectodermal abnormalities, MIM#620519
Skeletal Dysplasia_Fetal v0.210 SP7 Zornitza Stark Marked gene: SP7 as ready
Skeletal Dysplasia_Fetal v0.210 SP7 Zornitza Stark Gene: sp7 has been classified as Red List (Low Evidence).
Skeletal Dysplasia_Fetal v0.210 SP7 Zornitza Stark Phenotypes for gene: SP7 were changed from to Osteogenesis imperfecta, type XII, MIM# 613849
Skeletal Dysplasia_Fetal v0.209 SP7 Zornitza Stark Mode of inheritance for gene: SP7 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Skeletal Dysplasia_Fetal v0.208 SP7 Zornitza Stark Classified gene: SP7 as Red List (low evidence)
Skeletal Dysplasia_Fetal v0.208 SP7 Zornitza Stark Gene: sp7 has been classified as Red List (Low Evidence).
Skeletal Dysplasia_Fetal v0.207 SERPINF1 Zornitza Stark Marked gene: SERPINF1 as ready
Skeletal Dysplasia_Fetal v0.207 SERPINF1 Zornitza Stark Gene: serpinf1 has been classified as Red List (Low Evidence).
Skeletal Dysplasia_Fetal v0.207 SERPINF1 Zornitza Stark Classified gene: SERPINF1 as Red List (low evidence)
Skeletal Dysplasia_Fetal v0.207 SERPINF1 Zornitza Stark Gene: serpinf1 has been classified as Red List (Low Evidence).
Fetal anomalies v1.147 GNPNAT1 Zornitza Stark Marked gene: GNPNAT1 as ready
Fetal anomalies v1.147 GNPNAT1 Zornitza Stark Gene: gnpnat1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.147 GNPNAT1 Zornitza Stark Classified gene: GNPNAT1 as Amber List (moderate evidence)
Fetal anomalies v1.147 GNPNAT1 Zornitza Stark Gene: gnpnat1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.146 GNPNAT1 Zornitza Stark gene: GNPNAT1 was added
gene: GNPNAT1 was added to Fetal anomalies. Sources: Expert Review
Mode of inheritance for gene: GNPNAT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GNPNAT1 were set to 36097642; 35427807; 32591345
Phenotypes for gene: GNPNAT1 were set to Rhizomelic dysplasia, Ain-Naz type, MIM#619598
Review for gene: GNPNAT1 was set to AMBER
Added comment: 3 unrelated families reported with a skeletal dysplasia characterised by severe short stature and rhizomelic shortening. No antenatal features reported. The parents in PMID 36097642 had a medical termination of pregnancy at 4 months gestation for a fetus with skeletal anomalies - not genotyped.
Sources: Expert Review
Liverome Superpanel v1.1 Bryony Thompson Panel status changed from internal to public
Liverome Superpanel v1.0 Bryony Thompson Added Panel Liverome Superpanel
Set list of related panels to Abnormality of the liver; HP:0001392
Set child panels to: Liver Failure_Paediatric; Polycystic liver disease; Cholestasis; Porphyria
Set panel types to: Melbourne Genomics; Royal Melbourne Hospital
Genetic Epilepsy v0.1920 DEPDC5 Zornitza Stark Phenotypes for gene: DEPDC5 were changed from Epilepsy, familial focal, with variable foci 1 MIM#604364; Neurodevelopmental disorder, DEPDC5-related, MONDO:0700092 to Epilepsy, familial focal, with variable foci 1 MIM#604364; Developmental and epileptic encephalopathy 111, MIM# 620504
Mendeliome v1.1214 DEPDC5 Zornitza Stark Phenotypes for gene: DEPDC5 were changed from Epilepsy, familial focal, with variable foci 1, MIM#604364 to Epilepsy, familial focal, with variable foci 1, MIM#604364; Developmental and epileptic encephalopathy 111, MIM# 620504
Mendeliome v1.1213 CELA3B Zornitza Stark Phenotypes for gene: CELA3B were changed from Chronic pancreatitis to Chronic pancreatitis, MONDO:0008185, CELA3B-related
Mendeliome v1.1212 CDK5R1 Zornitza Stark Phenotypes for gene: CDK5R1 were changed from Intellectual disability; autism to Neurodevelopmental disorder, MONDO:0700092, CDK5R1-related
Mendeliome v1.1211 CDK5R1 Zornitza Stark edited their review of gene: CDK5R1: Changed phenotypes: Neurodevelopmental disorder, MONDO:0700092, CDK5R1-related
Mendeliome v1.1211 ASTN2 Zornitza Stark Phenotypes for gene: ASTN2 were changed from Intellectual disability to Neurodevelopmental disorder, MONDO:0700092, ASTN2-related
Mendeliome v1.1210 ASTN2 Zornitza Stark Publications for gene: ASTN2 were set to 28940097
Mendeliome v1.1209 CBY1 Zornitza Stark Phenotypes for gene: CBY1 were changed from intellectual disability; cerebellar ataxia; molar tooth sign; polydactyly; Joubert syndrome to Joubert syndrome, MONDO:0018772, CBY1-related
Mendeliome v1.1208 CAPZA2 Zornitza Stark Phenotypes for gene: CAPZA2 were changed from intellectual disability to Neurodevelopmental disorder, MONDO:0700092, CAPZA2-related
Mendeliome v1.1207 CACNB1 Zornitza Stark Phenotypes for gene: CACNB1 were changed from Malignant hyperthermia susceptibility to Malignant hyperthermia susceptibility, MONDO:0800188, CACNB1-related
Mendeliome v1.1206 CACNB1 Zornitza Stark edited their review of gene: CACNB1: Changed rating: RED; Changed phenotypes: Malignant hyperthermia susceptibility, MONDO:0800188, CACNB1-related
Mendeliome v1.1206 C1orf194 Zornitza Stark Phenotypes for gene: C1orf194 were changed from Charcot-Marie-Tooth disease, intermediate or demyelinating to Charcot-Marie-Tooth disease, intermediate or demyelinating, MONDO:0015626, C1orf194-related
Mendeliome v1.1205 C1orf194 Zornitza Stark edited their review of gene: C1orf194: Changed rating: AMBER; Changed phenotypes: Charcot-Marie-Tooth disease, intermediate or demyelinating, MONDO:0015626, C1orf194; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5482 BLOC1S1 Zornitza Stark Phenotypes for gene: BLOC1S1 were changed from severe intellectual disability; severe global developmental delay; epilepsy to Neurodevelopmental disorder, MONDO:0700092, BLOC1S1-related
Intellectual disability syndromic and non-syndromic v0.5481 BLOC1S1 Zornitza Stark edited their review of gene: BLOC1S1: Changed phenotypes: Neurodevelopmental disorder, MONDO:0700092, BLOC1S1-related
Mendeliome v1.1205 BLOC1S1 Zornitza Stark Phenotypes for gene: BLOC1S1 were changed from severe intellectual disability; severe global developmental delay; epilepsy to Neurodevelopmental disorder, MONDO:0700092, BLOC1S1-related
Mendeliome v1.1204 BLOC1S1 Zornitza Stark edited their review of gene: BLOC1S1: Changed phenotypes: Neurodevelopmental disorder, MONDO:0700092, BLOC1S1-related
Mendeliome v1.1204 BET1 Zornitza Stark Phenotypes for gene: BET1 were changed from Muscular dystrophy; Epilepsy to Muscular dystrophy, MONDO:0019950, BET1-related; Epilepsy
Mendeliome v1.1203 BCL9L Zornitza Stark Phenotypes for gene: BCL9L were changed from Heterotaxy; Congenital Heart Disease to Heterotaxy syndrome, MONDO:0018677, BCL9L-related
Mendeliome v1.1202 BCL9L Zornitza Stark edited their review of gene: BCL9L: Changed phenotypes: Heterotaxy syndrome, MONDO:0018677, BCL9L
Mendeliome v1.1202 B3GNT2 Zornitza Stark Phenotypes for gene: B3GNT2 were changed from Muscular dystrophy-dystroglycanopathy to Muscular dystrophy-dystroglycanopathy, MONDO:0018276, B3GNT2-related
Mendeliome v1.1201 B3GNT2 Zornitza Stark edited their review of gene: B3GNT2: Changed phenotypes: Muscular dystrophy-dystroglycanopathy, MONDO:0018276, B3GNT2-related
Mendeliome v1.1201 AXL Zornitza Stark Phenotypes for gene: AXL were changed from Kallman syndrome; normosmic idiopathic hypogonadotropic hypogonadism to Kallman syndrome, MONDO:0018800, AXL-related; normosmic idiopathic hypogonadotropic hypogonadism
Mendeliome v1.1200 ATXN2L Zornitza Stark Phenotypes for gene: ATXN2L were changed from macrocephaly; intellectual disability to Neurodevelopmental disorder, MONDO:0700092, ATXN2L-related
Mendeliome v1.1199 ATRIP Zornitza Stark Phenotypes for gene: ATRIP were changed from Seckel Syndrome to Seckel Syndrome, MONDO:0019342, ATRIP-related
Mendeliome v1.1198 ATP2B4 Zornitza Stark Phenotypes for gene: ATP2B4 were changed from Hereditary spastic paraplegia to Hereditary spastic paraplegia, MONDO:0019064, ATP2B4-related
Intellectual disability syndromic and non-syndromic v0.5481 ASTN2 Zornitza Stark Marked gene: ASTN2 as ready
Intellectual disability syndromic and non-syndromic v0.5481 ASTN2 Zornitza Stark Gene: astn2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5481 ASTN2 Zornitza Stark Classified gene: ASTN2 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.5481 ASTN2 Zornitza Stark Gene: astn2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1197 ASTN2 Zornitza Stark Mode of inheritance for gene: ASTN2 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5480 ASTN2 Zornitza Stark gene: ASTN2 was added
gene: ASTN2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: ASTN2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: ASTN2 were set to 28940097; 34412080; 27138430
Phenotypes for gene: ASTN2 were set to Neurodevelopmental disorder, MONDO:0700092, ASTN2-related
Review for gene: ASTN2 was set to AMBER
Added comment: Candidate gene reported by Anazi et al; rare CNVs also reported; other circumstantial evidence.
Sources: Literature
Mendeliome v1.1196 ASTN2 Zornitza Stark edited their review of gene: ASTN2: Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.1196 ASTN2 Zornitza Stark edited their review of gene: ASTN2: Changed publications: 28940097, 34412080, 27138430
Mendeliome v1.1196 ASTN2 Zornitza Stark edited their review of gene: ASTN2: Added comment: Rare CNVs also reported.; Changed publications: 28940097, 34412080
Mendeliome v1.1196 ASTN2 Zornitza Stark edited their review of gene: ASTN2: Changed phenotypes: Neurodevelopmental disorder, MONDO:0700092, ASTN2-related
Mendeliome v1.1196 ASTN1 Zornitza Stark Phenotypes for gene: ASTN1 were changed from Polymicrogyria; hypoplastic corpus callosum to Cerebral malformation, MONDO:0016054, ASTN1-related
Mendeliome v1.1195 ASTN1 Zornitza Stark edited their review of gene: ASTN1: Changed phenotypes: Cerebral malformation, MONDO:0016054, ASTN1-related
Intellectual disability syndromic and non-syndromic v0.5479 TTC37 Kaitlyn Dianna Weldon reviewed gene: TTC37: Rating: GREEN; Mode of pathogenicity: None; Publications: 29334452; Phenotypes: trichohepatoenteric syndrome 1 MONDO:0024541; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.26 GYG1 Bryony Thompson Marked gene: GYG1 as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.26 GYG1 Bryony Thompson Gene: gyg1 has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.26 GYG1 Bryony Thompson Classified gene: GYG1 as Green List (high evidence)
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.26 GYG1 Bryony Thompson Gene: gyg1 has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.25 GYG1 Bryony Thompson gene: GYG1 was added
gene: GYG1 was added to Limb-Girdle Muscular Dystrophy and Distal Myopathy. Sources: Literature
Mode of inheritance for gene: GYG1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GYG1 were set to 29422440; 32477874; 32528171
Phenotypes for gene: GYG1 were set to Polyglucosan body myopathy 2, MIM# 616199; Glycogen storage disease XV , MIM# 613507
Review for gene: GYG1 was set to GREEN
gene: GYG1 was marked as current diagnostic
Added comment: Limb-girdle muscle weakness can be a feature of this myopathy.
Sources: Literature
Aortopathy_Connective Tissue Disorders v1.79 ARIH1 Zornitza Stark Phenotypes for gene: ARIH1 were changed from Thoracic aortic aneurysm to Thoracic aortic aneurysm, MONDO:0005396, ARIH1-related
Mendeliome v1.1195 ARIH1 Zornitza Stark Phenotypes for gene: ARIH1 were changed from Thoracic aortic aneurysm to Thoracic aortic aneurysm, MONDO:0005396, ARIH1-related
Fetal anomalies v1.145 ARHGAP29 Zornitza Stark Phenotypes for gene: ARHGAP29 were changed from Cleft palate; cleft lip with or without cleft palate to Clefting disorder, MONDO:0000358, ARHGAP29-related
Clefting disorders v0.241 ARHGAP29 Zornitza Stark Phenotypes for gene: ARHGAP29 were changed from cleft lip with or without cleft palate; Cleft palate to Clefting disorder, MONDO:0000358, ARHGAP29-related
Mendeliome v1.1194 ARHGAP29 Zornitza Stark Phenotypes for gene: ARHGAP29 were changed from Cleft palate; cleft lip with or without cleft palate to Clefting disorder, MONDO:0000358, ARHGAP29-related
Mendeliome v1.1193 ARHGAP29 Zornitza Stark edited their review of gene: ARHGAP29: Changed phenotypes: Clefting disorder, MONDO:0000358, ARHGAP29-related
Proteinuria v0.221 ARHGAP24 Zornitza Stark Phenotypes for gene: ARHGAP24 were changed from FSGS to FSGS, MONDO:0005363, ARHGAP24-related
Proteinuria v0.220 ARHGAP24 Zornitza Stark edited their review of gene: ARHGAP24: Changed phenotypes: FSGS, MONDO:0005363, ARHGAP24-related
Mendeliome v1.1193 ARHGAP24 Zornitza Stark Phenotypes for gene: ARHGAP24 were changed from FSGS to FSGS, MONDO:0005363, ARHGAP24-related
Mendeliome v1.1192 ARHGAP24 Zornitza Stark edited their review of gene: ARHGAP24: Changed phenotypes: FSGS, MONDO:0005363, ARHGAP24-related
Dystonia - isolated/combined v1.36 ARFGEF3 Zornitza Stark Phenotypes for gene: ARFGEF3 were changed from Dystonia to Dystonia, MONDO:0044807, ARFGEF3-related
Mendeliome v1.1192 ARFGEF3 Zornitza Stark Phenotypes for gene: ARFGEF3 were changed from Dystonia to Dystonia, MONDO:0044807, ARFGEF3-related
Mendeliome v1.1191 ARF3 Zornitza Stark Phenotypes for gene: ARF3 were changed from Global developmental delay; Intellectual disability; Seizures; Morphological abnormality of the central nervous system to Neurodevelopmental disorder, MONDO:0700092, ARF3-related
Lymphoedema_nonsyndromic v0.34 ARAP3 Zornitza Stark Phenotypes for gene: ARAP3 were changed from Lymphoedema to Lymphoedema, MONDO:0019297, ARAP3-related
Lymphoedema_nonsyndromic v0.33 ARAP3 Zornitza Stark edited their review of gene: ARAP3: Changed phenotypes: Lymphoedema, MONDO:0019297, ARAP3-related
Mendeliome v1.1190 ARAP3 Zornitza Stark Phenotypes for gene: ARAP3 were changed from Lymphoedema to Lymphoedema, MONDO:0019297, ARAP3-related
Mendeliome v1.1189 ARAP3 Zornitza Stark edited their review of gene: ARAP3: Changed phenotypes: Lymphoedema, MONDO:0019297, ARAP3-related
Intellectual disability syndromic and non-syndromic v0.5479 MCCC1 Bryony Thompson Marked gene: MCCC1 as ready
Intellectual disability syndromic and non-syndromic v0.5479 MCCC1 Bryony Thompson Gene: mccc1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5479 MCCC1 Bryony Thompson Phenotypes for gene: MCCC1 were changed from to 3-Methylcrotonyl-CoA carboxylase 1 deficiency MIM#210200; Organic acidurias
Mendeliome v1.1189 MCCC1 Bryony Thompson Publications for gene: MCCC1 were set to 27604308; 11170888; 31730530
Intellectual disability syndromic and non-syndromic v0.5478 MCCC1 Bryony Thompson Publications for gene: MCCC1 were set to
Aminoacidopathy v1.5 MCCC1 Bryony Thompson Publications for gene: MCCC1 were set to 29152456; 31730530; 27604308; 11170888
Miscellaneous Metabolic Disorders v1.31 MCCC1 Bryony Thompson Publications for gene: MCCC1 were set to 27604308; 11170888
Miscellaneous Metabolic Disorders v1.30 MCCC1 Bryony Thompson reviewed gene: MCCC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 36822454, 31730530; Phenotypes: 3-Methylcrotonyl-CoA carboxylase 1 deficiency MIM#210200, Organic acidurias; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5477 MCCC1 Bryony Thompson Mode of inheritance for gene: MCCC1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Aminoacidopathy v1.4 MCCC1 Bryony Thompson reviewed gene: MCCC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 36822454, 31730530; Phenotypes: 3-Methylcrotonyl-CoA carboxylase 1 deficiency MIM#210200, Organic acidurias; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5476 MCCC1 Bryony Thompson Classified gene: MCCC1 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.5476 MCCC1 Bryony Thompson Gene: mccc1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5475 MCCC1 Bryony Thompson reviewed gene: MCCC1: Rating: AMBER; Mode of pathogenicity: None; Publications: 36822454, 31730530; Phenotypes: 3-Methylcrotonyl-CoA carboxylase 1 deficiency MIM#210200, Organic acidurias; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1188 MCCC1 Bryony Thompson reviewed gene: MCCC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 36822454, 31730530; Phenotypes: 3-Methylcrotonyl-CoA carboxylase 1 deficiency MIM#210200, Organic acidurias; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Aminoacidopathy v1.4 MCCC1 Bryony Thompson Deleted their review
Miscellaneous Metabolic Disorders v1.30 MCCC1 Bryony Thompson Deleted their review
Mendeliome v1.1188 MCCC1 Bryony Thompson Deleted their review
Mendeliome v1.1188 AP1B1 Zornitza Stark Phenotypes for gene: AP1B1 were changed from Intellectual disability; enteropathy; deafness; ichthyosis; keratoderma to Keratitis-ichthyosis-deafness syndrome, autosomal recessive, MIM# 242150
Mendeliome v1.1187 AP1B1 Zornitza Stark edited their review of gene: AP1B1: Changed phenotypes: Keratitis-ichthyosis-deafness syndrome, autosomal recessive, MIM# 242150
Mendeliome v1.1187 ANKZF1 Zornitza Stark Phenotypes for gene: ANKZF1 were changed from Infantile-onset inflammatory bowel disease to Infantile-onset inflammatory bowel disease, MONDO:0005265, ANKZF1-related
Inflammatory bowel disease v0.109 ANKZF1 Zornitza Stark Phenotypes for gene: ANKZF1 were changed from Infantile-onset inflammatory bowel disease to Infantile-onset inflammatory bowel disease, MONDO:0005265, ANKZF1-related
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.315 ANKRD31 Zornitza Stark Phenotypes for gene: ANKRD31 were changed from Premature ovarian failure to Premature ovarian failure, MONDO:0019852, ANKDR31-related
Mendeliome v1.1186 ANKRD31 Zornitza Stark Phenotypes for gene: ANKRD31 were changed from Premature ovarian failure to Premature ovarian failure, MONDO:0019852, ANKRD31-related
Mendeliome v1.1185 AMBRA1 Zornitza Stark Phenotypes for gene: AMBRA1 were changed from Neural tube defects to Neural tube defects, susceptibility to, MONDO:0020705, AMBRA1-related
Mendeliome v1.1184 ALPI Zornitza Stark Phenotypes for gene: ALPI were changed from Inflammatory bowel disease to Inflammatory bowel disease, MONDO:0005265, ALPI-related
Mendeliome v1.1183 ALPI Zornitza Stark edited their review of gene: ALPI: Changed phenotypes: Inflammatory bowel disease, MONDO:0005265, ALPI-related
Inflammatory bowel disease v0.108 ALPI Zornitza Stark Phenotypes for gene: ALPI were changed from Inflammatory bowel disease to Inflammatory bowel disease, MONDO:0005265, ALPI-related
Inflammatory bowel disease v0.107 ALPI Zornitza Stark edited their review of gene: ALPI: Changed phenotypes: Inflammatory bowel disease, MONDO:0005265, ALPI-related
Genetic Epilepsy v0.1919 ALG10 Zornitza Stark Phenotypes for gene: ALG10 were changed from Progressive myoclonus epilepsy; CDG to Congenital disorder of glycosylation, MONDO:0015286, ALG10-related
Genetic Epilepsy v0.1918 ALG10 Zornitza Stark edited their review of gene: ALG10: Changed phenotypes: Congenital disorder of glycosylation, MONDO:0015286, ALG10-related
Congenital Disorders of Glycosylation v1.36 ALG10 Zornitza Stark Phenotypes for gene: ALG10 were changed from Progressive myoclonus epilepsy; CDG to Congenital disorder of glycosylation, MONDO:0015286, ALG10-related
Mendeliome v1.1183 ALG10 Zornitza Stark Phenotypes for gene: ALG10 were changed from Progressive myoclonus epilepsy; CDG to Congenital disorder of glycosylation, MONDO:0015286, ALG10-related
Mendeliome v1.1182 ALG10 Zornitza Stark edited their review of gene: ALG10: Changed phenotypes: Congenital disorder of glycosylation, MONDO:0015286, ALG10-related
Mendeliome v1.1182 AKR1E2 Zornitza Stark Phenotypes for gene: AKR1E2 were changed from congenital cataracts to Cataract, MONDO:0005129, AKR1E2-related
Mendeliome v1.1181 AKR1E2 Zornitza Stark edited their review of gene: AKR1E2: Changed phenotypes: Cataract, MONDO:0005129, AKR1E2-related
Cataract v0.357 AKR1E2 Zornitza Stark Phenotypes for gene: AKR1E2 were changed from congenital cararact to Cataract, MONDO:0005129, AKR1E2-related
Cataract v0.356 AKR1E2 Zornitza Stark reviewed gene: AKR1E2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Cataract, MONDO:0005129, AKR1E2-related; Mode of inheritance: None
Mendeliome v1.1181 AKNA Zornitza Stark Phenotypes for gene: AKNA were changed from Primary ciliary dyskinesia to Primary ciliary dyskinesia, MONDO:0016575, AKNA-related
Mendeliome v1.1180 AKNA Zornitza Stark reviewed gene: AKNA: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Primary ciliary dyskinesia, MONDO:0016575, AKNA-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ciliary Dyskinesia v1.35 AKNA Zornitza Stark Phenotypes for gene: AKNA were changed from Primary ciliary dyskinesia to Primary ciliary dyskinesia, MONDO:0016575, AKNA-related
Ciliary Dyskinesia v1.34 AKNA Zornitza Stark edited their review of gene: AKNA: Changed phenotypes: Primary ciliary dyskinesia, MONDO:0016575, AKNA-related
Intellectual disability syndromic and non-syndromic v0.5475 AKAP6 Zornitza Stark Phenotypes for gene: AKAP6 were changed from Intellectual disability to Neurodevelopmental disorder, MONDO:0700092, AKAP6-related
Intellectual disability syndromic and non-syndromic v0.5474 AKAP6 Zornitza Stark edited their review of gene: AKAP6: Changed phenotypes: Neurodevelopmental disorder, MONDO:0700092, AKAP6-related
Mendeliome v1.1180 AKAP6 Zornitza Stark Phenotypes for gene: AKAP6 were changed from Intellectual disability to Neurodevelopmental disorder, MONDO:0700092, AKAP6-related
Mendeliome v1.1179 AKAP6 Zornitza Stark edited their review of gene: AKAP6: Changed phenotypes: Neurodevelopmental disorder, MONDO:0700092, AKAP6-related
Mendeliome v1.1179 AGO3 Zornitza Stark Phenotypes for gene: AGO3 were changed from Intellectual disability to Neurodevelopmental disorder, MONDO:0700092, AGO3-related
Microcephaly v1.231 AGMO Zornitza Stark Phenotypes for gene: AGMO were changed from microcephaly; intellectual disability; epilepsy to Neurodevelopmental disorder, MONDO:0700092, AGMO-related
Genetic Epilepsy v0.1918 AGMO Zornitza Stark Phenotypes for gene: AGMO were changed from microcephaly; intellectual disability; epilepsy to Neurodevelopmental disorder, MONDO:0700092, AGMO-related
Intellectual disability syndromic and non-syndromic v0.5474 AGMO Zornitza Stark Phenotypes for gene: AGMO were changed from microcephaly; intellectual disability; epilepsy to Neurodevelopmental disorder, MONDO:0700092, AGMO-related
Mendeliome v1.1178 AGMO Zornitza Stark Phenotypes for gene: AGMO were changed from microcephaly; intellectual disability; epilepsy to Neurodevelopmental disorder, MONDO:0700092, AGMO-related
Mendeliome v1.1177 AGMO Zornitza Stark reviewed gene: AGMO: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, AGMO-related; Mode of inheritance: None
Intellectual disability syndromic and non-syndromic v0.5473 ACTL6A Zornitza Stark Phenotypes for gene: ACTL6A were changed from Intellectual disability to Neurodevelopmental disorder, MONDO:0700092, ACTL6A-related
Intellectual disability syndromic and non-syndromic v0.5472 ACTL6A Zornitza Stark edited their review of gene: ACTL6A: Changed phenotypes: Neurodevelopmental disorder, MONDO:0700092, ACTL6A-related
Mendeliome v1.1177 ACTL6A Zornitza Stark Phenotypes for gene: ACTL6A were changed from Intellectual disability to Neurodevelopmental disorder, MONDO:0700092, ACTL6A-related
Mendeliome v1.1176 ACTL6A Zornitza Stark edited their review of gene: ACTL6A: Changed phenotypes: Neurodevelopmental disorder, MONDO:0700092, ACTL6A-related
Mendeliome v1.1176 ACER3 Zornitza Stark Classified gene: ACER3 as Green List (high evidence)
Mendeliome v1.1176 ACER3 Zornitza Stark Gene: acer3 has been classified as Green List (High Evidence).
Mendeliome v1.1175 ACADL Zornitza Stark Phenotypes for gene: ACADL were changed from Pulmonary surfactant dysfunction to Hereditary pulmonary alveoral proteinosis, MONDO:0012580, ACADL-related
Mendeliome v1.1174 ACADL Zornitza Stark edited their review of gene: ACADL: Changed phenotypes: Hereditary pulmonary alveoral proteinosis, MONDO:0012580, ACADL-related
Mendeliome v1.1174 SEMA3E Zornitza Stark Publications for gene: SEMA3E were set to 15235037; 31691538; 31464029
Paroxysmal Dyskinesia v0.125 ABAT Zornitza Stark Marked gene: ABAT as ready
Paroxysmal Dyskinesia v0.125 ABAT Zornitza Stark Gene: abat has been classified as Amber List (Moderate Evidence).
Paroxysmal Dyskinesia v0.125 ABAT Zornitza Stark Phenotypes for gene: ABAT were changed from intellectual disability; autism; DEE; epilepsy; paroxysmal dyskinesia to GABA-transaminase deficiency, MIM# 613163; intellectual disability; autism; DEE; epilepsy; paroxysmal dyskinesia
Paroxysmal Dyskinesia v0.124 ABAT Zornitza Stark Classified gene: ABAT as Amber List (moderate evidence)
Paroxysmal Dyskinesia v0.124 ABAT Zornitza Stark Gene: abat has been classified as Amber List (Moderate Evidence).
Paroxysmal Dyskinesia v0.123 PDE2A Zornitza Stark Publications for gene: PDE2A were set to 32467598; 32196122; 29392776
Paroxysmal Dyskinesia v0.122 XPR1 Zornitza Stark Marked gene: XPR1 as ready
Paroxysmal Dyskinesia v0.122 XPR1 Zornitza Stark Gene: xpr1 has been classified as Amber List (Moderate Evidence).
Paroxysmal Dyskinesia v0.122 XPR1 Zornitza Stark Phenotypes for gene: XPR1 were changed from brain calcification; basal ganglia calcification; paroxysmal dyskinesia; epilepsy; DEE to Basal ganglia calcification, idiopathic, 6, MIM# 616413; brain calcification; basal ganglia calcification; paroxysmal dyskinesia; epilepsy; DEE
Paroxysmal Dyskinesia v0.121 XPR1 Zornitza Stark Classified gene: XPR1 as Amber List (moderate evidence)
Paroxysmal Dyskinesia v0.121 XPR1 Zornitza Stark Gene: xpr1 has been classified as Amber List (Moderate Evidence).
Paroxysmal Dyskinesia v0.120 CLDN5 Zornitza Stark Marked gene: CLDN5 as ready
Paroxysmal Dyskinesia v0.120 CLDN5 Zornitza Stark Gene: cldn5 has been classified as Green List (High Evidence).
Paroxysmal Dyskinesia v0.120 CLDN5 Zornitza Stark Classified gene: CLDN5 as Green List (high evidence)
Paroxysmal Dyskinesia v0.120 CLDN5 Zornitza Stark Gene: cldn5 has been classified as Green List (High Evidence).
Paroxysmal Dyskinesia v0.119 CLDN5 Zornitza Stark Phenotypes for gene: CLDN5 were changed from familial migraine; alternating hemiplegia; hemiplegic migraine; brain calcification; acquired microcephaly; epilepsy to Syndromic disorder, MONDO:0002254, CLDN5-related; familial migraine; alternating hemiplegia; hemiplegic migraine; brain calcification; acquired microcephaly; epilepsy
Paroxysmal Dyskinesia v0.119 CLDN5 Zornitza Stark Classified gene: CLDN5 as Green List (high evidence)
Paroxysmal Dyskinesia v0.119 CLDN5 Zornitza Stark Gene: cldn5 has been classified as Green List (High Evidence).
Paroxysmal Dyskinesia v0.118 KIAA1161 Zornitza Stark Marked gene: KIAA1161 as ready
Paroxysmal Dyskinesia v0.118 KIAA1161 Zornitza Stark Gene: kiaa1161 has been classified as Green List (High Evidence).
Paroxysmal Dyskinesia v0.118 KIAA1161 Zornitza Stark Phenotypes for gene: KIAA1161 were changed from paroxysmal dyskinesia; brain calcification; episodic hemiparesis to Basal ganglia calcification, idiopathic, 7, autosomal recessive, OMIM #618317; paroxysmal dyskinesia; brain calcification; episodic hemiparesis
Paroxysmal Dyskinesia v0.117 KIAA1161 Zornitza Stark Classified gene: KIAA1161 as Green List (high evidence)
Paroxysmal Dyskinesia v0.117 KIAA1161 Zornitza Stark Gene: kiaa1161 has been classified as Green List (High Evidence).
Paroxysmal Dyskinesia v0.116 PRKN Zornitza Stark Marked gene: PRKN as ready
Paroxysmal Dyskinesia v0.116 PRKN Zornitza Stark Gene: prkn has been classified as Amber List (Moderate Evidence).
Paroxysmal Dyskinesia v0.116 PRKN Zornitza Stark Phenotypes for gene: PRKN were changed from paroxysmal exercise induced dyskinesia; fasting induced dyskinesia; early onset parkinsonism to Parkinson disease, juvenile, type 2 MIM#600116; paroxysmal exercise induced dyskinesia; fasting induced dyskinesia; early onset parkinsonism
Paroxysmal Dyskinesia v0.115 PRKN Zornitza Stark Classified gene: PRKN as Amber List (moderate evidence)
Paroxysmal Dyskinesia v0.115 PRKN Zornitza Stark Gene: prkn has been classified as Amber List (Moderate Evidence).
Paroxysmal Dyskinesia v0.114 NBEA Zornitza Stark Marked gene: NBEA as ready
Paroxysmal Dyskinesia v0.114 NBEA Zornitza Stark Gene: nbea has been classified as Amber List (Moderate Evidence).
Paroxysmal Dyskinesia v0.114 NBEA Zornitza Stark Phenotypes for gene: NBEA were changed from Paroxysmal Kinesigenic Dyskinesia; DEE; autism; intellectual disability to Neurodevelopmental disorder with or without early-onset generalized epilepsy, MIM# 619157; Paroxysmal Kinesigenic Dyskinesia; DEE; autism; intellectual disability
Paroxysmal Dyskinesia v0.113 NBEA Zornitza Stark Classified gene: NBEA as Amber List (moderate evidence)
Paroxysmal Dyskinesia v0.113 NBEA Zornitza Stark Gene: nbea has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5472 TUBB3 Zornitza Stark Marked gene: TUBB3 as ready
Intellectual disability syndromic and non-syndromic v0.5472 TUBB3 Zornitza Stark Gene: tubb3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5472 TUBB3 Zornitza Stark Phenotypes for gene: TUBB3 were changed from to complex cortical dysplasia with other brain malformations 1 MONDO:0013541
Intellectual disability syndromic and non-syndromic v0.5471 TUBB3 Zornitza Stark Publications for gene: TUBB3 were set to
Intellectual disability syndromic and non-syndromic v0.5470 TUBB3 Zornitza Stark Mode of inheritance for gene: TUBB3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5469 TUBB4A Zornitza Stark Marked gene: TUBB4A as ready
Intellectual disability syndromic and non-syndromic v0.5469 TUBB4A Zornitza Stark Gene: tubb4a has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5469 TUBB4A Zornitza Stark Phenotypes for gene: TUBB4A were changed from to hypomyelinating leukodystrophy 6 MONDO:0012905
Intellectual disability syndromic and non-syndromic v0.5468 TUBB4A Zornitza Stark Publications for gene: TUBB4A were set to
Intellectual disability syndromic and non-syndromic v0.5467 TUBB4A Zornitza Stark Mode of inheritance for gene: TUBB4A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5466 TH Zornitza Stark Marked gene: TH as ready
Intellectual disability syndromic and non-syndromic v0.5466 TH Zornitza Stark Gene: th has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5466 TH Zornitza Stark Phenotypes for gene: TH were changed from to Segawa syndrome, recessive MIM#605407
Intellectual disability syndromic and non-syndromic v0.5465 TH Zornitza Stark Publications for gene: TH were set to
Intellectual disability syndromic and non-syndromic v0.5464 TH Zornitza Stark Mode of inheritance for gene: TH was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5463 TH Zornitza Stark Tag treatable tag was added to gene: TH.
Intellectual disability syndromic and non-syndromic v0.5463 PTEN Zornitza Stark Marked gene: PTEN as ready
Intellectual disability syndromic and non-syndromic v0.5463 PTEN Zornitza Stark Gene: pten has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5463 PTEN Zornitza Stark Phenotypes for gene: PTEN were changed from to Cowden syndrome 1 MIM#158350; Macrocephaly/autism syndrome MIM#605309
Intellectual disability syndromic and non-syndromic v0.5462 PTEN Zornitza Stark Mode of inheritance for gene: PTEN was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5461 TUBG1 Zornitza Stark Marked gene: TUBG1 as ready
Intellectual disability syndromic and non-syndromic v0.5461 TUBG1 Zornitza Stark Gene: tubg1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5461 TUBG1 Zornitza Stark Phenotypes for gene: TUBG1 were changed from to complex cortical dysplasia with other brain malformations 4 MONDO:0014171
Intellectual disability syndromic and non-syndromic v0.5460 TUBG1 Zornitza Stark Publications for gene: TUBG1 were set to
Intellectual disability syndromic and non-syndromic v0.5459 TUBG1 Zornitza Stark Mode of inheritance for gene: TUBG1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5458 TWIST1 Zornitza Stark Marked gene: TWIST1 as ready
Intellectual disability syndromic and non-syndromic v0.5458 TWIST1 Zornitza Stark Gene: twist1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5458 TWIST1 Zornitza Stark Phenotypes for gene: TWIST1 were changed from to Saethre-Chotzen syndrome MONDO:0007042
Intellectual disability syndromic and non-syndromic v0.5457 TWIST1 Zornitza Stark Publications for gene: TWIST1 were set to
Intellectual disability syndromic and non-syndromic v0.5456 TWIST1 Zornitza Stark Mode of inheritance for gene: TWIST1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5455 UBA5 Zornitza Stark Marked gene: UBA5 as ready
Intellectual disability syndromic and non-syndromic v0.5455 UBA5 Zornitza Stark Gene: uba5 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5455 UBA5 Zornitza Stark Phenotypes for gene: UBA5 were changed from to Epileptic encephalopathy, early infantile, 44 (MIM#617132)
Intellectual disability syndromic and non-syndromic v0.5454 UBA5 Zornitza Stark Publications for gene: UBA5 were set to 33811063
Intellectual disability syndromic and non-syndromic v0.5453 UBA5 Zornitza Stark Publications for gene: UBA5 were set to
Intellectual disability syndromic and non-syndromic v0.5452 UBA5 Zornitza Stark Mode of inheritance for gene: UBA5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5451 UBE3A Zornitza Stark Marked gene: UBE3A as ready
Intellectual disability syndromic and non-syndromic v0.5451 UBE3A Zornitza Stark Gene: ube3a has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5451 UBE3A Zornitza Stark Phenotypes for gene: UBE3A were changed from to Angelman syndrome MONDO:0007113
Intellectual disability syndromic and non-syndromic v0.5450 UBE3A Zornitza Stark Publications for gene: UBE3A were set to
Intellectual disability syndromic and non-syndromic v0.5449 UBE3A Zornitza Stark Mode of inheritance for gene: UBE3A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
Intellectual disability syndromic and non-syndromic v0.5448 SDHA Zornitza Stark Marked gene: SDHA as ready
Intellectual disability syndromic and non-syndromic v0.5448 SDHA Zornitza Stark Gene: sdha has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5448 SDHA Zornitza Stark Phenotypes for gene: SDHA were changed from to Mitochondrial complex II deficiency, nuclear type 1 MIM#252011
Intellectual disability syndromic and non-syndromic v0.5447 SDHA Zornitza Stark Publications for gene: SDHA were set to
Intellectual disability syndromic and non-syndromic v0.5446 SDHA Zornitza Stark Mode of inheritance for gene: SDHA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5445 VLDLR Zornitza Stark Marked gene: VLDLR as ready
Intellectual disability syndromic and non-syndromic v0.5445 VLDLR Zornitza Stark Gene: vldlr has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5445 VLDLR Zornitza Stark Phenotypes for gene: VLDLR were changed from to cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 1 MONDO:0024542
Intellectual disability syndromic and non-syndromic v0.5444 VLDLR Zornitza Stark Publications for gene: VLDLR were set to
Intellectual disability syndromic and non-syndromic v0.5443 VLDLR Zornitza Stark Mode of inheritance for gene: VLDLR was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5442 VPS13B Zornitza Stark Marked gene: VPS13B as ready
Intellectual disability syndromic and non-syndromic v0.5442 VPS13B Zornitza Stark Gene: vps13b has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5442 VPS13B Zornitza Stark Phenotypes for gene: VPS13B were changed from to Cohen syndrome MONDO:0008999
Intellectual disability syndromic and non-syndromic v0.5441 VPS13B Zornitza Stark Publications for gene: VPS13B were set to
Intellectual disability syndromic and non-syndromic v0.5440 VPS13B Zornitza Stark Mode of inheritance for gene: VPS13B was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1173 SEMA3E Lucy Spencer reviewed gene: SEMA3E: Rating: AMBER; Mode of pathogenicity: None; Publications: 15235037, 31691538, 31464029, 35628442, 32441320; Phenotypes: CHARGE syndrome MONDO:0008965, SEMA3E-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v1.144 SCAF4 Zornitza Stark Phenotypes for gene: SCAF4 were changed from Neurodevelopmental disorder MONDO#0700092, SCAF4-related to Fliedner-Zweier syndrome, MIM#620511
Fetal anomalies v1.143 SCAF4 Zornitza Stark reviewed gene: SCAF4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Fliedner-Zweier syndrome, MIM#620511; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5439 SCAF4 Zornitza Stark Phenotypes for gene: SCAF4 were changed from Mild intellectual disability; seizures; behavioral abnormalities to Fliedner-Zweier syndrome, MIM#620511
Intellectual disability syndromic and non-syndromic v0.5438 SCAF4 Zornitza Stark reviewed gene: SCAF4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Fliedner-Zweier syndrome, MIM#620511; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.1917 SCAF4 Zornitza Stark Phenotypes for gene: SCAF4 were changed from Mild intellectual disability; seizures; behavioral abnormalities to Fliedner-Zweier syndrome, MIM#620511
Genetic Epilepsy v0.1916 SCAF4 Zornitza Stark reviewed gene: SCAF4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Fliedner-Zweier syndrome, MIM#620511; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.1173 SCAF4 Zornitza Stark Phenotypes for gene: SCAF4 were changed from Mild intellectual disability; seizures; behavioral abnormalities to Fliedner-Zweier syndrome, MIM#620511
Mendeliome v1.1172 SCAF4 Zornitza Stark reviewed gene: SCAF4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Fliedner-Zweier syndrome, MIM#620511; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5438 VRK1 Zornitza Stark Marked gene: VRK1 as ready
Intellectual disability syndromic and non-syndromic v0.5438 VRK1 Zornitza Stark Gene: vrk1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5438 VRK1 Zornitza Stark Phenotypes for gene: VRK1 were changed from to pontocerebellar hypoplasia type 1A MONDO:0011866
Intellectual disability syndromic and non-syndromic v0.5437 VRK1 Zornitza Stark Publications for gene: VRK1 were set to
Intellectual disability syndromic and non-syndromic v0.5436 VRK1 Zornitza Stark Mode of inheritance for gene: VRK1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5435 WDR45 Zornitza Stark Marked gene: WDR45 as ready
Intellectual disability syndromic and non-syndromic v0.5435 WDR45 Zornitza Stark Gene: wdr45 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5435 WDR45 Zornitza Stark Phenotypes for gene: WDR45 were changed from to X-linked complex neurodevelopmental disorder MONDO:0100148; neurodegeneration with brain iron accumulation 5 MONDO:0010476
Intellectual disability syndromic and non-syndromic v0.5434 WDR45 Zornitza Stark Publications for gene: WDR45 were set to
Intellectual disability syndromic and non-syndromic v0.5433 WDR45 Zornitza Stark 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)
Intellectual disability syndromic and non-syndromic v0.5432 WDR73 Zornitza Stark Marked gene: WDR73 as ready
Intellectual disability syndromic and non-syndromic v0.5432 WDR73 Zornitza Stark Gene: wdr73 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5432 WDR73 Zornitza Stark Phenotypes for gene: WDR73 were changed from to Galloway-Mowat syndrome 1 MONDO:0033005
Intellectual disability syndromic and non-syndromic v0.5431 WDR73 Zornitza Stark Publications for gene: WDR73 were set to
Intellectual disability syndromic and non-syndromic v0.5430 WDR73 Zornitza Stark Mode of inheritance for gene: WDR73 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5429 SMAD4 Zornitza Stark Marked gene: SMAD4 as ready
Intellectual disability syndromic and non-syndromic v0.5429 SMAD4 Zornitza Stark Gene: smad4 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5429 SMAD4 Zornitza Stark Phenotypes for gene: SMAD4 were changed from to Myhre syndrome MIM#139210
Intellectual disability syndromic and non-syndromic v0.5428 SMAD4 Zornitza Stark Publications for gene: SMAD4 were set to
Intellectual disability syndromic and non-syndromic v0.5427 SMAD4 Zornitza Stark Mode of inheritance for gene: SMAD4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5426 WWOX Zornitza Stark Marked gene: WWOX as ready
Intellectual disability syndromic and non-syndromic v0.5426 WWOX Zornitza Stark Gene: wwox has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5426 WWOX Zornitza Stark Phenotypes for gene: WWOX were changed from to developmental and epileptic encephalopathy, 28 MONDO:0014533; autosomal recessive spinocerebellar ataxia 12 MONDO:0013687
Intellectual disability syndromic and non-syndromic v0.5425 WWOX Zornitza Stark Publications for gene: WWOX were set to
Intellectual disability syndromic and non-syndromic v0.5424 WWOX Zornitza Stark Mode of inheritance for gene: WWOX was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5423 XRCC4 Zornitza Stark Marked gene: XRCC4 as ready
Intellectual disability syndromic and non-syndromic v0.5423 XRCC4 Zornitza Stark Gene: xrcc4 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5423 XRCC4 Zornitza Stark Phenotypes for gene: XRCC4 were changed from to Short stature, microcephaly, and endocrine dysfunction MIM#616541, MONDO:0014686
Intellectual disability syndromic and non-syndromic v0.5422 XRCC4 Zornitza Stark Publications for gene: XRCC4 were set to
Intellectual disability syndromic and non-syndromic v0.5421 XRCC4 Zornitza Stark Mode of inheritance for gene: XRCC4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5420 TUBB2B Zornitza Stark Marked gene: TUBB2B as ready
Intellectual disability syndromic and non-syndromic v0.5420 TUBB2B Zornitza Stark Gene: tubb2b has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5420 TUBB2B Zornitza Stark Phenotypes for gene: TUBB2B were changed from to Cortical dysplasia, complex, with other brain malformations 7 MIM#610031
Intellectual disability syndromic and non-syndromic v0.5419 TUBB2B Zornitza Stark Publications for gene: TUBB2B were set to
Intellectual disability syndromic and non-syndromic v0.5418 TUBB2B Zornitza Stark Mode of inheritance for gene: TUBB2B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5417 ZDHHC9 Zornitza Stark Marked gene: ZDHHC9 as ready
Intellectual disability syndromic and non-syndromic v0.5417 ZDHHC9 Zornitza Stark Gene: zdhhc9 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5417 ZDHHC9 Zornitza Stark Phenotypes for gene: ZDHHC9 were changed from to Syndromic X-linked intellectual disability Raymond type MONDO:0010427
Intellectual disability syndromic and non-syndromic v0.5416 ZDHHC9 Zornitza Stark Publications for gene: ZDHHC9 were set to
Intellectual disability syndromic and non-syndromic v0.5415 ZDHHC9 Zornitza Stark Mode of inheritance for gene: ZDHHC9 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.5414 ZFYVE26 Zornitza Stark Marked gene: ZFYVE26 as ready
Intellectual disability syndromic and non-syndromic v0.5414 ZFYVE26 Zornitza Stark Gene: zfyve26 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5414 ZFYVE26 Zornitza Stark Phenotypes for gene: ZFYVE26 were changed from to Spastic paraplegia 15, autosomal recessive, MIM# 270700; hereditary spastic paraplegia 15, MONDO:0010044
Intellectual disability syndromic and non-syndromic v0.5413 ZFYVE26 Zornitza Stark Publications for gene: ZFYVE26 were set to
Intellectual disability syndromic and non-syndromic v0.5412 ZFYVE26 Zornitza Stark Mode of inheritance for gene: ZFYVE26 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5411 ZIC2 Zornitza Stark Marked gene: ZIC2 as ready
Intellectual disability syndromic and non-syndromic v0.5411 ZIC2 Zornitza Stark Gene: zic2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5411 ZIC2 Zornitza Stark Phenotypes for gene: ZIC2 were changed from to Holoprosencephaly 5 MONDO:0012322
Intellectual disability syndromic and non-syndromic v0.5410 ZIC2 Zornitza Stark Publications for gene: ZIC2 were set to
Intellectual disability syndromic and non-syndromic v0.5409 ZIC2 Zornitza Stark Mode of inheritance for gene: ZIC2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Leukodystrophy - adult onset v0.118 EIF2B5 Zornitza Stark Marked gene: EIF2B5 as ready
Leukodystrophy - adult onset v0.118 EIF2B5 Zornitza Stark Gene: eif2b5 has been classified as Green List (High Evidence).
Leukodystrophy - adult onset v0.118 EIF2B5 Zornitza Stark Publications for gene: EIF2B5 were set to
Leukodystrophy - adult onset v0.117 EIF2B4 Zornitza Stark Marked gene: EIF2B4 as ready
Leukodystrophy - adult onset v0.117 EIF2B4 Zornitza Stark Gene: eif2b4 has been classified as Green List (High Evidence).
Leukodystrophy - adult onset v0.117 EIF2B4 Zornitza Stark Phenotypes for gene: EIF2B4 were changed from Leukoencephalopathy with vanishing white matter, 603896 to Leukoencephalopathy with vanishing white matter, MIM#603896, MONDO:0011380
Leukodystrophy - adult onset v0.116 EIF2B4 Zornitza Stark Publications for gene: EIF2B4 were set to
Leukodystrophy - adult onset v0.115 EIF2B3 Zornitza Stark Marked gene: EIF2B3 as ready
Leukodystrophy - adult onset v0.115 EIF2B3 Zornitza Stark Gene: eif2b3 has been classified as Green List (High Evidence).
Leukodystrophy - adult onset v0.115 EIF2B3 Zornitza Stark Phenotypes for gene: EIF2B3 were changed from Leukoencephalopathy with vanishing white matter, 603896 to Leukoencephalopathy with vanishing white matter, MIM#603896, MONDO:0011380
Leukodystrophy - adult onset v0.114 EIF2B3 Zornitza Stark Publications for gene: EIF2B3 were set to
Leukodystrophy - adult onset v0.113 EIF2B2 Zornitza Stark Marked gene: EIF2B2 as ready
Leukodystrophy - adult onset v0.113 EIF2B2 Zornitza Stark Gene: eif2b2 has been classified as Green List (High Evidence).
Leukodystrophy - adult onset v0.113 EIF2B2 Zornitza Stark Phenotypes for gene: EIF2B2 were changed from Leukoencephalopathy with vanishing white matter, Ovarioleukodystrophy, 603896 to Leukoencephalopathy with vanishing white matter MONDO:0011380
Leukodystrophy - adult onset v0.112 EIF2B2 Zornitza Stark Publications for gene: EIF2B2 were set to
Leukodystrophy - adult onset v0.111 EIF2B1 Zornitza Stark Marked gene: EIF2B1 as ready
Leukodystrophy - adult onset v0.111 EIF2B1 Zornitza Stark Gene: eif2b1 has been classified as Green List (High Evidence).
Leukodystrophy - adult onset v0.111 EIF2B1 Zornitza Stark Publications for gene: EIF2B1 were set to
Leukodystrophy - adult onset v0.110 PSAP Zornitza Stark Marked gene: PSAP as ready
Leukodystrophy - adult onset v0.110 PSAP Zornitza Stark Gene: psap has been classified as Green List (High Evidence).
Leukodystrophy - adult onset v0.110 PSAP Zornitza Stark Publications for gene: PSAP were set to
Intellectual disability syndromic and non-syndromic v0.5408 TSC1 Zornitza Stark Marked gene: TSC1 as ready
Intellectual disability syndromic and non-syndromic v0.5408 TSC1 Zornitza Stark Gene: tsc1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5408 TSC1 Zornitza Stark Phenotypes for gene: TSC1 were changed from to Tuberous sclerosis MIM#191100
Intellectual disability syndromic and non-syndromic v0.5407 TSC1 Zornitza Stark Publications for gene: TSC1 were set to
Intellectual disability syndromic and non-syndromic v0.5406 TSC1 Zornitza Stark Mode of inheritance for gene: TSC1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5405 TSC2 Zornitza Stark Marked gene: TSC2 as ready
Intellectual disability syndromic and non-syndromic v0.5405 TSC2 Zornitza Stark Gene: tsc2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5405 TSC2 Zornitza Stark Phenotypes for gene: TSC2 were changed from to Tuberous sclerosis MIM#613254
Intellectual disability syndromic and non-syndromic v0.5404 TSC2 Zornitza Stark Publications for gene: TSC2 were set to
Intellectual disability syndromic and non-syndromic v0.5403 TSC2 Zornitza Stark Mode of inheritance for gene: TSC2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.1172 NR2F2 Zornitza Stark Phenotypes for gene: NR2F2 were changed from 46,XX sex reversal 5 - MIM#618901; Congenital heart defects, multiple types, 4 - MIM#615779 to Krithika Murali (Victorian Clinical Genetics Services) 46,XX sex reversal 5 - MIM#618901; Congenital heart defects, multiple types, 4 - MIM#615779 Current 46,XX sex reversal 5 - MIM#618901; Congenital heart defects, multiple types, 4 - MIM#615779 Edit; 46,XX sex reversal 5 - MIM#618901; Congenital heart defects, multiple types, 4 - MIM#615779
Mendeliome v1.1171 NR2F2 Zornitza Stark Publications for gene: NR2F2 were set to 24702954; 29478779; 31687637; 27363585; 29222010; 29663647
Mendeliome v1.1170 NR2F2 Zornitza Stark reviewed gene: NR2F2: Rating: GREEN; Mode of pathogenicity: None; Publications: 37500725; Phenotypes: Syndromic disease, MONDO:0002254, NR2F2-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Differences of Sex Development v0.283 NR2F2 Zornitza Stark Phenotypes for gene: NR2F2 were changed from 46,XX disorder of sex development (DSD) and congenital heart defects to 46XX sex reversal 5, MIM# 618901
Differences of Sex Development v0.282 NR2F2 Zornitza Stark edited their review of gene: NR2F2: Changed phenotypes: 46XX sex reversal 5, MIM# 618901
Intellectual disability syndromic and non-syndromic v0.5402 NR2F2 Zornitza Stark Marked gene: NR2F2 as ready
Intellectual disability syndromic and non-syndromic v0.5402 NR2F2 Zornitza Stark Gene: nr2f2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5402 NR2F2 Zornitza Stark Phenotypes for gene: NR2F2 were changed from mild intellectual disability; congenital heart disease; disorder of sexual differentiation; dysmorphic features to Syndromic disease, MONDO:0002254, NR2F2-related
Intellectual disability syndromic and non-syndromic v0.5401 NR2F2 Zornitza Stark Publications for gene: NR2F2 were set to 29478779; 29663647
Intellectual disability syndromic and non-syndromic v0.5400 NR2F2 Zornitza Stark Classified gene: NR2F2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5400 NR2F2 Zornitza Stark Gene: nr2f2 has been classified as Green List (High Evidence).
Mendeliome v1.1170 DBR1 Zornitza Stark Phenotypes for gene: DBR1 were changed from {Encephalitis, acute, infection (viral)-induced, susceptibility to, 11}, MIM# 619441; Viral infections of the brainstem; Ichthyosis (MONDO#0019269), DBR1-related to {Encephalitis, acute, infection (viral)-induced, susceptibility to, 11}, MIM# 619441; Viral infections of the brainstem; Xerosis and growth failure with immune and pulmonary dysfunction syndrome, MIM# 620510
Ichthyosis v1.9 DBR1 Zornitza Stark Phenotypes for gene: DBR1 were changed from Ichthyosis (MONDO#0019269), DBR1-related to Xerosis and growth failure with immune and pulmonary dysfunction syndrome, MIM# 620510
Ichthyosis v1.8 DBR1 Zornitza Stark reviewed gene: DBR1: Rating: AMBER; Mode of pathogenicity: None; Publications: 37656279; Phenotypes: Xerosis and growth failure with immune and pulmonary dysfunction syndrome, MIM# 620510; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v1.23 TRAC Zornitza Stark Marked gene: TRAC as ready
BabyScreen+ newborn screening v1.23 TRAC Zornitza Stark Gene: trac has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v1.23 TRAC Zornitza Stark gene: TRAC was added
gene: TRAC was added to BabyScreen+ newborn screening. Sources: Expert Review
founder, technically challenging tags were added to gene: TRAC.
Mode of inheritance for gene: TRAC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRAC were set to 21206088
Phenotypes for gene: TRAC were set to Immunodeficiency 7, TCR-alpha/beta deficient, MIM#615387
Review for gene: TRAC was set to RED
Added comment: Single variant reported to date in 6 patients; 2 unrelated children from consanguineous families of Pakistani descent (PMID: 21206088); 1 non-consanguineous family from North-west India (PMID: 33909184) and 1 consanguineous parents of East Indian (https://lymphosign.com/doi/10.14785/lymphosign-2022-0001)

Also note annotation issues in certain variant curation and annotation tools.
Sources: Expert Review
Mendeliome v1.1169 TRAC Zornitza Stark Tag technically challenging tag was added to gene: TRAC.
BabyScreen+ newborn screening v1.22 NCF1 Zornitza Stark Classified gene: NCF1 as Amber List (moderate evidence)
BabyScreen+ newborn screening v1.22 NCF1 Zornitza Stark Gene: ncf1 has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v1.21 NCF1 Zornitza Stark edited their review of gene: NCF1: Changed rating: AMBER
Paroxysmal Dyskinesia v0.112 ABAT Shekeeb Mohammad gene: ABAT was added
gene: ABAT was added to Paroxysmal Dyskinesia. Sources: Literature
Mode of inheritance for gene: ABAT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ABAT were set to 30617166
Phenotypes for gene: ABAT were set to intellectual disability; autism; DEE; epilepsy; paroxysmal dyskinesia
Review for gene: ABAT was set to AMBER
gene: ABAT was marked as current diagnostic
Added comment: Sources: Literature
Paroxysmal Dyskinesia v0.112 PDE2A Shekeeb Mohammad reviewed gene: PDE2A: Rating: GREEN; Mode of pathogenicity: None; Publications: 37317634; Phenotypes: paroxysmal dyskinesia, intellectual disability, drug resistant epilepsy, progressive neurological decline, chorea; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Paroxysmal Dyskinesia v0.112 XPR1 Shekeeb Mohammad gene: XPR1 was added
gene: XPR1 was added to Paroxysmal Dyskinesia. Sources: Literature
Mode of inheritance for gene: XPR1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: XPR1 were set to 33433330
Phenotypes for gene: XPR1 were set to brain calcification; basal ganglia calcification; paroxysmal dyskinesia; epilepsy; DEE
Review for gene: XPR1 was set to AMBER
gene: XPR1 was marked as current diagnostic
Added comment: Sources: Literature
Paroxysmal Dyskinesia v0.112 CLDN5 Shekeeb Mohammad gene: CLDN5 was added
gene: CLDN5 was added to Paroxysmal Dyskinesia. Sources: Literature
Mode of inheritance for gene: CLDN5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CLDN5 were set to 35714222; 36825455
Phenotypes for gene: CLDN5 were set to familial migraine; alternating hemiplegia; hemiplegic migraine; brain calcification; acquired microcephaly; epilepsy
Penetrance for gene: CLDN5 were set to Incomplete
Review for gene: CLDN5 was set to GREEN
gene: CLDN5 was marked as current diagnostic
Added comment: Sources: Literature
Paroxysmal Dyskinesia v0.112 KIAA1161 Shekeeb Mohammad gene: KIAA1161 was added
gene: KIAA1161 was added to Paroxysmal Dyskinesia. Sources: Literature
Mode of inheritance for gene: KIAA1161 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIAA1161 were set to 34346093; 34783389; 32303062
Phenotypes for gene: KIAA1161 were set to paroxysmal dyskinesia; brain calcification; episodic hemiparesis
Penetrance for gene: KIAA1161 were set to Complete
Review for gene: KIAA1161 was set to GREEN
gene: KIAA1161 was marked as current diagnostic
Added comment: Sources: Literature
Paroxysmal Dyskinesia v0.112 PRKN Shekeeb Mohammad gene: PRKN was added
gene: PRKN was added to Paroxysmal Dyskinesia. Sources: Literature
Mode of inheritance for gene: PRKN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PRKN were set to 37205242
Phenotypes for gene: PRKN were set to paroxysmal exercise induced dyskinesia; fasting induced dyskinesia; early onset parkinsonism
Penetrance for gene: PRKN were set to Incomplete
Review for gene: PRKN was set to AMBER
Added comment: Only a single report but the phenotypic description and accompanying parkinsonism make this a likely robust finding.
Sources: Literature
Paroxysmal Dyskinesia v0.112 NBEA Shekeeb Mohammad gene: NBEA was added
gene: NBEA was added to Paroxysmal Dyskinesia. Sources: Literature
Mode of inheritance for gene: NBEA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NBEA were set to 33692494
Phenotypes for gene: NBEA were set to Paroxysmal Kinesigenic Dyskinesia; DEE; autism; intellectual disability
Penetrance for gene: NBEA were set to unknown
Review for gene: NBEA was set to AMBER
Added comment: only one report and I have seen a poster from an independent group (not published yet)
Sources: Literature
BabyScreen+ newborn screening v1.21 HBA1 Zornitza Stark Tag for review was removed from gene: HBA1.
Tag treatable tag was added to gene: HBA1.
BabyScreen+ newborn screening v1.21 HBA2 Zornitza Stark Tag for review was removed from gene: HBA2.
Tag technically challenging tag was added to gene: HBA2.
BabyScreen+ newborn screening v1.21 HBA1 Zornitza Stark Tag technically challenging tag was added to gene: HBA1.
BabyScreen+ newborn screening v1.21 IKBKG Zornitza Stark Tag technically challenging tag was added to gene: IKBKG.
BabyScreen+ newborn screening v1.21 IGHM Zornitza Stark Classified gene: IGHM as Green List (high evidence)
BabyScreen+ newborn screening v1.21 IGHM Zornitza Stark Gene: ighm has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.20 IGHM Zornitza Stark changed review comment from: RefSeq annotation issues.; to: RefSeq annotation issues. Specific rescue loop built to capture variants.
BabyScreen+ newborn screening v1.20 IGHM Zornitza Stark edited their review of gene: IGHM: Changed rating: GREEN
Intellectual disability syndromic and non-syndromic v0.5399 TUBB3 Kaitlyn Dianna Weldon reviewed gene: TUBB3: Rating: GREEN; Mode of pathogenicity: None; Publications: 20829227; Phenotypes: complex cortical dysplasia with other brain malformations 1 MONDO:0013541; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5399 TUBB4A Kaitlyn Dianna Weldon reviewed gene: TUBB4A: Rating: GREEN; Mode of pathogenicity: None; Publications: 37529938, 35661708, 27538619, 24526230; Phenotypes: hypomyelinating leukodystrophy 6 MONDO:0012905, torsion dystonia 4 MONDO:0007493; Mode of inheritance: None
Intellectual disability syndromic and non-syndromic v0.5399 TH Claire Fryer-Smith reviewed gene: TH: Rating: GREEN; Mode of pathogenicity: None; Publications: 22815559, 11196107, 10585338; Phenotypes: Segawa syndrome, recessive MIM#605407; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5399 PTEN Claire Fryer-Smith reviewed gene: PTEN: Rating: GREEN; Mode of pathogenicity: None; Publications: 21194675, 1859181, 23470840; Phenotypes: Cowden syndrome 1 MIM#158350, Lhermitte-Duclos disease MIM#158350, Macrocephaly/autism syndrome MIM#605309, Prostate cancer, somatic MIM#176807; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5399 TUBG1 Kaitlyn Dianna Weldon reviewed gene: TUBG1: Rating: GREEN; Mode of pathogenicity: None; Publications: 29706637, 23603762; Phenotypes: complex cortical dysplasia with other brain malformations 4 MONDO:0014171, lissencephaly spectrum disorders MONDO:0018838; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5399 TWIST1 Kaitlyn Dianna Weldon reviewed gene: TWIST1: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301368; Phenotypes: Saethre-Chotzen syndrome MONDO:0007042; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5399 UBA5 Kaitlyn Dianna Weldon reviewed gene: UBA5: Rating: GREEN; Mode of pathogenicity: None; Publications: 33811063; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5399 UBE3A Kaitlyn Dianna Weldon reviewed gene: UBE3A: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301323; Phenotypes: Angelman syndrome MONDO:0007113; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
Intellectual disability syndromic and non-syndromic v0.5399 SDHA Claire Fryer-Smith reviewed gene: SDHA: Rating: GREEN; Mode of pathogenicity: None; Publications: 1492653, 23322652; Phenotypes: Cardiomyopathy, dilated, 1GG MIM#613642, Mitochondrial complex II deficiency, nuclear type 1 MIM#252011, Neurodegeneration with ataxia and late-onset optic atrophy MIM#619259, Paragangliomas MIM#614165; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1169 KLK11 Zornitza Stark Marked gene: KLK11 as ready
Mendeliome v1.1169 KLK11 Zornitza Stark Gene: klk11 has been classified as Green List (High Evidence).
Mendeliome v1.1169 KLK11 Zornitza Stark Classified gene: KLK11 as Green List (high evidence)
Mendeliome v1.1169 KLK11 Zornitza Stark Gene: klk11 has been classified as Green List (High Evidence).
Mendeliome v1.1168 KLK11 Zornitza Stark gene: KLK11 was added
gene: KLK11 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: KLK11 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KLK11 were set to 36689511; 37212630
Phenotypes for gene: KLK11 were set to Ichthyosis with erythrokeratoderma, MIM# 620507
Review for gene: KLK11 was set to GREEN
Added comment: Four families reported: one multiplex with variant segregating with disease in 4 affected and 4 unaffected individuals. Three additional families with de novo variants.
Sources: Literature
Ichthyosis v1.8 KLK11 Zornitza Stark Marked gene: KLK11 as ready
Ichthyosis v1.8 KLK11 Zornitza Stark Gene: klk11 has been classified as Green List (High Evidence).
Ichthyosis v1.8 KLK11 Zornitza Stark Classified gene: KLK11 as Green List (high evidence)
Ichthyosis v1.8 KLK11 Zornitza Stark Gene: klk11 has been classified as Green List (High Evidence).
Ichthyosis v1.7 KLK11 Zornitza Stark gene: KLK11 was added
gene: KLK11 was added to Ichthyosis. Sources: Literature
Mode of inheritance for gene: KLK11 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KLK11 were set to 36689511; 37212630
Phenotypes for gene: KLK11 were set to Ichthyosis with erythrokeratoderma, MIM# 620507
Review for gene: KLK11 was set to GREEN
Added comment: Four families reported: one multiplex with variant segregating with disease in 4 affected and 4 unaffected individuals. Three additional families with de novo variants.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5399 VLDLR Kaitlyn Dianna Weldon reviewed gene: VLDLR: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301729; Phenotypes: cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 1 MONDO:0024542; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5399 VPS13B Kaitlyn Dianna Weldon reviewed gene: VPS13B: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301655; Phenotypes: Cohen syndrome MONDO:0008999; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5399 VRK1 Kaitlyn Dianna Weldon reviewed gene: VRK1: Rating: GREEN; Mode of pathogenicity: None; Publications: 19646678; Phenotypes: pontocerebellar hypoplasia type 1A MONDO:0011866; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5399 WDR45 Kaitlyn Dianna Weldon reviewed gene: WDR45: Rating: GREEN; Mode of pathogenicity: None; Publications: 28211668; Phenotypes: X-linked complex neurodevelopmental disorder MONDO:0100148, neurodegeneration with brain iron accumulation 5 MONDO:0010476; 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 v0.5399 WDR73 Kaitlyn Dianna Weldon reviewed gene: WDR73: Rating: GREEN; Mode of pathogenicity: None; Publications: 26123727; Phenotypes: Galloway-Mowat syndrome 1 MONDO:0033005; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5399 SMAD4 Claire Fryer-Smith reviewed gene: SMAD4: Rating: GREEN; Mode of pathogenicity: None; Publications: 9843046, 22243968, 7296942, 8261650; Phenotypes: Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome MIM#175050, Myhre syndrome MIM#139210, Pancreatic cancer, somatic MIM#260350, Polyposis, juvenile intestinal MIM#174900; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5399 WWOX Kaitlyn Dianna Weldon reviewed gene: WWOX: Rating: GREEN; Mode of pathogenicity: None; Publications: 25411445, 24369382; Phenotypes: developmental and epileptic encephalopathy, 28 MONDO:0014533, autosomal recessive spinocerebellar ataxia 12 MONDO:0013687; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5399 XRCC4 Claire Fryer-Smith reviewed gene: XRCC4: Rating: GREEN; Mode of pathogenicity: None; Publications: 25872942, 25839420, 18695064; Phenotypes: Short stature, microcephaly, and endocrine dysfunction MIM#616541; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5399 XRCC4 Kaitlyn Dianna Weldon reviewed gene: XRCC4: Rating: GREEN; Mode of pathogenicity: None; Publications: 25728776; Phenotypes: short stature, microcephaly, and endocrine dysfunction MONDO:0014686; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5399 TUBB2B Claire Fryer-Smith reviewed gene: TUBB2B: Rating: GREEN; Mode of pathogenicity: None; Publications: 11425694, 23001566, 19465910, 22333901; Phenotypes: Cortical dysplasia, complex, with other brain malformations 7 MIM#610031; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5399 ZDHHC9 Kaitlyn Dianna Weldon reviewed gene: ZDHHC9: Rating: GREEN; Mode of pathogenicity: None; Publications: 17436253; Phenotypes: Syndromic X-linked intellectual disability Raymond type MONDO:0010427; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.5399 ZFYVE26 Kaitlyn Dianna Weldon reviewed gene: ZFYVE26: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301682; Phenotypes: hereditary spastic paraplegia 15 MONDO:0010044; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5399 ZIC2 Kaitlyn Dianna Weldon reviewed gene: ZIC2: Rating: GREEN; Mode of pathogenicity: None; Publications: 21940735; Phenotypes: holoprosencephaly 5 MONDO:0012322; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Leukodystrophy - adult onset v0.109 EIF2B5 Kaitlyn Dianna Weldon reviewed gene: EIF2B5: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301435; Phenotypes: leukoencephalopathy with vanishing white matter MONDO:0011380; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Leukodystrophy - adult onset v0.109 EIF2B4 Kaitlyn Dianna Weldon reviewed gene: EIF2B4: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301435; Phenotypes: leukoencephalopathy with vanishing white matter MONDO:0011380; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Leukodystrophy - adult onset v0.109 EIF2B3 Kaitlyn Dianna Weldon reviewed gene: EIF2B3: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301435; Phenotypes: leukoencephalopathy with vanishing white matter MONDO:0011380; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Leukodystrophy - adult onset v0.109 EIF2B2 Kaitlyn Dianna Weldon reviewed gene: EIF2B2: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301435; Phenotypes: leukoencephalopathy with vanishing white matter MONDO:0011380; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Leukodystrophy - adult onset v0.109 EIF2B1 Kaitlyn Dianna Weldon reviewed gene: EIF2B1: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301435; Phenotypes: leukoencephalopathy with vanishing white matter MONDO:0011380; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Leukodystrophy - adult onset v0.109 PSAP Kaitlyn Dianna Weldon edited their review of gene: PSAP: Added comment: This is a well established leukodystrophy gene; Changed phenotypes: metachromatic leukodystrophy due to saposin B deficiency MONDO:0009590
Leukodystrophy - adult onset v0.109 PSAP Kaitlyn Dianna Weldon reviewed gene: PSAP: Rating: GREEN; Mode of pathogenicity: None; Publications: 26462614; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Rhabdomyolysis and Metabolic Myopathy v1.1 HMBS Bryony Thompson Classified gene: HMBS as Green List (high evidence)
Rhabdomyolysis and Metabolic Myopathy v1.1 HMBS Bryony Thompson Gene: hmbs has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v1.0 HMBS Bryony Thompson reviewed gene: HMBS: Rating: GREEN; Mode of pathogenicity: None; Publications: 37113461, 25389600, 18647325, 36335232, 34187794, 30778035, 18816221, 15298749; Phenotypes: Porphyria, acute intermittent MIM#176000; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Rhabdomyolysis and Metabolic Myopathy v1.0 HMBS Bryony Thompson Deleted their review
Intellectual disability syndromic and non-syndromic v0.5399 TSC1 Claire Fryer-Smith reviewed gene: TSC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 10533067, 18830229, 15798777, 17304050; Phenotypes: Tuberous sclerosis-1 MIM#191100; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5399 TSC2 Claire Fryer-Smith reviewed gene: TSC2: Rating: GREEN; Mode of pathogenicity: None; Publications: 14985384, 10533067, 10205261, 17304050; Phenotypes: Tuberous sclerosis-2 MIM#613254; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5399 NR2F2 Achchuthan Shanmugasundram reviewed gene: NR2F2: Rating: GREEN; Mode of pathogenicity: None; Publications: 37500725; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v1.20 NCF1 Zornitza Stark Classified gene: NCF1 as Green List (high evidence)
BabyScreen+ newborn screening v1.20 NCF1 Zornitza Stark Gene: ncf1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.19 NCF1 Zornitza Stark edited their review of gene: NCF1: Changed rating: GREEN
BabyScreen+ newborn screening v1.19 NCF1 Zornitza Stark Classified gene: NCF1 as Amber List (moderate evidence)
BabyScreen+ newborn screening v1.19 NCF1 Zornitza Stark Gene: ncf1 has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v1.18 NCF1 Zornitza Stark Tag technically challenging tag was added to gene: NCF1.
BabyScreen+ newborn screening v1.18 NCF1 Zornitza Stark edited their review of gene: NCF1: Added comment: Mappability issues.; Changed rating: AMBER
BabyScreen+ newborn screening v1.18 CYP21A2 Zornitza Stark Classified gene: CYP21A2 as Green List (high evidence)
BabyScreen+ newborn screening v1.18 CYP21A2 Zornitza Stark Gene: cyp21a2 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.17 CYP21A2 Zornitza Stark Tag treatable tag was added to gene: CYP21A2.
Tag endocrine tag was added to gene: CYP21A2.
Tag technically challenging tag was added to gene: CYP21A2.
BabyScreen+ newborn screening v1.17 CYP21A2 Zornitza Stark edited their review of gene: CYP21A2: Added comment: Part of Victorian sNBS, therefore include, although technically challenging.; Changed rating: GREEN
BabyScreen+ newborn screening v1.17 CORO1A Zornitza Stark Tag technically challenging tag was added to gene: CORO1A.
BabyScreen+ newborn screening v1.17 F8 Zornitza Stark Tag for review was removed from gene: F8.
Tag technically challenging tag was added to gene: F8.
BabyScreen+ newborn screening v1.17 GBA Zornitza Stark Tag technically challenging tag was added to gene: GBA.
BabyScreen+ newborn screening v1.17 PMS2 Zornitza Stark Classified gene: PMS2 as Amber List (moderate evidence)
BabyScreen+ newborn screening v1.17 PMS2 Zornitza Stark Gene: pms2 has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v1.16 PMS2 Zornitza Stark Tag technically challenging tag was added to gene: PMS2.
BabyScreen+ newborn screening v1.16 PMS2 Zornitza Stark edited their review of gene: PMS2: Added comment: Mappability issues.; Changed rating: AMBER
BabyScreen+ newborn screening v1.16 IGHM Zornitza Stark Classified gene: IGHM as Amber List (moderate evidence)
BabyScreen+ newborn screening v1.16 IGHM Zornitza Stark Gene: ighm has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v1.15 IGHM Zornitza Stark Tag technically challenging tag was added to gene: IGHM.
BabyScreen+ newborn screening v1.15 IGHM Zornitza Stark edited their review of gene: IGHM: Changed rating: AMBER
BabyScreen+ newborn screening v1.15 IGHM Zornitza Stark commented on gene: IGHM: RefSeq annotation issues.
BabyScreen+ newborn screening v1.15 STRC Zornitza Stark Classified gene: STRC as Amber List (moderate evidence)
BabyScreen+ newborn screening v1.15 STRC Zornitza Stark Gene: strc has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v1.14 STRC Zornitza Stark Tag technically challenging tag was added to gene: STRC.
BabyScreen+ newborn screening v1.14 STRC Zornitza Stark edited their review of gene: STRC: Added comment: Technical issues with multi-mapping, therefore exclude for now.; Changed rating: AMBER
Genetic Epilepsy v0.1916 GABBR1 Zornitza Stark Phenotypes for gene: GABBR1 were changed from Neurodevelopmental disorder, GABBR1-related, MONDO:0700092 to Neurodevelopmental disorder with language delay and variable cognitive abnormalities, MIM#620502
Intellectual disability syndromic and non-syndromic v0.5399 GABBR1 Zornitza Stark Phenotypes for gene: GABBR1 were changed from Neurodevelopmental disorder, GABBR1-related, MONDO:0700092 to Neurodevelopmental disorder with language delay and variable cognitive abnormalities, MIM#620502
Mendeliome v1.1167 GABBR1 Zornitza Stark Phenotypes for gene: GABBR1 were changed from Neurodevelopmental disorder, GABBR1-related, MONDO:0700092 to Neurodevelopmental disorder with language delay and variable cognitive abnormalities, MIM#620502
Mendeliome v1.1166 GABBR1 Zornitza Stark edited their review of gene: GABBR1: Changed phenotypes: Neurodevelopmental disorder with language delay and variable cognitive abnormalities, MIM#620502
Leukodystrophy - adult onset v0.109 SLC17A5 Kaitlyn Dianna Weldon reviewed gene: SLC17A5: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301643; Phenotypes: Salla disease MONDO:0011449; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Leukodystrophy - adult onset v0.109 RNASEH2C Kaitlyn Dianna Weldon reviewed gene: RNASEH2C: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301648; Phenotypes: Aicardi-Goutieres syndrome 2 MONDO:0012471; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Leukodystrophy - adult onset v0.109 RNASEH2B Kaitlyn Dianna Weldon reviewed gene: RNASEH2B: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301648; Phenotypes: Aicardi-Goutieres syndrome 4 MONDO:0012472; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Leukodystrophy - adult onset v0.109 RNASEH2A Kaitlyn Dianna Weldon reviewed gene: RNASEH2A: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301648; Phenotypes: Aicardi-Goutieres syndrome 4 MONDO:0012472; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Leukodystrophy - adult onset v0.109 GLB1 Kaitlyn Dianna Weldon reviewed gene: GLB1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24156116; Phenotypes: GM1 gangliosidosis type 3 MONDO:0009262; Mode of inheritance: None
Intellectual disability syndromic and non-syndromic v0.5398 TAB2 Zornitza Stark Marked gene: TAB2 as ready
Intellectual disability syndromic and non-syndromic v0.5398 TAB2 Zornitza Stark Gene: tab2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5398 TAB2 Zornitza Stark Classified gene: TAB2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5398 TAB2 Zornitza Stark Gene: tab2 has been classified as Green List (High Evidence).
Leukodystrophy - adult onset v0.109 GBE1 Kaitlyn Dianna Weldon reviewed gene: GBE1: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301758; Phenotypes: adult polyglucosan body disease MONDO:0009897; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Motor Neurone Disease v1.7 MATR3 Bryony Thompson Publications for gene: MATR3 were set to
Motor Neurone Disease v1.6 MATR3 Bryony Thompson Mode of inheritance for gene: MATR3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Combined Immunodeficiency v1.43 REL Peter McNaughton reviewed gene: REL: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 34623332; Phenotypes: Immunodeficiency 92, MIM# 619652, Combined immunodeficiency, T cells: normal, decreased memory CD4, poor proliferation, B cells: low, mostly naive, few switched memory B cells, impaired proliferation, Recurrent infections with bacteria, mycobacteria, salmonella and opportunistic organisms, Defective innate immunity; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendelian susceptibility to Immune Disorders v0.35 IL23R Peter McNaughton gene: IL23R was added
gene: IL23R was added to Mendelian susceptibility to Immune Disorders. Sources: Literature
Mode of inheritance for gene: IL23R was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IL23R were set to PMID: 36763636
Phenotypes for gene: IL23R were set to Susceptibility to mycobacterial disease
Review for gene: IL23R was set to GREEN
Added comment: Six patients from four unrelated Iranian kindreds with AR complete IL-23R deficiency presenting MSMD with complete penetrance. Also some patients with susceptibility to CMC with incomplete penetrance.
Sources: Literature
BabyScreen+ newborn screening v1.14 KCNA5 Zornitza Stark Marked gene: KCNA5 as ready
BabyScreen+ newborn screening v1.14 KCNA5 Zornitza Stark Gene: kcna5 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v1.14 KCNA5 Zornitza Stark Phenotypes for gene: KCNA5 were changed from Atrial fibrillation to Atrial fibrillation, familial, 7, MIM# 612240
BabyScreen+ newborn screening v1.13 KCNA5 Zornitza Stark Classified gene: KCNA5 as Red List (low evidence)
BabyScreen+ newborn screening v1.13 KCNA5 Zornitza Stark Gene: kcna5 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v1.12 KCNA5 Zornitza Stark reviewed gene: KCNA5: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Atrial fibrillation, familial, 7, MIM# 612240; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v1.12 GABRG2 Zornitza Stark Marked gene: GABRG2 as ready
BabyScreen+ newborn screening v1.12 GABRG2 Zornitza Stark Gene: gabrg2 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v1.12 GABRG2 Zornitza Stark Classified gene: GABRG2 as Red List (low evidence)
BabyScreen+ newborn screening v1.12 GABRG2 Zornitza Stark Gene: gabrg2 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v1.12 GABRG2 Zornitza Stark Classified gene: GABRG2 as Red List (low evidence)
BabyScreen+ newborn screening v1.12 GABRG2 Zornitza Stark Gene: gabrg2 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v1.11 GABRG2 Zornitza Stark reviewed gene: GABRG2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Epileptic encephalopathy, early infantile, 74 618396, Epilepsy, generalized, with febrile seizures plus, type 3 607681; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v1.11 DKC1 Zornitza Stark Marked gene: DKC1 as ready
BabyScreen+ newborn screening v1.11 DKC1 Zornitza Stark Gene: dkc1 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v1.11 DKC1 Zornitza Stark Phenotypes for gene: DKC1 were changed from Dyskeratosis congenita, X-linked, MIM# 305000; Dyskeratosis congenita to Dyskeratosis congenita, X-linked, MIM# 305000
BabyScreen+ newborn screening v1.10 DKC1 Zornitza Stark Classified gene: DKC1 as Red List (low evidence)
BabyScreen+ newborn screening v1.10 DKC1 Zornitza Stark Gene: dkc1 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v1.9 DKC1 Zornitza Stark reviewed gene: DKC1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Dyskeratosis congenita, X-linked, MIM# 305000; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
BabyScreen+ newborn screening v1.9 CDKN2A Zornitza Stark Marked gene: CDKN2A as ready
BabyScreen+ newborn screening v1.9 CDKN2A Zornitza Stark Gene: cdkn2a has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v1.9 CDKN2A Zornitza Stark Phenotypes for gene: CDKN2A were changed from Melanoma to {Melanoma, cutaneous malignant, 2}, MIM# 155601
BabyScreen+ newborn screening v1.8 CDKN2A Zornitza Stark Classified gene: CDKN2A as Red List (low evidence)
BabyScreen+ newborn screening v1.8 CDKN2A Zornitza Stark Gene: cdkn2a has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v1.7 CDKN2A Zornitza Stark reviewed gene: CDKN2A: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: {Melanoma, cutaneous malignant, 2}, MIM# 155601; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v1.7 BMPR2 Zornitza Stark Marked gene: BMPR2 as ready
BabyScreen+ newborn screening v1.7 BMPR2 Zornitza Stark Gene: bmpr2 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v1.7 BMPR2 Zornitza Stark Phenotypes for gene: BMPR2 were changed from Pulmonary hypertension, familial primary to Pulmonary hypertension, familial primary, 1, with or without HHT, MIM# 178600
BabyScreen+ newborn screening v1.6 BMPR2 Zornitza Stark Classified gene: BMPR2 as Red List (low evidence)
BabyScreen+ newborn screening v1.6 BMPR2 Zornitza Stark Gene: bmpr2 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v1.5 BMPR2 Zornitza Stark reviewed gene: BMPR2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Pulmonary hypertension, familial primary, 1, with or without HHT, MIM# 178600; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v1.5 AIP Zornitza Stark Classified gene: AIP as Red List (low evidence)
BabyScreen+ newborn screening v1.5 AIP Zornitza Stark Gene: aip has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v1.4 AIP Zornitza Stark edited their review of gene: AIP: Changed rating: RED
BabyScreen+ newborn screening v1.4 PHOX2B Zornitza Stark Marked gene: PHOX2B as ready
BabyScreen+ newborn screening v1.4 PHOX2B Zornitza Stark Gene: phox2b has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v1.4 PHOX2B Zornitza Stark Phenotypes for gene: PHOX2B were changed from Central hypoventilation syndrome to Central hypoventilation syndrome, congenital, 1, with or without Hirschsprung disease, MIM# 209880
BabyScreen+ newborn screening v1.3 PHOX2B Zornitza Stark Classified gene: PHOX2B as Red List (low evidence)
BabyScreen+ newborn screening v1.3 PHOX2B Zornitza Stark Gene: phox2b has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v1.2 PHOX2B Zornitza Stark reviewed gene: PHOX2B: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Central hypoventilation syndrome, congenital, 1, with or without Hirschsprung disease, MIM# 209880; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v1.2 AIP Zornitza Stark Marked gene: AIP as ready
BabyScreen+ newborn screening v1.2 AIP Zornitza Stark Gene: aip has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v1.2 AIP Zornitza Stark Phenotypes for gene: AIP were changed from Pituitary adenoma to Pituitary adenoma predisposition, MIM# 102200
BabyScreen+ newborn screening v1.1 AIP Zornitza Stark reviewed gene: AIP: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Pituitary adenoma predisposition, MIM# 102200; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Miscellaneous Metabolic Disorders v1.30 FTCD Bryony Thompson Publications for gene: FTCD were set to 27604308; 12815595
Miscellaneous Metabolic Disorders v1.29 FTCD Bryony Thompson reviewed gene: FTCD: Rating: GREEN; Mode of pathogenicity: None; Publications: http://iembase.com/disorder/47; Phenotypes: Glutamate formiminotransferase deficiency MIM#229100, Disorders of histidine, tryptophan or lysine metabolism; Mode of inheritance: None
Miscellaneous Metabolic Disorders v1.29 FTCD Bryony Thompson Deleted their review
Miscellaneous Metabolic Disorders v1.29 FTCD Bryony Thompson edited their review of gene: FTCD: Changed publications: http://iembase.com/disorder/47
Miscellaneous Metabolic Disorders v1.29 FTCD Bryony Thompson changed review comment from: Well-established gene-disease association (see OMIM entry). Glutamate formiminotransferase deficiency is classified as a metabolic disorder by the NIH GARD (https://rarediseases.info.nih.gov/diseases/diseases-by-category/14/metabolic-disorders), and is an inborn error of amino acid metabolism.
Sources: NHS GMS; to: Glutamate formiminotransferase deficiency is classified as a benign form of folate metabolism disorder and an inborn error of amino acid metabolism without clinically significant phenotype (http://iembase.com/disorder/47).
Intellectual disability syndromic and non-syndromic v0.5397 FTCD Bryony Thompson Marked gene: FTCD as ready
Intellectual disability syndromic and non-syndromic v0.5397 FTCD Bryony Thompson Gene: ftcd has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5397 FTCD Bryony Thompson Phenotypes for gene: FTCD were changed from to Glutamate formiminotransferase deficiency MIM#229100
Intellectual disability syndromic and non-syndromic v0.5396 FTCD Bryony Thompson Publications for gene: FTCD were set to
Intellectual disability syndromic and non-syndromic v0.5395 FTCD Bryony Thompson Mode of inheritance for gene: FTCD was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1166 FTCD Bryony Thompson Publications for gene: FTCD were set to 27604308; 12815595
Mendeliome v1.1165 FTCD Bryony Thompson edited their review of gene: FTCD: Changed publications: http://iembase.com/disorder/47
Mendeliome v1.1165 FTCD Bryony Thompson changed review comment from: Well-established gene-disease association (see OMIM entry). Glutamate formiminotransferase deficiency is classified as a metabolic disorder by the NIH GARD (https://rarediseases.info.nih.gov/diseases/diseases-by-category/14/metabolic-disorders), and is an inborn error of amino acid metabolism.
Sources: NHS GMS; to: Glutamate formiminotransferase deficiency is classified as a benign form of folate metabolism disorder and an inborn error of amino acid metabolism without clinically significant phenotype (http://iembase.com/disorder/47).
Intellectual disability syndromic and non-syndromic v0.5394 FTCD Bryony Thompson Classified gene: FTCD as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.5394 FTCD Bryony Thompson Added comment: Comment on list classification: According to IEMbase this gene is associated with a benign form of disorder of folate metabolism with no clinical significance
Intellectual disability syndromic and non-syndromic v0.5394 FTCD Bryony Thompson Gene: ftcd has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1165 MAP1B Zornitza Stark Phenotypes for gene: MAP1B were changed from Intellectual disability; seizures; PVNH; dysmorphic features; Periventricular nodular heterotopia 9, MIM# 618918 to Intellectual disability; seizures; PVNH; dysmorphic features; Periventricular nodular heterotopia 9, MIM# 618918; Deafness, autosomal dominant 83, MIM# 619808
Mendeliome v1.1164 MAP1B Zornitza Stark edited their review of gene: MAP1B: Added comment: At least 3 families reported with isolated deafness and mono-allelic variants.; Changed phenotypes: Intellectual disability, seizures, PVNH, dysmorphic features, Periventricular nodular heterotopia 9, MIM# 618918, Deafness, autosomal dominant 83, MIM# 619808
Deafness_IsolatedAndComplex v1.161 MAP1B Zornitza Stark Phenotypes for gene: MAP1B were changed from Periventricular nodular heterotopia 9 MIM#618918; sensorineural hearing loss to Deafness, autosomal dominant 83, MIM# 619808
Deafness_IsolatedAndComplex v1.160 MAP1B Zornitza Stark reviewed gene: MAP1B: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Deafness, autosomal dominant 83, MIM# 619808; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Leukodystrophy - adult onset v0.109 GLA Claire Fryer-Smith reviewed gene: GLA: Rating: GREEN; Mode of pathogenicity: None; Publications: 30757954, 12786754, 15924232, 31200018, 31519519; Phenotypes: Fabry disease (MIM# 301500); Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Leukodystrophy - adult onset v0.109 CYP27A1 Kaitlyn Dianna Weldon reviewed gene: CYP27A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301583; Phenotypes: cerebrotendinous xanthomatosis MONDO:0008948; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Leukodystrophy - adult onset v0.109 CSF1R Kaitlyn Dianna Weldon reviewed gene: CSF1R: Rating: GREEN; Mode of pathogenicity: None; Publications: 22934315; Phenotypes: brain abnormalities, neurodegeneration, and dysosteosclerosis MONDO:0032772; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Leukodystrophy - adult onset v0.109 COL4A1 Kaitlyn Dianna Weldon reviewed gene: COL4A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301768; Phenotypes: brain small vessel disease 1 with or without ocular anomalies MONDO:0008289; Mode of inheritance: None
Leukodystrophy - adult onset v0.109 ADAR Kaitlyn Dianna Weldon reviewed gene: ADAR: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301648; Phenotypes: Aicardi-Goutieres syndrome 6 MONDO:0014007; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Leukodystrophy - adult onset v0.109 ABCD1 Kaitlyn Dianna Weldon reviewed gene: ABCD1: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301491; Phenotypes: adrenoleukodystrophy MONDO:0018544, X-linked cerebral adrenoleukodystrophy MONDO:0010247; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Leukodystrophy - adult onset v0.109 AARS2 Kaitlyn Dianna Weldon reviewed gene: AARS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 34285876, 35084689; Phenotypes: leukodystrophy MONDO:0019046; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.264 WDR45 Kaitlyn Dianna Weldon reviewed gene: WDR45: Rating: GREEN; Mode of pathogenicity: None; Publications: 28211668; Phenotypes: neurodegeneration with brain iron accumulation 5 MONDO:0010476, X-linked complex neurodevelopmental disorder MONDO:0100148; 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 v0.264 VPS13A Kaitlyn Dianna Weldon reviewed gene: VPS13A: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301561, 37636221; Phenotypes: chorea-acanthocytosis MONDO:0008695; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.264 TUBB4A Kaitlyn Dianna Weldon reviewed gene: TUBB4A: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.264 TH Kaitlyn Dianna Weldon reviewed gene: TH: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301334, 20301610; Phenotypes: TH-deficient dopa-responsive dystonia MONDO:0011551, tyrosine hydroxylase deficiency MONDO:0100064; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.264 SPR Claire Fryer-Smith reviewed gene: SPR: Rating: AMBER; Mode of pathogenicity: None; Publications: 22522443, 11920285, 14663042, 16443856, 21782285, 32813147; Phenotypes: Dystonia, dopa-responsive, due to sepiapterin reductase deficiency (MIM# 612716); Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genetic Epilepsy v0.1915 PIP5K1C Zornitza Stark Marked gene: PIP5K1C as ready
Genetic Epilepsy v0.1915 PIP5K1C Zornitza Stark Gene: pip5k1c has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1915 PIP5K1C Zornitza Stark Classified gene: PIP5K1C as Green List (high evidence)
Genetic Epilepsy v0.1915 PIP5K1C Zornitza Stark Gene: pip5k1c has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1914 PIP5K1C Zornitza Stark gene: PIP5K1C was added
gene: PIP5K1C was added to Genetic Epilepsy. Sources: Expert Review
Mode of inheritance for gene: PIP5K1C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PIP5K1C were set to 37451268
Phenotypes for gene: PIP5K1C were set to Neurodevelopmental disorder and microcephaly, MONDO:0700092, PIP5K1C-related
Review for gene: PIP5K1C was set to GREEN
Added comment: Three de novo heterozygous missense variants in PIP5K1C (p.Glu146Lys, p.Tyr205Cys & p.Tyr221Cys) were identified in nine unrelated children exhibiting intellectual disability, developmental delay, acquired microcephaly, seizures, visual abnormalities, and dysmorphic features. Intellectual disability was reported in all nine children and seizures were present in seven children, of which three had developmental and epileptic encephalopathy. In addition, there is functional evidence available, which includes an in vivo zebrafish model that recapitulates the human phenotype (developmental defects affecting the forebrain, including the eyes, as well as craniofacial abnormalities) (PMID:37451268).
Sources: Expert Review
Mendeliome v1.1164 GJA4 Zornitza Stark Marked gene: GJA4 as ready
Mendeliome v1.1164 GJA4 Zornitza Stark Gene: gja4 has been classified as Green List (High Evidence).
Mendeliome v1.1164 GJA4 Zornitza Stark Classified gene: GJA4 as Green List (high evidence)
Mendeliome v1.1164 GJA4 Zornitza Stark Gene: gja4 has been classified as Green List (High Evidence).
Mendeliome v1.1163 GJA4 Zornitza Stark gene: GJA4 was added
gene: GJA4 was added to Mendeliome. Sources: Expert Review
somatic tags were added to gene: GJA4.
Mode of inheritance for gene: GJA4 was set to Other
Publications for gene: GJA4 were set to 33912852
Phenotypes for gene: GJA4 were set to Cavernous hemangioma, MONDO:0003155, GJA4-related
Review for gene: GJA4 was set to GREEN
Added comment: Recurrent somatic GJA4 c.121G>T (p.Gly41Cys) mutation as a driver of hepatic (n=12) and cutaneous (n=3) vascular malformations. Induced changes in cell morphology and activated serum/glucocorticoid-regulated kinase 1 (SGK1), a serine/threonine kinase known to regulate cell proliferation and apoptosis, via non-canonical activation, in lentiviral transduction of primary human endothelial cells.
Sources: Expert Review
Ataxia - paediatric v1.11 AGTPBP1 Zornitza Stark Marked gene: AGTPBP1 as ready
Ataxia - paediatric v1.11 AGTPBP1 Zornitza Stark Gene: agtpbp1 has been classified as Green List (High Evidence).
Ataxia - paediatric v1.11 AGTPBP1 Zornitza Stark Classified gene: AGTPBP1 as Green List (high evidence)
Ataxia - paediatric v1.11 AGTPBP1 Zornitza Stark Gene: agtpbp1 has been classified as Green List (High Evidence).
Ataxia - paediatric v1.10 AGTPBP1 Zornitza Stark gene: AGTPBP1 was added
gene: AGTPBP1 was added to Ataxia - paediatric. Sources: Expert Review
Mode of inheritance for gene: AGTPBP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AGTPBP1 were set to 30420557
Phenotypes for gene: AGTPBP1 were set to Early onset cerebellar atrophy, developmental delay, and feeding and respiratory difficulties, severe motor neuronopathy; Neurodegeneration, childhood-onset, with cerebellar atrophy, 618276
Review for gene: AGTPBP1 was set to GREEN
Added comment: Thirteen individuals with bi-allelic variants in this gene, complex neurological phenotype of dev delay/ID, cerebellar atrophy and neuropathy, severe progressive course in six.
Sources: Expert Review
Skeletal dysplasia v0.253 MAB21L2 Zornitza Stark Marked gene: MAB21L2 as ready
Skeletal dysplasia v0.253 MAB21L2 Zornitza Stark Gene: mab21l2 has been classified as Green List (High Evidence).
Skeletal dysplasia v0.253 MAB21L2 Zornitza Stark Classified gene: MAB21L2 as Green List (high evidence)
Skeletal dysplasia v0.253 MAB21L2 Zornitza Stark Gene: mab21l2 has been classified as Green List (High Evidence).
Skeletal dysplasia v0.252 MAB21L2 Zornitza Stark gene: MAB21L2 was added
gene: MAB21L2 was added to Skeletal dysplasia. Sources: Expert Review
Mode of inheritance for gene: MAB21L2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAB21L2 were set to 24906020; 25719200; 31037784; 30375740; 30073347; 26116559
Phenotypes for gene: MAB21L2 were set to Microphthalmia/coloboma and skeletal dysplasia syndrome, MIM# 615877
Review for gene: MAB21L2 was set to GREEN
Added comment: More than 7 unrelated families reported with microphthalmia/anophthalmia/coloboma and rhizomelia. Several individuals with the c.151C > T (p.Arg51Cys) variant also had ID.

One family reported with eye phenotype and bi-allelic missense variants, LIMITED evidence for bi-allelic disease.

Three different animal models support gene-disease association.
Sources: Expert Review
Early-onset Parkinson disease v0.264 SPG11 Claire Fryer-Smith reviewed gene: SPG11: Rating: GREEN; Mode of pathogenicity: None; Publications: 35036589, 23121729, 21381113, 27217339; Phenotypes: Amyotrophic lateral sclerosis 5, juvenile (MIM# 602099), Charcot-Marie-Tooth disease, axonal, type 2X (MIM# 616668), Spastic paraplegia 11, autosomal recessive (MIM# 604360); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Additional findings_Adult v0.166 PTEN Zornitza Stark Phenotypes for gene: PTEN were changed from Cowden syndrome 1, MIM# 158350 to Cowden syndrome 1, MIM# 158350; PTEN hamartoma tumour syndrome (MONDO#0017623)
Additional findings_Adult v0.165 PTEN Zornitza Stark Mode of inheritance for gene: PTEN was changed from MONOALLELIC, autosomal or pseudoautosomal, maternally imprinted (paternal allele expressed) to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cardiomyopathy_Paediatric v0.169 CAP2 Zornitza Stark Marked gene: CAP2 as ready
Cardiomyopathy_Paediatric v0.169 CAP2 Zornitza Stark Gene: cap2 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v0.169 CAP2 Zornitza Stark Classified gene: CAP2 as Green List (high evidence)
Cardiomyopathy_Paediatric v0.169 CAP2 Zornitza Stark Gene: cap2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5393 COL4A3BP Zornitza Stark Phenotypes for gene: COL4A3BP were changed from Mental retardation, autosomal dominant 34, MIM# 616351 to Intellectual developmental disorder 34 (MIM#616351)
Intellectual disability syndromic and non-syndromic v0.5392 COL4A3BP Zornitza Stark Publications for gene: COL4A3BP were set to 25533962
Intellectual disability syndromic and non-syndromic v0.5391 COL4A3BP Zornitza Stark Mode of pathogenicity for gene: COL4A3BP was changed from to Other
Mendeliome v1.1162 COL4A3BP Zornitza Stark Phenotypes for gene: COL4A3BP were changed from Mental retardation, autosomal dominant 34, MIM# 616351 to Intellectual developmental disorder 34 (MIM#616351)
Mendeliome v1.1161 COL4A3BP Zornitza Stark Publications for gene: COL4A3BP were set to 25533962
Mendeliome v1.1160 COL4A3BP Zornitza Stark Mode of pathogenicity for gene: COL4A3BP was changed from to Other
Genetic Epilepsy v0.1913 COL4A3BP Zornitza Stark Marked gene: COL4A3BP as ready
Genetic Epilepsy v0.1913 COL4A3BP Zornitza Stark Gene: col4a3bp has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1913 COL4A3BP Zornitza Stark Classified gene: COL4A3BP as Green List (high evidence)
Genetic Epilepsy v0.1913 COL4A3BP Zornitza Stark Gene: col4a3bp has been classified as Green List (High Evidence).
Paroxysmal Dyskinesia v0.112 GABRB3 Zornitza Stark Marked gene: GABRB3 as ready
Paroxysmal Dyskinesia v0.112 GABRB3 Zornitza Stark Gene: gabrb3 has been classified as Green List (High Evidence).
Paroxysmal Dyskinesia v0.112 GABRB3 Zornitza Stark Classified gene: GABRB3 as Green List (high evidence)
Paroxysmal Dyskinesia v0.112 GABRB3 Zornitza Stark Gene: gabrb3 has been classified as Green List (High Evidence).
Mendeliome v1.1159 DBR1 Zornitza Stark Phenotypes for gene: DBR1 were changed from {Encephalitis, acute, infection (viral)-induced, susceptibility to, 11}, MIM# 619441; Viral infections of the brainstem to {Encephalitis, acute, infection (viral)-induced, susceptibility to, 11}, MIM# 619441; Viral infections of the brainstem; Ichthyosis (MONDO#0019269), DBR1-related
Mendeliome v1.1158 DBR1 Zornitza Stark edited their review of gene: DBR1: Added comment: PMID: 37656279:
- A homozygous missense as a founder recessive DBR1 variant in four consanguineous families.
- Total of 7 affected children. WES done for one proband from each family.
- Consistent features include prematurity, severe intrauterine growth deficiency, congenital ichthyosis-like presentation (collodion membrane, severe skin peeling and xerosis), and death before the first year of life.
- RNA and protein studies using fibroblasts derived from a patient are supportive of pathogenicity: RNA-seq, rt-qPCR and western blotting, showing marked reduction of DBR1 level and intronic RNA lariat accumulation in the patient sample.
- Haplotype analysis revealed that the four families all share a haplotype extending at least 2.27 Mb around the c.200A>G p.(Tyr67Cys) DBR1 founder variant.
- Authors proposed this is a novel DBR1-related developmental disorder that is distinct from DBR1-related encephalitis susceptibility, and highlighted the apparent lack of correlation with the degree of DBR1 deficiency.; Changed publications: 29474921, 37656279; Changed phenotypes: {Encephalitis, acute, infection (viral)-induced, susceptibility to, 11}, MIM# 619441, Viral infections of the brainstem, Ichthyosis (MONDO#0019269), DBR1-related
Fetal anomalies v1.143 DBR1 Zornitza Stark Tag founder tag was added to gene: DBR1.
Ichthyosis v1.6 DBR1 Zornitza Stark Tag founder tag was added to gene: DBR1.
Dystonia - isolated/combined v1.35 GABRB3 Zornitza Stark Marked gene: GABRB3 as ready
Dystonia - isolated/combined v1.35 GABRB3 Zornitza Stark Gene: gabrb3 has been classified as Green List (High Evidence).
Dystonia - isolated/combined v1.35 GABRB3 Zornitza Stark Classified gene: GABRB3 as Green List (high evidence)
Dystonia - isolated/combined v1.35 GABRB3 Zornitza Stark Gene: gabrb3 has been classified as Green List (High Evidence).
Microcephaly v1.230 GABRB3 Zornitza Stark Marked gene: GABRB3 as ready
Microcephaly v1.230 GABRB3 Zornitza Stark Gene: gabrb3 has been classified as Green List (High Evidence).
Microcephaly v1.230 GABRB3 Zornitza Stark Classified gene: GABRB3 as Green List (high evidence)
Microcephaly v1.230 GABRB3 Zornitza Stark Gene: gabrb3 has been classified as Green List (High Evidence).
Mendeliome v1.1158 APOO Zornitza Stark Phenotypes for gene: APOO were changed from Developmental delay; Lactic acidosis; Muscle weakness; Hypotonia; Repetitive infections; Cognitive impairment; Autistic behaviour to Mitochondrial disease, MONDO:0044970, APOO-related; Developmental delay; Lactic acidosis; Muscle weakness; Hypotonia; Repetitive infections; Cognitive impairment; Autistic behaviour
Mendeliome v1.1157 APOO Zornitza Stark Publications for gene: APOO were set to 32439808
Mendeliome v1.1156 APOO Zornitza Stark edited their review of gene: APOO: Added comment: PMID: 37649161
1 family, 2 individuals (male & female) with same NMD variant c.532G>T (p.E178*), maternally inherited (mother unaffected).

Both died before 18 months of age with partial agenesis of the corpus callosum, bilateral congenital cataract, hypothyroidism, and severe immune deficiencies.
Other phenotypes included partial syndactyly of the 2nd and 3rd toes, wrinkled palm, and sole skin.

Functional studies included site directed mutagenesis. This mutation resulted in a highly unstable and degradation
prone MIC26 protein, yet the remaining minute amounts of mutant MIC26 correctly localized to mitochondria and
interacted physically with other MICOS subunits. MIC26 KO cells expressing MIC26 harboring the respective APOO/MIC26 mutation showed mitochondria with perturbed cristae architecture and fragmented morphology resembling MIC26 KO cells.; Changed publications: 37649161; Changed phenotypes: Mitochondrial disease, MONDO:0044970, APOO-related, Developmental delay, Lactic acidosis, Muscle weakness, Hypotonia, Repetitive infections, Cognitive impairment, Autistic behaviour
Mitochondrial disease v0.891 APOO Zornitza Stark Phenotypes for gene: APOO were changed from Developmental delay; Lactic acidosis; Muscle weakness; Hypotonia; Repetitive infections; Cognitive impairment; Autistic behaviour to Mitochondrial disease, MONDO:0044970, APOO-related; Developmental delay; Lactic acidosis; Muscle weakness; Hypotonia; Repetitive infections; Cognitive impairment; Autistic behaviour
Mitochondrial disease v0.890 APOO Zornitza Stark Publications for gene: APOO were set to 32439808
Mitochondrial disease v0.889 APOO Zornitza Stark edited their review of gene: APOO: Changed phenotypes: Mitochondrial disease, MONDO:0044970, APOO-related, Developmental delay, Lactic acidosis, Muscle weakness, Hypotonia, Repetitive infections, Cognitive impairment, Autistic behaviour
Ciliopathies v1.45 RAB34 Zornitza Stark Marked gene: RAB34 as ready
Ciliopathies v1.45 RAB34 Zornitza Stark Gene: rab34 has been classified as Green List (High Evidence).
Ciliopathies v1.45 RAB34 Zornitza Stark Classified gene: RAB34 as Green List (high evidence)
Ciliopathies v1.45 RAB34 Zornitza Stark Gene: rab34 has been classified as Green List (High Evidence).
Skeletal Dysplasia_Fetal v0.206 RAB34 Zornitza Stark Marked gene: RAB34 as ready
Skeletal Dysplasia_Fetal v0.206 RAB34 Zornitza Stark Gene: rab34 has been classified as Green List (High Evidence).
Skeletal Dysplasia_Fetal v0.206 RAB34 Zornitza Stark Classified gene: RAB34 as Green List (high evidence)
Skeletal Dysplasia_Fetal v0.206 RAB34 Zornitza Stark Gene: rab34 has been classified as Green List (High Evidence).
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v1.10 RAB34 Zornitza Stark Marked gene: RAB34 as ready
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v1.10 RAB34 Zornitza Stark Gene: rab34 has been classified as Green List (High Evidence).
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v1.10 RAB34 Zornitza Stark Classified gene: RAB34 as Green List (high evidence)
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v1.10 RAB34 Zornitza Stark Gene: rab34 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.264 SLC30A10 Claire Fryer-Smith reviewed gene: SLC30A10: Rating: GREEN; Mode of pathogenicity: None; Publications: 22341971, 22341972; Phenotypes: Hypermanganesemia with dystonia 1 (MIM# 613280); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Disorders of immune dysregulation v0.179 COL4A3BP Zornitza Stark Marked gene: COL4A3BP as ready
Disorders of immune dysregulation v0.179 COL4A3BP Zornitza Stark Gene: col4a3bp has been classified as Green List (High Evidence).
Disorders of immune dysregulation v0.179 COL4A3BP Zornitza Stark Classified gene: COL4A3BP as Green List (high evidence)
Disorders of immune dysregulation v0.179 COL4A3BP Zornitza Stark Gene: col4a3bp has been classified as Green List (High Evidence).
Disorders of immune dysregulation v0.178 COL4A3BP Zornitza Stark Tag new gene name tag was added to gene: COL4A3BP.
Early-onset Parkinson disease v0.264 SLC39A14 Zornitza Stark Marked gene: SLC39A14 as ready
Early-onset Parkinson disease v0.264 SLC39A14 Zornitza Stark Gene: slc39a14 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.264 SLC39A14 Zornitza Stark Phenotypes for gene: SLC39A14 were changed from to Hypermanganesemia with dystonia 2 (MIM# 617013)
Early-onset Parkinson disease v0.263 SLC39A14 Zornitza Stark Publications for gene: SLC39A14 were set to
Early-onset Parkinson disease v0.262 SLC39A14 Zornitza Stark Mode of inheritance for gene: SLC39A14 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.261 SLC39A14 Zornitza Stark Mode of inheritance for gene: SLC39A14 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.260 SLC39A14 Claire Fryer-Smith reviewed gene: SLC39A14: Rating: GREEN; Mode of pathogenicity: None; Publications: 27231142, 32626807, 29685658, 30232769; Phenotypes: Hypermanganesemia with dystonia 2 (MIM# 617013); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Disorders of immune dysregulation v0.178 COL4A3BP Ee Ming Wong gene: COL4A3BP was added
gene: COL4A3BP was added to Disorders of immune dysregulation. Sources: Literature
Mode of inheritance for gene: COL4A3BP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: COL4A3BP were set to PMID: 36976648
Phenotypes for gene: COL4A3BP were set to Intellectual developmental disorder 34 (MIM#616351)
Mode of pathogenicity for gene: COL4A3BP was set to Other
Review for gene: COL4A3BP was set to GREEN
gene: COL4A3BP was marked as current diagnostic
Added comment: - current HGNC symbol: CERT1
- Thirty-one unrelated individuals with twenty-two distinct missense variants. The majority of variants were de novo.
- Several variants transfected into HeLa cells demonstrated gain of CERT activity
- CERT gain of function in Drosophila melanogaster led to head and brain size defects and impaired locomotor activity, which was corrected by pharmacological inhibition of CERT
Sources: Literature
Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy v1.9 RAB34 Melanie Marty gene: RAB34 was added
gene: RAB34 was added to Short Rib Polydactyly_Jeune Asphyxiating Thoracic Dystrophy_Skeletal Ciliopathy. Sources: Literature
Mode of inheritance for gene: RAB34 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RAB34 were set to PMID: 37619988; PMID: 37384395
Phenotypes for gene: RAB34 were set to Multiple congenital anomalies, (MONDO:0019042), RAB34-related
Review for gene: RAB34 was set to GREEN
Added comment: PMID: 37619988 Compound heterozygous variants identified in RAB34 in a fetus with multiple malformations, including posterior neck edema, micrognathia, low-set and small ears, auricular hypoplasia, cleft lip and palate, short extremities, and a combination of rarely occurring pre- and postaxial polydactyly.

PMID: 37384395 Biallelic variants in RAB34 were identified in 3 unrelated families. Affected individuals presented a novel form of OFDS accompanied by cardiac, cerebral, skeletal (eg. Shortening of long bones), and anorectal defects. Onset is prenatal (multiple developmental defects including short femur, polydactyly, heart malformations, kidney malformations, and brain malformations), resulting in medical termination for three probands.
Sources: Literature
Mitochondrial disease v0.889 APOO Karina Sandoval reviewed gene: APOO: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 37649161; Phenotypes: agenesis of the corpus callosum, bilateral congenital cataract, hypothyroidism, severe immune deficiencies; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Skeletal Dysplasia_Fetal v0.205 RAB34 Melanie Marty gene: RAB34 was added
gene: RAB34 was added to Skeletal Dysplasia_Fetal. Sources: Literature
Mode of inheritance for gene: RAB34 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RAB34 were set to PMID: 37619988; PMID: 37384395
Phenotypes for gene: RAB34 were set to Multiple congenital anomalies, (MONDO:0019042), RAB34-related
Review for gene: RAB34 was set to GREEN
Added comment: PMID: 37619988 Compound heterozygous variants identified in RAB34 in a fetus with multiple malformations, including posterior neck edema, micrognathia, low-set and small ears, auricular hypoplasia, cleft lip and palate, short extremities, and a combination of rarely occurring pre- and postaxial polydactyly.

PMID: 37384395 Biallelic variants in RAB34 were identified in 3 unrelated families. Affected individuals presented a novel form of OFDS accompanied by cardiac, cerebral, skeletal (eg. Shortening of long bones), and anorectal defects. Onset is prenatal (multiple developmental defects including short femur, polydactyly, heart malformations, kidney malformations, and brain malformations), resulting in medical termination for three probands.
Sources: Literature
Cataract v0.356 COL4A2 Zornitza Stark Marked gene: COL4A2 as ready
Cataract v0.356 COL4A2 Zornitza Stark Gene: col4a2 has been classified as Amber List (Moderate Evidence).
Cataract v0.356 COL4A2 Zornitza Stark Classified gene: COL4A2 as Amber List (moderate evidence)
Cataract v0.356 COL4A2 Zornitza Stark Gene: col4a2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1156 RAB5C Rylee Peters changed review comment from: 12 individuals with nine different heterozygous de novo variants in RAB5C.
9 with missense, 1 inframe duplication and 2 stop-gains (clinically more severe).
All has mild-severe ID, 4/12 have epilepsy, 6/12 have macrocephaly (more than 3 SD).
Sources: Literature; to: 12 individuals with nine different heterozygous de novo variants in RAB5C.
9 with missense, 1 inframe duplication and 2 stop-gains (clinically more severe).
All have mild-severe ID, 4/12 have epilepsy, 6/12 have macrocephaly (more than 3 SD).
Sources: Literature
Microcephaly v1.229 GABRB3 Michelle Torres gene: GABRB3 was added
gene: GABRB3 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: GABRB3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GABRB3 were set to 37647766
Phenotypes for gene: GABRB3 were set to Developmental and epileptic encephalopathy 43 MIM#617113
Mode of pathogenicity for gene: GABRB3 was set to Other
Review for gene: GABRB3 was set to GREEN
Added comment: Voltage-clamp electrophysiology studies have shown that gain-of-function variants clustering in the transmembrane regions part of the channel pore result in a more severe phenotype, including movement disorders (dystonia and dyskinesia) and microcephaly.

Gain-of-function variants clustered in the coupling loops responsible for receptor activation are not associated with movement disorder and microcephaly.

LoF variants have not been associated with microcephaly and movement disorders either.
Sources: Literature
Macrocephaly_Megalencephaly v0.132 RAB5C Rylee Peters changed review comment from: 12 individuals with nine different heterozygous de novo variants in RAB5C.
9 with missense, 1 inframe duplication and 2 stop-gains (clinically more severe).
All has mild-severe ID, 4/12 have epilepsy, 6/12 have macrocephaly (more than 3 SD).
Sources: Literature; to: 12 individuals with nine different heterozygous de novo variants in RAB5C.
9 with missense, 1 inframe duplication and 2 stop-gains (clinically more severe).
All have mild-severe ID, 4/12 have epilepsy, 6/12 have macrocephaly (more than 3 SD).
Sources: Literature
Genetic Epilepsy v0.1912 RAB5C Rylee Peters changed review comment from: 12 individuals with nine different heterozygous de novo variants in RAB5C.
9 with missense, 1 inframe duplication and 2 stop-gains (clinically more severe).
All has mild-severe ID, 4/12 have epilepsy, 6/12 have macrocephaly (more than 3 SD).
Sources: Literature; to: 12 individuals with nine different heterozygous de novo variants in RAB5C.
9 with missense, 1 inframe duplication and 2 stop-gains (clinically more severe).
All have mild-severe ID, 4/12 have epilepsy, 6/12 have macrocephaly (more than 3 SD).
Sources: Literature
Ciliopathies v1.44 RAB34 Melanie Marty gene: RAB34 was added
gene: RAB34 was added to Ciliopathies. Sources: Literature
Mode of inheritance for gene: RAB34 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RAB34 were set to PMID: 37619988; PMID: 37384395
Phenotypes for gene: RAB34 were set to Multiple congenital anomalies, (MONDO:0019042), RAB34-related
Review for gene: RAB34 was set to GREEN
Added comment: PMID: 37619988 Compound heterozygous variants identified in RAB34 in a fetus with multiple malformations, including posterior neck edema, micrognathia, low-set and small ears, auricular hypoplasia, cleft lip and palate, short extremities, and a combination of rarely occurring pre- and postaxial polydactyly.

PMID: 37384395 Biallelic variants in RAB34 were identified in 3 unrelated families. Affected individuals presented a novel form of OFDS accompanied by cardiac, cerebral, skeletal (eg. Shortening of long bones), and anorectal defects. Onset is prenatal (multiple developmental defects including short femur, polydactyly, heart malformations, kidney malformations, and brain malformations), resulting in medical termination for three probands.
Sources: Literature
Muscular dystrophy and myopathy_Paediatric v1.7 DHX16 Seb Lunke Publications for gene: DHX16 were set to 36211162
Dystonia - isolated/combined v1.34 GABRB3 Michelle Torres reviewed gene: GABRB3: Rating: GREEN; Mode of pathogenicity: Other; Publications: 37647766; Phenotypes: Developmental and epileptic encephalopathy 43 MIM#617113; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Ichthyosis v1.6 DBR1 Seb Lunke Marked gene: DBR1 as ready
Ichthyosis v1.6 DBR1 Seb Lunke Gene: dbr1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.143 DBR1 Seb Lunke Marked gene: DBR1 as ready
Fetal anomalies v1.143 DBR1 Seb Lunke Gene: dbr1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1156 DBR1 Chern Lim reviewed gene: DBR1: Rating: AMBER; Mode of pathogenicity: None; Publications: 37656279; Phenotypes: Ichthyosis (MONDO#0019269), DBR1-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Dystonia - isolated/combined v1.34 GABRB3 Michelle Torres Deleted their review
Ichthyosis v1.6 DBR1 Seb Lunke Phenotypes for gene: DBR1 were changed from Prematurity, severe intrauterine growth deficiency, congenital ichthyosis-like presentation, and death before the first year of life to Ichthyosis (MONDO#0019269), DBR1-related
Genetic Epilepsy v0.1912 RAB5C Ain Roesley Marked gene: RAB5C as ready
Genetic Epilepsy v0.1912 RAB5C Ain Roesley Gene: rab5c has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1912 RAB5C Ain Roesley Classified gene: RAB5C as Green List (high evidence)
Genetic Epilepsy v0.1912 RAB5C Ain Roesley Gene: rab5c has been classified as Green List (High Evidence).
Paroxysmal Dyskinesia v0.111 GABRB3 Michelle Torres gene: GABRB3 was added
gene: GABRB3 was added to Paroxysmal Dyskinesia. Sources: Literature
Mode of inheritance for gene: GABRB3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GABRB3 were set to 37647766
Phenotypes for gene: GABRB3 were set to Developmental and epileptic encephalopathy 43 MIM#617113
Mode of pathogenicity for gene: GABRB3 was set to Other
Review for gene: GABRB3 was set to GREEN
Added comment: Voltage-clamp electrophysiology studies have shown that gain-of-function variants clustering in the transmembrane regions part of the channel pore result in a more severe phenotype, including movement disorders (dystonia and dyskinesia) and microcephaly.

Gain-of-function variants clustered in the coupling loops responsible for receptor activation are not associated with movement disorder and microcephaly.

LoF variants have not been associated with microcephaly and movement disorders either.
Sources: Literature
Muscular dystrophy and myopathy_Paediatric v1.6 DHX16 Seb Lunke Classified gene: DHX16 as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v1.6 DHX16 Seb Lunke Gene: dhx16 has been classified as Green List (High Evidence).
Fetal anomalies v1.143 DBR1 Seb Lunke Phenotypes for gene: DBR1 were changed from Prematurity, severe intrauterine growth deficiency, congenital ichthyosis-like presentation, and death before the first year of life to Ichthyosis (MONDO#0019269), DBR1-related
Fetal anomalies v1.142 DBR1 Chern Lim Deleted their comment
Genetic Epilepsy v0.1911 COL4A3BP Ee Ming Wong gene: COL4A3BP was added
gene: COL4A3BP was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: COL4A3BP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: COL4A3BP were set to PMID: 36976648
Phenotypes for gene: COL4A3BP were set to Intellectual developmental disorder 34 (MIM#616351)
Mode of pathogenicity for gene: COL4A3BP was set to Other
Review for gene: COL4A3BP was set to GREEN
gene: COL4A3BP was marked as current diagnostic
Added comment: - current HGNC symbol: CERT1
- Thirty-one unrelated individuals with twenty-two distinct missense variants. The majority of variants were de novo
- Several variants transfected into HeLa cells demonstrated gain of CERT activity
- CERT gain of function in Drosophila melanogaster led to head and brain size defects and impaired locomotor activity, which was corrected by pharmacological inhibition of CERT
Sources: Literature
Fetal anomalies v1.142 DBR1 Chern Lim edited their review of gene: DBR1: Added comment: PMID: 37656279:
- A homozygous missense as a founder recessive DBR1 variant in four consanguineous families.
- Total of 7 affected children. WES done for one proband from each family.
- Consistent features include prematurity, severe intrauterine growth deficiency, congenital ichthyosis-like presentation (collodion membrane, severe skin peeling and xerosis), and death before the first year of life.
- RNA and protein studies using fibroblasts derived from a patient are supportive of pathogenicity: RNA-seq, rt-qPCR and western blotting, showing marked reduction of DBR1 level and intronic RNA lariat accumulation in the patient sample.
- Haplotype analysis revealed that the four families all share a haplotype extending at least 2.27 Mb around the c.200A>G p.(Tyr67Cys) DBR1 founder variant.
- Authors proposed this is a novel DBR1-related developmental disorder that is distinct from DBR1-related encephalitis susceptibility, and highlighted the apparent lack of correlation with the degree of DBR1 deficiency.; Changed phenotypes: Ichthyosis (MONDO#0019269), DBR1-related
Mendeliome v1.1156 CAP2 Zornitza Stark Phenotypes for gene: CAP2 were changed from Dilated cardiomyopathy to Cardiomyopathy, dilated, 2I (MIM#620462)
Ichthyosis v1.5 DBR1 Chern Lim Deleted their comment
Mendeliome v1.1155 COL4A3BP Ee Ming Wong changed review comment from: - Thirty-one unrelated individuals with twenty-two distinct missense variants. The majority of variants were de novo.
- Several variants transfected into HeLa cells demonstrated gain of CERT activity
- CERT gain of function in Drosophila melanogaster led to head and brain size defects and impaired locomotor activity, which was corrected by pharmacological inhibition of CERT; to: - current HGNC symbol: CERT1
- Thirty-one unrelated individuals with twenty-two distinct missense variants. The majority of variants were de novo.
- Several variants transfected into HeLa cells demonstrated gain of CERT activity
- CERT gain of function in Drosophila melanogaster led to head and brain size defects and impaired locomotor activity, which was corrected by pharmacological inhibition of CERT
Ichthyosis v1.5 DBR1 Chern Lim edited their review of gene: DBR1: Added comment: PMID: 37656279:
- A homozygous missense as a founder recessive DBR1 variant in four consanguineous families.
- Total of 7 affected children. WES done for one proband from each family.
- Consistent features include prematurity, severe intrauterine growth deficiency, congenital ichthyosis-like presentation (collodion membrane, severe skin peeling and xerosis), and death before the first year of life.
- RNA and protein studies using fibroblasts derived from a patient are supportive of pathogenicity: RNA-seq, rt-qPCR and western blotting, showing marked reduction of DBR1 level and intronic RNA lariat accumulation in the patient sample.
- Haplotype analysis revealed that the four families all share a haplotype extending at least 2.27 Mb around the c.200A>G p.(Tyr67Cys) DBR1 founder variant.
- Authors proposed this is a novel DBR1-related developmental disorder that is distinct from DBR1-related encephalitis susceptibility, and highlighted the apparent lack of correlation with the degree of DBR1 deficiency.; Changed phenotypes: Ichthyosis (MONDO#0019269), DBR1-related
Intellectual disability syndromic and non-syndromic v0.5390 COL4A3BP Ee Ming Wong changed review comment from: - Thirty-one unrelated individuals with twenty-two distinct missense variants. The majority of variants were de novo.
- Several variants transfected into HeLa cells demonstrated gain of CERT activity
- CERT gain of function in Drosophila melanogaster led to head and brain size defects and impaired locomotor activity, which was corrected by pharmacological inhibition of CERT; to: - current HGNC symbol: CERT1
- Thirty-one unrelated individuals with twenty-two distinct missense variants. The majority of variants were de novo.
- Several variants transfected into HeLa cells demonstrated gain of CERT activity
- CERT gain of function in Drosophila melanogaster led to head and brain size defects and impaired locomotor activity, which was corrected by pharmacological inhibition of CERT
Mendeliome v1.1155 CAP2 Zornitza Stark Publications for gene: CAP2 were set to 30518548
Genetic Epilepsy v0.1911 RAB5C Rylee Peters gene: RAB5C was added
gene: RAB5C was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: RAB5C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RAB5C were set to PMID: 37552066
Phenotypes for gene: RAB5C were set to Neurodevelopmental disorder MONDO:0700092, RAB5C-related
Penetrance for gene: RAB5C were set to Complete
Review for gene: RAB5C was set to GREEN
gene: RAB5C was marked as current diagnostic
Added comment: 12 individuals with nine different heterozygous de novo variants in RAB5C.
9 with missense, 1 inframe duplication and 2 stop-gains (clinically more severe).
All has mild-severe ID, 4/12 have epilepsy, 6/12 have macrocephaly (more than 3 SD).
Sources: Literature
Cardiomyopathy_Paediatric v0.168 CAP2 Daniel Flanagan gene: CAP2 was added
gene: CAP2 was added to Cardiomyopathy_Paediatric. Sources: Expert list
Mode of inheritance for gene: CAP2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CAP2 were set to PMID: 30518548; 33083013; 34862840
Phenotypes for gene: CAP2 were set to Cardiomyopathy, dilated, 2I (MIM#620462)
Review for gene: CAP2 was set to GREEN
Added comment: Four patients from three families with homozygous variants and early onset DCM. Knockout mouse model shows DCM and cardiac conduction disease.

PMID: 33083013: Cheema
Homozygous nonsense (p.(Tyr316*)) reported in a DCM and heart failure patient. Two siblings deceased due to DCM but not tested.

PMID: 34862840: Gurunathan
Homozygous PTC identified in an infant with severe dilated cardiomyopathy, biventricular dysfunction and left ventricular noncompaction. Carrier parents unaffected.

PMID: 30518548: Aspit
Homozygous canonical splice variant in two cousins from a consanguineous family with DCM. All carriers unaffected. Knockout mouse model shows DCM and cardiac conduction disease.
Sources: Expert list
Mendeliome v1.1154 CAP2 Zornitza Stark Classified gene: CAP2 as Green List (high evidence)
Mendeliome v1.1154 CAP2 Zornitza Stark Gene: cap2 has been classified as Green List (High Evidence).
Dystonia - isolated/combined v1.34 GABRB3 Michelle Torres gene: GABRB3 was added
gene: GABRB3 was added to Dystonia - isolated/combined. Sources: Literature
Mode of inheritance for gene: GABRB3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GABRB3 were set to 37647766
Phenotypes for gene: GABRB3 were set to Developmental and epileptic encephalopathy 43 MIM#617113
Mode of pathogenicity for gene: GABRB3 was set to Other
Review for gene: GABRB3 was set to GREEN
Added comment: Voltage-clamp electrophysiology studies have shown that gain-of-function variants clustering in the transmembrane regions part of the channel pore result in a more severe phenotype, including movement disorders (dystonia and dyskinesia) and microcephaly.

Variants clustered in the coupling loops responsible for receptor activation are not associated with movement disorder and microcephaly.

LoF variants have not been associated with microcephaly and movement disorders.
Sources: Literature
Macrocephaly_Megalencephaly v0.132 RAB5C Ain Roesley Marked gene: RAB5C as ready
Macrocephaly_Megalencephaly v0.132 RAB5C Ain Roesley Gene: rab5c has been classified as Green List (High Evidence).
Mendeliome v1.1153 CAP2 Zornitza Stark reviewed gene: CAP2: Rating: GREEN; Mode of pathogenicity: None; Publications: 30518548, 33083013, 34862840; Phenotypes: Cardiomyopathy, dilated, 2I (MIM#620462); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Macrocephaly_Megalencephaly v0.132 RAB5C Ain Roesley Classified gene: RAB5C as Green List (high evidence)
Macrocephaly_Megalencephaly v0.132 RAB5C Ain Roesley Gene: rab5c has been classified as Green List (High Evidence).
Macrocephaly_Megalencephaly v0.131 RAB5C Ain Roesley Classified gene: RAB5C as Green List (high evidence)
Macrocephaly_Megalencephaly v0.131 RAB5C Ain Roesley Gene: rab5c has been classified as Green List (High Evidence).
Dilated Cardiomyopathy v1.23 CAP2 Zornitza Stark Marked gene: CAP2 as ready
Dilated Cardiomyopathy v1.23 CAP2 Zornitza Stark Gene: cap2 has been classified as Green List (High Evidence).
Mendeliome v1.1153 COL4A3BP Ee Ming Wong reviewed gene: COL4A3BP: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 36976648; Phenotypes: Intellectual developmental disorder 34 (MIM#616351); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Macrocephaly_Megalencephaly v0.130 RAB5C Rylee Peters gene: RAB5C was added
gene: RAB5C was added to Macrocephaly_Megalencephaly. Sources: Literature
Mode of inheritance for gene: RAB5C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RAB5C were set to PMID: 37552066
Phenotypes for gene: RAB5C were set to Neurodevelopmental disorder MONDO:0700092, RAB5C-related
Penetrance for gene: RAB5C were set to Complete
Review for gene: RAB5C was set to GREEN
gene: RAB5C was marked as current diagnostic
Added comment: 12 individuals with nine different heterozygous de novo variants in RAB5C.
9 with missense, 1 inframe duplication and 2 stop-gains (clinically more severe).
All has mild-severe ID, 4/12 have epilepsy, 6/12 have macrocephaly (more than 3 SD).
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5390 COL4A3BP Ee Ming Wong changed review comment from: - Thirty-one unrelated individuals with twenty-two distinct missense variants. The majority of variants were de novo.
- Several variants transfected into HeLa cells demonstrated gain of CERT activity
- CERT gain of function in Drosophila melanogaster led to head and brain size defects and impaired locomotor activity,
which was corrected by pharmacological inhibition of CERT; to: - Thirty-one unrelated individuals with twenty-two distinct missense variants. The majority of variants were de novo.
- Several variants transfected into HeLa cells demonstrated gain of CERT activity
- CERT gain of function in Drosophila melanogaster led to head and brain size defects and impaired locomotor activity, which was corrected by pharmacological inhibition of CERT
Dilated Cardiomyopathy v1.23 CAP2 Zornitza Stark Classified gene: CAP2 as Green List (high evidence)
Dilated Cardiomyopathy v1.23 CAP2 Zornitza Stark Gene: cap2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5390 COL4A3BP Ee Ming Wong changed review comment from: - Thirty-one unrelated individuals with twenty-two distinct missense variants. The majority of variants were de novo.
- Several variants transfected into HeLa cells demonstrated gain of CERT activity
- CERT gain of function in Drosophila melanogaster led to head and brain size defects and impaired locomotor activity,
which was corrected by pharmacological inhibition of CERT; to: - Thirty-one unrelated individuals with twenty-two distinct missense variants. The majority of variants were de novo.
- Several variants transfected into HeLa cells demonstrated gain of CERT activity
- CERT gain of function in Drosophila melanogaster led to head and brain size defects and impaired locomotor activity,
which was corrected by pharmacological inhibition of CERT
Dilated Cardiomyopathy v1.22 CAP2 Daniel Flanagan gene: CAP2 was added
gene: CAP2 was added to Dilated Cardiomyopathy. Sources: Expert list
Mode of inheritance for gene: CAP2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CAP2 were set to PMID: 30518548; 33083013; 34862840
Phenotypes for gene: CAP2 were set to Cardiomyopathy, dilated, 2I (MIM#620462)
Review for gene: CAP2 was set to GREEN
Added comment: Four patients from three families with homozygous variants and early onset DCM. Knockout mouse model shows DCM and cardiac conduction disease.

PMID: 33083013: Cheema
Homozygous nonsense (p.(Tyr316*)) reported in a DCM and heart failure patient. Two siblings deceased due to DCM but not tested.

PMID: 34862840: Gurunathan
Homozygous PTC identified in an infant with severe dilated cardiomyopathy, biventricular dysfunction and left ventricular noncompaction. Carrier parents unaffected.

PMID: 30518548: Aspit
Homozygous canonical splice variant in two cousins from a consanguineous family with DCM. All carriers unaffected. Knockout mouse model shows DCM and cardiac conduction disease.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.5390 COL4A3BP Ee Ming Wong reviewed gene: COL4A3BP: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 36976648; Phenotypes: Intellectual developmental disorder 34 (MIM#616351); Mode of inheritance: None; Current diagnostic: yes
Fetal anomalies v1.142 LNPK Zornitza Stark Marked gene: LNPK as ready
Fetal anomalies v1.142 LNPK Zornitza Stark Gene: lnpk has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v1.5 DHX16 Belinda Chong reviewed gene: DHX16: Rating: GREEN; Mode of pathogenicity: None; Publications: 37664979, 37574199; Phenotypes: Neuromuscular disease and ocular or auditory anomalies with or without seizures (MIM#618733, MONDO:0032890); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Fetal anomalies v1.142 LNPK Zornitza Stark Classified gene: LNPK as Green List (high evidence)
Fetal anomalies v1.142 LNPK Zornitza Stark Gene: lnpk has been classified as Green List (High Evidence).
Ichthyosis v1.5 DBR1 Seb Lunke Classified gene: DBR1 as Amber List (moderate evidence)
Ichthyosis v1.5 DBR1 Seb Lunke Gene: dbr1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5390 RAB5C Rylee Peters changed review comment from: 12 individuals with nine different heterozygous de novo variants in RAB5C.
9 with missense, 1 inframe duplication and 2 stop-gains (clinically more severe).
All has mild-severe ID, 4/12 have epilepsy, 6/12 have macrocephaly (more than 3 SD).
Sources: Literature; to: 12 individuals with nine different heterozygous de novo variants in RAB5C.
9 with missense, 1 inframe duplication and 2 stop-gains (clinically more severe).
All have mild to severe ID, 4/12 have epilepsy, 6/12 have macrocephaly (more than 3 SD).
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5390 RAB5C Ain Roesley Marked gene: RAB5C as ready
Intellectual disability syndromic and non-syndromic v0.5390 RAB5C Ain Roesley Gene: rab5c has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5390 RAB5C Ain Roesley Classified gene: RAB5C as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5390 RAB5C Ain Roesley Gene: rab5c has been classified as Green List (High Evidence).
Mendeliome v1.1153 RAB5C Ain Roesley Marked gene: RAB5C as ready
Mendeliome v1.1153 RAB5C Ain Roesley Gene: rab5c has been classified as Green List (High Evidence).
Mendeliome v1.1153 RAB5C Ain Roesley Classified gene: RAB5C as Green List (high evidence)
Mendeliome v1.1153 RAB5C Ain Roesley Gene: rab5c has been classified as Green List (High Evidence).
Mendeliome v1.1153 RAB5C Ain Roesley Classified gene: RAB5C as Green List (high evidence)
Mendeliome v1.1153 RAB5C Ain Roesley Gene: rab5c has been classified as Green List (High Evidence).
Macrocephaly_Megalencephaly v0.130 AXIN1 Elena Savva Classified gene: AXIN1 as Green List (high evidence)
Macrocephaly_Megalencephaly v0.130 AXIN1 Elena Savva Gene: axin1 has been classified as Green List (High Evidence).
Macrocephaly_Megalencephaly v0.129 AXIN1 Elena Savva Classified gene: AXIN1 as Green List (high evidence)
Macrocephaly_Megalencephaly v0.129 AXIN1 Elena Savva Gene: axin1 has been classified as Green List (High Evidence).
Mendeliome v1.1152 RAB5C Rylee Peters gene: RAB5C was added
gene: RAB5C was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RAB5C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RAB5C were set to PMID: 37552066
Phenotypes for gene: RAB5C were set to Neurodevelopmental disorder MONDO:0700092, RAB5C-related
Penetrance for gene: RAB5C were set to Complete
Review for gene: RAB5C was set to GREEN
gene: RAB5C was marked as current diagnostic
Added comment: 12 individuals with nine different heterozygous de novo variants in RAB5C.
9 with missense, 1 inframe duplication and 2 stop-gains (clinically more severe).
All has mild-severe ID, 4/12 have epilepsy, 6/12 have macrocephaly (more than 3 SD).
Sources: Literature
Macrocephaly_Megalencephaly v0.129 AXIN1 Elena Savva Classified gene: AXIN1 as Green List (high evidence)
Macrocephaly_Megalencephaly v0.129 AXIN1 Elena Savva Gene: axin1 has been classified as Green List (High Evidence).
Mendeliome v1.1152 AXIN1 Elena Savva Phenotypes for gene: AXIN1 were changed from Caudal duplication anomaly, MIM# 607864 to Caudal duplication anomaly, MIM# 607864; Syndromic disease, (MONDO:0002254), AXIN1-related
Mendeliome v1.1152 AXIN1 Elena Savva Publications for gene: AXIN1 were set to 9335612
Fetal anomalies v1.141 DBR1 Seb Lunke Classified gene: DBR1 as Amber List (moderate evidence)
Fetal anomalies v1.141 DBR1 Seb Lunke Gene: dbr1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1151 AXIN1 Elena Savva Classified gene: AXIN1 as Green List (high evidence)
Mendeliome v1.1151 AXIN1 Elena Savva Gene: axin1 has been classified as Green List (High Evidence).
Mendeliome v1.1151 AXIN1 Elena Savva Mode of inheritance for gene: AXIN1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5389 AXIN1 Elena Savva Classified gene: AXIN1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5389 AXIN1 Elena Savva Gene: axin1 has been classified as Green List (High Evidence).
Macrocephaly_Megalencephaly v0.128 AXIN1 Elena Savva Marked gene: AXIN1 as ready
Macrocephaly_Megalencephaly v0.128 AXIN1 Elena Savva Gene: axin1 has been classified as Red List (Low Evidence).
Mendeliome v1.1150 AXIN1 Elena Savva Classified gene: AXIN1 as Green List (high evidence)
Mendeliome v1.1150 AXIN1 Elena Savva Gene: axin1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5388 AXIN1 Elena Savva Classified gene: AXIN1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5388 AXIN1 Elena Savva Gene: axin1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5387 RAB5C Rylee Peters gene: RAB5C was added
gene: RAB5C was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: RAB5C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RAB5C were set to PMID: 37552066
Phenotypes for gene: RAB5C were set to Neurodevelopmental disorder MONDO:0700092, RAB5C-related
Penetrance for gene: RAB5C were set to Complete
Review for gene: RAB5C was set to GREEN
gene: RAB5C was marked as current diagnostic
Added comment: 12 individuals with nine different heterozygous de novo variants in RAB5C.
9 with missense, 1 inframe duplication and 2 stop-gains (clinically more severe).
All has mild-severe ID, 4/12 have epilepsy, 6/12 have macrocephaly (more than 3 SD).
Sources: Literature
Skeletal dysplasia v0.251 AXIN1 Elena Savva Classified gene: AXIN1 as Green List (high evidence)
Skeletal dysplasia v0.251 AXIN1 Elena Savva Gene: axin1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5387 AXIN1 Elena Savva Marked gene: AXIN1 as ready
Intellectual disability syndromic and non-syndromic v0.5387 AXIN1 Elena Savva Gene: axin1 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.5387 COL4A3BP Zornitza Stark Tag new gene name tag was added to gene: COL4A3BP.
Skeletal dysplasia v0.250 AXIN1 Elena Savva Marked gene: AXIN1 as ready
Skeletal dysplasia v0.250 AXIN1 Elena Savva Gene: axin1 has been classified as Green List (High Evidence).
Skeletal dysplasia v0.250 AXIN1 Elena Savva Marked gene: AXIN1 as ready
Skeletal dysplasia v0.250 AXIN1 Elena Savva Gene: axin1 has been classified as Green List (High Evidence).
Skeletal dysplasia v0.250 AXIN1 Elena Savva Classified gene: AXIN1 as Green List (high evidence)
Skeletal dysplasia v0.250 AXIN1 Elena Savva Gene: axin1 has been classified as Green List (High Evidence).
Fetal anomalies v1.140 LNPK Lilian Downie gene: LNPK was added
gene: LNPK was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: LNPK was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LNPK were set to PMID: 30032983, PMID:35599435, https://academic.oup.com/braincomms/advance-article/doi/10.1093/braincomms/fcad222/7243438?login=true
Phenotypes for gene: LNPK were set to Neurodevelopmental disorder with epilepsy and hypoplasia of the corpus callosum MIM#618090
Review for gene: LNPK was set to GREEN
Added comment: Moderate to severe ID, majority of patients 10/15 have period of regression
Epilepsy (myoclonic frequently)
Structural brain anomalies 'ear of the lynx sign', callosal hypoplasia, mild brain including cerebellar atrophy.
Microcephaly, macrocephaly and normal head circumference described.
Sources: Literature
Mendeliome v1.1149 COL4A3BP Zornitza Stark Tag new gene name tag was added to gene: COL4A3BP.
Genetic Epilepsy v0.1911 PPP1R3F Zornitza Stark Marked gene: PPP1R3F as ready
Genetic Epilepsy v0.1911 PPP1R3F Zornitza Stark Gene: ppp1r3f has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1911 PPP1R3F Zornitza Stark Classified gene: PPP1R3F as Green List (high evidence)
Genetic Epilepsy v0.1911 PPP1R3F Zornitza Stark Gene: ppp1r3f has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1910 PPP1R3F Andrew Fennell gene: PPP1R3F was added
gene: PPP1R3F was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: PPP1R3F was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: PPP1R3F were set to 37531237
Phenotypes for gene: PPP1R3F were set to Neurodevelopmental Disorder, MONDO:0700092,PPP1R3F-related
Review for gene: PPP1R3F was set to GREEN
Added comment: 13 unrelated hemizygous individuals with a neurodevelopmental disorder were reported, with functional evidence.
6/13 (46%) were reported with heterogeneous seizure types including generalized, nocturnal, tonic, atonic, focal, myoclonic, and atypical absence.
Sources: Literature
Fetal anomalies v1.140 DBR1 Chern Lim gene: DBR1 was added
gene: DBR1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: DBR1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DBR1 were set to 37656279
Phenotypes for gene: DBR1 were set to Prematurity, severe intrauterine growth deficiency, congenital ichthyosis-like presentation, and death before the first year of life
Review for gene: DBR1 was set to AMBER
gene: DBR1 was marked as current diagnostic
Added comment: PMID: 37656279:
- A homozygous missense as a founder recessive DBR1 variant in four consanguineous families.
- Consistent features include prematurity, severe intrauterine growth deficiency, congenital ichthyosis-like presentation (collodion membrane, severe skin peeling and xerosis), and death before the first year of life.
- RNA and protein studies using fibroblasts derived from a patient are supportive of pathogenicity: RNA-seq, rt-qPCR and western blotting, showing marked reduction of DBR1 level and intronic RNA lariat accumulation in the patient sample.
- Haplotype analysis revealed that the four families all share a haplotype extending at least 2.27 Mb around the c.200A>G p.(Tyr67Cys) DBR1 founder variant.
- Authors proposed this is a novel DBR1-related developmental disorder that is distinct from DBR1-related encephalitis susceptibility, and highlighted the apparent lack of correlation with the degree of DBR1 deficiency.
Sources: Literature
Ichthyosis v1.4 DBR1 Chern Lim gene: DBR1 was added
gene: DBR1 was added to Ichthyosis. Sources: Literature
Mode of inheritance for gene: DBR1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DBR1 were set to 37656279
Phenotypes for gene: DBR1 were set to Prematurity, severe intrauterine growth deficiency, congenital ichthyosis-like presentation, and death before the first year of life
Review for gene: DBR1 was set to AMBER
gene: DBR1 was marked as current diagnostic
Added comment: PMID: 37656279:
- A homozygous missense as a founder recessive DBR1 variant in four consanguineous families.
- Consistent features include prematurity, severe intrauterine growth deficiency, congenital ichthyosis-like presentation (collodion membrane, severe skin peeling and xerosis), and death before the first year of life.
- RNA and protein studies using fibroblasts derived from a patient are supportive of pathogenicity: RNA-seq, rt-qPCR and western blotting, showing marked reduction of DBR1 level and intronic RNA lariat accumulation in the patient sample.
- Haplotype analysis revealed that the four families all share a haplotype extending at least 2.27 Mb around the c.200A>G p.(Tyr67Cys) DBR1 founder variant.
- Authors proposed this is a novel DBR1-related developmental disorder that is distinct from DBR1-related encephalitis susceptibility, and highlighted the apparent lack of correlation with the degree of DBR1 deficiency.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5387 AXIN1 Elena Savva gene: AXIN1 was added
gene: AXIN1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: AXIN1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AXIN1 were set to PMID: 37582359
Phenotypes for gene: AXIN1 were set to Syndromic disease, (MONDO:0002254), AXIN1-related
Review for gene: AXIN1 was set to GREEN
Added comment: PMID: 37582359
- four families (7 individuals) with three homozygous truncating variants.
- all variant shown to result in reduced protein, though 1/3 would be NMD predicted
- Probands had macrocephaly (4/6), GDD (3/7), hip dysplasia (5/6), cardiac anomalies eg. VSD/ASD (3/7), cranial hyperostosis and vertebral endplate sclerosis
Sources: Literature
Macrocephaly_Megalencephaly v0.128 AXIN1 Elena Savva gene: AXIN1 was added
gene: AXIN1 was added to Macrocephaly_Megalencephaly. Sources: Literature
Mode of inheritance for gene: AXIN1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AXIN1 were set to PMID: 37582359
Phenotypes for gene: AXIN1 were set to Syndromic disease, (MONDO:0002254), AXIN1-related
Review for gene: AXIN1 was set to GREEN
Added comment: PMID: 37582359
- four families (7 individuals) with three homozygous truncating variants.
- all variant shown to result in reduced protein, though 1/3 would be NMD predicted
- Probands had macrocephaly (4/6), GDD (3/7), hip dysplasia (5/6), cardiac anomalies eg. VSD/ASD (3/7), cranial hyperostosis and vertebral endplate sclerosis
Sources: Literature
Skeletal dysplasia v0.249 AXIN1 Elena Savva gene: AXIN1 was added
gene: AXIN1 was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: AXIN1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AXIN1 were set to PMID: 37582359
Phenotypes for gene: AXIN1 were set to Syndromic disease, (MONDO:0002254), AXIN1-related
Review for gene: AXIN1 was set to GREEN
Added comment: PMID: 37582359
- four families (7 individuals) with three homozygous truncating variants.
- all variant shown to result in reduced protein, though 1/3 would be NMD predicted
- Probands had macrocephaly (4/6), GDD (3/7), hip dysplasia (5/6), cardiac anomalies eg. VSD/ASD (3/7), cranial hyperostosis and vertebral endplate sclerosis
Sources: Literature
Fetal anomalies v1.140 CUL3 Zornitza Stark Marked gene: CUL3 as ready
Fetal anomalies v1.140 CUL3 Zornitza Stark Gene: cul3 has been classified as Green List (High Evidence).
Fetal anomalies v1.140 CUL3 Zornitza Stark Classified gene: CUL3 as Green List (high evidence)
Fetal anomalies v1.140 CUL3 Zornitza Stark Gene: cul3 has been classified as Green List (High Evidence).
Callosome v0.505 LNPK Zornitza Stark Marked gene: LNPK as ready
Callosome v0.505 LNPK Zornitza Stark Gene: lnpk has been classified as Green List (High Evidence).
Callosome v0.505 LNPK Zornitza Stark Publications for gene: LNPK were set to PMID: 35599435, 30032983
Regression v0.533 LNPK Lilian Downie gene: LNPK was added
gene: LNPK was added to Regression. Sources: Literature
Mode of inheritance for gene: LNPK was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LNPK were set to PMID: 35599435, https://academic.oup.com/braincomms/advance-article/doi/10.1093/braincomms/fcad222/7243438?login=true
Phenotypes for gene: LNPK were set to Neurodevelopmental disorder with epilepsy and hypoplasia of the corpus callosum MIM#618090
Review for gene: LNPK was set to GREEN
Added comment: Moderate to severe ID, majority of patients 10/15 have period of regression
Epilepsy (myoclonic frequently)
Structural brain anomalies 'ear of the lynx sign', callosal hypoplasia, mild brain including cerebellar atrophy.
Microcephaly, macrocephaly and normal head circumference described.
Sources: Literature
Fetal anomalies v1.139 CUL3 Lucy Spencer gene: CUL3 was added
gene: CUL3 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: CUL3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CUL3 were set to 37665043
Phenotypes for gene: CUL3 were set to Neurodevelopmental disorder with or without autism or seizures (MIM#619239); Pseudohypoaldosteronism, type IIE (MIM#614496)
Review for gene: CUL3 was set to GREEN
Added comment: PMID: 37665043
1 case study and a review of the literature. 5 patients with de novo variants (PTCs and missense) in CUL3 who have various cardiac phenotypes: atrial septal defects, left ventricular outflow tract obstruction. Hypertrophic right ventricle pulmonary atresia, and other congenital heart defects. 2 of these patients have a neurological phenotype as well, while the other three are not reported to have one (but at least one was a terminated pregnancy).
Sources: Literature
Congenital Heart Defect v0.294 CUL3 Zornitza Stark Marked gene: CUL3 as ready
Congenital Heart Defect v0.294 CUL3 Zornitza Stark Gene: cul3 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.294 CUL3 Zornitza Stark Phenotypes for gene: CUL3 were changed from Neurodevelopmental disorder with or without autism or seizures (MIM#619239); Pseudohypoaldosteronism, type IIE (MIM#614496) to Neurodevelopmental disorder with or without autism or seizures (MIM#619239)
Congenital Heart Defect v0.293 CUL3 Zornitza Stark Classified gene: CUL3 as Green List (high evidence)
Congenital Heart Defect v0.293 CUL3 Zornitza Stark Gene: cul3 has been classified as Green List (High Evidence).
Mendeliome v1.1149 PPP1R3F Andrew Fennell changed review comment from: Sources: Literature; to: 13 unrelated hemizygous individuals reported with functional evidence
Sources: Literature
Mendeliome v1.1149 PPP1R3F Zornitza Stark Marked gene: PPP1R3F as ready
Mendeliome v1.1149 PPP1R3F Zornitza Stark Gene: ppp1r3f has been classified as Green List (High Evidence).
Mendeliome v1.1149 PPP1R3F Zornitza Stark Classified gene: PPP1R3F as Green List (high evidence)
Mendeliome v1.1149 PPP1R3F Zornitza Stark Gene: ppp1r3f has been classified as Green List (High Evidence).
Mendeliome v1.1148 PPP1R3F Andrew Fennell gene: PPP1R3F was added
gene: PPP1R3F was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PPP1R3F was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: PPP1R3F were set to 37531237
Phenotypes for gene: PPP1R3F were set to Neurodevelopmental Disorder, MONDO:0700092,PPP1R3F-related
Review for gene: PPP1R3F was set to GREEN
Added comment: Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5386 PPP1R3F Zornitza Stark Marked gene: PPP1R3F as ready
Intellectual disability syndromic and non-syndromic v0.5386 PPP1R3F Zornitza Stark Gene: ppp1r3f has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5386 PPP1R3F Zornitza Stark Classified gene: PPP1R3F as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5386 PPP1R3F Zornitza Stark Gene: ppp1r3f has been classified as Green List (High Evidence).
Callosome v0.504 LNPK Lilian Downie reviewed gene: LNPK: Rating: GREEN; Mode of pathogenicity: None; Publications: https://academic.oup.com/braincomms/advance-article/doi/10.1093/braincomms/fcad222/7243438?login=true; Phenotypes: Neurodevelopmental disorder with epilepsy and hypoplasia of the corpus callosum, MIM# 618090; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Heart Defect v0.292 CUL3 Lucy Spencer gene: CUL3 was added
gene: CUL3 was added to Congenital Heart Defect. Sources: Literature
Mode of inheritance for gene: CUL3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CUL3 were set to 37665043
Phenotypes for gene: CUL3 were set to Neurodevelopmental disorder with or without autism or seizures (MIM#619239); Pseudohypoaldosteronism, type IIE (MIM#614496)
Review for gene: CUL3 was set to GREEN
Added comment: PMID: 37665043
1 case study and a review of the literature. 5 patients with de novo variants (PTCs and missense) in CUL3 who have various cardiac phenotypes: atrial septal defects, left ventricular outflow tract obstruction. Hypertrophic right ventricle pulmonary atresia, and other congenital heart defects. 2 of these patients have a neurological phenotype as well, while the other three are not reported to have one (but at least one was a terminated pregnancy).
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5385 PPP1R3F Andrew Fennell gene: PPP1R3F was added
gene: PPP1R3F was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: PPP1R3F was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: PPP1R3F were set to 37531237
Phenotypes for gene: PPP1R3F were set to Neurodevelopmental Disorder, MONDO:0700092,PPP1R3F-related
Review for gene: PPP1R3F was set to GREEN
Added comment: 13 unrelated hemizygous individuals reported with functional evidence
Sources: Literature
Early-onset Parkinson disease v0.260 RAB39B Claire Fryer-Smith reviewed gene: RAB39B: Rating: GREEN; Mode of pathogenicity: None; Publications: 25434005, 26399558, 26739247; Phenotypes: Waisman syndrome (MIM#311510), Intellectual developmental disorder, X-linked 72 (MIM#300271); Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Congenital Heart Defect v0.292 LAMA3 Bryony Thompson Marked gene: LAMA3 as ready
Congenital Heart Defect v0.292 LAMA3 Bryony Thompson Gene: lama3 has been classified as Amber List (Moderate Evidence).
Additional findings_Adult v0.164 PTEN Chern Lim reviewed gene: PTEN: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: PTEN hamartoma tumour syndrome (MONDO#0017623); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Vascular Malformations_Germline v1.10 PTEN Chern Lim reviewed gene: PTEN: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: PTEN hamartoma tumour syndrome (MONDO#0017623); Mode of inheritance: None
Mendeliome v1.1148 LAMA3 Bryony Thompson Publications for gene: LAMA3 were set to 7633458; 8530087; 11810295; 10366601
Congenital Heart Defect v0.292 LAMA3 Bryony Thompson Classified gene: LAMA3 as Amber List (moderate evidence)
Congenital Heart Defect v0.292 LAMA3 Bryony Thompson Gene: lama3 has been classified as Amber List (Moderate Evidence).
Congenital Heart Defect v0.291 LAMA3 Bryony Thompson gene: LAMA3 was added
gene: LAMA3 was added to Congenital Heart Defect. Sources: Literature
Mode of inheritance for gene: LAMA3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: LAMA3 were set to 37635785
Phenotypes for gene: LAMA3 were set to Ebstein anomaly MONDO:0009144
Review for gene: LAMA3 was set to AMBER
Added comment: Single study with heterozygous nonsense variants identified in LAMA3 in two families with incomplete penetrance (a trio with one unaffected parent and a family with 2 affected and 1 unaffected carrier). p.Arg1126Ter has 5 hets in gnomAD v2.1 & p.Gln1507Ter has 4 hets in gnomAD v2.1. Variant filtering (including CNV detection algorithms) was conducted on WGS/WES from the trio and 2 affected individuals from the family.
Cardiac phenotypes in carriers of the junctional EB families harbouring LAMA3 pathogenic variants have not been reported. Lama3 +/- mice demonstrated abnormalities in the tricuspid valve and RV, similar to phenotypes observed in human Ebstein’s anomaly. Lama3 -/- mice were embryonic lethal.
Sources: Literature
Neurodegeneration with brain iron accumulation v0.30 FTH1 Bryony Thompson Marked gene: FTH1 as ready
Neurodegeneration with brain iron accumulation v0.30 FTH1 Bryony Thompson Gene: fth1 has been classified as Green List (High Evidence).
Neurodegeneration with brain iron accumulation v0.30 FTH1 Bryony Thompson Classified gene: FTH1 as Green List (high evidence)
Neurodegeneration with brain iron accumulation v0.30 FTH1 Bryony Thompson Added comment: Comment on list classification: Article describing the gene-disease association with neuroferritinopathy now published in HGG advances
Neurodegeneration with brain iron accumulation v0.30 FTH1 Bryony Thompson Gene: fth1 has been classified as Green List (High Evidence).
Neurodegeneration with brain iron accumulation v0.29 FTH1 Bryony Thompson Publications for gene: FTH1 were set to 36778397
Cerebellar and Pontocerebellar Hypoplasia v1.62 FTH1 Bryony Thompson Publications for gene: FTH1 were set to 36778397
Cerebellar and Pontocerebellar Hypoplasia v1.61 FTH1 Bryony Thompson Classified gene: FTH1 as Green List (high evidence)
Cerebellar and Pontocerebellar Hypoplasia v1.61 FTH1 Bryony Thompson Added comment: Comment on list classification: Article describing the gene-disease association with neuroferritinopathy now published in HGG advances
Cerebellar and Pontocerebellar Hypoplasia v1.61 FTH1 Bryony Thompson Gene: fth1 has been classified as Green List (High Evidence).
Regression v0.533 FTH1 Bryony Thompson Publications for gene: FTH1 were set to 36778397
Regression v0.532 FTH1 Bryony Thompson Classified gene: FTH1 as Green List (high evidence)
Regression v0.532 FTH1 Bryony Thompson Added comment: Comment on list classification: Article describing the gene-disease association with neuroferritinopathy now published in HGG advances
Regression v0.532 FTH1 Bryony Thompson Gene: fth1 has been classified as Green List (High Evidence).
Mendeliome v1.1147 FTH1 Bryony Thompson Publications for gene: FTH1 were set to 11389486; 36778397
Mendeliome v1.1146 FTH1 Bryony Thompson Mode of pathogenicity for gene: FTH1 was changed from None to Other
Mendeliome v1.1145 FTH1 Bryony Thompson Classified gene: FTH1 as Green List (high evidence)
Mendeliome v1.1145 FTH1 Bryony Thompson Added comment: Comment on list classification: Article describing the gene-disease association with neuroferritinopathy now published in HGG advances
Mendeliome v1.1145 FTH1 Bryony Thompson Gene: fth1 has been classified as Green List (High Evidence).
Mendeliome v1.1144 C3 Ain Roesley Phenotypes for gene: C3 were changed from C3 deficiency MIM#613779 to C3 deficiency MIM#613779; C3 deficiency MIM#613779; {Hemolytic uremic syndrome, atypical, susceptibility to, 5}, MIM# 612925
Mendeliome v1.1143 C3 Ain Roesley Publications for gene: C3 were set to 15781264; 1944729; 11813855; 26847111
Mendeliome v1.1143 C3 Ain Roesley Mode of inheritance for gene: C3 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.1142 C3 Ain Roesley edited their review of gene: C3: Changed phenotypes: C3 deficiency MIM#613779, {Hemolytic uremic syndrome, atypical, susceptibility to, 5}, MIM# 612925
Mendeliome v1.1142 C3 Ain Roesley edited their review of gene: C3: Added comment: Multiple individuals reported with mono-allelic variants and aHUS. At least one report of biallelic variants.; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5385 ATM Zornitza Stark Marked gene: ATM as ready
Intellectual disability syndromic and non-syndromic v0.5385 ATM Zornitza Stark Gene: atm has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5385 ATM Zornitza Stark Phenotypes for gene: ATM were changed from to Ataxia-telangiectasia, MIM#208900
Intellectual disability syndromic and non-syndromic v0.5384 ATM Zornitza Stark Classified gene: ATM as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.5384 ATM Zornitza Stark Gene: atm has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5383 ATM Zornitza Stark edited their review of gene: ATM: Added comment: Progressive cerebellar dysfunction. Intellectual ability is typically normal. However, learning can be impaired due to motor and speech difficulties.; Changed rating: AMBER
Cataract v0.355 COL4A2 Ee Ming Wong gene: COL4A2 was added
gene: COL4A2 was added to Cataract. Sources: Literature
Mode of inheritance for gene: COL4A2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: COL4A2 were set to PMID: 26708157; 24203695
Phenotypes for gene: COL4A2 were set to Cataract (MONDO:0005129), COL4A2-related
Review for gene: COL4A2 was set to AMBER
gene: COL4A2 was marked as current diagnostic
Added comment: - PMID: 26708157: One family with an autosomal dominant disorder comprising porencephaly, focal epilepsy, and lens opacities where p.Gly800Glu was identified in affected family members. The cataracts identified in this family was considered a phenotypic expansion associated with COL4A2 mutation.
- PMID: 24203695: Heterozygous mice carrying the COL4A2 p.(Gly646Asp) variant demonstrated cerebral, muscular and ocular phenotypes including cataract.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5383 ATM Zornitza Stark reviewed gene: ATM: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Ataxia-telangiectasia, MIM#208900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebral Palsy v1.188 ESAM Zornitza Stark Marked gene: ESAM as ready
Cerebral Palsy v1.188 ESAM Zornitza Stark Gene: esam has been classified as Green List (High Evidence).
Cerebral Palsy v1.188 ESAM Zornitza Stark Classified gene: ESAM as Green List (high evidence)
Cerebral Palsy v1.188 ESAM Zornitza Stark Gene: esam has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v0.168 TBX20 Zornitza Stark Publications for gene: TBX20 were set to 26118961; 17668378; 27510170; 35282022
Cerebral Palsy v1.187 ESAM Luisa Weiss changed review comment from: Lecca et al. reported 13 individuals from 8 families (4 of which coming from the same geographical region) with a severe neurodevelopmental disorder. Although no formal diagnosis of CP was made, all patients had spasticity and most patients showed spastic tetraparesis. Many patients showed additional phenotypic features (like dysmorphism). All mutations were predicted to be Loss of function mutations.

ESAM encodes an endothelial cell adhesion molecule. A recurrent variant (c.115del;p.(Arg39Glyfs∗33)) was functionally analyzed and showed to impair the in vitro tubulogenic process of endothelial colony-forming cells and to caus lack of ESAM expression in the capillary endothelial cells of damaged brain.
Sources: Literature; to: Lecca et al. reported 13 individuals from 8 families (4 of which coming from the same geographical region) with a severe neurodevelopmental disorder. Although no formal diagnosis of CP was made, all patients had spasticity and most patients showed spastic tetraparesis. Many patients showed additional phenotypic features (like dysmorphism). All mutations were predicted to be Loss of function mutations.

ESAM encodes an endothelial cell adhesion molecule. A recurrent variant (c.115del;p.(Arg39Glyfs∗33)) was functionally analyzed and showed to impair the in vitro tubulogenic process of endothelial colony-forming cells and to cause lack of ESAM expression in the capillary endothelial cells of damaged brain.
Sources: Literature
Cerebral Palsy v1.187 ESAM Luisa Weiss gene: ESAM was added
gene: ESAM was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: ESAM was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ESAM were set to 36996813
Phenotypes for gene: ESAM were set to Neurodevelopmental disorder with intracranial hemorrhage, seizures, and spasticity MIM#620371
Review for gene: ESAM was set to GREEN
Added comment: Lecca et al. reported 13 individuals from 8 families (4 of which coming from the same geographical region) with a severe neurodevelopmental disorder. Although no formal diagnosis of CP was made, all patients had spasticity and most patients showed spastic tetraparesis. Many patients showed additional phenotypic features (like dysmorphism). All mutations were predicted to be Loss of function mutations.

ESAM encodes an endothelial cell adhesion molecule. A recurrent variant (c.115del;p.(Arg39Glyfs∗33)) was functionally analyzed and showed to impair the in vitro tubulogenic process of endothelial colony-forming cells and to caus lack of ESAM expression in the capillary endothelial cells of damaged brain.
Sources: Literature
Cardiomyopathy_Paediatric v0.167 TBX20 Ivan Macciocca reviewed gene: TBX20: Rating: ; Mode of pathogenicity: None; Publications: 37657916; Phenotypes: ; Mode of inheritance: None
Differences of Sex Development v0.282 SOX11 Zornitza Stark Marked gene: SOX11 as ready
Differences of Sex Development v0.282 SOX11 Zornitza Stark Gene: sox11 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v1.5 CAPN3 Zornitza Stark changed review comment from: More appropriate for LGMD panel.; to: More appropriate for LGMD panel but rate Amber here to avoid missing diagnoses.
Muscular dystrophy and myopathy_Paediatric v1.5 CAPN3 Zornitza Stark edited their review of gene: CAPN3: Changed rating: AMBER
Muscular dystrophy and myopathy_Paediatric v1.5 CAPN3 Zornitza Stark Classified gene: CAPN3 as Amber List (moderate evidence)
Muscular dystrophy and myopathy_Paediatric v1.5 CAPN3 Zornitza Stark Gene: capn3 has been classified as Amber List (Moderate Evidence).
Bone Marrow Failure v1.51 SLC30A7 Zornitza Stark Marked gene: SLC30A7 as ready
Bone Marrow Failure v1.51 SLC30A7 Zornitza Stark Gene: slc30a7 has been classified as Red List (Low Evidence).
Bone Marrow Failure v1.51 SLC30A7 Zornitza Stark gene: SLC30A7 was added
gene: SLC30A7 was added to Bone Marrow Failure. Sources: Expert Review
Mode of inheritance for gene: SLC30A7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC30A7 were set to 36821639
Phenotypes for gene: SLC30A7 were set to Ziegler-Huang syndrome, MIM# 620501
Review for gene: SLC30A7 was set to RED
Added comment: Two sibs reported with compound het variants in this gene and severe growth failure, testicular hypoplasia and progressive bone marrow failure.
Sources: Expert Review
Growth failure v1.69 SLC30A7 Zornitza Stark Marked gene: SLC30A7 as ready
Growth failure v1.69 SLC30A7 Zornitza Stark Gene: slc30a7 has been classified as Red List (Low Evidence).
Growth failure v1.69 SLC30A7 Zornitza Stark gene: SLC30A7 was added
gene: SLC30A7 was added to Growth failure. Sources: Expert Review
Mode of inheritance for gene: SLC30A7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC30A7 were set to 36821639
Phenotypes for gene: SLC30A7 were set to Ziegler-Huang syndrome, MIM# 620501
Review for gene: SLC30A7 was set to RED
Added comment: Two sibs reported with compound het variants in this gene and severe growth failure, testicular hypoplasia and progressive bone marrow failure.
Sources: Expert Review
Mendeliome v1.1142 SLC30A7 Zornitza Stark reviewed gene: SLC30A7: Rating: RED; Mode of pathogenicity: None; Publications: 36821639; Phenotypes: Ziegler-Huang syndrome, MIM# 620501; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.282 SOX11 Zornitza Stark Classified gene: SOX11 as Green List (high evidence)
Differences of Sex Development v0.282 SOX11 Zornitza Stark Gene: sox11 has been classified as Green List (High Evidence).
Differences of Sex Development v0.281 SOX11 Zornitza Stark gene: SOX11 was added
gene: SOX11 was added to Differences of Sex Development. Sources: Expert Review
Mode of inheritance for gene: SOX11 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SOX11 were set to 29459093; 24886874; 33086258; 33785884; 35642566; 35341651
Phenotypes for gene: SOX11 were set to Intellectual developmental disorder with microcephaly and with or without ocular malformations or hypogonadotropic hypogonadism, MIM# 615866
Review for gene: SOX11 was set to GREEN
Added comment: Over 40 individuals reported, e.g. PMID 35341651. The phenotype that has emerged over time is distinct from patients with mutations in ARID1B (614556) and Coffin-Siris syndrome-1 (135900). Patients with IDDMOH tend to be microcephalic and have ocular motor apraxia, abnormal eye morphology, or hypogonadotropic hypogonadism.
Sources: Expert Review
Microcephaly v1.229 SOX11 Zornitza Stark changed review comment from: Over 40 additional individuals reported, e.g. PMID 35341651. The phenotype that has emerged over time is distinct from patients with mutations in ARID1B (614556) and Coffin-Siris syndrome-1 (135900). Patients with IDDMOH tend to be microcephalic and have ocular motor apraxia, abnormal eye morphology, or hypogonadotropic hypogonadism.
Sources: Expert Review; to: Over 40 individuals reported, e.g. PMID 35341651. The phenotype that has emerged over time is distinct from patients with mutations in ARID1B (614556) and Coffin-Siris syndrome-1 (135900). Patients with IDDMOH tend to be microcephalic and have ocular motor apraxia, abnormal eye morphology, or hypogonadotropic hypogonadism.
Sources: Expert Review
Microcephaly v1.229 SOX11 Zornitza Stark Marked gene: SOX11 as ready
Microcephaly v1.229 SOX11 Zornitza Stark Gene: sox11 has been classified as Green List (High Evidence).
Microcephaly v1.229 SOX11 Zornitza Stark Classified gene: SOX11 as Green List (high evidence)
Microcephaly v1.229 SOX11 Zornitza Stark Gene: sox11 has been classified as Green List (High Evidence).
Microcephaly v1.228 SOX11 Zornitza Stark gene: SOX11 was added
gene: SOX11 was added to Microcephaly. Sources: Expert Review
Mode of inheritance for gene: SOX11 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SOX11 were set to 29459093; 24886874; 33086258; 33785884; 35642566; 35341651
Phenotypes for gene: SOX11 were set to Intellectual developmental disorder with microcephaly and with or without ocular malformations or hypogonadotropic hypogonadism, MIM# 615866
Review for gene: SOX11 was set to GREEN
Added comment: Over 40 additional individuals reported, e.g. PMID 35341651. The phenotype that has emerged over time is distinct from patients with mutations in ARID1B (614556) and Coffin-Siris syndrome-1 (135900). Patients with IDDMOH tend to be microcephalic and have ocular motor apraxia, abnormal eye morphology, or hypogonadotropic hypogonadism.
Sources: Expert Review
Fetal anomalies v1.139 SOX11 Zornitza Stark reviewed gene: SOX11: Rating: GREEN; Mode of pathogenicity: None; Publications: 29459093, 24886874, 33086258, 33785884, 35642566, 35341651; Phenotypes: Intellectual developmental disorder with microcephaly and with or without ocular malformations or hypogonadotropic hypogonadism, MIM# 615866; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5383 SOX11 Zornitza Stark Phenotypes for gene: SOX11 were changed from Coffin-Siris syndrome 9, OMIM # 615866 to Intellectual developmental disorder with microcephaly and with or without ocular malformations or hypogonadotropic hypogonadism, MIM# 615866
Intellectual disability syndromic and non-syndromic v0.5382 SOX11 Zornitza Stark Publications for gene: SOX11 were set to 24886874; 33785884; 33430815; 33086258; 31530938
Intellectual disability syndromic and non-syndromic v0.5381 SOX11 Zornitza Stark reviewed gene: SOX11: Rating: GREEN; Mode of pathogenicity: None; Publications: 29459093, 24886874, 33086258, 33785884, 35642566, 35341651; Phenotypes: Intellectual developmental disorder with microcephaly and with or without ocular malformations or hypogonadotropic hypogonadism, MIM# 615866; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.1142 SOX11 Zornitza Stark Phenotypes for gene: SOX11 were changed from Coffin-Siris syndrome 9, MIM# 615866; Congenital abnormalities of the kidneys and urinary tract to Intellectual developmental disorder with microcephaly and with or without ocular malformations or hypogonadotropic hypogonadism, MIM# 615866; Congenital abnormalities of the kidneys and urinary tract
Mendeliome v1.1141 SOX11 Zornitza Stark Publications for gene: SOX11 were set to 29459093; 24886874
Mendeliome v1.1140 SOX11 Zornitza Stark edited their review of gene: SOX11: Added comment: Over 40 additional individuals reported, e.g. PMID 35341651. The phenotype that has emerged over time is distinct from patients with mutations in ARID1B (614556) and Coffin-Siris syndrome-1 (135900). Patients with IDDMOH tend to be microcephalic and have ocular motor apraxia, abnormal eye morphology, or hypogonadotropic hypogonadism.; Changed publications: 29459093, 24886874, 33086258, 33785884, 35642566, 35341651
Mendeliome v1.1140 SOX11 Zornitza Stark edited their review of gene: SOX11: Changed phenotypes: Intellectual developmental disorder with microcephaly and with or without ocular malformations or hypogonadotropic hypogonadism, MIM# 615866, Congenital abnormalities of the kidneys and urinary tract
Genetic Epilepsy v0.1910 ATP5O Zornitza Stark Marked gene: ATP5O as ready
Genetic Epilepsy v0.1910 ATP5O Zornitza Stark Gene: atp5o has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1910 ATP5O Zornitza Stark Classified gene: ATP5O as Green List (high evidence)
Genetic Epilepsy v0.1910 ATP5O Zornitza Stark Gene: atp5o has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1909 ATP5O Zornitza Stark gene: ATP5O was added
gene: ATP5O was added to Genetic Epilepsy. Sources: Expert list
Mode of inheritance for gene: ATP5O was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATP5O were set to 35621276; 34954817
Phenotypes for gene: ATP5O were set to Mitochondrial complex V (ATP synthase) deficiency, nuclear type 7, MIM# 620359
Review for gene: ATP5O was set to GREEN
Added comment: Three unrelated families reported. Presenting features included DD, hypotonia, seizures.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.5381 ATP5O Zornitza Stark Classified gene: ATP5O as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5381 ATP5O Zornitza Stark Gene: atp5o has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5380 ATP5O Zornitza Stark Classified gene: ATP5O as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5380 ATP5O Zornitza Stark Gene: atp5o has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5379 ATP5O Zornitza Stark Marked gene: ATP5O as ready
Intellectual disability syndromic and non-syndromic v0.5379 ATP5O Zornitza Stark Gene: atp5o has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.5379 ATP5O Zornitza Stark gene: ATP5O was added
gene: ATP5O was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list
Mode of inheritance for gene: ATP5O was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATP5O were set to 35621276; 34954817
Phenotypes for gene: ATP5O were set to Mitochondrial complex V (ATP synthase) deficiency, nuclear type 7, MIM# 620359
Review for gene: ATP5O was set to GREEN
Added comment: Three unrelated families reported. Presenting features included DD, hypotonia, seizures.
Sources: Expert list
Fetal anomalies v1.139 ATP5O Zornitza Stark Marked gene: ATP5O as ready
Fetal anomalies v1.139 ATP5O Zornitza Stark Gene: atp5o has been classified as Green List (High Evidence).
Fetal anomalies v1.139 ATP5O Zornitza Stark Classified gene: ATP5O as Green List (high evidence)
Fetal anomalies v1.139 ATP5O Zornitza Stark Gene: atp5o has been classified as Green List (High Evidence).
Fetal anomalies v1.138 ATP5O Zornitza Stark gene: ATP5O was added
gene: ATP5O was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: ATP5O was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATP5O were set to 35621276; 34954817
Phenotypes for gene: ATP5O were set to Mitochondrial complex V (ATP synthase) deficiency, nuclear type 7, MIM# 620359
Review for gene: ATP5O was set to GREEN
Added comment: Prenatal phenotypes reported (IUGR, CHD, oligohydramnios)
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.5378 HIKESHI Zornitza Stark Marked gene: HIKESHI as ready
Intellectual disability syndromic and non-syndromic v0.5378 HIKESHI Zornitza Stark Gene: hikeshi has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5378 HIKESHI Zornitza Stark Classified gene: HIKESHI as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5378 HIKESHI Zornitza Stark Gene: hikeshi has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5377 HIKESHI Zornitza Stark gene: HIKESHI was added
gene: HIKESHI was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list
Mode of inheritance for gene: HIKESHI was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HIKESHI were set to 34111619; 26545878
Phenotypes for gene: HIKESHI were set to Leukodystrophy, hypomyelinating, 13, MIM# 616881
Review for gene: HIKESHI was set to GREEN
Added comment: Over 10 individuals reported with recurrent homozygous c.160G>C;p.(Val54Leu) variant, high carrier frequency in the Ashkenazi Jewish population. Optic atrophy reported in several.
Sources: Expert list
Optic Atrophy v1.22 HIKESHI Zornitza Stark Marked gene: HIKESHI as ready
Optic Atrophy v1.22 HIKESHI Zornitza Stark Gene: hikeshi has been classified as Green List (High Evidence).
Optic Atrophy v1.22 HIKESHI Zornitza Stark Classified gene: HIKESHI as Green List (high evidence)
Optic Atrophy v1.22 HIKESHI Zornitza Stark Gene: hikeshi has been classified as Green List (High Evidence).
Optic Atrophy v1.21 HIKESHI Zornitza Stark gene: HIKESHI was added
gene: HIKESHI was added to Optic Atrophy. Sources: Expert list
Mode of inheritance for gene: HIKESHI was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HIKESHI were set to 34111619; 26545878
Phenotypes for gene: HIKESHI were set to Leukodystrophy, hypomyelinating, 13, MIM# 616881
Review for gene: HIKESHI was set to GREEN
Added comment: Over 10 individuals reported with recurrent homozygous c.160G>C;p.(Val54Leu) variant, high carrier frequency in the Ashkenazi Jewish population. Optic atrophy reported in several.
Sources: Expert list
Anophthalmia_Microphthalmia_Coloboma v1.34 MPDZ Zornitza Stark Marked gene: MPDZ as ready
Anophthalmia_Microphthalmia_Coloboma v1.34 MPDZ Zornitza Stark Gene: mpdz has been classified as Green List (High Evidence).
Anophthalmia_Microphthalmia_Coloboma v1.34 MPDZ Zornitza Stark Classified gene: MPDZ as Green List (high evidence)
Anophthalmia_Microphthalmia_Coloboma v1.34 MPDZ Zornitza Stark Gene: mpdz has been classified as Green List (High Evidence).
Anophthalmia_Microphthalmia_Coloboma v1.33 MPDZ Zornitza Stark gene: MPDZ was added
gene: MPDZ was added to Anophthalmia_Microphthalmia_Coloboma. Sources: Expert list
Mode of inheritance for gene: MPDZ was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MPDZ were set to 28556411; 36429029; 36594712
Phenotypes for gene: MPDZ were set to Hydrocephalus, congenital, 2, with or without brain or eye anomalies, MIM# 615219
Review for gene: MPDZ was set to GREEN
Added comment: PMID:28556411 - Three unrelated patients were reported with biallelic MPDZ variants and congenital hydrocephalus and eye/ brain anomalies. The 2.5 year-old with homozygous variant (p.Gln1490Argfs*19) had macular hypoplasia, 8 year-old boy with compound heterozygous variants (p.Arg744Ter & p.Arg1071Ter) had foveal dysplasia with thin inner retina, and 15-month old boy with homozygous variant (p.Ala1760Thr) had iris coloboma and prominent optic nerve. This 15-month old boy also had cholestasis and liver failure associated with a variant in the TJP2 gene (p.[Leu192Profs*3]).

PMID:36429029 - A Chinese proband with isolated bilateral macular coloboma was identified with compound heterozygous variants (p.Asp1434fs*3 & p.Ser1752Ter). In addition, results from in silico analysis and phenotypes observed in zebrafish knockdown model recapitulate the phenotypes observed in the proband.

PMID:36594712 - A 4 year-old proband presenting with intermittent exotropia and decreased vision in both eyes was identified with compound heterozygous variants in MPDZ gene (c.3100C>T/ p.Arg1034Ter & c.747 + 2T>G). This patient had macular colobomas and far temporal chorioretinal atrophy in both eyes. His 9 year-old older brother with the same variants had a visual acuity of 20/25 in the right eye and 20/40 in the left eye and was found to have subtle changes in the foveal reflex of both eyes.
Sources: Expert list
Genetic Epilepsy v0.1908 PABPC1 Zornitza Stark Marked gene: PABPC1 as ready
Genetic Epilepsy v0.1908 PABPC1 Zornitza Stark Gene: pabpc1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1908 PABPC1 Zornitza Stark Classified gene: PABPC1 as Green List (high evidence)
Genetic Epilepsy v0.1908 PABPC1 Zornitza Stark Gene: pabpc1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1907 PABPC1 Zornitza Stark gene: PABPC1 was added
gene: PABPC1 was added to Genetic Epilepsy. Sources: Expert Review
Mode of inheritance for gene: PABPC1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PABPC1 were set to 35511136
Phenotypes for gene: PABPC1 were set to Neurodevelopmental disorder, PABPC1-related (MONDO#0700092)
Review for gene: PABPC1 was set to GREEN
Added comment: PMID: 35511136 - 4 probands with an overlapping phenotype of DD, expressive speech delay, and autistic features and heterozygous de novo variants that cluster in the PABP domain of PABPC1. Intellectual disability ranged in the cases from profound (1/4), IQ: 61 (1/4) and IQ: 79 (2/4). Seizures were apparent in the all of the three cases where it was assessed.

Electroporation of mouse embryo brains showed that Pabpc1 knockdown decreases the proliferation of neural progenitor cells. Wild-type Pabpc1 could rescue this disturbance, whereas 3 of the 4 variants did not.
Sources: Expert Review
Intellectual disability syndromic and non-syndromic v0.5376 FAM111A Zornitza Stark Marked gene: FAM111A as ready
Intellectual disability syndromic and non-syndromic v0.5376 FAM111A Zornitza Stark Gene: fam111a has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.5376 FAM111A Zornitza Stark Phenotypes for gene: FAM111A were changed from to Kenny-Caffey syndrome, type 2, MIM# 127000
Intellectual disability syndromic and non-syndromic v0.5375 FAM111A Zornitza Stark Mode of inheritance for gene: FAM111A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5374 FAM111A Zornitza Stark Classified gene: FAM111A as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.5374 FAM111A Zornitza Stark Gene: fam111a has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.5373 FAM111A Zornitza Stark reviewed gene: FAM111A: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Kenny-Caffey syndrome, type 2, MIM# 127000; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v1.137 RAP1B Zornitza Stark Phenotypes for gene: RAP1B were changed from Syndromic intellectual disability; short stature to Syndromic disease, MONDO:0002254, RAP1B-related
Growth failure v1.68 RAP1B Zornitza Stark Phenotypes for gene: RAP1B were changed from Syndromic intellectual disability; short stature to Syndromic disease, MONDO:0002254, RAP1B-related
Growth failure v1.67 RAP1B Zornitza Stark edited their review of gene: RAP1B: Changed phenotypes: Syndromic disease, MONDO:0002254, RAP1B-related
Intellectual disability syndromic and non-syndromic v0.5373 RAP1B Zornitza Stark Phenotypes for gene: RAP1B were changed from RAP1B‐associated phenotype, no OMIM # to Syndromic disease, MONDO:0002254, RAP1B-related
Intellectual disability syndromic and non-syndromic v0.5372 RAP1B Zornitza Stark edited their review of gene: RAP1B: Changed phenotypes: Syndromic disease, MONDO:0002254, RAP1B-related
Mendeliome v1.1140 RAP1B Zornitza Stark Phenotypes for gene: RAP1B were changed from RAP1B‐associated syndrome; intellectual disability; microcephaly; thrombocytopaenia to Syndromic disease, MONDO:0002254, RAP1B-related; intellectual disability; microcephaly; thrombocytopaenia
Kabuki syndrome v0.14 RAP1B Zornitza Stark Phenotypes for gene: RAP1B were changed from Kabuki syndrome to Syndromic disease, MONDO:0002254, RAP1B-related; Kabuki-like syndrome
Kabuki syndrome v0.13 RAP1B Zornitza Stark edited their review of gene: RAP1B: Changed phenotypes: Syndromic disease, MONDO:0002254, RAP1B-related, Kabuki-like syndrome
Bone Marrow Failure v1.50 RAP1B Zornitza Stark Marked gene: RAP1B as ready
Bone Marrow Failure v1.50 RAP1B Zornitza Stark Gene: rap1b has been classified as Amber List (Moderate Evidence).
Bone Marrow Failure v1.50 RAP1B Zornitza Stark Classified gene: RAP1B as Amber List (moderate evidence)
Bone Marrow Failure v1.50 RAP1B Zornitza Stark Gene: rap1b has been classified as Amber List (Moderate Evidence).
Bone Marrow Failure v1.49 RAP1B Zornitza Stark gene: RAP1B was added
gene: RAP1B was added to Bone Marrow Failure. Sources: Expert list
Mode of inheritance for gene: RAP1B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RAP1B were set to 35451551; 32627184; 26280580
Phenotypes for gene: RAP1B were set to Syndromic disease, MONDO:0002254, RAP1B-related
Review for gene: RAP1B was set to AMBER
Added comment: PMID: 32627184 describes 2 patients.
36 yo patient of non-consanguineous parents. Had unclear pancytopenia, multiple congenital malformations, mild intellectual disability, endocrine disorders (short stature with growth hormone deficiency), dysmorphism and other features. Parents and sibling unaffected.
13 yo of non-consanguineous parents with thrombocytopenia, multiple congenital anomalies and learning difficulties. He had normal developmental milestones, walk was achieved at 14 months and there was no speech delay. He attended mainstream school with auxiliary help because of learning difficulties with graphism, syntaxic comprehension, logical reasoning and attention deficit. Parents and siblings unaffected.

PMID: 26280580 describes another patient with variant in RAP1B. The clinical features can be found in supplementary table 2. The table lists ID, but doesn't say severity and lists a host of other features including short stature, facial dysmorphism and skeletal findings. Cytopenia is not a feature for this patient.

PMID 35451551: New patient reported with mild intellectual disability, bicuspid aortic valve, dilation of aortic root and ascending aorta, hearing loss, and long‐standing thrombocytopenia with lymphopenia. Found to have a novel, missense mutation in RAP1B (p.Ala59Gly) - neighbouring amino acid to one of the previously reported variants.
Sources: Expert list
Microcephaly v1.227 ATP6V0C Zornitza Stark Marked gene: ATP6V0C as ready
Microcephaly v1.227 ATP6V0C Zornitza Stark Gene: atp6v0c has been classified as Green List (High Evidence).
Microcephaly v1.227 ATP6V0C Zornitza Stark Classified gene: ATP6V0C as Green List (high evidence)
Microcephaly v1.227 ATP6V0C Zornitza Stark Gene: atp6v0c has been classified as Green List (High Evidence).
Microcephaly v1.226 ATP6V0C Zornitza Stark gene: ATP6V0C was added
gene: ATP6V0C was added to Microcephaly. Sources: Expert Review
Mode of inheritance for gene: ATP6V0C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ATP6V0C were set to 33190975; 33090716; 36074901
Phenotypes for gene: ATP6V0C were set to Epilepsy, early-onset, 3, with or without developmental delay, OMIM:620465
Review for gene: ATP6V0C was set to GREEN
Added comment: PMID:36074901 - 5 out of 27 patients had severe microcephaly (having occipitofrontal circumference (OFC) beyond 3 SD below the mean for their age).
Sources: Expert Review
Microcephaly v1.225 HPDL Zornitza Stark Marked gene: HPDL as ready
Microcephaly v1.225 HPDL Zornitza Stark Gene: hpdl has been classified as Green List (High Evidence).
Deafness_Isolated v1.48 GOSR2 Zornitza Stark Marked gene: GOSR2 as ready
Deafness_Isolated v1.48 GOSR2 Zornitza Stark Gene: gosr2 has been classified as Red List (Low Evidence).
Deafness_Isolated v1.48 GOSR2 Zornitza Stark gene: GOSR2 was added
gene: GOSR2 was added to Deafness_Isolated. Sources: Expert Review
Mode of inheritance for gene: GOSR2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GOSR2 were set to 37074134
Phenotypes for gene: GOSR2 were set to hearing loss, autosomal recessive, MONDO:0019588, GOSR2-related
Review for gene: GOSR2 was set to RED
Added comment: Four children from two sibships from an extended consanguineous Palestinian family were reported with congenital profound hearing loss, whereas the parents of both sibships are first cousins with normal hearing. The families reported occasional febrile seizures in infancy for each of the deaf children, but these did not persist into adolescence. These affected children were identified with autosomal recessive GOSR2 variant, c.1A > C, p.Met1Leu. This variant is present in one het in gnomad, and not in any of ~2000 in-house controls of Palestinian ancestry.

All previously reported cases with biallelic GOSR2 variants had normal hearing and hence the differences in translation efficiency due to the effect of this variant may be responsible for this hearing loss phenotype (PMID:37074134).
Sources: Expert Review
Microcephaly v1.225 HPDL Zornitza Stark Classified gene: HPDL as Green List (high evidence)
Microcephaly v1.225 HPDL Zornitza Stark Gene: hpdl has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5372 ATP5E Zornitza Stark Tag new gene name tag was added to gene: ATP5E.
Intellectual disability syndromic and non-syndromic v0.5372 ATP5E Zornitza Stark Marked gene: ATP5E as ready
Intellectual disability syndromic and non-syndromic v0.5372 ATP5E Zornitza Stark Gene: atp5e has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5372 ATP5E Zornitza Stark Classified gene: ATP5E as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.5372 ATP5E Zornitza Stark Gene: atp5e has been classified as Amber List (Moderate Evidence).
Optic Atrophy v1.20 PTCD3 Zornitza Stark Marked gene: PTCD3 as ready
Optic Atrophy v1.20 PTCD3 Zornitza Stark Gene: ptcd3 has been classified as Green List (High Evidence).
Optic Atrophy v1.20 PTCD3 Zornitza Stark Classified gene: PTCD3 as Green List (high evidence)
Optic Atrophy v1.20 PTCD3 Zornitza Stark Gene: ptcd3 has been classified as Green List (High Evidence).
Optic Atrophy v1.19 PTCD3 Zornitza Stark gene: PTCD3 was added
gene: PTCD3 was added to Optic Atrophy. Sources: Expert list
Mode of inheritance for gene: PTCD3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PTCD3 were set to 30607703; 19427859; 36450274
Phenotypes for gene: PTCD3 were set to Combined oxidative phosphorylation deficiency-51, MIM#619057; Intellectual disability; optic atrophy; Leigh-like syndrome
Review for gene: PTCD3 was set to GREEN
Added comment: Four families reported plus functional data. Optic atrophy is a feature.
Sources: Expert list
Mendeliome v1.1139 PTCD3 Zornitza Stark Publications for gene: PTCD3 were set to 30607703; 19427859
Mendeliome v1.1138 PTCD3 Zornitza Stark Classified gene: PTCD3 as Green List (high evidence)
Mendeliome v1.1138 PTCD3 Zornitza Stark Gene: ptcd3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5371 PTCD3 Zornitza Stark Marked gene: PTCD3 as ready
Intellectual disability syndromic and non-syndromic v0.5371 PTCD3 Zornitza Stark Gene: ptcd3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5371 PTCD3 Zornitza Stark Classified gene: PTCD3 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5371 PTCD3 Zornitza Stark Gene: ptcd3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5370 PTCD3 Zornitza Stark gene: PTCD3 was added
gene: PTCD3 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review
Mode of inheritance for gene: PTCD3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PTCD3 were set to 30607703; 19427859; 36450274
Phenotypes for gene: PTCD3 were set to Combined oxidative phosphorylation deficiency-51, MIM#619057; Intellectual disability; optic atrophy; Leigh-like syndrome
Review for gene: PTCD3 was set to GREEN
Added comment: Four families and functional data. ID is a feature.
Sources: Expert Review
Mendeliome v1.1137 PTCD3 Zornitza Stark edited their review of gene: PTCD3: Added comment: Three additional families reported.; Changed rating: GREEN; Changed publications: 30607703, 19427859, 36450274
Mitochondrial disease v0.889 PTCD3 Zornitza Stark Publications for gene: PTCD3 were set to 30607703; 19427859
Mitochondrial disease v0.888 PTCD3 Zornitza Stark Classified gene: PTCD3 as Green List (high evidence)
Mitochondrial disease v0.888 PTCD3 Zornitza Stark Gene: ptcd3 has been classified as Green List (High Evidence).
Severe early-onset obesity v1.9 ADCY3 Achchuthan Shanmugasundram changed review comment from: PMID:29311636 - Founder canonical splice variant (c.2433-1G>A) reported in Greenlandic populations demonstrate higher risk of obesity and type 2 diabetes in homozygous individuals.

PMID:29311637 - Four children from three consanguineous Pakistani families were reported with severe early-onset obesity and identified with three different homozygous variants in ADCY3 gene. In addition, an obese boy of European-American descent was identified with heterozygous ADCY3 variants.

PMID:35026759 - Two additional heterozygous variants (c.1658C>T/ p.Ala553Val & c.489C>G/ p.His163Gln) were identified in six Qatari individuals with obesity. However, the authors of this publication struggle to draw a conclusion on the impact of the dominant effect of the variants due to the genetic and biological overlap between monogenic and the common form of obesity.; to: PMID:29311636 - Founder canonical splice variant (c.2433-1G>A) reported in Greenlandic populations demonstrate higher risk of obesity and type 2 diabetes in homozygous individuals.

PMID:29311637 - Four children from three consanguineous Pakistani families were reported with severe early-onset obesity and identified with three different homozygous variants in ADCY3 gene. In addition, an obese boy of European-American descent was identified with heterozygous ADCY3 variants.

PMID:35026759 - Two additional heterozygous variants (c.1658C>T/ p.Ala553Val & c.489C>G/ p.His163Gln) were identified in six Qatari individuals with obesity. However, the authors of this publication struggle to draw a conclusion on the impact of the dominant effect of the variants due to the genetic and biological overlap between monogenic and the common form of obesity.

The phenotypes of biallelic variants appear severe and early-onset. The age of patients with monoallelic variants ranged from 28 and 57 and its was not clear whether the patients had either monogenic or common form of obesity. Hence, the MOI should be set as "BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal".
Mitochondrial disease v0.887 PTCD3 Zornitza Stark edited their review of gene: PTCD3: Added comment: Three additional families reported.; Changed rating: GREEN; Changed publications: 36450274
Severe early-onset obesity v1.9 ADCY3 Achchuthan Shanmugasundram reviewed gene: ADCY3: Rating: GREEN; Mode of pathogenicity: None; Publications: 29311636, 29311637, 35026759; Phenotypes: {Obesity, susceptibility to, BMIQ19}, OMIM:617885; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v1.1137 MRM2 Zornitza Stark Phenotypes for gene: MRM2 were changed from MELAS-like to Mitochondrial DNA depletion syndrome 17, MIM# 618567
Mendeliome v1.1136 MRM2 Zornitza Stark Classified gene: MRM2 as Green List (high evidence)
Mendeliome v1.1136 MRM2 Zornitza Stark Gene: mrm2 has been classified as Green List (High Evidence).
Mendeliome v1.1135 MRM2 Zornitza Stark edited their review of gene: MRM2: Added comment: Two additional families reported.; Changed rating: GREEN; Changed publications: 28973171, 36002240; Changed phenotypes: Mitochondrial DNA depletion syndrome 17, MIM# 618567
Mitochondrial disease v0.887 MRM2 Zornitza Stark Phenotypes for gene: MRM2 were changed from MELAS-like to Mitochondrial DNA depletion syndrome 17, MIM# 618567
Mitochondrial disease v0.886 MRM2 Zornitza Stark Publications for gene: MRM2 were set to 28973171
Mitochondrial disease v0.885 MRM2 Zornitza Stark Classified gene: MRM2 as Green List (high evidence)
Mitochondrial disease v0.885 MRM2 Zornitza Stark Gene: mrm2 has been classified as Green List (High Evidence).
Mitochondrial disease v0.884 MRM2 Zornitza Stark edited their review of gene: MRM2: Added comment: Two additional families reported.; Changed rating: GREEN; Changed publications: 28973171, 36002240
Mendeliome v1.1135 COX5A Zornitza Stark Publications for gene: COX5A were set to 2824752
Mendeliome v1.1134 COX5A Zornitza Stark Classified gene: COX5A as Amber List (moderate evidence)
Mendeliome v1.1134 COX5A Zornitza Stark Gene: cox5a has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1133 COX5A Zornitza Stark edited their review of gene: COX5A: Added comment: Second family reported, albeit hmz missense.; Changed rating: AMBER; Changed publications: 35246835, 28247525
Mitochondrial disease v0.884 COX5A Zornitza Stark Publications for gene: COX5A were set to 28247525; 35246835
Mitochondrial disease v0.884 COX5A Zornitza Stark Publications for gene: COX5A were set to 28247525
Mitochondrial disease v0.883 COX5A Zornitza Stark Classified gene: COX5A as Amber List (moderate evidence)
Mitochondrial disease v0.883 COX5A Zornitza Stark Gene: cox5a has been classified as Amber List (Moderate Evidence).
Mitochondrial disease v0.882 COX5A Zornitza Stark edited their review of gene: COX5A: Added comment: Second family reported, albeit hmz missense.; Changed rating: AMBER; Changed publications: 35246835
Cardiomyopathy_Paediatric v0.167 UQCRB Zornitza Stark Marked gene: UQCRB as ready
Cardiomyopathy_Paediatric v0.167 UQCRB Zornitza Stark Gene: uqcrb has been classified as Amber List (Moderate Evidence).
Cardiomyopathy_Paediatric v0.167 UQCRB Zornitza Stark Classified gene: UQCRB as Amber List (moderate evidence)
Cardiomyopathy_Paediatric v0.167 UQCRB Zornitza Stark Gene: uqcrb has been classified as Amber List (Moderate Evidence).
Cardiomyopathy_Paediatric v0.166 UQCRB Zornitza Stark reviewed gene: UQCRB: Rating: AMBER; Mode of pathogenicity: None; Publications: 12709789, 25446085, 28604960; Phenotypes: Mitochondrial complex III deficiency, nuclear type 3, 615158; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1133 CRELD1 Zornitza Stark Phenotypes for gene: CRELD1 were changed from Atrioventricular septal defect, partial, with heterotaxy syndrome, MIM# 606217 to Developmental and epileptic encephalopathy, MONDO:0100062, CRELD1-related; Atrioventricular septal defect, partial, with heterotaxy syndrome, MIM# 606217
Mendeliome v1.1132 CRELD1 Zornitza Stark Mode of inheritance for gene: CRELD1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.1131 CRELD1 Zornitza Stark Classified gene: CRELD1 as Green List (high evidence)
Mendeliome v1.1131 CRELD1 Zornitza Stark Gene: creld1 has been classified as Green List (High Evidence).
Mendeliome v1.1130 CRELD1 Zornitza Stark edited their review of gene: CRELD1: Added comment: Emerging association between bi-alleic variants in CRELD1 and DEE.; Changed rating: GREEN; Changed phenotypes: Developmental and epileptic encephalopathy, MONDO:0100062, CRELD1-related, Atrioventricular septal defect, partial, with heterotaxy syndrome, MIM# 606217; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genetic Epilepsy v0.1906 CRELD1 Zornitza Stark Marked gene: CRELD1 as ready
Genetic Epilepsy v0.1906 CRELD1 Zornitza Stark Gene: creld1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1906 CRELD1 Zornitza Stark Classified gene: CRELD1 as Green List (high evidence)
Genetic Epilepsy v0.1906 CRELD1 Zornitza Stark Gene: creld1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1905 CRELD1 Zornitza Stark gene: CRELD1 was added
gene: CRELD1 was added to Genetic Epilepsy. Sources: Expert list
Mode of inheritance for gene: CRELD1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CRELD1 were set to Developmental and epileptic encephalopathy, MONDO:0100062, CRELD1-related
Review for gene: CRELD1 was set to GREEN
Added comment: Emerging evidence of association between bi-allelic variants and DEE (>10 families).
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.5369 ASS1 Zornitza Stark Marked gene: ASS1 as ready
Intellectual disability syndromic and non-syndromic v0.5369 ASS1 Zornitza Stark Gene: ass1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5369 ASS1 Zornitza Stark Phenotypes for gene: ASS1 were changed from to Citrullinemia MIM#215700
Intellectual disability syndromic and non-syndromic v0.5368 ASS1 Zornitza Stark Mode of inheritance for gene: ASS1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5367 ASS1 Zornitza Stark reviewed gene: ASS1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Citrullinemia MIM#215700; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5367 ASPA Zornitza Stark Marked gene: ASPA as ready
Intellectual disability syndromic and non-syndromic v0.5367 ASPA Zornitza Stark Gene: aspa has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5367 ASPA Zornitza Stark Phenotypes for gene: ASPA were changed from to Canavan disease MIM#271900
Intellectual disability syndromic and non-syndromic v0.5366 ASPA Zornitza Stark Mode of inheritance for gene: ASPA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5365 ASPA Zornitza Stark reviewed gene: ASPA: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Canavan disease MIM#271900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5365 ARX Zornitza Stark Marked gene: ARX as ready
Intellectual disability syndromic and non-syndromic v0.5365 ARX Zornitza Stark Gene: arx has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5365 ARX Zornitza Stark Phenotypes for gene: ARX were changed from to Lissencephaly, X-linked 2, MIM# 300215
Intellectual disability syndromic and non-syndromic v0.5364 ARX Zornitza Stark Mode of inheritance for gene: ARX was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.5363 ARX Zornitza Stark reviewed gene: ARX: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Lissencephaly, X-linked 2, MIM# 300215; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.5363 ARV1 Zornitza Stark Marked gene: ARV1 as ready
Intellectual disability syndromic and non-syndromic v0.5363 ARV1 Zornitza Stark Gene: arv1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5363 ARV1 Zornitza Stark Phenotypes for gene: ARV1 were changed from to Developmental and epileptic encephalopathy 38, MIM# 617020
Intellectual disability syndromic and non-syndromic v0.5362 ARV1 Zornitza Stark Publications for gene: ARV1 were set to
Intellectual disability syndromic and non-syndromic v0.5361 ARV1 Zornitza Stark Mode of inheritance for gene: ARV1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5360 ARV1 Zornitza Stark reviewed gene: ARV1: Rating: GREEN; Mode of pathogenicity: None; Publications: 35227294, 27270415, 25558065; Phenotypes: Developmental and epileptic encephalopathy 38, MIM# 617020; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5360 ARID1A Zornitza Stark Marked gene: ARID1A as ready
Intellectual disability syndromic and non-syndromic v0.5360 ARID1A Zornitza Stark Gene: arid1a has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5360 ARID1A Zornitza Stark Phenotypes for gene: ARID1A were changed from to Coffin-Siris syndrome 2 (MIM#614607)
Intellectual disability syndromic and non-syndromic v0.5359 ARID1A Zornitza Stark Publications for gene: ARID1A were set to
Intellectual disability syndromic and non-syndromic v0.5358 ARID1A Zornitza Stark Mode of inheritance for gene: ARID1A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.1904 UBAP2L Zornitza Stark Phenotypes for gene: UBAP2L were changed from Neurodevelopmental disorder with impaired language, behavioral abnormalities, and dysmorphic facies, MIM# 620494; Delayed speech and language development; Motor delay; Intellectual disability; Autistic behavior; Seizures; Microcephaly; Abnormality of head or neck; Short stature; Abnormality of the skeletal system to Neurodevelopmental disorder with impaired language, behavioral abnormalities, and dysmorphic facies, MIM# 620494; Delayed speech and language development; Motor delay; Intellectual disability; Autistic behavior; Seizures; Microcephaly; Abnormality of head or neck; Short stature; Abnormality of the skeletal system
Genetic Epilepsy v0.1904 UBAP2L Zornitza Stark Phenotypes for gene: UBAP2L were changed from Neurodevelopmental disorder, MONDO:0700092, UBAP2L-related; Delayed speech and language development; Motor delay; Intellectual disability; Autistic behavior; Seizures; Microcephaly; Abnormality of head or neck; Short stature; Abnormality of the skeletal system to Neurodevelopmental disorder with impaired language, behavioral abnormalities, and dysmorphic facies, MIM# 620494; Delayed speech and language development; Motor delay; Intellectual disability; Autistic behavior; Seizures; Microcephaly; Abnormality of head or neck; Short stature; Abnormality of the skeletal system
Genetic Epilepsy v0.1903 UBAP2L Zornitza Stark edited their review of gene: UBAP2L: Changed phenotypes: Neurodevelopmental disorder with impaired language, behavioral abnormalities, and dysmorphic facies, MIM# 620494
Mendeliome v1.1130 UBAP2L Zornitza Stark Phenotypes for gene: UBAP2L were changed from Neurodevelopmental disorder, MONDO:0700092, UBAP2L-related to Neurodevelopmental disorder with impaired language, behavioral abnormalities, and dysmorphic facies, MIM# 620494
Mendeliome v1.1129 UBAP2L Zornitza Stark edited their review of gene: UBAP2L: Changed phenotypes: Neurodevelopmental disorder with impaired language, behavioral abnormalities, and dysmorphic facies, MIM# 620494
Intellectual disability syndromic and non-syndromic v0.5357 UBAP2L Zornitza Stark Phenotypes for gene: UBAP2L were changed from Neurodevelopmental disorder, MONDO:0700092, UBAP2L-related; Delayed speech and language development; Motor delay; Intellectual disability; Autistic behavior; Seizures; Microcephaly; Abnormality of head or neck; Short stature; Abnormality of the skeletal system to Neurodevelopmental disorder with impaired language, behavioral abnormalities, and dysmorphic facies, MIM# 620494; Delayed speech and language development; Motor delay; Intellectual disability; Autistic behavior; Seizures; Microcephaly; Abnormality of head or neck; Short stature; Abnormality of the skeletal system
Intellectual disability syndromic and non-syndromic v0.5356 UBAP2L Zornitza Stark edited their review of gene: UBAP2L: Changed phenotypes: Neurodevelopmental disorder with impaired language, behavioral abnormalities, and dysmorphic facies, MIM# 620494
Intellectual disability syndromic and non-syndromic v0.5356 AP3B1 Zornitza Stark Marked gene: AP3B1 as ready
Intellectual disability syndromic and non-syndromic v0.5356 AP3B1 Zornitza Stark Gene: ap3b1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5356 AP3B1 Zornitza Stark Phenotypes for gene: AP3B1 were changed from to Hermansky-Pudlak syndrome 2, MIM# 608233; MONDO:0011997
Intellectual disability syndromic and non-syndromic v0.5355 AP3B1 Zornitza Stark Publications for gene: AP3B1 were set to
Intellectual disability syndromic and non-syndromic v0.5354 AP3B1 Zornitza Stark Mode of inheritance for gene: AP3B1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5353 AP3B1 Zornitza Stark reviewed gene: AP3B1: Rating: GREEN; Mode of pathogenicity: None; Publications: 10024875, 11809908, 14566336; Phenotypes: Hermansky-Pudlak syndrome 2, MIM# 608233, MONDO:0011997; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Callosome v0.504 AMT Zornitza Stark Marked gene: AMT as ready
Callosome v0.504 AMT Zornitza Stark Gene: amt has been classified as Green List (High Evidence).
Callosome v0.504 AMT Zornitza Stark Phenotypes for gene: AMT were changed from to Glycine encephalopathy MIM#605899
Callosome v0.503 AMT Zornitza Stark Publications for gene: AMT were set to
Callosome v0.502 AMT Zornitza Stark Mode of inheritance for gene: AMT was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Callosome v0.501 AMT Zornitza Stark reviewed gene: AMT: Rating: GREEN; Mode of pathogenicity: None; Publications: 33791923; Phenotypes: Glycine encephalopathy MIM#605899; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5353 AMT Zornitza Stark Marked gene: AMT as ready
Intellectual disability syndromic and non-syndromic v0.5353 AMT Zornitza Stark Gene: amt has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5353 AMT Zornitza Stark Phenotypes for gene: AMT were changed from to Glycine encephalopathy MIM#605899
Intellectual disability syndromic and non-syndromic v0.5352 AMT Zornitza Stark Mode of inheritance for gene: AMT was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5351 AMT Zornitza Stark reviewed gene: AMT: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Glycine encephalopathy MIM#605899; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5351 ALDH18A1 Zornitza Stark Marked gene: ALDH18A1 as ready
Intellectual disability syndromic and non-syndromic v0.5351 ALDH18A1 Zornitza Stark Gene: aldh18a1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5351 ALDH18A1 Zornitza Stark Phenotypes for gene: ALDH18A1 were changed from to Spastic paraplegia 9B, autosomal recessive, MIM# 616586
Intellectual disability syndromic and non-syndromic v0.5350 ALDH18A1 Zornitza Stark Mode of inheritance for gene: ALDH18A1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5349 ALDH18A1 Zornitza Stark reviewed gene: ALDH18A1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Spastic paraplegia 9B, autosomal recessive, MIM# 616586; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5349 AIFM1 Zornitza Stark Marked gene: AIFM1 as ready
Intellectual disability syndromic and non-syndromic v0.5349 AIFM1 Zornitza Stark Gene: aifm1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5349 AIFM1 Zornitza Stark Phenotypes for gene: AIFM1 were changed from to Combined oxidative phosphorylation deficiency 6, 300816; Cowchock syndrome, 310490; Spondyloepimetaphyseal dysplasia, X-linked, with hypomyelinating leukodystrophy, 300232
Intellectual disability syndromic and non-syndromic v0.5348 AIFM1 Zornitza Stark Mode of inheritance for gene: AIFM1 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.5347 AIFM1 Zornitza Stark reviewed gene: AIFM1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Combined oxidative phosphorylation deficiency 6, 300816, Cowchock syndrome, 310490, Spondyloepimetaphyseal dysplasia, X-linked, with hypomyelinating leukodystrophy, 300232; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.5347 ADSL Zornitza Stark Marked gene: ADSL as ready
Intellectual disability syndromic and non-syndromic v0.5347 ADSL Zornitza Stark Gene: adsl has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5347 ADSL Zornitza Stark Phenotypes for gene: ADSL were changed from to Adenylosuccinase deficiency, MIM# 103050
Intellectual disability syndromic and non-syndromic v0.5346 ADSL Zornitza Stark Mode of inheritance for gene: ADSL was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5345 ADSL Zornitza Stark reviewed gene: ADSL: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Adenylosuccinase deficiency, MIM# 103050; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5345 ADGRG1 Zornitza Stark Marked gene: ADGRG1 as ready
Intellectual disability syndromic and non-syndromic v0.5345 ADGRG1 Zornitza Stark Gene: adgrg1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5345 ADGRG1 Zornitza Stark Phenotypes for gene: ADGRG1 were changed from to Polymicrogyria, bilateral frontoparietal, MIM# 606854
Intellectual disability syndromic and non-syndromic v0.5344 ADGRG1 Zornitza Stark Publications for gene: ADGRG1 were set to
Intellectual disability syndromic and non-syndromic v0.5343 ADGRG1 Zornitza Stark Mode of inheritance for gene: ADGRG1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5342 ADGRG1 Zornitza Stark Tag 5'UTR tag was added to gene: ADGRG1.
Intellectual disability syndromic and non-syndromic v0.5342 ADGRG1 Zornitza Stark reviewed gene: ADGRG1: Rating: GREEN; Mode of pathogenicity: None; Publications: 16240336; Phenotypes: Polymicrogyria, bilateral frontoparietal 606854; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5342 NEUROG1 Zornitza Stark Marked gene: NEUROG1 as ready
Intellectual disability syndromic and non-syndromic v0.5342 NEUROG1 Zornitza Stark Gene: neurog1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5342 NEUROG1 Zornitza Stark Classified gene: NEUROG1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5342 NEUROG1 Zornitza Stark Gene: neurog1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5341 NEUROG1 Zornitza Stark gene: NEUROG1 was added
gene: NEUROG1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: NEUROG1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NEUROG1 were set to 23419067; 26077850; 33439489; 36647078
Phenotypes for gene: NEUROG1 were set to Cranial dysinnervation disorder, congenital, with absent corneal reflex and developmental delay, OMIM:620469
Review for gene: NEUROG1 was set to GREEN
Added comment: There are four unrelated cases reported with global developmental delay/ intellectual disability.

PMID:23419067 - A homozygous micro deletion of NEUROG1 was identified in a six year-old boy presenting with profound sensorineural deafness, balance disorder, severe disorder of oral motor function, and mild global developmental delay. His IQ was normal.

PMID:26077850 - A homozygous NEUROG1 variant (p.Arg116Leu) was identified in a 12 year-old boy presented with syndromic corneal opacity, mild intellectual disability and absent corneal reflex.

PMID:33439489 - A homozygous loss-of-function variant (p.Glu68Ter) was identified in a 12 year-old boy presenting with hypotonia, global developmental delay, sensorineural hearing loss, and keratoconjunctivitis due to lack of corneal reflex. This patient had a global IQ of 62 at the age of ten.

PMID:36647078 - A female proband was identified with a novel homozygous truncating frameshift variant (p.Thr78ProfsTer122 and was reported with profound global developmental delay, autism spectrum disorder, hearing loss, corneal opacity and no eye blinking. Her sister also had a similar, but less severe phenotype and also harboured the same variant at homozygous state.
Sources: Literature
Mendeliome v1.1129 NEUROG1 Zornitza Stark Marked gene: NEUROG1 as ready
Mendeliome v1.1129 NEUROG1 Zornitza Stark Gene: neurog1 has been classified as Green List (High Evidence).
Mendeliome v1.1129 NEUROG1 Zornitza Stark Classified gene: NEUROG1 as Green List (high evidence)
Mendeliome v1.1129 NEUROG1 Zornitza Stark Gene: neurog1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5340 SRSF1 Zornitza Stark Phenotypes for gene: SRSF1 were changed from Neurodevelopmental disorder, SRSF1-related MONDO:0700092 to Neurodevelopmental disorder with dysmorphic facies and behavioral abnormalities, MIM# 620489
Intellectual disability syndromic and non-syndromic v0.5339 SRSF1 Zornitza Stark reviewed gene: SRSF1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with dysmorphic facies and behavioral abnormalities, MIM# 620489; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.1128 SRSF1 Zornitza Stark Phenotypes for gene: SRSF1 were changed from Neurodevelopmental disorder, SRSF1-related MONDO:0700092 to Neurodevelopmental disorder with dysmorphic facies and behavioral abnormalities, MIM# 620489
Mendeliome v1.1127 SRSF1 Zornitza Stark reviewed gene: SRSF1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with dysmorphic facies and behavioral abnormalities, MIM# 620489; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Transplant Co-Morbidity Superpanel v0.17 TPM4 Zornitza Stark Phenotypes for gene: TPM4 were changed from leeding disorder, platelet-type, 25, MIM# 620486 to Bleeding disorder, platelet-type, 25, MIM# 620486
Transplant Co-Morbidity Superpanel v0.16 TPM4 Zornitza Stark Marked gene: TPM4 as ready
Transplant Co-Morbidity Superpanel v0.16 TPM4 Zornitza Stark Gene: tpm4 has been classified as Green List (High Evidence).
Transplant Co-Morbidity Superpanel v0.16 TPM4 Zornitza Stark Phenotypes for gene: TPM4 were changed from Macrothrombocytopenia to leeding disorder, platelet-type, 25, MIM# 620486
Transplant Co-Morbidity Superpanel v0.15 TPM4 Zornitza Stark reviewed gene: TPM4: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Bleeding disorder, platelet-type, 25, MIM# 620486; Mode of inheritance: None
Mendeliome v1.1127 TPM4 Zornitza Stark Phenotypes for gene: TPM4 were changed from Macrothrombocytopaenia to Bleeding disorder, platelet-type, 25, MIM# 620486
Mendeliome v1.1126 TPM4 Zornitza Stark edited their review of gene: TPM4: Changed phenotypes: Bleeding disorder, platelet-type, 25, MIM# 620486
Bleeding and Platelet Disorders v1.26 TPM4 Zornitza Stark Phenotypes for gene: TPM4 were changed from Macrothrombocytopenia to Bleeding disorder, platelet-type, 25, MIM# 620486
Bleeding and Platelet Disorders v1.25 TPM4 Zornitza Stark edited their review of gene: TPM4: Changed phenotypes: Bleeding disorder, platelet-type, 25, MIM# 620486
Mendeliome v1.1126 PTPRJ Zornitza Stark Phenotypes for gene: PTPRJ were changed from Thrombocytopaenia to Thrombocytopenia 10, MIM# 620484
Mendeliome v1.1125 PTPRJ Zornitza Stark edited their review of gene: PTPRJ: Changed phenotypes: Thrombocytopenia 10, MIM# 620484
Bleeding and Platelet Disorders v1.25 PTPRJ Zornitza Stark Phenotypes for gene: PTPRJ were changed from Thrombocytopaenia to Thrombocytopenia 10, MIM# 620484
Bleeding and Platelet Disorders v1.24 PTPRJ Zornitza Stark edited their review of gene: PTPRJ: Changed phenotypes: Thrombocytopenia 10, MIM# 620484
Bone Marrow Failure v1.48 THPO Zornitza Stark Marked gene: THPO as ready
Bone Marrow Failure v1.48 THPO Zornitza Stark Gene: thpo has been classified as Green List (High Evidence).
Bone Marrow Failure v1.48 THPO Zornitza Stark Classified gene: THPO as Green List (high evidence)
Bone Marrow Failure v1.48 THPO Zornitza Stark Gene: thpo has been classified as Green List (High Evidence).
Bone Marrow Failure v1.47 THPO Zornitza Stark gene: THPO was added
gene: THPO was added to Bone Marrow Failure. Sources: Expert Review
Mode of inheritance for gene: THPO was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: THPO were set to 24085763; 28559357; 29191945; 36226497
Phenotypes for gene: THPO were set to Amegakaryocytic thrombocytopenia, congenital, 2, MIM# 620481
Review for gene: THPO was set to GREEN
Added comment: 5 families reported with bi-allelic variants and thrombocytopenia with progression to pancytopenia, aplastic anemia, and bone marrow failure.
Sources: Expert Review
Mendeliome v1.1125 THPO Zornitza Stark edited their review of gene: THPO: Added comment: 5 families reported with bi-allelic variants and thrombocytopenia with progression to pancytopenia, aplastic anemia, and bone marrow failure.; Changed publications: 9425899, 10583217, 32150607, 28466964, 24085763, 28559357, 29191945, 36226497; Changed phenotypes: Thrombocythemia 1, MIM# 187950, Thrombocytopenia 9, MIM# 620478, Amegakaryocytic thrombocytopenia, congenital, 2, MIM# 620481; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Bleeding and Platelet Disorders v1.24 THPO Zornitza Stark Phenotypes for gene: THPO were changed from Thrombocythemia 1, MIM# 187950; Thrombocytopenia 9, MIM# 620478 to Thrombocythemia 1, MIM# 187950; Thrombocytopenia 9, MIM# 620478; Amegakaryocytic thrombocytopenia, congenital, 2, MIM# 620481
Bleeding and Platelet Disorders v1.23 THPO Zornitza Stark Publications for gene: THPO were set to 9425899; 10583217; 32150607; 28466964
Bleeding and Platelet Disorders v1.22 THPO Zornitza Stark edited their review of gene: THPO: Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Bleeding and Platelet Disorders v1.22 THPO Zornitza Stark Mode of inheritance for gene: THPO was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Bleeding and Platelet Disorders v1.21 THPO Zornitza Stark edited their review of gene: THPO: Added comment: 5 families reported with bi-allelic variants and thrombocytopenia with progression to pancytopenia, aplastic anemia, and bone marrow failure.; Changed publications: 9425899, 10583217, 32150607, 28466964, 24085763, 28559357, 29191945, 36226497; Changed phenotypes: Thrombocythemia 1, MIM# 187950, Thrombocytopenia 9, MIM# 620478, Amegakaryocytic thrombocytopenia, congenital, 2, MIM# 620481; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5339 CCDC115 Elena Savva Classified gene: CCDC115 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5339 CCDC115 Elena Savva Gene: ccdc115 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5339 CCDC115 Elena Savva Classified gene: CCDC115 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5339 CCDC115 Elena Savva Gene: ccdc115 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5338 CCDC115 Elena Savva Marked gene: CCDC115 as ready
Intellectual disability syndromic and non-syndromic v0.5338 CCDC115 Elena Savva Gene: ccdc115 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.5338 CCDC115 Elena Savva gene: CCDC115 was added
gene: CCDC115 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: CCDC115 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CCDC115 were set to Congenital disorder of glycosylation, type IIo MIM# 616828
Review for gene: CCDC115 was set to GREEN
Added comment: Added following CAM discussion
Sources: Literature
Mendeliome v1.1125 NEUROG1 Achchuthan Shanmugasundram gene: NEUROG1 was added
gene: NEUROG1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NEUROG1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NEUROG1 were set to 23419067; 26077850; 33439489; 36647078
Phenotypes for gene: NEUROG1 were set to Cranial dysinnervation disorder, congenital, with absent corneal reflex and developmental delay, OMIM:620469
Review for gene: NEUROG1 was set to GREEN
Added comment: There are four unrelated cases reported with global developmental delay/ intellectual disability. Hence, this gene can be added with green rating in the intellectual disability panel.

PMID:23419067 - A homozygous micro deletion of NEUROG1 was identified in a six year-old boy presenting with profound sensorineural deafness, balance disorder, severe disorder of oral motor function, and mild global developmental delay. His IQ was normal.

PMID:26077850 - A homozygous NEUROG1 variant (p.Arg116Leu) was identified in a 12 year-old boy presented with syndromic corneal opacity, mild intellectual disability and absent corneal reflex.

PMID:33439489 - A homozygous loss-of-function variant (p.Glu68Ter) was identified in a 12 year-old boy presenting with hypotonia, global developmental delay, sensorineural hearing loss, and keratoconjunctivitis due to lack of corneal reflex. This patient had a global IQ of 62 at the age of ten.

PMID:36647078 - A female proband was identified with a novel homozygous truncating frameshift variant (p.Thr78ProfsTer122 and was reported with profound global developmental delay, autism spectrum disorder, hearing loss, corneal opacity and no eye blinking. Her sister also had a similar, but less severe phenotype and also harboured the same variant at homozygous state.

This gene has been associated with relevant phenotypes in OMIM (MIM #620469), but not in Gene2Phenotype.
Sources: Literature
Early-onset Parkinson disease v0.260 PANK2 Zornitza Stark Phenotypes for gene: PANK2 were changed from pantothenate kinase-associated neurodegeneration MONDO:0009319 to pantothenate kinase-associated neurodegeneration MONDO:0009319
Early-onset Parkinson disease v0.259 PANK2 Zornitza Stark Marked gene: PANK2 as ready
Early-onset Parkinson disease v0.259 PANK2 Zornitza Stark Gene: pank2 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.259 PANK2 Zornitza Stark Phenotypes for gene: PANK2 were changed from pantothenate kinase-associated neurodegeneration MONDO:0009319 to pantothenate kinase-associated neurodegeneration MONDO:0009319
Early-onset Parkinson disease v0.258 PANK2 Zornitza Stark Phenotypes for gene: PANK2 were changed from to pantothenate kinase-associated neurodegeneration MONDO:0009319
Early-onset Parkinson disease v0.257 PANK2 Zornitza Stark Publications for gene: PANK2 were set to
Early-onset Parkinson disease v0.256 PANK2 Zornitza Stark Mode of inheritance for gene: PANK2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.255 PLA2G6 Zornitza Stark Marked gene: PLA2G6 as ready
Early-onset Parkinson disease v0.255 PLA2G6 Zornitza Stark Gene: pla2g6 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.255 PLA2G6 Zornitza Stark Phenotypes for gene: PLA2G6 were changed from to autosomal recessive Parkinson disease 14 MONDO:0013060
Early-onset Parkinson disease v0.254 PLA2G6 Zornitza Stark Publications for gene: PLA2G6 were set to
Early-onset Parkinson disease v0.253 PLA2G6 Zornitza Stark Mode of inheritance for gene: PLA2G6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.252 POLG Zornitza Stark Marked gene: POLG as ready
Early-onset Parkinson disease v0.252 POLG Zornitza Stark Gene: polg has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.252 POLG Zornitza Stark Phenotypes for gene: POLG were changed from to autosomal dominant progressive external ophthalmoplegia MONDO:0008003
Early-onset Parkinson disease v0.251 POLG Zornitza Stark Publications for gene: POLG were set to
Early-onset Parkinson disease v0.250 POLG Zornitza Stark Mode of inheritance for gene: POLG was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.249 PRKRA Zornitza Stark Marked gene: PRKRA as ready
Early-onset Parkinson disease v0.249 PRKRA Zornitza Stark Gene: prkra has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.249 PRKRA Zornitza Stark Phenotypes for gene: PRKRA were changed from to dystonia 16 MONDO:0012789
Early-onset Parkinson disease v0.248 PRKRA Zornitza Stark Publications for gene: PRKRA were set to
Early-onset Parkinson disease v0.247 PRKRA Zornitza Stark Mode of inheritance for gene: PRKRA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.246 PRNP Zornitza Stark Marked gene: PRNP as ready
Early-onset Parkinson disease v0.246 PRNP Zornitza Stark Gene: prnp has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.246 PRNP Zornitza Stark Phenotypes for gene: PRNP were changed from to inherited Creutzfeldt-Jakob disease MONDO:0007403; Gerstmann-Straussler-Scheinker syndrome MONDO:0007656
Early-onset Parkinson disease v0.245 PRNP Zornitza Stark Publications for gene: PRNP were set to
Early-onset Parkinson disease v0.244 PRNP Zornitza Stark Mode of inheritance for gene: PRNP was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.1125 STAT5B Zornitza Stark Tag somatic tag was added to gene: STAT5B.
Mendeliome v1.1125 STAT5B Zornitza Stark changed review comment from: Both bi-allelic and mono allelic (GoF) inheritance reported. AD GoF phenotype: increased IgE, growth failure, eczema but no immune defects compared to AR phenotype (modestly decreased T cells, reduced Tregs and function, hypergammaglobulinaemia, increased IgE).; to: Both bi-allelic and mono allelic (GoF) inheritance reported. AD GoF phenotype: increased IgE, growth failure, eczema but no immune defects compared to AR phenotype (modestly decreased T cells, reduced Tregs and function, hypergammaglobulinaemia, increased IgE).

Somatic variants also reported.
Combined Immunodeficiency v1.43 STAT5B Zornitza Stark Tag somatic tag was added to gene: STAT5B.
Mendeliome v1.1125 RRM2B Zornitza Stark Mode of inheritance for gene: RRM2B was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Motor Neurone Disease v1.5 SQSTM1 Bryony Thompson Mode of inheritance for gene: SQSTM1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Transplant Co-Morbidity Superpanel v0.15 TPMT Bryony Thompson Classified gene: TPMT as Green List (high evidence)
Transplant Co-Morbidity Superpanel v0.15 TPMT Bryony Thompson Gene: tpmt has been classified as Green List (High Evidence).
Transplant Co-Morbidity Superpanel v0.14 SLCO1B1 Bryony Thompson Marked gene: SLCO1B1 as ready
Transplant Co-Morbidity Superpanel v0.14 SLCO1B1 Bryony Thompson Gene: slco1b1 has been classified as Green List (High Evidence).
Transplant Co-Morbidity Superpanel v0.14 SLCO1B1 Bryony Thompson Classified gene: SLCO1B1 as Green List (high evidence)
Transplant Co-Morbidity Superpanel v0.14 SLCO1B1 Bryony Thompson Gene: slco1b1 has been classified as Green List (High Evidence).
Transplant Co-Morbidity Superpanel v0.13 NUDT15 Bryony Thompson Marked gene: NUDT15 as ready
Transplant Co-Morbidity Superpanel v0.13 NUDT15 Bryony Thompson Gene: nudt15 has been classified as Green List (High Evidence).
Transplant Co-Morbidity Superpanel v0.13 NUDT15 Bryony Thompson Classified gene: NUDT15 as Green List (high evidence)
Transplant Co-Morbidity Superpanel v0.13 NUDT15 Bryony Thompson Gene: nudt15 has been classified as Green List (High Evidence).
Transplant Co-Morbidity Superpanel v0.12 MT-RNR1 Bryony Thompson Marked gene: MT-RNR1 as ready
Transplant Co-Morbidity Superpanel v0.12 MT-RNR1 Bryony Thompson Gene: mt-rnr1 has been classified as Green List (High Evidence).
Transplant Co-Morbidity Superpanel v0.12 MT-RNR1 Bryony Thompson Classified gene: MT-RNR1 as Green List (high evidence)
Transplant Co-Morbidity Superpanel v0.12 MT-RNR1 Bryony Thompson Gene: mt-rnr1 has been classified as Green List (High Evidence).
Transplant Co-Morbidity Superpanel v0.11 IFNL3 Bryony Thompson Marked gene: IFNL3 as ready
Transplant Co-Morbidity Superpanel v0.11 IFNL3 Bryony Thompson Gene: ifnl3 has been classified as Green List (High Evidence).
Transplant Co-Morbidity Superpanel v0.11 IFNL3 Bryony Thompson Classified gene: IFNL3 as Green List (high evidence)
Transplant Co-Morbidity Superpanel v0.11 IFNL3 Bryony Thompson Gene: ifnl3 has been classified as Green List (High Evidence).
Transplant Co-Morbidity Superpanel v0.10 DPYD Bryony Thompson Marked gene: DPYD as ready
Transplant Co-Morbidity Superpanel v0.10 DPYD Bryony Thompson Gene: dpyd has been classified as Green List (High Evidence).
Transplant Co-Morbidity Superpanel v0.10 DPYD Bryony Thompson Classified gene: DPYD as Green List (high evidence)
Transplant Co-Morbidity Superpanel v0.10 DPYD Bryony Thompson Gene: dpyd has been classified as Green List (High Evidence).
Transplant Co-Morbidity Superpanel v0.9 CYP4F2 Bryony Thompson Marked gene: CYP4F2 as ready
Transplant Co-Morbidity Superpanel v0.9 CYP4F2 Bryony Thompson Gene: cyp4f2 has been classified as Green List (High Evidence).
Transplant Co-Morbidity Superpanel v0.9 CYP4F2 Bryony Thompson Classified gene: CYP4F2 as Green List (high evidence)
Transplant Co-Morbidity Superpanel v0.9 CYP4F2 Bryony Thompson Gene: cyp4f2 has been classified as Green List (High Evidence).
Transplant Co-Morbidity Superpanel v0.8 UGT1A1 Bryony Thompson Marked gene: UGT1A1 as ready
Transplant Co-Morbidity Superpanel v0.8 UGT1A1 Bryony Thompson Gene: ugt1a1 has been classified as Green List (High Evidence).
Transplant Co-Morbidity Superpanel v0.8 UGT1A1 Bryony Thompson Classified gene: UGT1A1 as Green List (high evidence)
Transplant Co-Morbidity Superpanel v0.8 UGT1A1 Bryony Thompson Gene: ugt1a1 has been classified as Green List (High Evidence).
Transplant Co-Morbidity Superpanel v0.7 CYP3A5 Bryony Thompson Marked gene: CYP3A5 as ready
Transplant Co-Morbidity Superpanel v0.7 CYP3A5 Bryony Thompson Gene: cyp3a5 has been classified as Green List (High Evidence).
Transplant Co-Morbidity Superpanel v0.7 CYP3A5 Bryony Thompson Classified gene: CYP3A5 as Green List (high evidence)
Transplant Co-Morbidity Superpanel v0.7 CYP3A5 Bryony Thompson Gene: cyp3a5 has been classified as Green List (High Evidence).
Transplant Co-Morbidity Superpanel v0.6 CYP2C9 Bryony Thompson Marked gene: CYP2C9 as ready
Transplant Co-Morbidity Superpanel v0.6 CYP2C9 Bryony Thompson Gene: cyp2c9 has been classified as Green List (High Evidence).
Transplant Co-Morbidity Superpanel v0.6 CYP2C9 Bryony Thompson Classified gene: CYP2C9 as Green List (high evidence)
Transplant Co-Morbidity Superpanel v0.6 CYP2C9 Bryony Thompson Gene: cyp2c9 has been classified as Green List (High Evidence).
Transplant Co-Morbidity Superpanel v0.5 CYP2C19 Bryony Thompson Marked gene: CYP2C19 as ready
Transplant Co-Morbidity Superpanel v0.5 CYP2C19 Bryony Thompson Gene: cyp2c19 has been classified as Green List (High Evidence).
Transplant Co-Morbidity Superpanel v0.5 CYP2C19 Bryony Thompson Classified gene: CYP2C19 as Green List (high evidence)
Transplant Co-Morbidity Superpanel v0.5 CYP2C19 Bryony Thompson Gene: cyp2c19 has been classified as Green List (High Evidence).
Cerebral Palsy v1.187 FBXO31 Ain Roesley Phenotypes for gene: FBXO31 were changed from Cerebral palsy to Cerebral palsy, MONDO:0006497, FBXO31-related
Combined Immunodeficiency v1.43 STAT5B Peter McNaughton reviewed gene: STAT5B: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 27956386; Phenotypes: Eosinophilia; Mode of inheritance: Other
Intellectual disability syndromic and non-syndromic v0.5337 FBXO31 Ain Roesley reviewed gene: FBXO31: Rating: AMBER; Mode of pathogenicity: None; Publications: 35019165, 24623383; Phenotypes: intellectual developmental disorder 45 (MIM#615979); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Ataxia - adult onset v1.4 CCDC88C Zornitza Stark Marked gene: CCDC88C as ready
Ataxia - adult onset v1.4 CCDC88C Zornitza Stark Gene: ccdc88c has been classified as Amber List (Moderate Evidence).
Haem degradation and bilirubin metabolism defects v0.15 PPOX Zornitza Stark Phenotypes for gene: PPOX were changed from Porphyria variegata, MIM# 176200 to Porphyria variegata, MIM# 176200; Variegate porphyria, childhood-onset, MIM# 620483
Haem degradation and bilirubin metabolism defects v0.14 PPOX Zornitza Stark Publications for gene: PPOX were set to 27982422
Haem degradation and bilirubin metabolism defects v0.13 PPOX Zornitza Stark edited their review of gene: PPOX: Changed publications: 9811936, 11286631, 33159949
Haem degradation and bilirubin metabolism defects v0.13 PPOX Zornitza Stark reviewed gene: PPOX: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Variegate porphyria, childhood-onset, MIM# 620483; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Neuropathy - complex v1.3 PPOX Zornitza Stark Phenotypes for gene: PPOX were changed from Porphyria variegata, MIM# 176200 to Porphyria variegata, MIM# 176200; Variegate porphyria, childhood-onset, MIM# 620483
Hereditary Neuropathy - complex v1.2 PPOX Zornitza Stark Publications for gene: PPOX were set to
Hereditary Neuropathy - complex v1.1 PPOX Zornitza Stark Mode of inheritance for gene: PPOX was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hereditary Neuropathy - complex v1.0 PPOX Zornitza Stark edited their review of gene: PPOX: Added comment: Bi-allelic variants cause childhood onset disease.; Changed publications: 9811936, 11286631, 33159949; Changed phenotypes: Porphyria variegata, MIM# 176200, Variegate porphyria, childhood-onset, MIM# 620483; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Photosensitivity Syndromes v1.7 PPOX Zornitza Stark Publications for gene: PPOX were set to 12357337; 32247286; 23324528
Photosensitivity Syndromes v1.6 PPOX Zornitza Stark Mode of inheritance for gene: PPOX was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Photosensitivity Syndromes v1.5 PPOX Zornitza Stark reviewed gene: PPOX: Rating: GREEN; Mode of pathogenicity: None; Publications: 9811936, 11286631, 33159949; Phenotypes: Variegate porphyria, childhood-onset, MIM# 620483; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1124 PPOX Zornitza Stark Phenotypes for gene: PPOX were changed from Porphyria variegata , MIM#176200 to Porphyria variegata , MIM#176200; Variegate porphyria, childhood-onset, MIM# 620483
Mendeliome v1.1123 PPOX Zornitza Stark Publications for gene: PPOX were set to 12357337; 32247286; 23324528; 27982422
Mendeliome v1.1122 PPOX Zornitza Stark Mode of inheritance for gene: PPOX was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.1121 PPOX Zornitza Stark edited their review of gene: PPOX: Added comment: Bi-allelic variants cause childhood onset disease.; Changed publications: 12357337, 32247286, 23324528, 27982422, 9811936, 11286631, 33159949; Changed phenotypes: Porphyria variegata , MIM#176200, Variegate porphyria, childhood-onset, MIM# 620483; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.1121 THPO Zornitza Stark Phenotypes for gene: THPO were changed from Thrombocythemia 1, MIM# 187950 to Thrombocythemia 1, MIM# 187950; Thrombocytopenia 9, MIM# 620478
Mendeliome v1.1120 THPO Zornitza Stark Publications for gene: THPO were set to 9425899; 10583217
Mendeliome v1.1119 THPO Zornitza Stark edited their review of gene: THPO: Added comment: Thrombocytopenia: 5 unrelated families reported.; Changed publications: 9425899, 10583217, 32150607, 28466964; Changed phenotypes: Thrombocythemia 1, MIM# 187950, Thrombocytopenia 9, MIM# 620478
Bleeding and Platelet Disorders v1.21 THPO Zornitza Stark Publications for gene: THPO were set to 9425899; 10583217
Bleeding and Platelet Disorders v1.20 THPO Zornitza Stark Phenotypes for gene: THPO were changed from Thrombocythemia 1, MIM# 187950 to Thrombocythemia 1, MIM# 187950; Thrombocytopenia 9, MIM# 620478
Bleeding and Platelet Disorders v1.19 THPO Zornitza Stark edited their review of gene: THPO: Added comment: Thrombocytopenia: 5 unrelated families reported.; Changed publications: 9425899, 10583217, 32150607, 28466964; Changed phenotypes: Thrombocythemia 1, MIM# 187950, Thrombocytopenia 9, MIM# 620478
Intellectual disability syndromic and non-syndromic v0.5337 ACTB Zornitza Stark Phenotypes for gene: ACTB were changed from Baraitser-Winter syndrome 1, MIM# 243310; ACTB-related neurodevelopment disorder to Baraitser-Winter syndrome 1, MIM# 243310; Thrombocytopenia 8, with dysmorphic features and developmental delay, MIM# 620475; ACTB-related neurodevelopment disorder
Intellectual disability syndromic and non-syndromic v0.5336 ACTB Zornitza Stark edited their review of gene: ACTB: Changed phenotypes: Baraitser-Winter syndrome 1 243310, ACTB-related neurodevelopment disorder, Thrombocytopenia 8, with dysmorphic features and developmental delay, MIM# 620475
Mendeliome v1.1119 ACTB Zornitza Stark Phenotypes for gene: ACTB were changed from Baraitser-Winter syndrome 1 243310; ACTB-related neurodevelopment disorder to Baraitser-Winter syndrome 1 243310; Thrombocytopenia 8, with dysmorphic features and developmental delay, MIM# 620475; ACTB-related neurodevelopment disorder
Mendeliome v1.1118 ACTB Zornitza Stark reviewed gene: ACTB: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Thrombocytopenia 8, with dysmorphic features and developmental delay, MIM# 620475; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Bleeding and Platelet Disorders v1.19 ACTB Zornitza Stark Phenotypes for gene: ACTB were changed from Syndromic thrombocytopaenia to Thrombocytopenia 8, with dysmorphic features and developmental delay, MIM# 620475
Bleeding and Platelet Disorders v1.18 ACTB Zornitza Stark edited their review of gene: ACTB: Changed phenotypes: Thrombocytopenia 8, with dysmorphic features and developmental delay, MIM# 620475
Early-onset Parkinson disease v0.243 PSEN1 Kaitlyn Dianna Weldon reviewed gene: PSEN1: Rating: GREEN; Mode of pathogenicity: None; Publications: 3548932, 34843019, 36825052; Phenotypes: early-onset parkinsons disease; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Transplant Co-Morbidity Superpanel v0.4 MT-RNR1 Claire Fryer-Smith gene: MT-RNR1 was added
gene: MT-RNR1 was added to Transplant Co-Morbidity Superpanel. Sources: Expert list
Mode of inheritance for gene gene: MT-RNR1 was set to MITOCHONDRIAL
Phenotypes for gene: MT-RNR1 were set to Deafness, mitochondrial, modifier of MIM# 580000
Review for gene: MT-RNR1 was set to GREEN
Added comment: Multiple variations within the MT-RNR1 gene have been associated with the development of hearing loss in patients who receive aminoglycoside antibiotics. Aminoglycosides are a class of antibiotics that includes drugs such as streptomycin, kanamycin, gentamycin and tobramycin, among others.

https://www.pharmgkb.org/gene/PA31274

The 1555A>G variation in the MT-RNR1 gene is strongly associated with the development of bilateral, sensorineural, nonsyndromic hearing loss following aminoglycoside antibiotic use: across 40 studies in either family pedigrees or groups of patients with hearing loss, 100% of those with the MT-RNR1 1555G variant who received an aminoglycoside antibiotic developed hearing loss. (PMID:9164619)
Sources: Expert list
Transplant Co-Morbidity Superpanel v0.4 G6PD Claire Fryer-Smith reviewed gene: G6PD: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Hemolytic anemia, G6PD deficient (favism) MIM# 300908; 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 v0.243 PRNP Kaitlyn Dianna Weldon reviewed gene: PRNP: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301407; Phenotypes: inherited Creutzfeldt-Jakob disease MONDO:0007403, Gerstmann-Straussler-Scheinker syndrome MONDO:0007656; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Prepair 1000+ v1.1 AMN Crystle Lee gene: AMN was added
gene: AMN was added to Prepair 1000+. Sources: Literature
Mode of inheritance for gene: AMN was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: AMN were set to Imerslund-Grasbeck syndrome 2 (MIM#618882)
Review for gene: AMN was set to AMBER
Added comment: Well established gene-disease association.

Imerslund-Grasbeck syndrome-2 (IGS2) is an autosomal recessive disorder characterized by onset of megaloblastic anaemia associated with decreased serum vitamin B12 (cobalamin, Cbl) in infancy or early childhood.

Clinical features include failure to thrive, loss of appetite, fatigue, lethargy, and/or recurrent infections.
Sources: Literature
Transplant Co-Morbidity Superpanel v0.4 IFNL3 Claire Fryer-Smith gene: IFNL3 was added
gene: IFNL3 was added to Transplant Co-Morbidity Superpanel. Sources: Expert list
Mode of inheritance for gene: IFNL3 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: IFNL3 were set to 19749758; 19684573; 24752298
Phenotypes for gene: IFNL3 were set to Hepatitis C virus infection, response to therapy of MIM# 609532
Review for gene: IFNL3 was set to GREEN
Added comment: https://www.pharmgkb.org/gene/PA134952671/overview

IFNL3 encodes IL28B, a class II cytokine receptor.

Suppiah et al., (2009) reported an association to sustained virological response (SVR) within the gene region encoding interleukin 28B. IL28B contributes to viral resistance and is known to be upregulated by interferons and by RNA virus infection. This data suggests that host genetics may be useful for the prediction of drug response, and they also support the investigation of the role of IL28B in the treatment of HCV and in other diseases treated with IFN-alpha. (PMID: 19749758)

The CC genotype of rs12979860 was associated with an approximately 2-fold greater rate of SVR compared with the TT genotype (PMID: 19684573, 24752298).
Sources: Expert list
Early-onset Parkinson disease v0.243 PRKRA Kaitlyn Dianna Weldon reviewed gene: PRKRA: Rating: GREEN; Mode of pathogenicity: None; Publications: 33502045; Phenotypes: dystonia 16 MONDO:0012789; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.243 POLG Kaitlyn Dianna Weldon reviewed gene: POLG: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301791, 15351195; Phenotypes: autosomal dominant progressive external ophthalmoplegia MONDO:0008003; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Transplant Co-Morbidity Superpanel v0.4 RYR1 Claire Fryer-Smith reviewed gene: RYR1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Congenital myopathy 1A, autosomal dominant, with susceptibility to malignant hyperthermia MIM# 117000, Congenital myopathy 1B, autosomal recessive MIM# 255320, King-Denborough syndrome MIM# 619542, Malignant hyperthermia susceptibility MIM# 145600; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.243 PLA2G6 Kaitlyn Dianna Weldon reviewed gene: PLA2G6: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301718; Phenotypes: autosomal recessive Parkinson disease 14 MONDO:0013060; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.243 PANK2 Kaitlyn Dianna Weldon edited their review of gene: PANK2: Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.243 PARK7 Kaitlyn Dianna Weldon reviewed gene: PARK7: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301402; Phenotypes: Parkinson disease MONDO:0005180, autosomal recessive early-onset Parkinson disease 7 MONDO:0011658; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.243 PANK2 Kaitlyn Dianna Weldon reviewed gene: PANK2: Rating: ; Mode of pathogenicity: None; Publications: 23447832, 20301663; Phenotypes: pantothenate kinase-associated neurodegeneration MONDO:0009319; Mode of inheritance: None
Transplant Co-Morbidity Superpanel v0.4 CYP4F2 Claire Fryer-Smith gene: CYP4F2 was added
gene: CYP4F2 was added to Transplant Co-Morbidity Superpanel. Sources: Expert list
Mode of inheritance for gene: CYP4F2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CYP4F2 were set to 25370453; 20555338; 19207028; 18250228
Phenotypes for gene: CYP4F2 were set to Warfarin dosage sensitivity MIM# 122700
Review for gene: CYP4F2 was set to GREEN
Added comment: It is involved in guidelines for warfarin
https://www.pharmgkb.org/gene/PA27121/overview
Sources: Expert list
Mendeliome v1.1118 APOL1 Zornitza Stark Classified gene: APOL1 as Amber List (moderate evidence)
Mendeliome v1.1118 APOL1 Zornitza Stark Gene: apol1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1117 APOL1 Zornitza Stark edited their review of gene: APOL1: Added comment: Assigned Definitive gene-disease validity by the ClinGen Glomerulopathy GCEP - Classification - 09/28/2021
Increased risk of kidney and glomerular diseases in persons carrying two of the risk alleles in this gene: G1/G1, G2/G2 and compound heterozygous G1/G2.
PMID: 20647424 - first study to identify G1 & G2 alleles associated with risk of renal disease. Comparing participants with zero or 1 risk allele of APOL1 to participants with 2 risk alleles provided an odds ratio for FSGS of 10.5 (CI, 6.0-18.4). This analysis supported a completely recessive pattern of inheritance.
PMID: 25993319 - only G1 and G2 confer renal risk, and other common and rare APOL1 missense variants, including the archaic G3 haplotype, do not contribute to sporadic FSGS and HIVAN
rs73885319 (G1) OR 9.66, p=9.97E-25
rs60910145 (G1) OR 9.75, p=9.04E-24
rs71785313 (G2) OR 5.69, p=3.39E-06
2 APOL1 risk alleles OR 18.31, p=3.31E-58
PMID: 34350953 - recessive gain-of-function toxicity mouse model recapitulates human kidney disease
G1:
p.Ser342Gly, AFR/AA gnomAD v2.1 AF 0.2276 (5,671/24,920 alleles, 687 homozygotes)
p.Ile384Met, AFR/AA gnomAD v2.1 AF 0.2278 (5,487/24,082 alleles, 662 homozygotes)
G2:
p.Asn388_Tyr389del, AFR/AA gnomAD v2.1 AF 0.1402(3,402/24,268 alleles, 224 homozygotes

AMBER status due to these being susceptibility alleles, and evidence being limited to these specific variants.; Changed rating: AMBER
Early-onset Parkinson disease v0.243 MAPT Kaitlyn Dianna Weldon reviewed gene: MAPT: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301678; Phenotypes: late-onset Parkinson disease MONDO:0008199; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.243 LYST Kaitlyn Dianna Weldon reviewed gene: LYST: Rating: GREEN; Mode of pathogenicity: None; Publications: 23436631, 23521865, 20301751; Phenotypes: Chediak-Higashi syndrome MONDO:0008963; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.243 LRRK2 Kaitlyn Dianna Weldon reviewed gene: LRRK2: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301387; Phenotypes: autosomal dominant Parkinson disease 8 MONDO:0011764, obsolete hereditary late onset Parkinson disease MONDO:0018466, Parkinson disease MONDO:0005180; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.243 FTL Kaitlyn Dianna Weldon edited their review of gene: FTL: Changed rating: GREEN
Early-onset Parkinson disease v0.243 FTL Kaitlyn Dianna Weldon reviewed gene: FTL: Rating: ; Mode of pathogenicity: None; Publications: 23447832, 20301320; Phenotypes: neuroferritinopathy MONDO:0011638; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.243 FBXO7 Kaitlyn Dianna Weldon reviewed gene: FBXO7: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301402; Phenotypes: parkinsonian-pyramidal syndrome MONDO:0009830; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.243 DNAJC6 Kaitlyn Dianna Weldon reviewed gene: DNAJC6: Rating: GREEN; Mode of pathogenicity: None; Publications: 33983693; Phenotypes: juvenile onset Parkinson disease 19A MONDO:0014231; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.243 OPA3 Kaitlyn Dianna Weldon reviewed gene: OPA3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Transplant Co-Morbidity Superpanel v0.4 VKORC1 Claire Fryer-Smith reviewed gene: VKORC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 14765194, 18315553, 14765194, 19940803; Phenotypes: Vitamin K-dependent clotting factors, combined deficiency of, 2 MIM#607473, Warfarin resistance MIM# 122700; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Transplant Co-Morbidity Superpanel v0.4 NUDT15 Claire Fryer-Smith gene: NUDT15 was added
gene: NUDT15 was added to Transplant Co-Morbidity Superpanel. Sources: Expert list
Mode of inheritance for gene: NUDT15 was set to Other
Publications for gene: NUDT15 were set to 26878724
Phenotypes for gene: NUDT15 were set to Thiopurines, poor metabolism of, 2 MIM# 616903
Review for gene: NUDT15 was set to GREEN
Added comment: It is involved in guidelines for thiopurines including mercaptopurine and azathioprine.

https://www.pharmgkb.org/gene/PA134963132

Pathogenic variants in NUDT15 result in poor metabolism of thiopurines that was significantly associated with thiopurine-induced leukopenia. The NUDT15 deficiency trait follows an additive genetic mode of inheritance, with the severity of the phenotype proportional to the cumulative number of risk alleles in NUDT15.

Mechanistically, NUDT15 inactivated thiopurine metabolites and decreased thiopurine cytotoxicity in vitro, and patients with defective NUDT15 alleles showed excessive levels of thiopurine active metabolites and toxicity. (PMID: 26878724).
Sources: Expert list
Early-onset Parkinson disease v0.243 DCTN1 Kaitlyn Dianna Weldon reviewed gene: DCTN1: Rating: GREEN; Mode of pathogenicity: None; Publications: 20945553; Phenotypes: Perry syndrome MONDO:0008201; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.243 CSF1R Kaitlyn Dianna Weldon reviewed gene: CSF1R: Rating: GREEN; Mode of pathogenicity: None; Publications: 25935893, 22934315; Phenotypes: obsolete hereditary diffuse leukoencephalopathy with axonal spheroids and pigmented glia MONDO:0009096; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Transplant Co-Morbidity Superpanel v0.4 SLCO1B1 Claire Fryer-Smith gene: SLCO1B1 was added
gene: SLCO1B1 was added to Transplant Co-Morbidity Superpanel. Sources: Expert list
Mode of inheritance for gene: SLCO1B1 was set to Other
Publications for gene: SLCO1B1 were set to 19952871; 5152405; 35968761
Phenotypes for gene: SLCO1B1 were set to Hyperbilirubinemia, Rotor type, digenic MIM# 237450
Review for gene: SLCO1B1 was set to GREEN
Added comment: It is involved in guidelines for statins including CPIC guidelines for atorvastatin, simvastatin, and rosuvastatin. It is also implicated in a range of pharmacogenomic responses: https://www.pharmgkb.org/gene/PA134865839

Rotor type hyperbilirubinemia (HBLRR) is caused by digenic inheritance of homozygous mutations in the SLCO1B1 (MIM# 604843) and SLCO1B3 (MIM# 605495) genes. Van de Steeg et al. (2012) (PMID: 22232210) suggested that individuals with Rotor syndrome may also be at increased risk for drug toxicity, since these proteins are involved in the clearance of drug conjugates. SLCO1B1 single nucleotide polymorphisms and haplotypes have been implicated in altered pharmacokinetic handling and pharmacodynamic response

The solute carrier organic anion transporter family member 1B1 (SLCO1B1) gene encodes for a membrane-bound sodium-independent organic anion transporter protein (OATP1B1). OATP1B1 mediates active transport of many endogenous substrates, such as bile acids, xenobiotic compounds, and a wide panel of pharmaceutical compounds. (PMID: 19952871)

SLCO1B1 variants are known to be a strong predictor of statin-associated muscle symptoms (SAMS) risk with simvastatin (PMID: 5152405).

Allelic variants of SLCO1B1 and ABCB1 predict the lipid-lowering efficacy of atorvastatin (PMID:35968761).
Sources: Expert list
Early-onset Parkinson disease v0.243 C19orf12 Kaitlyn Dianna Weldon reviewed gene: C19orf12: Rating: GREEN; Mode of pathogenicity: None; Publications: 21981780, 23278385; Phenotypes: neurodegeneration with brain iron accumulation 4 MONDO:0013674; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Transplant Co-Morbidity Superpanel v0.4 CYP2C9 Claire Fryer-Smith gene: CYP2C9 was added
gene: CYP2C9 was added to Transplant Co-Morbidity Superpanel. Sources: Expert list
Mode of inheritance for gene: CYP2C9 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CYP2C9 were set to 12893985
Phenotypes for gene: CYP2C9 were set to Tolbutamide poor metabolizer, Warfarin sensitivity MIM# 122700
Review for gene: CYP2C9 was set to GREEN
Added comment: CYP2C9 is one of the major drug-metabolizing CYP450 isoforms. It is involved in guidelines for warfarin, phenytoin and NSAIDs (https://www.pharmgkb.org/gene/PA126).

CYP2C9 is the cytochrome P450 enzyme responsible for the metabolism of the isomer of warfarin (see 122700) that is principally responsible for the anticoagulant effect of the drug. Persons with the genotype of impaired metabolism require lower doses of warfarin to achieve an anticoagulant effect similar to that in patients with the normal genotype and are more likely to have an excessive anticoagulant response (PMID: 10073515).

Kirchheiner et al. (2003) (PMID: 12893985) studied the effects of CYP2C9 on celecoxib, a nonsteroidal antiinflammatory drug (NSAID) that is used to treat rheumatoid arthritis and osteoarthritis and exhibits antiinflammatory, analgesic, and antipyretic activity by selective inhibition of cyclooxygenase-2 (COX2; 600262). They found a more than 2-fold reduced oral clearance in homozygous carriers of CYP2C9*3; heterozygous carriers of 1 CYP2C9*3 allele were in between, whereas CYP2C9*2 had no significant influence on celecoxib pharmacokinetics.
Sources: Expert list
Early-onset Parkinson disease v0.243 ATP1A3 Kaitlyn Dianna Weldon reviewed gene: ATP1A3: Rating: GREEN; Mode of pathogenicity: None; Publications: 17282997, 15260953, 17595045, 17516473, 22534615; Phenotypes: ATP1A3-associated neurological disorder MONDO:0700002; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.243 ATP13A2 Kaitlyn Dianna Weldon reviewed gene: ATP13A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 25900096; Phenotypes: parkinsonism due to ATP13A2 deficiency MONDO:0017809; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Transplant Co-Morbidity Superpanel v0.4 CYP2C19 Claire Fryer-Smith gene: CYP2C19 was added
gene: CYP2C19 was added to Transplant Co-Morbidity Superpanel. Sources: Expert list
Mode of inheritance for gene: CYP2C19 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CYP2C19 were set to 12464799
Phenotypes for gene: CYP2C19 were set to DRUG METABOLISM, POOR, CYP2C19-RELATED, MEPHENYTOIN, POOR METABOLISM OF, INCLUDED OMEPRAZOLE, POOR METABOLISM OF, INCLUDED PROGUANIL, POOR METABOLISM OF, INCLUDED CLOPIDOGREL, POOR METABOLISM OF, INCLUDED MIM#609535
Review for gene: CYP2C19 was set to GREEN
Added comment: Genetic polymorphism in the metabolism of the anticonvulsant drug mephenytoin exhibits marked racial heterogeneity. Patients carrying any 2 CYP2C19 loss-of-function alleles (*2, *3, *4, or *5), had a higher event rate than patients with none.

CYP2C19 is a clinically important enzyme (EC 1.14.13.80) that metabolizes a wide variety of drugs, including the anticonvulsant mephenytoin, anti-ulcer drugs such as omeprazole, certain antidepressants, and the antimalarial drug proguanil. Mutation in the CYP2C19 gene causes poor metabolism of these drugs (PMID: 12464799).

It is involved in guidelines for antidepressants, clopidogrel and voriconazole.
https://www.pharmgkb.org/gene/PA124
Sources: Expert list
Genetic Epilepsy v0.1903 ATP13A2 Zornitza Stark Marked gene: ATP13A2 as ready
Genetic Epilepsy v0.1903 ATP13A2 Zornitza Stark Gene: atp13a2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1903 ATP13A2 Zornitza Stark Classified gene: ATP13A2 as Green List (high evidence)
Genetic Epilepsy v0.1903 ATP13A2 Zornitza Stark Gene: atp13a2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1902 ATP13A2 Zornitza Stark gene: ATP13A2 was added
gene: ATP13A2 was added to Genetic Epilepsy. Sources: Expert Review
Mode of inheritance for gene: ATP13A2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATP13A2 were set to 30868101; 21362476; 31588715; 22388936
Phenotypes for gene: ATP13A2 were set to Kufor-Rakeb syndrome MIM#606693
Review for gene: ATP13A2 was set to GREEN
Added comment: Progressive neurological disorder, seizures in some patients.
Sources: Expert Review
Genetic Epilepsy v0.1901 ZNF335 Zornitza Stark Marked gene: ZNF335 as ready
Genetic Epilepsy v0.1901 ZNF335 Zornitza Stark Gene: znf335 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1901 ZNF335 Zornitza Stark Classified gene: ZNF335 as Green List (high evidence)
Genetic Epilepsy v0.1901 ZNF335 Zornitza Stark Gene: znf335 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1900 ZNF335 Zornitza Stark gene: ZNF335 was added
gene: ZNF335 was added to Genetic Epilepsy. Sources: Expert Review
Mode of inheritance for gene: ZNF335 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZNF335 were set to 23178126; 27540107; 29652087
Phenotypes for gene: ZNF335 were set to Microcephaly 10, primary, autosomal recessive (MIM#615095)
Review for gene: ZNF335 was set to GREEN
Added comment: At least 6 unrelated families reported in literature with different biallelic variants in ZNF335. Microcephaly is the primary feature, but also commonly in association with a variable epilepsy phenotype.

Stouffs et al. (PMID:29652087) report 2 unrelated cases: patient A, demonstrating refractory seizures leading to death at age 5 days, whereas patient B lacked any clinical seizures, but had frequent spasms that have yet to be recorded by EEG. The proband in Sato et al. (PMID:27540107) had rare focal seizures controlled by treatment. Although not noted by Yang et al. (PMID:231781260), affected individuals in that family had seizures described as paroxysmal myoclonic jerks (personal communication with Stouffs et al). The case by Rana et al. (PMID:31187448) presented multifocal drug-resistant epilepsy, and while details were limited in McSherry et al. (PMID:30500859), authors did also note seizures.
Sources: Expert Review
Genetic Epilepsy v0.1899 USP18 Zornitza Stark Marked gene: USP18 as ready
Genetic Epilepsy v0.1899 USP18 Zornitza Stark Gene: usp18 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1899 USP18 Zornitza Stark Classified gene: USP18 as Green List (high evidence)
Genetic Epilepsy v0.1899 USP18 Zornitza Stark Gene: usp18 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1898 USP18 Zornitza Stark gene: USP18 was added
gene: USP18 was added to Genetic Epilepsy. Sources: Expert Review
treatable tags were added to gene: USP18.
Mode of inheritance for gene: USP18 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: USP18 were set to 12833411; 27325888; 31940699
Phenotypes for gene: USP18 were set to Pseudo-TORCH syndrome 2, MIM#617397
Review for gene: USP18 was set to GREEN
Added comment: - PMID: 27325888 (2016) - Three sibs from a consanguineous Turkish family with a homozygous variant (c.652C>T, p.Q218X) in USP18. Antenatal presentation in one sib led to termination of pregnancy at 22 wk of gestation, and in the remaining two children presentation was neonatal and resulted in death within 2 weeks of life. In the latter two individuals manifestations included severe intracerebral haemorrhages, liver dysfunction, ascites, and lactic acidosis. One sib additionally had severe thrombocytopenia with petechiae, while the other developed seizures.

Two German sibs, previously reported in PMID: 12833411 (2013), were found to be compound het for the same p.Q218X variant and a cryptic 3-prime deletion of the USP18 gene. They presented thrombocytopenia, petechiae, ascites, hepatomegaly, and systemic calcifications. Within the first days of life, they developed seizures and died from severe cerebral haemorrhage.

Haplotype analysis of the region containing the Q218X mutation suggested a common ancestor between the 2 families and a founder effect.

- PMID: 31940699 (2020) - One Saudi Arabian boy with a homozygous splice-site variant (c.1073+1G>A) in USP18, presented hydrocephalus with seizures, intraventricular haemorrhage, brain calcifications, necrotizing cellulitis, systemic inflammation, multiple organ failure, and respiratory failure. This was the only patient to survive beyond the perinatal period owing to supportive care and prompt treatment with ruxolitinib. At the time of publication, the child was 3-years-old and was in full remission of clinical manifestations while continuing to receive oral ruxolitinib. He continues to grow normally, however authors note delay in developmental milestones.
Sources: Expert Review
Genetic Epilepsy v0.1897 TUBGCP2 Zornitza Stark Marked gene: TUBGCP2 as ready
Genetic Epilepsy v0.1897 TUBGCP2 Zornitza Stark Gene: tubgcp2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1897 TUBGCP2 Zornitza Stark Classified gene: TUBGCP2 as Green List (high evidence)
Genetic Epilepsy v0.1897 TUBGCP2 Zornitza Stark Gene: tubgcp2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1896 TUBGCP2 Zornitza Stark gene: TUBGCP2 was added
gene: TUBGCP2 was added to Genetic Epilepsy. Sources: Expert Review
Mode of inheritance for gene: TUBGCP2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TUBGCP2 were set to 31630790
Phenotypes for gene: TUBGCP2 were set to Pachygyria, microcephaly, developmental delay, and dysmorphic facies, with or without seizures, OMIM # 618737
Review for gene: TUBGCP2 was set to GREEN
Added comment: PMID: 31630790 (2019) - Five patients from four families with biallelic variants in the TUBGCP2 gene. Affected individuals shared phenotypic features that included progressive microcephaly (4/4), developmental delay (5/5, mild-severe), generalised seizures (4/5, onset at 6yrs-9m, 5m, and 7m). All patients exhibited lissencephaly-spectrum phenotypes with varying degrees of cortical malformations on brain imaging including pachygyria and subcortical band heterotopia.

All variants segregated with disease in each family. Analysis of fibroblasts derived from one patient with a splice site variant revealed several abnormal transcripts, predicted to result in LoF. No further functional studies of other variants or patient cells were performed.
Sources: Expert Review
Genetic Epilepsy v0.1895 RNF113A Zornitza Stark Marked gene: RNF113A as ready
Genetic Epilepsy v0.1895 RNF113A Zornitza Stark Gene: rnf113a has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1895 RNF113A Zornitza Stark Classified gene: RNF113A as Green List (high evidence)
Genetic Epilepsy v0.1895 RNF113A Zornitza Stark Gene: rnf113a has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1894 RNF113A Zornitza Stark gene: RNF113A was added
gene: RNF113A was added to Genetic Epilepsy. Sources: Expert Review
Mode of inheritance for gene: RNF113A 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: RNF113A were set to 25612912; 31880405; 31793730; 29133357; 30506991; 15256591; 24026126; 23555887
Phenotypes for gene: RNF113A were set to Trichothiodystrophy 5, nonphotosensitive, MIM#300953
Review for gene: RNF113A was set to GREEN
Added comment: Seizures reported in a proportion of affected individuals.
Sources: Expert Review
Genetic Epilepsy v0.1893 RARS Zornitza Stark Marked gene: RARS as ready
Genetic Epilepsy v0.1893 RARS Zornitza Stark Gene: rars has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1893 RARS Zornitza Stark Classified gene: RARS as Green List (high evidence)
Genetic Epilepsy v0.1893 RARS Zornitza Stark Gene: rars has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1892 RARS Zornitza Stark gene: RARS was added
gene: RARS was added to Genetic Epilepsy. Sources: Expert Review
new gene name tags were added to gene: RARS.
Mode of inheritance for gene: RARS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RARS were set to 31814314
Phenotypes for gene: RARS were set to Leukodystrophy, hypomyelinating, 9 (# 616140)
Review for gene: RARS was set to GREEN
Added comment: PMID 31814314: Clinical presentation and severity can be highly variable. However, among the 15 patients of relevant age (5/20 deceased at an early age), ID was observed in 13 (in 6/13 mild-moderate, in 7/13 severe/profound). Epilepsy was reported in half (10/20) with seizures being refractory to treatment in most and the phenotype corresponding to an infantile epileptic encephalopathy. DD and seizures were the presenting feature in 7 and 5 patients respectively, while in other cases presenting features were less specific (eg. failure to thrive in 1/20, irritabilty in 2/20).
Sources: Expert Review
Genetic Epilepsy v0.1891 PGM2L1 Zornitza Stark Marked gene: PGM2L1 as ready
Genetic Epilepsy v0.1891 PGM2L1 Zornitza Stark Gene: pgm2l1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1891 PGM2L1 Zornitza Stark Classified gene: PGM2L1 as Green List (high evidence)
Genetic Epilepsy v0.1891 PGM2L1 Zornitza Stark Gene: pgm2l1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1890 PGM2L1 Zornitza Stark gene: PGM2L1 was added
gene: PGM2L1 was added to Genetic Epilepsy. Sources: Expert Review
Mode of inheritance for gene: PGM2L1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PGM2L1 were set to 33979636
Phenotypes for gene: PGM2L1 were set to Neurodevelopmental disorder, MONDO:0700092, PGM2L1-related
Review for gene: PGM2L1 was set to GREEN
Added comment: PMID: 33979636:
- Bi-allelic PTVs in 4 unrelated individuals. All four affected individuals had severe developmental and speech delay, dysmorphic facial features, ear anomalies, high arched palate, strabismus, hypotonia, and keratosis pilaris. Early obesity and seizures were present in three individuals.
- Studies on patient fibroblasts and cell lines indicated that PGM2L1 deficiency causes a decrease, but not a disappearance, of the sugar bisphosphates needed for the formation of NDP-sugars and that there is no evidence that this leads to a glycosylation defect.
Sources: Expert Review
Genetic Epilepsy v0.1889 MINPP1 Zornitza Stark Marked gene: MINPP1 as ready
Genetic Epilepsy v0.1889 MINPP1 Zornitza Stark Gene: minpp1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1889 MINPP1 Zornitza Stark Classified gene: MINPP1 as Green List (high evidence)
Genetic Epilepsy v0.1889 MINPP1 Zornitza Stark Gene: minpp1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1888 MINPP1 Zornitza Stark gene: MINPP1 was added
gene: MINPP1 was added to Genetic Epilepsy. Sources: Expert Review
Mode of inheritance for gene: MINPP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MINPP1 were set to 33257696
Phenotypes for gene: MINPP1 were set to Pontocerebellar hypoplasia, type 16, MIM# 619527
Review for gene: MINPP1 was set to GREEN
Added comment: 8 individuals from 6 unrelated families reported with bi-allelic LOF variants. All presented with almost complete absence of motor and cognitive development, progressive or congenital microcephaly, spastic tetraplegia or dystonia, and vision impairments. For most, the first symptoms included neonatal severe axial hypotonia and epilepsy that started during the first months or years of life. Prenatal symptoms of microcephaly associated with increased thalami echogenicity were detected in one, while the seven other individuals presented with progressive microcephaly. Some exhibited rapidly progressive phenotype and the affected children died in their infancy or middle-childhood. Strikingly, all the affected children had a unique brain MRI showing a mild to severe PCH, fluid-filled posterior fossa, with dilated lateral ventricles. In addition, severe atrophy at the level of the basal ganglia or thalami often associated with typical T2 hypersignal were identified in all the patients MRI.

Supportive functional data showing accumulation of highly phosphorylated inositols, mostly inositol hexakisphosphate (IP6), detected in HEK293 cells, fibroblasts, iPSCs and differentiating neurons lacking MINPP1. In mutant cells, higher IP6 level is expected to be associated with an increased chelation of intracellular cations, such as iron or calcium, resulting in decreased levels of available ions.
Sources: Expert Review
Genetic Epilepsy v0.1887 GLRA2 Zornitza Stark Marked gene: GLRA2 as ready
Genetic Epilepsy v0.1887 GLRA2 Zornitza Stark Gene: glra2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1887 GLRA2 Zornitza Stark Classified gene: GLRA2 as Green List (high evidence)
Genetic Epilepsy v0.1887 GLRA2 Zornitza Stark Gene: glra2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1886 GLRA2 Zornitza Stark gene: GLRA2 was added
gene: GLRA2 was added to Genetic Epilepsy. Sources: Expert Review
Mode of inheritance for gene: GLRA2 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: GLRA2 were set to 35294868
Phenotypes for gene: GLRA2 were set to Intellectual developmental disorder, X-linked, syndromic, Pilorge type, MIM# 301076
Review for gene: GLRA2 was set to GREEN
Added comment: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. PMID: 35294868 reports eight GLRA2 variants in affected females (n=8) and males (n=5). The variants in the females were de novo and c.887C>T,
p.Thr296Met (NC_000023.10, chrX: g.14627284C>T) was present in six individuals (PMID: 35294868, table 2) and was found to have a gain-of-function effect, which is in contrast to c.754C>T, p.Arg252Cys and c.407A>G, p.Asn136Ser (PMID: 2637014). All of the 13 GLRA2 variant carriers in PMID: 35294868 had developmental delay/intellectual disability and epilepsy was evident in 7/13 of the cases (PMID: 35294868, table 2). Supportive functional studies were also presented.
Sources: Expert Review
Genetic Epilepsy v0.1885 DTYMK Zornitza Stark Marked gene: DTYMK as ready
Genetic Epilepsy v0.1885 DTYMK Zornitza Stark Gene: dtymk has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.1885 DTYMK Zornitza Stark Classified gene: DTYMK as Amber List (moderate evidence)
Genetic Epilepsy v0.1885 DTYMK Zornitza Stark Gene: dtymk has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.1884 DTYMK Zornitza Stark gene: DTYMK was added
gene: DTYMK was added to Genetic Epilepsy. Sources: Expert Review
Mode of inheritance for gene: DTYMK was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: DTYMK were set to Neurodegeneration, childhood-onset, with progressive microcephaly (MIM# 619847)
Review for gene: DTYMK was set to AMBER
Added comment: Four individuals from three families reported. Two individuals had seizures (febrile seizures in one and myoclonic jerks in the other).
Sources: Expert Review
Genetic Epilepsy v0.1883 DDC Zornitza Stark Marked gene: DDC as ready
Genetic Epilepsy v0.1883 DDC Zornitza Stark Gene: ddc has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1883 DDC Zornitza Stark Classified gene: DDC as Green List (high evidence)
Genetic Epilepsy v0.1883 DDC Zornitza Stark Gene: ddc has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1882 DDC Zornitza Stark gene: DDC was added
gene: DDC was added to Genetic Epilepsy. Sources: Expert list
Mode of inheritance for gene: DDC was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: DDC were set to Aromatic L-amino acid decarboxylase deficiency, MIM# 608643
Review for gene: DDC was set to GREEN
Added comment: Seizures are rare but oculogyric crises, a key feature of this disorder, can be mistaken for seizures. Included for completeness.
Sources: Expert list
Transplant Co-Morbidity Superpanel v0.4 CFTR Claire Fryer-Smith gene: CFTR was added
gene: CFTR was added to Transplant Co-Morbidity Superpanel. Sources: Expert list
Mode of inheritance for gene: CFTR was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CFTR were set to Congenital bilateral absence of vas deferens MIM#277180; Cystic fibrosis MIM#219700
Added comment: https://www.pharmgkb.org/vip/PA166169453/overview
Sources: Expert list
Transplant Co-Morbidity Superpanel v0.4 CYP3A5 Claire Fryer-Smith gene: CYP3A5 was added
gene: CYP3A5 was added to Transplant Co-Morbidity Superpanel. Sources: Expert list
Mode of inheritance for gene: CYP3A5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: CYP3A5 were set to Hypertension, salt-sensitive essential, susceptibility to MIM#145500
Review for gene: CYP3A5 was set to GREEN
Added comment: Involved in guidelines for tacrolimus.
CYP3A5 expression has extreme interpopulation variability.
Allelic variants at locus increases susceptibility to hypertension.

https://www.pharmgkb.org/gene/PA131/overview
Sources: Expert list
Transplant Co-Morbidity Superpanel v0.4 TPMT Claire Fryer-Smith gene: TPMT was added
gene: TPMT was added to Transplant Co-Morbidity Superpanel. Sources: Expert list
Mode of inheritance for gene: TPMT was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: TPMT were set to Thiopurines, poor metabolism of, 1 MIM# 610460
Review for gene: TPMT was set to GREEN
Added comment: Alleles in TPMT are in guidelines for thiopurines including mercaptopurine and azathioprine.

https://www.pharmgkb.org/gene/PA356
Sources: Expert list
Transplant Co-Morbidity Superpanel v0.4 UGT1A1 Claire Fryer-Smith gene: UGT1A1 was added
gene: UGT1A1 was added to Transplant Co-Morbidity Superpanel. Sources: Expert list
Mode of inheritance for gene: UGT1A1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: UGT1A1 were set to Hyperbilirubinemia, familial transient neonatal MIM# 237900; Crigler-Najjar syndrome, type I MIM#218800; Crigler-Najjar syndrome, type II MIM#606785
Review for gene: UGT1A1 was set to GREEN
Added comment: Alleles in UGT1A1 are involved in guidelines for atazanavir and irinotecan.

https://www.pharmgkb.org/gene/PA420/overview
Sources: Expert list
Transplant Co-Morbidity Superpanel v0.4 DPYD Claire Fryer-Smith changed review comment from: Monoallelic loss of function variants in this gene are associated with an increased risk of toxicity in cancer patients receiving fluoropyrimidine chemotherapy. Biallelic variants result in dihydropyrimidine dehydrogenase deficiency, an error in pyrimidine metabolism associated with thymine-uraciluria.

https://www.pharmgkb.org/gene/PA145/overview
Sources: Expert list; to: Monoallelic loss of function variants in this gene are associated with an increased risk of toxicity in cancer patients receiving fluoropyrimidine chemotherapy. Biallelic variants result in dihydropyrimidine dehydrogenase deficiency, an error in pyrimidine metabolism associated with thymine-uraciluria.

https://www.pharmgkb.org/gene/PA145/overview
Sources: Expert list
Transplant Co-Morbidity Superpanel v0.4 DPYD Claire Fryer-Smith gene: DPYD was added
gene: DPYD was added to Transplant Co-Morbidity Superpanel. Sources: Expert list
Mode of inheritance for gene: DPYD was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: DPYD were set to Dihydropyrimidine dehydrogenase deficiency MIM#274270; 5-fluorouracil toxicity MIM#274270; Disorders of pyrimidine metabolism
Review for gene: DPYD was set to GREEN
Added comment: Monoallelic loss of function variants in this gene are associated with an increased risk of toxicity in cancer patients receiving fluoropyrimidine chemotherapy. Biallelic variants result in dihydropyrimidine dehydrogenase deficiency, an error in pyrimidine metabolism associated with thymine-uraciluria.

https://www.pharmgkb.org/gene/PA145/overview
Sources: Expert list
Systemic Autoinflammatory Disease_Periodic Fever v1.12 PSMA5 Peter McNaughton gene: PSMA5 was added
gene: PSMA5 was added to Systemic Autoinflammatory Disease_Periodic Fever. Sources: Literature
Mode of inheritance for gene: PSMA5 was set to Other
Publications for gene: PSMA5 were set to PMID: 37600812
Phenotypes for gene: PSMA5 were set to 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 v1.12 PSMB10 Peter McNaughton reviewed gene: PSMB10: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 37600812; Phenotypes: CANDLE/PRAAS; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Incidentalome v0.295 MLH3 Bryony Thompson Tag cancer tag was added to gene: MLH3.
Incidentalome v0.295 MLH1 Bryony Thompson Marked gene: MLH1 as ready
Incidentalome v0.295 MLH1 Bryony Thompson Gene: mlh1 has been classified as Green List (High Evidence).
Incidentalome v0.295 MLH1 Bryony Thompson Mode of inheritance for gene: MLH1 was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Incidentalome v0.294 MLH1 Bryony Thompson Tag cancer tag was added to gene: MLH1.
Incidentalome v0.294 MLH1 Bryony Thompson Phenotypes for gene: MLH1 were changed from to mismatch repair cancer syndrome 1 MONDO:0010159
Incidentalome v0.293 MEN1 Bryony Thompson Marked gene: MEN1 as ready
Incidentalome v0.293 MEN1 Bryony Thompson Gene: men1 has been classified as Green List (High Evidence).
Incidentalome v0.293 MEN1 Bryony Thompson Phenotypes for gene: MEN1 were changed from to Multiple endocrine neoplasia 1, MIM# 131100
Incidentalome v0.292 MEN1 Bryony Thompson Mode of inheritance for gene: MEN1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.291 MEN1 Bryony Thompson Tag cancer tag was added to gene: MEN1.
Incidentalome v0.291 MBD4 Bryony Thompson Tag cancer tag was added to gene: MBD4.
Incidentalome v0.291 MAPT Bryony Thompson Marked gene: MAPT as ready
Incidentalome v0.291 MAPT Bryony Thompson Gene: mapt has been classified as Green List (High Evidence).
Incidentalome v0.291 MAPT Bryony Thompson Phenotypes for gene: MAPT were changed from to Supranuclear palsy, progressive (MIM# 601104) AD; Supranuclear palsy, progressive atypical (MIM# 260540) AR
Incidentalome v0.290 MAPT Bryony Thompson Publications for gene: MAPT were set to
Incidentalome v0.289 MAPT Bryony Thompson Mode of inheritance for gene: MAPT was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.288 MAPT Bryony Thompson Tag adult onset neurodegenerative tag was added to gene: MAPT.
Incidentalome v0.288 LRRK2 Bryony Thompson Marked gene: LRRK2 as ready
Incidentalome v0.288 LRRK2 Bryony Thompson Gene: lrrk2 has been classified as Green List (High Evidence).
Incidentalome v0.288 LRRK2 Bryony Thompson Phenotypes for gene: LRRK2 were changed from to Parkinson Disease type 8 (MONDO:0005180, MIM#607060)
Incidentalome v0.287 LRRK2 Bryony Thompson Mode of pathogenicity for gene: LRRK2 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
Incidentalome v0.286 LRRK2 Bryony Thompson Publications for gene: LRRK2 were set to
Incidentalome v0.285 LRRK2 Bryony Thompson Mode of inheritance for gene: LRRK2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.284 LRRK2 Bryony Thompson Tag adult onset neurodegenerative tag was added to gene: LRRK2.
Incidentalome v0.284 LDLR Bryony Thompson Publications for gene: LDLR were set to
Incidentalome v0.283 LDLR Bryony Thompson Marked gene: LDLR as ready
Incidentalome v0.283 LDLR Bryony Thompson Gene: ldlr has been classified as Green List (High Evidence).
Incidentalome v0.283 LDLR Bryony Thompson Phenotypes for gene: LDLR were changed from to Hypercholesterolemia, familial, 1, MIM# 143890
Incidentalome v0.282 LDLR Bryony Thompson Tag cardiac tag was added to gene: LDLR.
Incidentalome v0.282 LDLR Bryony Thompson Mode of inheritance for gene: LDLR was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.281 ITM2B Bryony Thompson Tag adult onset neurodegenerative tag was added to gene: ITM2B.
Incidentalome v0.281 ITM2B Bryony Thompson Marked gene: ITM2B as ready
Incidentalome v0.281 ITM2B Bryony Thompson Gene: itm2b has been classified as Green List (High Evidence).
Incidentalome v0.281 ITM2B Bryony Thompson Publications for gene: ITM2B were set to
Incidentalome v0.280 ITM2B Bryony Thompson Mode of pathogenicity for gene: ITM2B was changed from None to Other
Incidentalome v0.279 GRN Bryony Thompson Marked gene: GRN as ready
Incidentalome v0.279 GRN Bryony Thompson Gene: grn has been classified as Green List (High Evidence).
Incidentalome v0.279 GRN Bryony Thompson Phenotypes for gene: GRN were changed from to frontotemporal dementia and/or amyotrophic lateral sclerosis MONDO:0030923
Incidentalome v0.278 GRN Bryony Thompson Publications for gene: GRN were set to
Incidentalome v0.277 GRN Bryony Thompson Mode of inheritance for gene: GRN was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.276 GRN Bryony Thompson Tag adult onset neurodegenerative tag was added to gene: GRN.
Incidentalome v0.276 GBA Bryony Thompson Marked gene: GBA as ready
Incidentalome v0.276 GBA Bryony Thompson Gene: gba has been classified as Green List (High Evidence).
Incidentalome v0.276 GBA Bryony Thompson Publications for gene: GBA were set to
Incidentalome v0.275 GBA Bryony Thompson Phenotypes for gene: GBA were changed from to Parkinson's disease, MONDO:0005180, GBA-related
Incidentalome v0.274 GBA Bryony Thompson Mode of inheritance for gene: GBA was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.273 GBA Bryony Thompson Tag adult onset neurodegenerative tag was added to gene: GBA.
Incidentalome v0.273 FUS Bryony Thompson Marked gene: FUS as ready
Incidentalome v0.273 FUS Bryony Thompson Gene: fus has been classified as Green List (High Evidence).
Incidentalome v0.273 FUS Bryony Thompson Tag adult onset neurodegenerative tag was added to gene: FUS.
Incidentalome v0.273 FUS Bryony Thompson Phenotypes for gene: FUS were changed from to Amyotrophic lateral sclerosis 6, with or without frontotemporal dementia, MIM# 608030
Incidentalome v0.272 FUS Bryony Thompson Publications for gene: FUS were set to
Deafness_IsolatedAndComplex v1.160 GJB6 Zornitza Stark Mode of inheritance for gene: GJB6 was changed from Unknown to Other
Deafness_IsolatedAndComplex v1.159 GJB6 Zornitza Stark edited their review of gene: GJB6: Changed mode of inheritance: Other
Deafness_IsolatedAndComplex v1.159 GJB6 Zornitza Stark Classified gene: GJB6 as Green List (high evidence)
Deafness_IsolatedAndComplex v1.159 GJB6 Zornitza Stark Gene: gjb6 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.158 GJB6 Zornitza Stark Tag SV/CNV tag was added to gene: GJB6.
Deafness_IsolatedAndComplex v1.158 GJB6 Zornitza Stark changed review comment from: Association with deafness classified as REFUTED by ClinGen.; to: Association os SNVs in this gene with isolated deafness classified as REFUTED by ClinGen.

The GJB6-D13S1830 deletion is a relatively common disease allele in many populations and is classified as pathogenic for hearing loss, frequently identified in homozygosity or in trans with a pathogenic GJB2 variant. This is a deletion of approximately 309kb of DNA including the 5' end of GJB6 and a region upstream of both GJB6 and the GJB2 gene. It has been proposed that GJB6 and GJB2 are co-regulated by a cis-acting element (Ahmad 2007 PMID 17227867).

GREEN rating on the panel relates to the DELETION ONLY.
Incidentalome v0.271 FUS Bryony Thompson Mode of inheritance for gene: FUS was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.270 FTL Bryony Thompson Marked gene: FTL as ready
Incidentalome v0.270 FTL Bryony Thompson Gene: ftl has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.158 GJB6 Zornitza Stark edited their review of gene: GJB6: Changed rating: GREEN
Incidentalome v0.270 FTL Bryony Thompson Phenotypes for gene: FTL were changed from to Neurodegeneration with brain iron accumulation 3, MIM# 606159
Incidentalome v0.269 FTL Bryony Thompson Publications for gene: FTL were set to
Motor Neurone Disease v1.4 CHMP2B Bryony Thompson Marked gene: CHMP2B as ready
Motor Neurone Disease v1.4 CHMP2B Bryony Thompson Gene: chmp2b has been classified as Green List (High Evidence).
Incidentalome v0.268 FTL Bryony Thompson Mode of inheritance for gene: FTL was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.267 FTL Bryony Thompson Tag neurological tag was added to gene: FTL.
Incidentalome v0.267 FIG4 Bryony Thompson Tag review tag was added to gene: FIG4.
Motor Neurone Disease v1.4 CHMP2B Bryony Thompson Phenotypes for gene: CHMP2B were changed from to Frontotemporal dementia and/or amyotrophic lateral sclerosis 7 (MIM#600795, MONDO:0010936)
Motor Neurone Disease v1.3 CHMP2B Bryony Thompson Publications for gene: CHMP2B were set to
Incidentalome v0.267 DICER1 Bryony Thompson Tag cancer tag was added to gene: DICER1.
Motor Neurone Disease v1.2 CHMP2B Bryony Thompson Mode of pathogenicity for gene: CHMP2B 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
Incidentalome v0.267 DDX41 Bryony Thompson Tag cancer tag was added to gene: DDX41.
Motor Neurone Disease v1.1 CHMP2B Bryony Thompson Mode of inheritance for gene: CHMP2B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.267 CLU Bryony Thompson Marked gene: CLU as ready
Incidentalome v0.267 CLU Bryony Thompson Gene: clu has been classified as Red List (Low Evidence).
Incidentalome v0.267 CLU Bryony Thompson Phenotypes for gene: CLU were changed from to Alzheimer's Disease (MIM#104300)
Early-onset Dementia v1.5 CHMP2B Bryony Thompson Marked gene: CHMP2B as ready
Early-onset Dementia v1.5 CHMP2B Bryony Thompson Gene: chmp2b has been classified as Green List (High Evidence).
Incidentalome v0.266 CLU Bryony Thompson Classified gene: CLU as Red List (low evidence)
Incidentalome v0.266 CLU Bryony Thompson Gene: clu has been classified as Red List (Low Evidence).
Early-onset Dementia v1.5 CHMP2B Bryony Thompson Phenotypes for gene: CHMP2B were changed from to Frontotemporal dementia and/or amyotrophic lateral sclerosis 7 (MIM#600795; MONDO:0010936)
Early-onset Dementia v1.4 CHMP2B Bryony Thompson Publications for gene: CHMP2B were set to
Incidentalome v0.265 CHMP2B Bryony Thompson Marked gene: CHMP2B as ready
Incidentalome v0.265 CHMP2B Bryony Thompson Gene: chmp2b has been classified as Green List (High Evidence).
Early-onset Dementia v1.3 CHMP2B Bryony Thompson Mode of pathogenicity for gene: CHMP2B was changed from Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Incidentalome v0.265 CHMP2B Bryony Thompson Tag adult onset neurodegenerative tag was added to gene: CHMP2B.
Incidentalome v0.265 CHMP2B Bryony Thompson Phenotypes for gene: CHMP2B were changed from to Frontotemporal dementia and/or amyotrophic lateral sclerosis 7 (MIM#600795; MONDO:0010936)
Early-onset Dementia v1.2 CHMP2B Bryony Thompson Mode of pathogenicity for gene: CHMP2B 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
Incidentalome v0.264 CHMP2B Bryony Thompson Publications for gene: CHMP2B were set to
Incidentalome v0.263 CHMP2B Bryony Thompson Mode of pathogenicity for gene: CHMP2B 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
Early-onset Dementia v1.1 CHMP2B Bryony Thompson Mode of inheritance for gene: CHMP2B was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.262 CHMP2B Bryony Thompson Mode of inheritance for gene: CHMP2B was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.262 CHMP2B Bryony Thompson Mode of inheritance for gene: CHMP2B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Dementia v1.1 CHMP2B Bryony Thompson Mode of inheritance for gene: CHMP2B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.261 CHEK2 Bryony Thompson Tag cancer tag was added to gene: CHEK2.
Incidentalome v0.261 CHCHD2 Bryony Thompson Marked gene: CHCHD2 as ready
Incidentalome v0.261 CHCHD2 Bryony Thompson Gene: chchd2 has been classified as Green List (High Evidence).
Incidentalome v0.261 CHCHD2 Bryony Thompson Tag adult onset neurodegenerative tag was added to gene: CHCHD2.
Incidentalome v0.261 CDH1 Bryony Thompson Tag cancer tag was added to gene: CDH1.
Incidentalome v0.261 CCNF Bryony Thompson Classified gene: CCNF as Amber List (moderate evidence)
Incidentalome v0.261 CCNF Bryony Thompson Added comment: Comment on list classification: Limited gene-disease validity assessment by ClinGen ALS spectrum disorders GCEP - 05/04/2022
Incidentalome v0.261 CCNF Bryony Thompson Gene: ccnf has been classified as Amber List (Moderate Evidence).
Incidentalome v0.260 CCNF Bryony Thompson Classified gene: CCNF as Amber List (moderate evidence)
Incidentalome v0.260 CCNF Bryony Thompson Gene: ccnf has been classified as Amber List (Moderate Evidence).
Incidentalome v0.259 CACNA1C Bryony Thompson Tag cardiac tag was added to gene: CACNA1C.
Incidentalome v0.259 CALHM1 Bryony Thompson Marked gene: CALHM1 as ready
Incidentalome v0.259 CALHM1 Bryony Thompson Gene: calhm1 has been classified as Red List (Low Evidence).
Incidentalome v0.259 CALHM1 Bryony Thompson Classified gene: CALHM1 as Red List (low evidence)
Incidentalome v0.259 CALHM1 Bryony Thompson Gene: calhm1 has been classified as Red List (Low Evidence).
Incidentalome v0.258 CACNA1S Bryony Thompson Tag review tag was added to gene: CACNA1S.
Incidentalome v0.258 BRCA2 Bryony Thompson Marked gene: BRCA2 as ready
Incidentalome v0.258 BRCA2 Bryony Thompson Gene: brca2 has been classified as Green List (High Evidence).
Incidentalome v0.258 BRCA2 Bryony Thompson Tag cancer tag was added to gene: BRCA2.
Incidentalome v0.258 BRCA2 Bryony Thompson Phenotypes for gene: BRCA2 were changed from to Breast-ovarian cancer, familial, 2, MIM#612555
Incidentalome v0.257 BRCA2 Bryony Thompson Mode of inheritance for gene: BRCA2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.256 BRCA1 Bryony Thompson Marked gene: BRCA1 as ready
Incidentalome v0.256 BRCA1 Bryony Thompson Gene: brca1 has been classified as Green List (High Evidence).
Incidentalome v0.256 BRCA1 Bryony Thompson Phenotypes for gene: BRCA1 were changed from to Breast-ovarian cancer, familial, 1, MIM# 604370
Incidentalome v0.255 BRCA1 Bryony Thompson Mode of inheritance for gene: BRCA1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.254 BAP1 Bryony Thompson Tag cancer tag was added to gene: BAP1.
Mendeliome v1.1117 GOSR2 Achchuthan Shanmugasundram changed review comment from: Four children from two sibships from an extended consanguineous Palestinian family were reported with congenital profound hearing loss, whereas the parents of both sibships are first cousins with normal hearing. The families reported occasional febrile seizures in infancy for each of the deaf children, but these did not persist into adolescence. These affected children were identified with autosomal recessive GOSR2 variant, c.1A > C, p.Met1Leu. This variant appeared once in the gnomAD database, as a heterozygote, and not in any of ~2000 in-house controls of Palestinian ancestry.

All previously reported cases with biallelic GOSR2 variants had normal hearing and hence the differences in translation efficiency due to the effect of this variant may be responsible for this hearing loss phenotype (PMID:37074134).; to: This gene should be added in 'Deafness_IsolatedAndComplex' panel with red rating.

Four children from two sibships from an extended consanguineous Palestinian family were reported with congenital profound hearing loss, whereas the parents of both sibships are first cousins with normal hearing. The families reported occasional febrile seizures in infancy for each of the deaf children, but these did not persist into adolescence. These affected children were identified with autosomal recessive GOSR2 variant, c.1A > C, p.Met1Leu. This variant appeared once in the gnomAD database, as a heterozygote, and not in any of ~2000 in-house controls of Palestinian ancestry.

All previously reported cases with biallelic GOSR2 variants had normal hearing and hence the differences in translation efficiency due to the effect of this variant may be responsible for this hearing loss phenotype (PMID:37074134).
Mendeliome v1.1117 GOSR2 Achchuthan Shanmugasundram reviewed gene: GOSR2: Rating: RED; Mode of pathogenicity: None; Publications: 37074134; Phenotypes: hearing loss, autosomal recessive, MONDO:0019588; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v1.1 UMPS Zornitza Stark Tag for review was removed from gene: UMPS.
BabyScreen+ newborn screening v1.1 SMN1 Zornitza Stark Tag for review was removed from gene: SMN1.
BabyScreen+ newborn screening v1.1 OAT Zornitza Stark Tag for review was removed from gene: OAT.
BabyScreen+ newborn screening v1.1 MLH1 Zornitza Stark Tag for review was removed from gene: MLH1.
BabyScreen+ newborn screening v1.1 KCNJ2 Zornitza Stark Tag for review was removed from gene: KCNJ2.
Tag treatable tag was added to gene: KCNJ2.
BabyScreen+ newborn screening v1.1 HIBCH Zornitza Stark Tag for review was removed from gene: HIBCH.
BabyScreen+ newborn screening v1.1 NIPAL4 Zornitza Stark Tag for review was removed from gene: NIPAL4.
Tag treatable tag was added to gene: NIPAL4.
Tag dermatological tag was added to gene: NIPAL4.
BabyScreen+ newborn screening v1.1 SAMD9 Zornitza Stark Tag treatable tag was added to gene: SAMD9.
Tag endocrine tag was added to gene: SAMD9.
Tag haematological tag was added to gene: SAMD9.
BabyScreen+ newborn screening v1.1 PDP1 Zornitza Stark Tag treatable tag was added to gene: PDP1.
Tag metabolic tag was added to gene: PDP1.
Phagocyte Defects v1.16 GFI1 Zornitza Stark Tag treatable tag was added to gene: GFI1.
Mendeliome v1.1117 GFI1 Zornitza Stark Tag treatable tag was added to gene: GFI1.
Bone Marrow Failure v1.46 GFI1 Zornitza Stark Tag treatable tag was added to gene: GFI1.
BabyScreen+ newborn screening v1.1 GFI1 Zornitza Stark Tag treatable tag was added to gene: GFI1.
Tag immunological tag was added to gene: GFI1.
BabyScreen+ newborn screening v1.1 DLAT Zornitza Stark Tag treatable tag was added to gene: DLAT.
Tag metabolic tag was added to gene: DLAT.
Severe Combined Immunodeficiency (absent T present B cells) v1.3 CORO1A Zornitza Stark Tag treatable tag was added to gene: CORO1A.
Mendeliome v1.1117 CORO1A Zornitza Stark Tag treatable tag was added to gene: CORO1A.
BabyScreen+ newborn screening v1.1 CORO1A Zornitza Stark Tag treatable tag was added to gene: CORO1A.
Tag immunological tag was added to gene: CORO1A.
Susceptibility to Viral Infections v0.113 CD70 Zornitza Stark Tag treatable tag was added to gene: CD70.
Disorders of immune dysregulation v0.178 CD70 Zornitza Stark Tag treatable tag was added to gene: CD70.
Mendeliome v1.1117 CD70 Zornitza Stark Tag treatable tag was added to gene: CD70.
BabyScreen+ newborn screening v1.1 CD70 Zornitza Stark Tag treatable tag was added to gene: CD70.
Tag immunological tag was added to gene: CD70.
Combined Immunodeficiency v1.43 CD40 Zornitza Stark Tag treatable tag was added to gene: CD40.
Mendeliome v1.1117 CD40 Zornitza Stark Tag treatable tag was added to gene: CD40.
BabyScreen+ newborn screening v1.1 CD40 Zornitza Stark Tag treatable tag was added to gene: CD40.
Tag immunological tag was added to gene: CD40.
BabyScreen+ newborn screening v1.1 BMP1 Zornitza Stark Tag skeletal tag was added to gene: BMP1.
Incidentalome v0.254 ATP7B Bryony Thompson Publications for gene: ATP7B were set to
Incidentalome v0.253 ATP7B Bryony Thompson Tag treatable tag was added to gene: ATP7B.
Incidentalome v0.253 ATP7B Bryony Thompson Mode of inheritance for gene: ATP7B was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Incidentalome v0.252 ATP7B Bryony Thompson Phenotypes for gene: ATP7B were changed from to Wilson Disease (MONDO:0010200; MIM #277900)
Incidentalome v0.251 ATP13A2 Bryony Thompson Marked gene: ATP13A2 as ready
Incidentalome v0.251 ATP13A2 Bryony Thompson Gene: atp13a2 has been classified as Green List (High Evidence).
Incidentalome v0.251 ATP13A2 Bryony Thompson Phenotypes for gene: ATP13A2 were changed from to Kufor-Rakeb syndrome, MIM# 606693
Incidentalome v0.250 ATP13A2 Bryony Thompson Mode of inheritance for gene: ATP13A2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Incidentalome v0.249 ATP13A2 Bryony Thompson Tag neurological tag was added to gene: ATP13A2.
Incidentalome v0.249 APP Bryony Thompson Marked gene: APP as ready
Incidentalome v0.249 APP Bryony Thompson Gene: app has been classified as Green List (High Evidence).
Incidentalome v0.249 APP Bryony Thompson Phenotypes for gene: APP were changed from to Alzheimer's Disease (MIM#104300)
Incidentalome v0.248 APP Bryony Thompson Publications for gene: APP were set to
Incidentalome v0.247 APP Bryony Thompson Mode of pathogenicity for gene: APP 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
Incidentalome v0.246 APP Bryony Thompson Mode of inheritance for gene: APP was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.245 APP Bryony Thompson Tag adult onset neurodegenerative tag was added to gene: APP.
Incidentalome v0.245 APOE Bryony Thompson Phenotypes for gene: APOE were changed from Alzheimer disease 2, MIM# 104310 to Alzheimer disease 2, MIM# 104310; Hyperlipoproteinemia, type III (MIM#617347); Sea-blue histiocyte disease (MIM#269600)
Incidentalome v0.244 APOE Bryony Thompson Tag adult onset neurodegenerative tag was added to gene: APOE.
Incidentalome v0.243 APOE Bryony Thompson Phenotypes for gene: APOE were changed from to Alzheimer disease 2, MIM# 104310
Incidentalome v0.242 APOB Bryony Thompson Marked gene: APOB as ready
Incidentalome v0.242 APOB Bryony Thompson Gene: apob has been classified as Green List (High Evidence).
Incidentalome v0.242 APOB Bryony Thompson Mode of inheritance for gene: APOB was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.241 APOB Bryony Thompson Phenotypes for gene: APOB were changed from to Hypercholesterolemia, familial, 2, MIM# 144010
Incidentalome v0.240 APOB Bryony Thompson Mode of inheritance for gene: APOB was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.239 APOB Bryony Thompson Tag treatable tag was added to gene: APOB.
Incidentalome v0.238 ANG Bryony Thompson Marked gene: ANG as ready
Incidentalome v0.238 ANG Bryony Thompson Gene: ang has been classified as Amber List (Moderate Evidence).
Incidentalome v0.238 ANG Bryony Thompson Phenotypes for gene: ANG were changed from to Amyotrophic Lateral Sclerosis (MONDO: 0012753; MIM#611895)
Incidentalome v0.237 ANG Bryony Thompson Publications for gene: ANG were set to
Incidentalome v0.236 ANG Bryony Thompson Tag neurological tag was added to gene: ANG.
Incidentalome v0.236 ANG Bryony Thompson Mode of inheritance for gene: ANG was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.235 ANG Bryony Thompson Mode of inheritance for gene: ANG was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.235 ANG Bryony Thompson Classified gene: ANG as Amber List (moderate evidence)
Incidentalome v0.235 ANG Bryony Thompson Gene: ang has been classified as Amber List (Moderate Evidence).
Motor Neurone Disease v1.0 Bryony Thompson promoted panel to version 1.0
Motor Neurone Disease v0.194 HNRNPA2B1 Bryony Thompson changed review comment from: Comment on list classification: Assigned amber because HNRNPA2B1 is a multisystem proteinopathy gene, with includes ALS in the spectrum of phenotypes; to: Comment on list classification: Assigned amber because HNRNPA2B1 is a multisystem proteinopathy gene, which includes ALS in the spectrum of phenotypes
Motor Neurone Disease v0.194 HNRNPA2B1 Bryony Thompson Classified gene: HNRNPA2B1 as Amber List (moderate evidence)
Motor Neurone Disease v0.194 HNRNPA2B1 Bryony Thompson Added comment: Comment on list classification: Assigned amber because HNRNPA2B1 is a multisystem proteinopathy gene, which includes ALS in the spectrum of phenotypes
Motor Neurone Disease v0.194 HNRNPA2B1 Bryony Thompson Gene: hnrnpa2b1 has been classified as Amber List (Moderate Evidence).
Motor Neurone Disease v0.194 HNRNPA2B1 Bryony Thompson Classified gene: HNRNPA2B1 as Amber List (moderate evidence)
Motor Neurone Disease v0.194 HNRNPA2B1 Bryony Thompson Added comment: Comment on list classification: Assigned amber because HNRNPA2B1 is a multisystem proteinopathy gene, with includes ALS in the spectrum of phenotypes
Motor Neurone Disease v0.194 HNRNPA2B1 Bryony Thompson Gene: hnrnpa2b1 has been classified as Amber List (Moderate Evidence).
Motor Neurone Disease v0.193 EWSR1 Bryony Thompson Marked gene: EWSR1 as ready
Motor Neurone Disease v0.193 EWSR1 Bryony Thompson Gene: ewsr1 has been classified as Red List (Low Evidence).
Motor Neurone Disease v0.193 ERLIN1 Bryony Thompson Marked gene: ERLIN1 as ready
Motor Neurone Disease v0.193 ERLIN1 Bryony Thompson Gene: erlin1 has been classified as Red List (Low Evidence).
Motor Neurone Disease v0.193 DAO Bryony Thompson Marked gene: DAO as ready
Motor Neurone Disease v0.193 DAO Bryony Thompson Gene: dao has been classified as Red List (Low Evidence).
Motor Neurone Disease v0.193 CCNF Bryony Thompson edited their review of gene: CCNF: Changed rating: AMBER
Early-onset Dementia v1.0 Bryony Thompson promoted panel to version 1.0
Early-onset Dementia v0.221 NR4A2 Bryony Thompson Marked gene: NR4A2 as ready
Early-onset Dementia v0.221 NR4A2 Bryony Thompson Gene: nr4a2 has been classified as Red List (Low Evidence).
Early-onset Dementia v0.221 HTRA2 Bryony Thompson Marked gene: HTRA2 as ready
Early-onset Dementia v0.221 HTRA2 Bryony Thompson Gene: htra2 has been classified as Red List (Low Evidence).
Early-onset Dementia v0.221 TIA1 Bryony Thompson Marked gene: TIA1 as ready
Early-onset Dementia v0.221 TIA1 Bryony Thompson Gene: tia1 has been classified as Amber List (Moderate Evidence).
Early-onset Dementia v0.221 TIA1 Bryony Thompson Classified gene: TIA1 as Amber List (moderate evidence)
Early-onset Dementia v0.221 TIA1 Bryony Thompson Gene: tia1 has been classified as Amber List (Moderate Evidence).
Early-onset Dementia v0.220 TIA1 Bryony Thompson gene: TIA1 was added
gene: TIA1 was added to Early-onset Dementia. Sources: Literature
Mode of inheritance for gene: TIA1 was set to Other
Publications for gene: TIA1 were set to 36861178; 29599744; 29457785
Phenotypes for gene: TIA1 were set to Multisystem proteinopathy
Review for gene: TIA1 was set to AMBER
Added comment: Digenic variants in SQSTM1 and TIA1 have been reported in multisystem proteinopathy which includes clinical combinations of inclusion body myopathy (IBM), neurodegeneration [motor neuron disorder (MND)/frontotemporal dementia (FTD)], and Paget disease of bone (PDB). FTD has reported in at least one individual with FTD as a feature of the phenotype.
Sources: Literature
Early-onset Dementia v0.219 HNRNPA1 Bryony Thompson Classified gene: HNRNPA1 as Amber List (moderate evidence)
Early-onset Dementia v0.219 HNRNPA1 Bryony Thompson Added comment: Comment on list classification: Included as an amber gene because the gene is associated with multisystem proteinopathy, which FTD can be a feature. No FTD has been reported in association with this gene.
Early-onset Dementia v0.219 HNRNPA1 Bryony Thompson Gene: hnrnpa1 has been classified as Amber List (Moderate Evidence).
Early-onset Dementia v0.218 GCH1 Bryony Thompson Marked gene: GCH1 as ready
Early-onset Dementia v0.218 GCH1 Bryony Thompson Gene: gch1 has been classified as Red List (Low Evidence).
Early-onset Dementia v0.218 FIG4 Bryony Thompson Marked gene: FIG4 as ready
Early-onset Dementia v0.218 FIG4 Bryony Thompson Gene: fig4 has been classified as Red List (Low Evidence).
Motor Neurone Disease v0.193 ANG Bryony Thompson Classified gene: ANG as Amber List (moderate evidence)
Motor Neurone Disease v0.193 ANG Bryony Thompson Gene: ang has been classified as Amber List (Moderate Evidence).
Early-onset Dementia v0.218 ANG Bryony Thompson Marked gene: ANG as ready
Early-onset Dementia v0.218 ANG Bryony Thompson Gene: ang has been classified as Red List (Low Evidence).
Early-onset Dementia v0.218 ALS2 Bryony Thompson Marked gene: ALS2 as ready
Early-onset Dementia v0.218 ALS2 Bryony Thompson Gene: als2 has been classified as Red List (Low Evidence).
Early-onset Dementia v0.218 SCA17 Bryony Thompson Classified STR: SCA17 as Green List (high evidence)
Early-onset Dementia v0.218 SCA17 Bryony Thompson Str: sca17 has been classified as Green List (High Evidence).
Early-onset Dementia v0.217 SCA17 Bryony Thompson Marked STR: SCA17 as ready
Early-onset Dementia v0.217 SCA17 Bryony Thompson Str: sca17 has been classified as Red List (Low Evidence).
Early-onset Dementia v0.217 SCA17 Bryony Thompson STR: SCA17 was added
STR: SCA17 was added to Early-onset Dementia. Sources: Expert list
Mode of inheritance for STR: SCA17 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: SCA17 were set to 10484774; 20301611
Phenotypes for STR: SCA17 were set to Spinocerebellar ataxia 17 MIM#607136
Review for STR: SCA17 was set to GREEN
STR: SCA17 was marked as clinically relevant
Added comment: NM_003194.4:c.172_174[X]
Mechanism of disease expected to be gain of function
Normal: ≤ 40 CAG/CAA repeats
Reduced-penetrance: 41-48 CAG/CAA repeats, individual may or may not develop symptoms.
Full-penetrance: ≥49 CAG/CAA repeats
Dementia is a feature of the condition
Sources: Expert list
Early-onset Dementia v0.216 XK Sangavi Sivagnanasundram Deleted their comment
Early-onset Dementia v0.216 XK Sangavi Sivagnanasundram edited their review of gene: XK: Added comment: McLeod Syndrome (MLS) is multisystem disorder with central nervous system (CNS), neuromuscular, cardiovascular, and hematologic manifestations in males.

Dementia is not a typical feature of MLS but cognitive impairment has been identified in multiple individuals with MLS.

PMID: 12899725
Reported in one individual with McLeod Syndrome (MLS) who developed mild dementia during disease progression (age of onset was later in life). Testing confirmed he has a complete deletion of exon 2.

PMID: 11761473
Approx 15 individuals identified with neurological impact to the central nervous system resulting in cognitive impairment.; Changed rating: GREEN; Changed publications: 12899725, 11761473
Early-onset Dementia v0.216 CCNF Bryony Thompson edited their review of gene: CCNF: Changed rating: AMBER
Skeletal dysplasia v0.248 RAB3GAP2 Ain Roesley Classified gene: RAB3GAP2 as Green List (high evidence)
Skeletal dysplasia v0.248 RAB3GAP2 Ain Roesley Gene: rab3gap2 has been classified as Green List (High Evidence).
Skeletal dysplasia v0.248 RAB3GAP2 Ain Roesley Marked gene: RAB3GAP2 as ready
Skeletal dysplasia v0.248 RAB3GAP2 Ain Roesley Gene: rab3gap2 has been classified as Green List (High Evidence).
Skeletal dysplasia v0.248 RAB3GAP2 Ain Roesley Mode of inheritance for gene: RAB3GAP2 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v0.248 RAB3GAP2 Ain Roesley Publications for gene: RAB3GAP2 were set to 23420520; 20967465
Skeletal dysplasia v0.247 RAB3GAP2 Ain Roesley Phenotypes for gene: RAB3GAP2 were changed from Warburg micro syndrome 2, MIM# 614225 to Martsolf syndrome 1 MIM#212720
Skeletal dysplasia v0.246 RAB3GAP2 Ain Roesley Phenotypes for gene: RAB3GAP2 were changed from Martsolf syndrome to Warburg micro syndrome 2, MIM# 614225
Skeletal dysplasia v0.246 RAB3GAP2 Ain Roesley Publications for gene: RAB3GAP2 were set to
Skeletal dysplasia v0.246 RAB3GAP2 Ain Roesley Mode of inheritance for gene: RAB3GAP2 was changed from to BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v0.246 RAB3GAP2 Ain Roesley Classified gene: RAB3GAP2 as Green List (high evidence)
Skeletal dysplasia v0.246 RAB3GAP2 Ain Roesley Gene: rab3gap2 has been classified as Green List (High Evidence).
Skeletal dysplasia v0.245 PHF6 Ain Roesley Marked gene: PHF6 as ready
Skeletal dysplasia v0.245 PHF6 Ain Roesley Gene: phf6 has been classified as Green List (High Evidence).
Skeletal dysplasia v0.245 PHF6 Ain Roesley Phenotypes for gene: PHF6 were changed from Coffin-Siris syndrome to Borjeson-Forssman-Lehmann syndrome, MIM# 301900
Skeletal dysplasia v0.245 PHF6 Ain Roesley Publications for gene: PHF6 were set to
Skeletal dysplasia v0.244 PHF6 Ain Roesley Mode of inheritance for gene: PHF6 was changed from to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Skeletal dysplasia v0.244 PHF6 Ain Roesley Classified gene: PHF6 as Green List (high evidence)
Skeletal dysplasia v0.244 PHF6 Ain Roesley Gene: phf6 has been classified as Green List (High Evidence).
Mendeliome v1.1117 DDRGK1 Ain Roesley Marked gene: DDRGK1 as ready
Mendeliome v1.1117 DDRGK1 Ain Roesley Gene: ddrgk1 has been classified as Green List (High Evidence).
Mendeliome v1.1117 DDRGK1 Ain Roesley Classified gene: DDRGK1 as Green List (high evidence)
Mendeliome v1.1117 DDRGK1 Ain Roesley Gene: ddrgk1 has been classified as Green List (High Evidence).
Mendeliome v1.1116 DDRGK1 Ain Roesley gene: DDRGK1 was added
gene: DDRGK1 was added to Mendeliome. Sources: Literature
founder tags were added to gene: DDRGK1.
Mode of inheritance for gene: DDRGK1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DDRGK1 were set to 28263186; 35377455; 35670300; 36243336
Phenotypes for gene: DDRGK1 were set to Spondyloepimetaphyseal dysplasia, Shohat type (MIM#602557)
Review for gene: DDRGK1 was set to GREEN
gene: DDRGK1 was marked as current diagnostic
Added comment: RNA and protein studies performed for the splice variant. These two variants likely represents founder variants

PMID:28263186 reported six individuals from three different families of Iraqi Jewish descent (three patients from family 1 and one individual each from families 2-4) identified with homozygous c.408+1G>A donor splice site loss-of-function mutation in DDRGK1 and presented with Shohat-type spondyloepimetaphyseal dysplasia (SEMD). It is a skeletal dysplasia that affects cartilage development.

PMID: 35670300 reported two unrelated cases of Moroccan descent identified with homozygous missense variant c.406G>A and presented with SEMD. PMID:36243336 reported an Omani female patient identified with the same homozygous variant as the Iraqi cases and was reported with SEMD.

In addition, studies on both zebrafish and mouse models confirms the physiological role of DDRGK1 in the development and maintenance of the growth plate cartilage and deficiency of DDRGK1 recapitulate the clinical phenotype of short stature and joint abnormalities observed in patients with Shohat type SEMD (PMID:28263186; PMID:35377455).
Sources: Literature
Skeletal dysplasia v0.243 DDRGK1 Ain Roesley Marked gene: DDRGK1 as ready
Skeletal dysplasia v0.243 DDRGK1 Ain Roesley Added comment: Comment when marking as ready: RNA and protein studies performed for the splice variant. These two variants likely represents founder variants
Skeletal dysplasia v0.243 DDRGK1 Ain Roesley Gene: ddrgk1 has been classified as Green List (High Evidence).
Skeletal dysplasia v0.243 DDRGK1 Ain Roesley Tag founder tag was added to gene: DDRGK1.
Skeletal dysplasia v0.243 DDRGK1 Ain Roesley Classified gene: DDRGK1 as Green List (high evidence)
Skeletal dysplasia v0.243 DDRGK1 Ain Roesley Gene: ddrgk1 has been classified as Green List (High Evidence).
Early-onset Dementia v0.216 NHLRC1 Zornitza Stark Marked gene: NHLRC1 as ready
Early-onset Dementia v0.216 NHLRC1 Zornitza Stark Gene: nhlrc1 has been classified as Green List (High Evidence).
Early-onset Dementia v0.216 NHLRC1 Zornitza Stark Phenotypes for gene: NHLRC1 were changed from to Epilepsy, progressive myoclonic 2B (Lafora Disease) MIM#254780
Early-onset Dementia v0.215 NHLRC1 Zornitza Stark Publications for gene: NHLRC1 were set to
Early-onset Dementia v0.214 NHLRC1 Zornitza Stark Mode of inheritance for gene: NHLRC1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Early-onset Dementia v0.213 NPC2 Zornitza Stark Marked gene: NPC2 as ready
Early-onset Dementia v0.213 NPC2 Zornitza Stark Gene: npc2 has been classified as Green List (High Evidence).
Early-onset Dementia v0.213 NPC2 Zornitza Stark Phenotypes for gene: NPC2 were changed from to Niemann-pick disease, type C2 MIM#607625
Early-onset Dementia v0.212 NPC2 Zornitza Stark Publications for gene: NPC2 were set to
Early-onset Dementia v0.211 NPC2 Zornitza Stark Mode of inheritance for gene: NPC2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Early-onset Dementia v0.210 OPTN Zornitza Stark Marked gene: OPTN as ready
Early-onset Dementia v0.210 OPTN Zornitza Stark Gene: optn has been classified as Green List (High Evidence).
Early-onset Dementia v0.210 OPTN Zornitza Stark Phenotypes for gene: OPTN were changed from to Amyotrophic lateral sclerosis 12 with or without frontotemporal dementia (MIM#613435)
Early-onset Dementia v0.209 OPTN Zornitza Stark Publications for gene: OPTN were set to
Early-onset Dementia v0.208 OPTN Zornitza Stark Mode of inheritance for gene: OPTN was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Early-onset Dementia v0.207 PANK2 Zornitza Stark Marked gene: PANK2 as ready
Early-onset Dementia v0.207 PANK2 Zornitza Stark Gene: pank2 has been classified as Green List (High Evidence).
Early-onset Dementia v0.207 PANK2 Zornitza Stark Phenotypes for gene: PANK2 were changed from to Neurodegeneration with brain iron accumulation 1 (MIM#234200)
Early-onset Dementia v0.206 PANK2 Zornitza Stark Publications for gene: PANK2 were set to
Early-onset Dementia v0.205 PANK2 Zornitza Stark Mode of inheritance for gene: PANK2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Early-onset Dementia v0.204 PRNP Zornitza Stark Marked gene: PRNP as ready
Early-onset Dementia v0.204 PRNP Zornitza Stark Gene: prnp has been classified as Green List (High Evidence).
Early-onset Dementia v0.204 PRNP Zornitza Stark Phenotypes for gene: PRNP were changed from to Prion Disease (MIM#176640); Creutzfeldt-Jakob disease (MIM#123400)
Early-onset Dementia v0.203 PRNP Zornitza Stark Publications for gene: PRNP were set to
Early-onset Dementia v0.202 PRNP Zornitza Stark Mode of inheritance for gene: PRNP was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Dementia v0.201 PSEN1 Zornitza Stark Marked gene: PSEN1 as ready
Early-onset Dementia v0.201 PSEN1 Zornitza Stark Gene: psen1 has been classified as Green List (High Evidence).
Early-onset Dementia v0.201 PSEN1 Zornitza Stark Phenotypes for gene: PSEN1 were changed from to Alzheimer disease, type 3 (MIM#607822; MONDO:0011913)
Early-onset Dementia v0.200 PSEN1 Zornitza Stark Publications for gene: PSEN1 were set to
Early-onset Dementia v0.199 PSEN1 Zornitza Stark Mode of inheritance for gene: PSEN1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Dementia v0.198 PSEN2 Zornitza Stark Marked gene: PSEN2 as ready
Early-onset Dementia v0.198 PSEN2 Zornitza Stark Gene: psen2 has been classified as Green List (High Evidence).
Early-onset Dementia v0.198 PSEN2 Zornitza Stark Phenotypes for gene: PSEN2 were changed from to Alzheimer disease-4 (MIM#606889)
Early-onset Dementia v0.197 PSEN2 Zornitza Stark Publications for gene: PSEN2 were set to
Early-onset Dementia v0.196 PSEN2 Zornitza Stark Mode of inheritance for gene: PSEN2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Dementia v0.195 SQSTM1 Zornitza Stark Marked gene: SQSTM1 as ready
Early-onset Dementia v0.195 SQSTM1 Zornitza Stark Gene: sqstm1 has been classified as Amber List (Moderate Evidence).
Early-onset Dementia v0.195 SQSTM1 Zornitza Stark Phenotypes for gene: SQSTM1 were changed from to Frontotemporal dementia and/or amyotrophic lateral sclerosis 3 (MIM#616437)
Early-onset Dementia v0.194 SQSTM1 Zornitza Stark Publications for gene: SQSTM1 were set to
Early-onset Dementia v0.193 SQSTM1 Zornitza Stark Mode of inheritance for gene: SQSTM1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Dementia v0.192 SQSTM1 Zornitza Stark Classified gene: SQSTM1 as Amber List (moderate evidence)
Early-onset Dementia v0.192 SQSTM1 Zornitza Stark Gene: sqstm1 has been classified as Amber List (Moderate Evidence).
Early-onset Dementia v0.191 TARDBP Zornitza Stark Marked gene: TARDBP as ready
Early-onset Dementia v0.191 TARDBP Zornitza Stark Gene: tardbp has been classified as Green List (High Evidence).
Early-onset Dementia v0.191 TARDBP Zornitza Stark Phenotypes for gene: TARDBP were changed from to Amyotrophic lateral sclerosis 10, with or without FTD (MIM#612069)
Early-onset Dementia v0.190 TARDBP Zornitza Stark Publications for gene: TARDBP were set to
Early-onset Dementia v0.189 TARDBP Zornitza Stark Mode of inheritance for gene: TARDBP was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Early-onset Dementia v0.188 TBK1 Zornitza Stark Marked gene: TBK1 as ready
Early-onset Dementia v0.188 TBK1 Zornitza Stark Gene: tbk1 has been classified as Green List (High Evidence).
Early-onset Dementia v0.188 TBK1 Zornitza Stark Phenotypes for gene: TBK1 were changed from to Frontotemporal dementia and/or amyotrophic lateral sclerosis 4, MIM# 616439
Early-onset Dementia v0.187 TBK1 Zornitza Stark Publications for gene: TBK1 were set to
Early-onset Dementia v0.186 TBK1 Zornitza Stark Mode of inheritance for gene: TBK1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Dementia v0.185 TYROBP Zornitza Stark Marked gene: TYROBP as ready
Early-onset Dementia v0.185 TYROBP Zornitza Stark Gene: tyrobp has been classified as Green List (High Evidence).
Early-onset Dementia v0.185 TYROBP Zornitza Stark Phenotypes for gene: TYROBP were changed from to Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 1 (MIM#221770)
Early-onset Dementia v0.184 TYROBP Zornitza Stark Publications for gene: TYROBP were set to
Early-onset Dementia v0.183 TYROBP Zornitza Stark Mode of inheritance for gene: TYROBP was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1115 FBXO31 Zornitza Stark Phenotypes for gene: FBXO31 were changed from Mental retardation, autosomal recessive 45, MIM#615979; Cerebral palsy, MONDO:0006497, FBXO31-related; Spastic-dystonic cerebral palsy, intellectual disability, de novo dominant to Intellectual developmental disorder, autosomal recessive 45 (MIM#615979; Cerebral palsy, MONDO:0006497, FBXO31-related; Spastic-dystonic cerebral palsy, intellectual disability, de novo dominant
Mendeliome v1.1114 FBXO31 Zornitza Stark Phenotypes for gene: FBXO31 were changed from Mental retardation, autosomal recessive 45, MIM#615979; Spastic-dystonic cerebral palsy, intellectual disability, de novo dominant to Mental retardation, autosomal recessive 45, MIM#615979; Cerebral palsy, MONDO:0006497, FBXO31-related; Spastic-dystonic cerebral palsy, intellectual disability, de novo dominant
Mendeliome v1.1113 FBXO31 Zornitza Stark Publications for gene: FBXO31 were set to 24623383; 32989326
Early-onset Dementia v0.182 PLA2G6 Zornitza Stark Marked gene: PLA2G6 as ready
Early-onset Dementia v0.182 PLA2G6 Zornitza Stark Gene: pla2g6 has been classified as Green List (High Evidence).
Early-onset Dementia v0.182 PLA2G6 Zornitza Stark Phenotypes for gene: PLA2G6 were changed from to Parkinson disease 14, autosomal recessive, MIM# 612953
Early-onset Dementia v0.181 PLA2G6 Zornitza Stark Publications for gene: PLA2G6 were set to
Early-onset Dementia v0.180 PLA2G6 Zornitza Stark Mode of inheritance for gene: PLA2G6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Inflammatory bowel disease v0.107 DOCK11 Zornitza Stark Marked gene: DOCK11 as ready
Inflammatory bowel disease v0.107 DOCK11 Zornitza Stark Gene: dock11 has been classified as Green List (High Evidence).
Inflammatory bowel disease v0.107 DOCK11 Zornitza Stark Phenotypes for gene: DOCK11 were changed from Inflammatory bowel disease to Autoimmune disease with immune dysregulation, X-linked (ADMIDX), MIM#301109; Inflammatory bowel disease
Inflammatory bowel disease v0.106 DOCK11 Zornitza Stark Classified gene: DOCK11 as Green List (high evidence)
Inflammatory bowel disease v0.106 DOCK11 Zornitza Stark Gene: dock11 has been classified as Green List (High Evidence).
Inflammatory bowel disease v0.105 DOCK11 Zornitza Stark reviewed gene: DOCK11: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Autoimmune disease with immune dysregulation, X-linked (ADMIDX), MIM#301109; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Skeletal dysplasia v0.242 Zornitza Stark removed gene:PLK4 from the panel
Skeletal dysplasia v0.241 PLK4 Zornitza Stark changed review comment from: At least 3 unrelated families reported with autosomal recessive developmental disorder characterised by delayed psychomotor development, visual impairment, and microcephaly.; to: At least 3 unrelated families reported with autosomal recessive developmental disorder characterised by delayed psychomotor development, visual impairment, and microcephaly.

Short stature but no specific skeletal abnormalities.
Skeletal dysplasia v0.241 PLK4 Zornitza Stark edited their review of gene: PLK4: Changed rating: RED
Skeletal dysplasia v0.241 PHF6 Zornitza Stark changed review comment from: Clinical features are quite variable, with the most consistent features being initial hypotonia, mild to moderate impaired intellectual development, large fleshy ears, underdeveloped genitalia, gynecomastia, truncal obesity, tapering fingers, and shortening of the fourth and fifth toes. Heterozygous females may have a milder similar clinical phenotype, which can include hypothyroidism; however, many carrier females appear unaffected.

More than 20 families reported.; to: Clinical features are quite variable, with the most consistent features being initial hypotonia, mild to moderate impaired intellectual development, large fleshy ears, underdeveloped genitalia, gynecomastia, truncal obesity, tapering fingers, and shortening of the fourth and fifth toes. Heterozygous females may have a milder similar clinical phenotype, which can include hypothyroidism; however, many carrier females appear unaffected.

More than 20 families reported.

Abnormal skeletal features including thickened calvarium and abnormal vertebrae reported.
Inflammatory bowel disease v0.105 DOCK11 Peter McNaughton gene: DOCK11 was added
gene: DOCK11 was added to Inflammatory bowel disease. Sources: Literature
Mode of inheritance for gene: DOCK11 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: DOCK11 were set to PMID: 37342957; PMID: 36952639
Phenotypes for gene: DOCK11 were set to Inflammatory bowel disease
Added comment: 12 patients across 2 studies described. Severe gastrointestinal disease was observed in most of the patients, manifested as ulcerative colitis-like or Crohn's disease-like inflammatory bowel disease, unspecified ileitis, and colitis. Oral and anal ulcerations or ileus affected 6 of the patients.
Sources: Literature
Callosome v0.501 ATP6V0C Zornitza Stark Phenotypes for gene: ATP6V0C were changed from neurodevelopmental disorder (MONDO:0700092), ATP6V0C-related to Epilepsy, early-onset, with or without developmental delay, MIM#620465; neurodevelopmental disorder (MONDO:0700092), ATP6V0C-related
Intellectual disability syndromic and non-syndromic v0.5336 ATP6V0C Zornitza Stark Phenotypes for gene: ATP6V0C were changed from Epilepsy; Intellectual Disability; microcephaly to Epilepsy, early-onset, with or without developmental delay, MIM#620465; Epilepsy; Intellectual Disability; microcephaly
Genetic Epilepsy v0.1881 ATP6V0C Zornitza Stark Phenotypes for gene: ATP6V0C were changed from Epilepsy; Intellectual Disability; microcephaly to Epilepsy, early-onset, with or without developmental delay, MIM#620465; Epilepsy; Intellectual Disability; microcephaly
Genetic Epilepsy v0.1880 ATP6V0C Zornitza Stark edited their review of gene: ATP6V0C: Changed phenotypes: Epilepsy, early-onset, with or without developmental delay, MIM#620465, Intellectual disability, seizures
Mendeliome v1.1112 ATP6V0C Zornitza Stark Phenotypes for gene: ATP6V0C were changed from Epilepsy; Intellectual Disability; microcephaly to Epilepsy, early-onset, with or without developmental delay, MIM#620465; Epilepsy; Intellectual Disability; microcephaly
Mendeliome v1.1111 ATP6V0C Zornitza Stark edited their review of gene: ATP6V0C: Changed phenotypes: Epilepsy, early-onset, with or without developmental delay, MIM#620465, Epilepsy, Intellectual Disability, microcephaly
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.24 HNRNPA1 Zornitza Stark changed review comment from: PMID 34722876: single multigenerational family reported with distal myopathy and 160bp deletion involving exon 10.; to: PMID 34722876: single multigenerational family reported with slowly progressive distal myopathy and 160bp deletion involving exon 10.
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.24 HNRNPA1 Zornitza Stark Phenotypes for gene: HNRNPA1 were changed from inclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia 3 MONDO:0014179 to Myopathy, distal, 3, MIM# 610099; inclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia 3 MONDO:0014179
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.23 HNRNPA1 Zornitza Stark Publications for gene: HNRNPA1 were set to 23455423; 27066560
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.22 HNRNPA1 Zornitza Stark edited their review of gene: HNRNPA1: Added comment: PMID 34722876: single multigenerational family reported with distal myopathy and 160bp deletion involving exon 10.; Changed publications: 23455423, 34291734, 34722876; Changed phenotypes: Amyotrophic lateral sclerosis 20 MIM#615426, Myopathy, distal, 3, MIM# 610099
Early-onset Dementia v0.179 PLA2G6 Sangavi Sivagnanasundram reviewed gene: PLA2G6: Rating: AMBER; Mode of pathogenicity: None; Publications: 25634434, 26836416, 22406380, 20938027; Phenotypes: Parkinson disease 14, autosomal recessive 612953; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1111 FBXO31 Ain Roesley reviewed gene: FBXO31: Rating: AMBER; Mode of pathogenicity: None; Publications: 35019165, 24623383; Phenotypes: Intellectual developmental disorder, autosomal recessive 45 (MIM#615979); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Early-onset Dementia v0.179 TYROBP Sangavi Sivagnanasundram reviewed gene: TYROBP: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301376; Phenotypes: Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 1 (MIM#221770); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early-onset Dementia v0.179 TBK1 Sangavi Sivagnanasundram reviewed gene: TBK1: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301623; Phenotypes: Frontotemporal dementia and/or amyotrophic lateral sclerosis 4 616439; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Dementia v0.179 TARDBP Sangavi Sivagnanasundram reviewed gene: TARDBP: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301761, 21803454; Phenotypes: Amyotrophic lateral sclerosis 10, with or without FTD (MIM#612069); Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Early-onset Dementia v0.179 SQSTM1 Sangavi Sivagnanasundram reviewed gene: SQSTM1: Rating: AMBER; Mode of pathogenicity: None; Publications: 22084127, 22972638; Phenotypes: Frontotemporal dementia and/or amyotrophic lateral sclerosis 3 (MIM#616437); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Early-onset Dementia v0.179 PSEN2 Sangavi Sivagnanasundram reviewed gene: PSEN2: Rating: GREEN; Mode of pathogenicity: Other; Publications: 22503161, 20301340, 25323700, 35491795; Phenotypes: Alzheimer disease-4 (MIM#606889); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Early-onset Dementia v0.179 PSEN1 Sangavi Sivagnanasundram reviewed gene: PSEN1: Rating: GREEN; Mode of pathogenicity: None; Publications: 22503161, 20301340; Phenotypes: Alzheimer disease, type 3 (MIM#607822, MONDO:0011913); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Dementia v0.179 PRNP Sangavi Sivagnanasundram reviewed gene: PRNP: Rating: GREEN; Mode of pathogenicity: None; Publications: 27910931, 19571725, 20301407, 6351815; Phenotypes: Prion Disease (MIM#176640), Creutzfeldt-Jakob disease (MIM#123400); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Early-onset Dementia v0.179 PANK2 Sangavi Sivagnanasundram reviewed gene: PANK2: Rating: GREEN; Mode of pathogenicity: None; Publications: 24600523, 23447832, 19480328; Phenotypes: Neurodegeneration with brain iron accumulation 1 (MIM#234200); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early-onset Dementia v0.179 OPTN Sangavi Sivagnanasundram reviewed gene: OPTN: Rating: GREEN; Mode of pathogenicity: None; Publications: 31838784, 20428114, 20301623; Phenotypes: Amyotrophic lateral sclerosis 12 with or without frontotemporal dementia (MIM#613435); Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Early-onset Dementia v0.179 NPC2 Sangavi Sivagnanasundram reviewed gene: NPC2: Rating: GREEN; Mode of pathogenicity: None; Publications: 27792009, 20525256; Phenotypes: Niemann-pick disease, type C2 MIM#607625; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early-onset Dementia v0.179 NPC1 Sangavi Sivagnanasundram edited their review of gene: NPC1: Changed rating: AMBER
Early-onset Dementia v0.179 NPC1 Sangavi Sivagnanasundram changed review comment from: NPC is a slowly progressive lysosomal disorder with subtle cognitive impairment in affected individuals at first which progresses to dementia during the disease course. LoF is the mechanism of disease.

PMID: 11182931
reported in one individual with NPC and dementia as a phenotype.; to: NPC is a slowly progressive lysosomal disorder with subtle cognitive impairment in affected individuals at first which progresses to dementia during the disease course. NPC type 1 is also known as "juvenile alzheimers disease". LoF is the mechanism of disease.

PMID: 11182931
reported in one individual with NPC and dementia as a phenotype.
Early-onset Dementia v0.179 NPC1 Sangavi Sivagnanasundram edited their review of gene: NPC1: Changed rating: GREEN; Changed publications: 20301473, 11182931, 22495346
Early-onset Dementia v0.179 NHLRC1 Sangavi Sivagnanasundram reviewed gene: NHLRC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28556688, 34117373; Phenotypes: Epilepsy, progressive myoclonic 2B (Lafora Disease) MIM#254780; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v1.1 Zornitza Stark Panel name changed from Baby Screen+ newborn screening to BabyScreen+ newborn screening
Hereditary Neuropathy - complex v1.0 Bryony Thompson promoted panel to version 1.0
Hereditary Neuropathy - complex v0.275 SPAST Bryony Thompson Marked gene: SPAST as ready
Hereditary Neuropathy - complex v0.275 SPAST Bryony Thompson Gene: spast has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v0.275 SPAST Sangavi Sivagnanasundram changed review comment from: Neuropathy is a feature in complex HSP which is caused by autosomal dominant mutations in SPAST or KIF5A.

PMID: 322442913; 22192498
3 unrelated individuals with HSP and polyneuropathy as a clinical feature however their WES remains undiagnosed.; to: Neuropathy is a feature in complex HSP which is caused by autosomal dominant mutations in SPAST or KIF5A.

PMID: 32242913; 22192498
3 unrelated individuals with HSP and polyneuropathy as a clinical feature however their WES remains undiagnosed.
Hereditary Neuropathy - complex v0.275 SPAST Sangavi Sivagnanasundram Deleted their comment
Hereditary Neuropathy - complex v0.275 SPAST Sangavi Sivagnanasundram edited their review of gene: SPAST: Changed publications: 32242913, 22192498, 26374131, 20301339
Hereditary Neuropathy - complex v0.275 HEXA Bryony Thompson Marked gene: HEXA as ready
Hereditary Neuropathy - complex v0.275 HEXA Bryony Thompson Gene: hexa has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v0.275 PLA2G6 Sangavi Sivagnanasundram edited their review of gene: PLA2G6: Added comment: Established gene-disease associated with neuropathy as a clinical feature.

PMID: 25164370
9 individuals from 6 unrelated families with motor or sensory-motor neuropathy. All individuals were found to share the p.V691del variant which is a founder variant in the North African population.; Changed rating: GREEN; Changed publications: 25164370
Hereditary Neuropathy - complex v0.275 PDHA1 Sangavi Sivagnanasundram edited their review of gene: PDHA1: Added comment: PMID: 33661577
Young boy from China with lethal neuropathy and the presence of a de novo mutation in PDHA1 (c.1167_1170del; p.Ser390LysfsTer33) that is clinically significant for Leigh Syndrome. PDCD is known a biochemical pathway in individuals with Leigh Syndrome.

PMID: 36693417
Multiple reported individual with sensory-motor polyneuropathy and a high serum lactate. One individual identified with a hemizygous mutation (p.Arg88Cys) causative of pyruvate dehydrogenase complex deficiency.; Changed rating: GREEN; Changed publications: 33661577, 36693417, 34138529; Changed phenotypes: Primary Pyruvate Dehydrogenase Complex Deficiency MIM#312170
Hereditary Neuropathy - complex v0.275 MTTP Sangavi Sivagnanasundram edited their review of gene: MTTP: Added comment: Reported in multiple individuals with progressive neuropathy due to the deficiency of fat-soluble vitamins (vitamins E, A, D, K). Neuropathy typically presents due to a lack of vitamin E in individuals.; Changed rating: GREEN; Changed publications: 10679949, 29540175
Hereditary Neuropathy - complex v0.275 HEXA Bryony Thompson Publications for gene: HEXA were set to
Hereditary Neuropathy - complex v0.274 ERCC8 Sangavi Sivagnanasundram edited their review of gene: ERCC8: Added comment: Established gene-disease association with progressive neuropathy a feature in individuals with Cockayne Syndrome.

PMID: 29422660
In vitro minigene assay was conducted to test the splice effect of c.173+1119G>C which showed the introduction of a premature termination codon at the end of exon resulting in loss of function of the ERCC8 protein.; Changed rating: GREEN; Changed publications: 25453614, 29422660, 4320535
Hereditary Neuropathy - complex v0.274 ERCC6 Sangavi Sivagnanasundram edited their review of gene: ERCC6: Added comment: PMID: 25376329
Two siblings from a consanguineous family with bilateral peripheral neuropathy and a homozygous splice variant in ERCC6 (c.1992+3A>G).

PMID: 25453614
Progressive neuropathy has been identified in multiple individuals with Cockayne Syndrome.; Changed rating: GREEN; Changed publications: 25376329, 25453614
Hereditary Neuropathy - complex v0.274 ASAH1 Sangavi Sivagnanasundram edited their review of gene: ASAH1: Added comment: PMID:27026573
Siblings from a consanguineous family with SMA phenotype and a homozygous mutation in ASAH1.

PMID: 22703880
5 individuals from 2 unrelated families with SMA and a homozygous mutation (Thr42Met) in ASAH1.

In vivo functional assay using Zebrafish model showed a loss in motor neuron axonal branching and increased apotheosis in the spinal cord suggesting that ASAH plays an integral role in motor-axonal branching and in the survival of spinal cord neurons.; Changed rating: GREEN; Changed publications: 27026573, 22703880; Changed phenotypes: Spinal muscular atrophy with progressive myoclonic epilepsy (MIM#159950)
Hereditary Neuropathy - complex v0.274 SPAST Sangavi Sivagnanasundram edited their review of gene: SPAST: Added comment: Neuropathy is a feature in complex HSP which is caused by autosomal dominant mutations in SPAST or KIF5A.

PMID: 322442913; 22192498
3 unrelated individuals with HSP and polyneuropathy as a clinical feature however their WES remains undiagnosed.; Changed rating: GREEN; Changed publications: 322442913, 22192498, 26374131, 20301339
Hereditary Neuropathy - complex v0.274 HEXA Sangavi Sivagnanasundram changed review comment from: HEXA is associated with the clinical phenotype known as Tay-Sachs disease.
Evidence of sensory neuropathy was present in two unrelated individuals with tay Sachs disease however genetic testing wasn’t conducted to confirm the presence of a HEXA genetic variant in either individual.; to: PMID: 3159334, 1838393: HEXA is associated with the clinical phenotype known as Tay-Sachs disease.
Evidence of sensory neuropathy was present in two unrelated individuals with tay Sachs disease however genetic testing wasn’t conducted to identify genetic pathogenesis.
Hereditary Neuropathy - complex v0.274 HEXA Sangavi Sivagnanasundram edited their review of gene: HEXA: Added comment: Established gene disease associated with >3 unrelated individuals with neuropathy as a clinical feature.
Mutations in HEXA gene cause juvenile gm2 gangliosidosis (jGM2) and Tay Sachs is a well established form of jGM2.

PMID: 17015493
One individual with variant in HEXA and diagnosis of Tay Sachs

PMID: 18642377
Multiple individuals diagnosed with late onset tay-Sachs and identified to have axonal polyneuropathy in 8 individuals.; Changed rating: GREEN; Changed publications: 17015493, 18642377, 3159334, 1838393
Mendeliome v1.1111 TBL1XR1 Achchuthan Shanmugasundram reviewed gene: TBL1XR1: Rating: AMBER; Mode of pathogenicity: None; Publications: 28687524, 37010288; Phenotypes: Pierpont syndrome, OMIM:602342; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.1111 NEB Achchuthan Shanmugasundram reviewed gene: NEB: Rating: AMBER; Mode of pathogenicity: None; Publications: 12207937, 21798101, 33376055, 37010288; Phenotypes: Arthrogryposis multiplex congenita 6, OMIM:619334; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1111 ECEL1 Achchuthan Shanmugasundram reviewed gene: ECEL1: Rating: AMBER; Mode of pathogenicity: None; Publications: 30131190, 37010288; Phenotypes: Arthrogryposis, distal, type 5D, OMIM:615065; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early-onset Dementia v0.179 NPC1 Zornitza Stark Marked gene: NPC1 as ready
Early-onset Dementia v0.179 NPC1 Zornitza Stark Gene: npc1 has been classified as Green List (High Evidence).
Early-onset Dementia v0.179 NPC1 Zornitza Stark Phenotypes for gene: NPC1 were changed from to Niemann-Pick disease, type C1 (MIM#257220; MONDO:0009757)
Early-onset Dementia v0.178 NPC1 Zornitza Stark Publications for gene: NPC1 were set to
Early-onset Dementia v0.177 NPC1 Zornitza Stark Mode of inheritance for gene: NPC1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Early-onset Dementia v0.176 UBQLN2 Zornitza Stark Phenotypes for gene: UBQLN2 were changed from Amyotrophic lateral sclerosis 15, with or without frontotemporal dementia (MIM#300857) to Amyotrophic lateral sclerosis 15, with or without frontotemporal dementia (MIM#300857)
Early-onset Dementia v0.175 UBQLN2 Zornitza Stark Marked gene: UBQLN2 as ready
Early-onset Dementia v0.175 UBQLN2 Zornitza Stark Gene: ubqln2 has been classified as Green List (High Evidence).
Early-onset Dementia v0.175 UBQLN2 Zornitza Stark Phenotypes for gene: UBQLN2 were changed from to Amyotrophic lateral sclerosis 15, with or without frontotemporal dementia (MIM#300857)
Early-onset Dementia v0.174 UBQLN2 Zornitza Stark Publications for gene: UBQLN2 were set to
Early-onset Dementia v0.173 UBQLN2 Zornitza Stark Mode of inheritance for gene: UBQLN2 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)
Hereditary Neuropathy - complex v0.274 IFRD1 Zornitza Stark Tag refuted tag was added to gene: IFRD1.
Early-onset Dementia v0.172 VCP Zornitza Stark Marked gene: VCP as ready
Early-onset Dementia v0.172 VCP Zornitza Stark Gene: vcp has been classified as Green List (High Evidence).
Early-onset Dementia v0.172 VCP Zornitza Stark Phenotypes for gene: VCP were changed from to Inclusion body myopathy with early-onset Paget disease and frontotemporal dementia 1 (MIM#167320); Frontotemporal dementia and/or amyotrophic lateral sclerosis 6 (MIM#613954)
Early-onset Dementia v0.171 VCP Zornitza Stark Publications for gene: VCP were set to
Early-onset Dementia v0.170 VCP Zornitza Stark Mode of inheritance for gene: VCP was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Dementia v0.169 XK Zornitza Stark Marked gene: XK as ready
Early-onset Dementia v0.169 XK Zornitza Stark Gene: xk has been classified as Green List (High Evidence).
Early-onset Dementia v0.169 XK Zornitza Stark Phenotypes for gene: XK were changed from to McLeod syndrome with or without chronic granulomatous disease (MIM#300842)
Early-onset Dementia v0.168 XK Zornitza Stark Publications for gene: XK were set to
Early-onset Dementia v0.167 XK Zornitza Stark Mode of inheritance for gene: XK was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Early-onset Dementia v0.166 XK Zornitza Stark reviewed gene: XK: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: McLeod syndrome with or without chronic granulomatous disease (MIM#300842); 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 Dementia v0.166 GRN Zornitza Stark Marked gene: GRN as ready
Early-onset Dementia v0.166 GRN Zornitza Stark Gene: grn has been classified as Green List (High Evidence).
Early-onset Dementia v0.166 GRN Zornitza Stark Phenotypes for gene: GRN were changed from to frontotemporal dementia and/or amyotrophic lateral sclerosis MONDO:0030923
Early-onset Dementia v0.165 GRN Zornitza Stark Publications for gene: GRN were set to
Early-onset Dementia v0.164 GRN Zornitza Stark Mode of inheritance for gene: GRN was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Dementia v0.163 EPM2A Zornitza Stark Marked gene: EPM2A as ready
Early-onset Dementia v0.163 EPM2A Zornitza Stark Gene: epm2a has been classified as Green List (High Evidence).
Early-onset Dementia v0.163 EPM2A Zornitza Stark Phenotypes for gene: EPM2A were changed from to Epilepsy, progressive myoclonic 2A (Lafora) MIM#254780
Early-onset Dementia v0.162 EPM2A Zornitza Stark Publications for gene: EPM2A were set to
Early-onset Dementia v0.161 EPM2A Zornitza Stark Mode of inheritance for gene: EPM2A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Early-onset Dementia v0.160 NPC1 Sangavi Sivagnanasundram reviewed gene: NPC1: Rating: AMBER; Mode of pathogenicity: None; Publications: 20301473, 11182931; Phenotypes: Niemann-Pick disease, type C1 (MIM#257220, MONDO:0009757); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Neuropathy - complex v0.274 PEX12 Bryony Thompson Marked gene: PEX12 as ready
Hereditary Neuropathy - complex v0.274 PEX12 Bryony Thompson Gene: pex12 has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v0.274 PEX12 Bryony Thompson Publications for gene: PEX12 were set to 24627108
Hereditary Neuropathy - complex v0.273 PEX12 Bryony Thompson Classified gene: PEX12 as Green List (high evidence)
Hereditary Neuropathy - complex v0.273 PEX12 Bryony Thompson Gene: pex12 has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v0.272 PEX12 Bryony Thompson Deleted their comment
Hereditary Neuropathy - complex v0.272 PEX12 Bryony Thompson edited their review of gene: PEX12: Added comment: Neuropathy as a feature of the conditon in 45% (9/14) families with an Egyptian founder variant ((c.1047_1049del p.(Gln349del)) and also in an additional proband.; Changed rating: GREEN; Changed publications: 24627108, 33123925
Hereditary Neuropathy - complex v0.272 NIPA1 Bryony Thompson Marked gene: NIPA1 as ready
Hereditary Neuropathy - complex v0.272 NIPA1 Bryony Thompson Gene: nipa1 has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v0.272 NIPA1 Bryony Thompson Classified gene: NIPA1 as Green List (high evidence)
Hereditary Neuropathy - complex v0.272 NIPA1 Bryony Thompson Gene: nipa1 has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v0.271 NIPA1 Bryony Thompson edited their review of gene: NIPA1: Added comment: Neuropathy is not a prominent feature of the complicated HSP sometimes reported associated with this gene. However, it has been reported in 6/110 (5.5%) of NIPA1-associated complicated HSP cases.; Changed rating: GREEN; Changed publications: 34863451
Hereditary Neuropathy - complex v0.271 NIPA1 Bryony Thompson Deleted their comment
Early-onset Dementia v0.160 UBQLN2 Sangavi Sivagnanasundram reviewed gene: UBQLN2: Rating: AMBER; Mode of pathogenicity: None; Publications: 20301623, 31319884, 21857683, 30348461; Phenotypes: Amyotrophic lateral sclerosis 15, with or without frontotemporal dementia (MIM#300857); Mode of inheritance: None
Hereditary Neuropathy - complex v0.271 IFRD1 Bryony Thompson Marked gene: IFRD1 as ready
Hereditary Neuropathy - complex v0.271 IFRD1 Bryony Thompson Gene: ifrd1 has been classified as Red List (Low Evidence).
Hereditary Neuropathy - complex v0.271 DCAF8 Bryony Thompson Marked gene: DCAF8 as ready
Hereditary Neuropathy - complex v0.271 DCAF8 Bryony Thompson Gene: dcaf8 has been classified as Amber List (Moderate Evidence).
Hereditary Neuropathy - complex v0.271 DCAF8 Bryony Thompson Publications for gene: DCAF8 were set to
Hereditary Neuropathy - complex v0.270 CCT5 Bryony Thompson Marked gene: CCT5 as ready
Hereditary Neuropathy - complex v0.270 CCT5 Bryony Thompson Gene: cct5 has been classified as Amber List (Moderate Evidence).
Hereditary Neuropathy - complex v0.270 CCT5 Bryony Thompson Publications for gene: CCT5 were set to
Hereditary Neuropathy - complex v0.269 CCT5 Bryony Thompson edited their review of gene: CCT5: Added comment: Now two families reported with two different missense variants (Leu224Val and His147Arg).; Changed publications: 16399879, 25124038, 25345891, 33076433, 37237456
Mendeliome v1.1111 CCT5 Bryony Thompson edited their review of gene: CCT5: Added comment: Now two families reported with two different missense variants (Leu224Val and His147Arg).; Changed publications: 16399879, 25124038, 25345891, 33076433, 37237456
Early-onset Dementia v0.160 VCP Sangavi Sivagnanasundram reviewed gene: VCP: Rating: GREEN; Mode of pathogenicity: None; Publications: 15034582, 30103325, 21145000; Phenotypes: Inclusion body myopathy with early-onset Paget disease and frontotemporal dementia 1 (MIM#167320), Frontotemporal dementia and/or amyotrophic lateral sclerosis 6 (MIM#613954); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Dementia v0.160 XK Sangavi Sivagnanasundram reviewed gene: XK: Rating: RED; Mode of pathogenicity: None; Publications: 12899725; Phenotypes: McLeod syndrome with or without chronic granulomatous disease (MIM#300842); Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Hereditary Neuropathy - complex v0.269 TYMP Bryony Thompson Marked gene: TYMP as ready
Hereditary Neuropathy - complex v0.269 TYMP Bryony Thompson Gene: tymp has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v0.269 PMM2 Bryony Thompson Marked gene: PMM2 as ready
Hereditary Neuropathy - complex v0.269 PMM2 Bryony Thompson Gene: pmm2 has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v0.269 PMM2 Bryony Thompson Publications for gene: PMM2 were set to
Hereditary Neuropathy - complex v0.268 PRNP Bryony Thompson Marked gene: PRNP as ready
Hereditary Neuropathy - complex v0.268 PRNP Bryony Thompson Gene: prnp has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v0.268 PRNP Bryony Thompson Phenotypes for gene: PRNP were changed from Prion diseases to Prion diseases; peripheral neuropathy; chronic diarrhea; dementia
Hereditary Neuropathy - complex v0.267 PRNP Bryony Thompson Publications for gene: PRNP were set to
Hereditary Neuropathy - complex v0.266 PRNP Bryony Thompson reviewed gene: PRNP: Rating: GREEN; Mode of pathogenicity: None; Publications: 31953922, 31907995, 29928661, 27716661, 26926995, 24224623, 26768678; Phenotypes: peripheral neuropathy, chronic diarrhea, dementia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5335 ZFHX4 Ain Roesley Phenotypes for gene: ZFHX4 were changed from Developmental disorders; intellectual disability, dysmorphic features to neurodevelopmental disorder, ZFHX4-related (MONDO:0700092)
Hereditary Neuropathy - complex v0.266 PMM2 Sangavi Sivagnanasundram edited their review of gene: PMM2: Changed rating: GREEN
Mendeliome v1.1111 ZFHX4 Ain Roesley Phenotypes for gene: ZFHX4 were changed from Developmental disorders to neurodevelopmental disorder, ZFHX4-related (MONDO:0700092)
Hereditary Neuropathy - complex v0.266 GLA Bryony Thompson Marked gene: GLA as ready
Hereditary Neuropathy - complex v0.266 GLA Bryony Thompson Gene: gla has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v0.266 GLA Bryony Thompson Publications for gene: GLA were set to
Hereditary Neuropathy - complex v0.265 EXOSC8 Bryony Thompson Deleted their review
Hereditary Neuropathy - complex v0.265 EXOSC8 Bryony Thompson commented on gene: EXOSC8
Hereditary Neuropathy - complex v0.265 EXOSC8 Bryony Thompson Deleted their review
Early-onset Dementia v0.160 GRN Sangavi Sivagnanasundram reviewed gene: GRN: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301545, 17436289; Phenotypes: frontotemporal dementia and/or amyotrophic lateral sclerosis MONDO:0030923; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary Neuropathy - complex v0.265 DARS2 Bryony Thompson Marked gene: DARS2 as ready
Hereditary Neuropathy - complex v0.265 DARS2 Bryony Thompson Gene: dars2 has been classified as Green List (High Evidence).
Early-onset Dementia v0.160 EPM2A Sangavi Sivagnanasundram reviewed gene: EPM2A: Rating: GREEN; Mode of pathogenicity: None; Publications: 12019207; Phenotypes: Epilepsy, progressive myoclonic 2A (Lafora) MIM#254780; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Regression v0.531 RNH1 Zornitza Stark Phenotypes for gene: RNH1 were changed from Neurodevelopmental disorder, MONDO:0700092, RNH1-related; encephalopathy, acute, infection-induced (MONDO:0000166), RNH1-related to Neurodevelopmental disorder, MONDO:0700092, RNH1-related; {Encephalopathy, acute, infection-induced, susceptibiliyt to, 12}, MIM# 620461
Genetic Epilepsy v0.1880 RNH1 Zornitza Stark Phenotypes for gene: RNH1 were changed from Neurodevelopmental disorder, MONDO:0700092, RNH1-related; encephalopathy, acute, infection-induced (MONDO:0000166), RNH1-related to Neurodevelopmental disorder, MONDO:0700092, RNH1-related; {Encephalopathy, acute, infection-induced, susceptibiliyt to, 12}, MIM# 620461
Mendeliome v1.1110 RNH1 Zornitza Stark Phenotypes for gene: RNH1 were changed from Neurodevelopmental disorder, MONDO:0700092, RNH1-related; encephalopathy, acute, infection-induced (MONDO:0000166), RNH1-related to Neurodevelopmental disorder, MONDO:0700092, RNH1-related; {Encephalopathy, acute, infection-induced, susceptibiliyt to, 12}, MIM# 620461
Early-onset Dementia v0.160 DNMT1 Sangavi Sivagnanasundram reviewed gene: DNMT1: Rating: AMBER; Mode of pathogenicity: None; Publications: 21532572; Phenotypes: Neuropathy, hereditary sensory, type IE (MIM#614116); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Early-onset Dementia v0.160 DNAJC5 Sangavi Sivagnanasundram reviewed gene: DNAJC5: Rating: GREEN; Mode of pathogenicity: None; Publications: 6153706, 11489285, 12112194, 12790899; Phenotypes: Ceroid lipofuscinosis, neuronal, 4 (Kufs type), autosomal dominant (MIM#162350); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Early-onset Dementia v0.160 CSF1R Sangavi Sivagnanasundram reviewed gene: CSF1R: Rating: GREEN; Mode of pathogenicity: Other; Publications: 22934315, 24336230; Phenotypes: Leukoencephalopathy, diffuse hereditary, with spheroids 1 (MIM#221820); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Early-onset Dementia v0.160 CHMP2B Sangavi Sivagnanasundram reviewed gene: CHMP2B: 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: 20301378, 16041373; Phenotypes: Frontotemporal dementia and/or amyotrophic lateral sclerosis 7 (MIM#600795, MONDO:0010936); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mosaic skin disorders v1.12 ACTB Zornitza Stark Phenotypes for gene: ACTB were changed from Becker's naevus to Becker nevus, somatic mosaic, MIM# 604919
Mosaic skin disorders v1.11 ACTB Zornitza Stark reviewed gene: ACTB: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Becker nevus, somatic mosaic, MIM# 604919; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Dementia v0.160 APP Sangavi Sivagnanasundram reviewed gene: APP: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301340, 1671712, 1678058, 1908231, 1302033; Phenotypes: Alzheimer disease (MIM#104300, MONDO:0007088); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Hereditary Neuropathy - complex v0.265 SPAST Sangavi Sivagnanasundram reviewed gene: SPAST: Rating: RED; Mode of pathogenicity: None; Publications: 20301339; Phenotypes: Spastic paraplegia 4, autosomal dominant 182601; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary Neuropathy - complex v0.265 PMM2 Sangavi Sivagnanasundram reviewed gene: PMM2: Rating: RED; Mode of pathogenicity: None; Publications: 20301507, 20301289; Phenotypes: Congenital disorder of glycosylation, type Ia (MIM#212065); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Predominantly Antibody Deficiency v0.125 FNIP1 Peter McNaughton gene: FNIP1 was added
gene: FNIP1 was added to Predominantly Antibody Deficiency. Sources: Literature
Mode of inheritance for gene: FNIP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FNIP1 were set to PMID: 37522988; PMID: 32181500; PMID: 32905580 (2020)
Phenotypes for gene: FNIP1 were set to Hypertrophic Cardiomyopathy; Primary Immunodeficiency; Agammaglobulinemia; Neutropenia; Immunodeficiency 93 and hypertrophic cardiomyopathy, MIM# 619705
Review for gene: FNIP1 was set to GREEN
Added comment: PMID: 37522988 (2023)- Additional patient with - Peripheral B cell deficiency, severe hypogammaglobulinemia/agammaglobulinemia, intermittent neutropenia responsive to G-CSF treatment, in conjunction with hypertrophic cardiomyopathy of the ventricle associated with Wolff-Parkinson-White Syndrome, and psycho-motor as well as intellectual developmental delay.

PMID: 32181500 (2020) - Three patients from two independent consanguineous families with homozygous variants (c.3353G>A, p.Ser1118Asn and c.1289delA, p.His430Profs7*) in the FNIP1 gene. Both variants segregated with the disease phenotype in each family. Clinically, patients presented with combined immunodeficiency, cardiac findings (hypertrophic cardiomyopathy, Wolff‐Parkinson‐White syndrome), and myopathy of skeletal muscles with motor DD. Authors note phenotypic overlap with the murine model of FNIP1 deficiency, but no functional analyses of the variants or patient cells were performed.

- PMID: 32905580 (2020) - Three cases from unrelated families, all harbouring novel biallelic variants in FNIP1. Clinical manifestations in all patients include hypertrophic cardiomyopathy, severe and/or recurrent infections, absent circulating B-cells, and agammaglobulinemia; as well as either severe or intermittent neutropenia in two cases. Functional studies showed impairment of B-cell metabolism, including disruptions to mitochondrial numbers/activity and the PI3K/AKT pathway.
Sources: Literature
Hereditary Neuropathy - complex v0.265 HEXA Sangavi Sivagnanasundram reviewed gene: HEXA: Rating: RED; Mode of pathogenicity: None; Publications: 3159334, 1838393; Phenotypes: Tay-Sachs disease MIM#272800; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Neuropathy - complex v0.265 ASAH1 Sangavi Sivagnanasundram reviewed gene: ASAH1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Farber lipogranulomatosis (MIM#228000), Spinal muscular atrophy with progressive myoclonic epilepsy (MIM#159950); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1109 HNRNPC Zornitza Stark Marked gene: HNRNPC as ready
Mendeliome v1.1109 HNRNPC Zornitza Stark Gene: hnrnpc has been classified as Green List (High Evidence).
Mendeliome v1.1109 HNRNPC Zornitza Stark Classified gene: HNRNPC as Green List (high evidence)
Mendeliome v1.1109 HNRNPC Zornitza Stark Gene: hnrnpc has been classified as Green List (High Evidence).
Mendeliome v1.1108 HNRNPC Zornitza Stark gene: HNRNPC was added
gene: HNRNPC was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: HNRNPC was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HNRNPC were set to 37541189
Phenotypes for gene: HNRNPC were set to Neurodevelopmental disorder (MONDO:0700092), HNRNPC-related
Review for gene: HNRNPC was set to GREEN
Added comment: 13 individuals with global developmental delay, intellectual disability, behavioral abnormalities, and subtle facial dysmorphology with heterozygous HNRNPC germline variants. Five had an identical in-frame deletion of nine amino acids in the extreme C terminus. Supportive functional data; haploinsufficiency is the mechanism.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5334 HNRNPC Zornitza Stark Marked gene: HNRNPC as ready
Intellectual disability syndromic and non-syndromic v0.5334 HNRNPC Zornitza Stark Gene: hnrnpc has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5334 HNRNPC Zornitza Stark Classified gene: HNRNPC as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5334 HNRNPC Zornitza Stark Gene: hnrnpc has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5333 HNRNPC Zornitza Stark gene: HNRNPC was added
gene: HNRNPC was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: HNRNPC was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HNRNPC were set to 37541189
Phenotypes for gene: HNRNPC were set to Neurodevelopmental disorder (MONDO:0700092), HNRNPC-related
Review for gene: HNRNPC was set to GREEN
Added comment: 13 individuals with global developmental delay, intellectual disability, behavioral abnormalities, and subtle facial dysmorphology with heterozygous HNRNPC germline variants. Five had an identical in-frame deletion of nine amino acids in the extreme C terminus.

Supportive functional data; haploinsufficiency is the mechanism.
Sources: Literature
Hereditary Neuropathy - complex v0.265 XK Zornitza Stark Marked gene: XK as ready
Hereditary Neuropathy - complex v0.265 XK Zornitza Stark Gene: xk has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v0.265 XK Zornitza Stark Phenotypes for gene: XK were changed from McLeod syndrome with or without chronic granulomatous disease, 300842; acanthocytes and Huntington-like syndrome, also epilepsy, cardiomyopathy, axonal motor neuropathy to McLeod syndrome with or without chronic granulomatous disease (MIM#300842)
Hereditary Neuropathy - complex v0.264 XK Zornitza Stark Publications for gene: XK were set to
Hereditary Neuropathy - complex v0.263 TWNK Zornitza Stark Marked gene: TWNK as ready
Hereditary Neuropathy - complex v0.263 TWNK Zornitza Stark Gene: twnk has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v0.263 TWNK Zornitza Stark Phenotypes for gene: TWNK were changed from HMSN; Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3 to Perrault syndrome (MIM#616138); Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3, MIM# 609286
Hereditary Neuropathy - complex v0.262 TWNK Zornitza Stark Publications for gene: TWNK were set to 25254289; 25355836; 27650058; 28178980
Hereditary Neuropathy - complex v0.261 TWNK Zornitza Stark Mode of inheritance for gene: TWNK was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hereditary Neuropathy - complex v0.261 TWNK Zornitza Stark Mode of inheritance for gene: TWNK was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hereditary Neuropathy - complex v0.260 TWNK Zornitza Stark reviewed gene: TWNK: Rating: GREEN; Mode of pathogenicity: None; Publications: 35011763; Phenotypes: Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3, MIM# 609286; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hereditary Neuropathy - complex v0.260 TWNK Zornitza Stark Publications for gene: TWNK were set to
Hereditary Neuropathy - complex v0.259 TWNK Zornitza Stark Mode of inheritance for gene: TWNK was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BIALLELIC, autosomal or pseudoautosomal
Hereditary Neuropathy - complex v0.258 TUBB3 Zornitza Stark Marked gene: TUBB3 as ready
Hereditary Neuropathy - complex v0.258 TUBB3 Zornitza Stark Gene: tubb3 has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v0.258 TUBB3 Zornitza Stark Phenotypes for gene: TUBB3 were changed from Fibrosis of extraocular muscles, congenital, 3A; HMSN to Fibrosis of extraocular muscles, congenital, 3A (MIM#600638); Neuropathy
Hereditary Neuropathy - complex v0.257 TUBB3 Zornitza Stark Publications for gene: TUBB3 were set to
Hereditary Neuropathy - complex v0.256 TUBB3 Zornitza Stark reviewed gene: TUBB3: Rating: GREEN; Mode of pathogenicity: None; Publications: 34652576; Phenotypes: Fibrosis of extraocular muscles, congenital, 3A (MIM#600638), Neuropathy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary Neuropathy - complex v0.256 TTR Zornitza Stark Marked gene: TTR as ready
Hereditary Neuropathy - complex v0.256 TTR Zornitza Stark Gene: ttr has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v0.256 TTR Zornitza Stark Phenotypes for gene: TTR were changed from Cardiomyopathy; Amyloidogenic transthyretin amyloidosis; HSAN/SFN to Amyloidosis, hereditary, transthyretin-related MIM#105210; Cardiomyopathy; Amyloidogenic transthyretin amyloidosis; HSAN/SFN
Hereditary Neuropathy - complex v0.255 TTR Zornitza Stark Publications for gene: TTR were set to
Hereditary Neuropathy - complex v0.254 SUCLA2 Zornitza Stark Marked gene: SUCLA2 as ready
Hereditary Neuropathy - complex v0.254 SUCLA2 Zornitza Stark Gene: sucla2 has been classified as Amber List (Moderate Evidence).
Hereditary Neuropathy - complex v0.254 SUCLA2 Zornitza Stark Phenotypes for gene: SUCLA2 were changed from ‘Leigh’-like syndrome, deafness, progressive dystonia, mild methylmaolnic acidaemia, peripheral neuropathy to Mitochondrial DNA depletion syndrome 5 (encephalomyopathic with or without methylmalonic aciduria) (MONDO:0012791; MIM#612073); ‘Leigh’-like syndrome, deafness, progressive dystonia, mild methylmaolnic acidaemia, peripheral neuropathy
Hereditary Neuropathy - complex v0.253 SUCLA2 Zornitza Stark Publications for gene: SUCLA2 were set to
Hereditary Neuropathy - complex v0.252 SUCLA2 Zornitza Stark Classified gene: SUCLA2 as Amber List (moderate evidence)
Hereditary Neuropathy - complex v0.252 SUCLA2 Zornitza Stark Gene: sucla2 has been classified as Amber List (Moderate Evidence).
Hereditary Neuropathy - complex v0.251 SUCLA2 Zornitza Stark reviewed gene: SUCLA2: Rating: AMBER; Mode of pathogenicity: None; Publications: 35235001; Phenotypes: Mitochondrial DNA depletion syndrome 5 (encephalomyopathic with or without methylmalonic aciduria) (MONDO:0012791, MIM#612073); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1107 PSMC3 Zornitza Stark Phenotypes for gene: PSMC3 were changed from Deafness, cataract, impaired intellectual development, and polyneuropathy, MIM#619354 to neurodevelopmental disorder, MONDO:0700092, PSMC3-related; Deafness, cataract, impaired intellectual development, and polyneuropathy, MIM#619354
Mendeliome v1.1106 PSMC3 Zornitza Stark Publications for gene: PSMC3 were set to 32500975
Mendeliome v1.1105 PSMC3 Zornitza Stark Mode of inheritance for gene: PSMC3 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.1104 PSMC3 Zornitza Stark Classified gene: PSMC3 as Green List (high evidence)
Mendeliome v1.1104 PSMC3 Zornitza Stark Gene: psmc3 has been classified as Green List (High Evidence).
Mendeliome v1.1103 PSMC3 Zornitza Stark edited their review of gene: PSMC3: Added comment: PMID:37256937 - 23 individuals with neurodevelopmental disorder was identified with 15 different de novo missense variants. Apart from one child (patient 2), all others had developmental delay characterised by speech delay (19/19) alone or with intellectual disability (16/18) and motor delay (15/19). In addition, structural modeling as well as proteomic and transcriptomic analyses of T cells derived from patients with PSMC3 variants implicated the PSMC3 variants in proteasome dysfunction through disruption of substrate translocation, induction of proteotoxic stress, and alterations in proteins controlling developmental and innate immune program.; Changed rating: GREEN; Changed publications: 32500975, 37256937; Changed phenotypes: neurodevelopmental disorder, MONDO:0700092, PSMC3-related, Deafness, cataract, impaired intellectual development, and polyneuropathy, MIM#619354; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5332 PSMC3 Zornitza Stark Mode of inheritance for gene: PSMC3 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5331 PSMC3 Zornitza Stark Mode of inheritance for gene: PSMC3 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5330 PSMC3 Zornitza Stark Phenotypes for gene: PSMC3 were changed from Deafness, cataract, impaired intellectual development, and polyneuropathy, MIM#619354 to neurodevelopmental disorder, MONDO:0700092, PSMC3-related; Deafness, cataract, impaired intellectual development, and polyneuropathy, MIM#619354
Intellectual disability syndromic and non-syndromic v0.5329 PSMC3 Zornitza Stark Publications for gene: PSMC3 were set to 32500975
Intellectual disability syndromic and non-syndromic v0.5328 PSMC3 Zornitza Stark Mode of inheritance for gene: PSMC3 was changed from BIALLELIC, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5327 PSMC3 Zornitza Stark Classified gene: PSMC3 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5327 PSMC3 Zornitza Stark Gene: psmc3 has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v0.251 SOX10 Zornitza Stark Marked gene: SOX10 as ready
Hereditary Neuropathy - complex v0.251 SOX10 Zornitza Stark Gene: sox10 has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v0.251 SOX10 Zornitza Stark Phenotypes for gene: SOX10 were changed from PCWH syndrome, 609136; Waardenburg syndrome, type 4C, 613266; Hypopigmentation of the hair and skin, sensory hearing loss, demyelinating neuropathy, dysmyelinating leukodystrophy, developmental delay, spasticity, ataxia, Hirschsprung disease; Waardenburg syndrome, type 2E, with or without neurologic involvement, 611584; HMSN to PCWH Syndrome (MIM#609136; MONDO:0012198); Waardenburg syndrome, type 4C, 613266; Hypopigmentation of the hair and skin, sensory hearing loss, demyelinating neuropathy, dysmyelinating leukodystrophy, developmental delay, spasticity, ataxia, Hirschsprung disease; Waardenburg syndrome, type 2E, with or without neurologic involvement, 611584; HMSN
Hereditary Neuropathy - complex v0.250 SOX10 Zornitza Stark Publications for gene: SOX10 were set to
Hereditary Neuropathy - complex v0.249 SNAP29 Zornitza Stark Marked gene: SNAP29 as ready
Hereditary Neuropathy - complex v0.249 SNAP29 Zornitza Stark Gene: snap29 has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v0.249 SNAP29 Zornitza Stark Phenotypes for gene: SNAP29 were changed from Cerebral Dysgenesis and severe psychomotor retardation, axonal sensory-motor Neuropathy, Ichthyosis, palmoplantar Keratoderma, fatal by second decade of life to Cerebral dysgenesis, neuropathy, ichthyosis, and palmoplantar keratoderma syndrome (CEDNIK) Syndrome (MONDO:0012290) (MIM#609528); Cerebral Dysgenesis and severe psychomotor retardation, axonal sensory-motor Neuropathy, Ichthyosis, palmoplantar Keratoderma, fatal by second decade of life
Hereditary Neuropathy - complex v0.248 SNAP29 Zornitza Stark Publications for gene: SNAP29 were set to
Hereditary Neuropathy - complex v0.247 SLC52A3 Zornitza Stark Marked gene: SLC52A3 as ready
Hereditary Neuropathy - complex v0.247 SLC52A3 Zornitza Stark Gene: slc52a3 has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v0.247 SLC52A3 Zornitza Stark Phenotypes for gene: SLC52A3 were changed from dHMN; Brown-Vialetto-Van Laere syndrome 1; Fazio-Londe disease to Brown-Vialetto-Van Laere syndrome 1 (MIM#211530); dHMN; Brown-Vialetto-Van Laere syndrome 1; Fazio-Londe disease
Hereditary Neuropathy - complex v0.246 SLC52A3 Zornitza Stark Publications for gene: SLC52A3 were set to
Mendeliome v1.1103 EMC1 Zornitza Stark Publications for gene: EMC1 were set to 26942288; 29271071
Mendeliome v1.1102 EMC1 Zornitza Stark Mode of inheritance for gene: EMC1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5326 EMC1 Zornitza Stark Publications for gene: EMC1 were set to 26942288; 29271071
Intellectual disability syndromic and non-syndromic v0.5325 EMC1 Zornitza Stark Mode of inheritance for gene: EMC1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hereditary Neuropathy - complex v0.245 SLC52A2 Zornitza Stark Marked gene: SLC52A2 as ready
Hereditary Neuropathy - complex v0.245 SLC52A2 Zornitza Stark Gene: slc52a2 has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v0.245 SLC52A2 Zornitza Stark Phenotypes for gene: SLC52A2 were changed from Brown-Vialetto-Van Laere syndrome 2 to Brown-Vialetto-van Laere syndrome 2 (BVVLS2) (MONDO:0013867)
Hereditary Neuropathy - complex v0.244 SLC52A2 Zornitza Stark Publications for gene: SLC52A2 were set to
Hereditary Neuropathy - complex v0.243 SCYL1 Zornitza Stark Marked gene: SCYL1 as ready
Hereditary Neuropathy - complex v0.243 SCYL1 Zornitza Stark Gene: scyl1 has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v0.243 SCYL1 Zornitza Stark Phenotypes for gene: SCYL1 were changed from Spinocerebellar ataxia, autosomal recessive 21; Early-onset ataxia (<1 year) with recurrent episodes of liver failure, sensory-motor axonal neuropathy, cerebellar atrophy to Spinocerebellar ataxia, autosomal recessive 21 (MIM#616719); acute infantile liver failure-cerebellar ataxia-peripheral sensory motor neuropathy syndrome (MONDO:0014744); Spinocerebellar ataxia, autosomal recessive 21; Early-onset ataxia (<1 year) with recurrent episodes of liver failure, sensory-motor axonal neuropathy, cerebellar atrophy
Hereditary Neuropathy - complex v0.242 SCYL1 Zornitza Stark Publications for gene: SCYL1 were set to
Hereditary Neuropathy - complex v0.241 SACS Zornitza Stark Marked gene: SACS as ready
Hereditary Neuropathy - complex v0.241 SACS Zornitza Stark Gene: sacs has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v0.241 SACS Zornitza Stark Phenotypes for gene: SACS were changed from Spastic ataxia Charlevoix-Saguenay type; HMSN to Charlevoix-Saguenay spastic ataxia (MONDO:0010041; MIM#270550)
Hereditary Neuropathy - complex v0.240 SACS Zornitza Stark Publications for gene: SACS were set to
Hereditary Neuropathy - complex v0.239 SACS Zornitza Stark Tag SV/CNV tag was added to gene: SACS.
Hereditary Neuropathy - complex v0.239 PTRH2 Zornitza Stark Marked gene: PTRH2 as ready
Hereditary Neuropathy - complex v0.239 PTRH2 Zornitza Stark Gene: ptrh2 has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v0.239 PTRH2 Zornitza Stark Phenotypes for gene: PTRH2 were changed from Infantile-onset multisystem disease with intellectual disability, microcephaly, progressive ataxia, sensory neuronal hearing loss, hepatomegaly, pancreatic insufficiency, proximal placement of thumb, SNCV neuropathy to Infantile multisystem neurologic, endocrine, and pancreatic disease (IMNPED) (MIM#616263); Infantile-onset multisystem disease with intellectual disability, microcephaly, progressive ataxia, sensory neuronal hearing loss, hepatomegaly, pancreatic insufficiency, proximal placement of thumb, SNCV neuropathy
Hereditary Neuropathy - complex v0.238 PTRH2 Zornitza Stark Publications for gene: PTRH2 were set to
Hereditary Neuropathy - complex v0.237 XK Sangavi Sivagnanasundram reviewed gene: XK: Rating: GREEN; Mode of pathogenicity: None; Publications: 11761473; Phenotypes: McLeod syndrome with or without chronic granulomatous disease (MIM#300842); Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Hereditary Neuropathy - complex v0.237 TWNK Sangavi Sivagnanasundram reviewed gene: TWNK: Rating: GREEN; Mode of pathogenicity: None; Publications: 25254289, 25355836, 27650058, 28178980; Phenotypes: Perrault syndrome (MIM#616138); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Neuropathy - complex v0.237 TUBB3 Sangavi Sivagnanasundram reviewed gene: TUBB3: Rating: AMBER; Mode of pathogenicity: None; Publications: 20074521; Phenotypes: Fibrosis of extraocular muscles, congenital, 3A (MIM#600638); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Hereditary Neuropathy - complex v0.237 TTR Sangavi Sivagnanasundram reviewed gene: TTR: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301373, 8071954, 19180884, 24101130; Phenotypes: Amyloidosis, hereditary, transthyretin-related MIM#105210; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary Neuropathy - complex v0.237 SUCLA2 Sangavi Sivagnanasundram reviewed gene: SUCLA2: Rating: RED; Mode of pathogenicity: None; Publications: 20301762; Phenotypes: Mitochondrial DNA depletion syndrome 5 (encephalomyopathic with or without methylmalonic aciduria) (MONDO:0012791, MIM#612073); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5324 PSMC3 Achchuthan Shanmugasundram reviewed gene: PSMC3: Rating: GREEN; Mode of pathogenicity: None; Publications: 37256937; Phenotypes: neurodevelopmental disorder, MONDO:0700092; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary Neuropathy - complex v0.237 SOX10 Sangavi Sivagnanasundram reviewed gene: SOX10: Rating: AMBER; Mode of pathogenicity: None; Publications: 15004559; Phenotypes: PCWH Syndrome (MIM#609136, MONDO:0012198); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Hereditary Neuropathy - complex v0.237 SNAP29 Sangavi Sivagnanasundram reviewed gene: SNAP29: Rating: AMBER; Mode of pathogenicity: None; Publications: 33977139; Phenotypes: Cerebral dysgenesis, neuropathy, ichthyosis, and palmoplantar keratoderma syndrome (CEDNIK) Syndrome (MONDO:0012290) (MIM#609528); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Neuropathy - complex v0.237 SLC52A3 Sangavi Sivagnanasundram reviewed gene: SLC52A3: Rating: GREEN; Mode of pathogenicity: None; Publications: 20206331; Phenotypes: Brown-Vialetto-Van Laere syndrome 1 (MIM#211530); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1101 EMC1 Chern Lim edited their review of gene: EMC1: Changed rating: GREEN
Mendeliome v1.1101 EMC1 Chern Lim reviewed gene: EMC1: Rating: ; Mode of pathogenicity: None; Publications: 35234901, 26942288; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.5324 EMC1 Chern Lim reviewed gene: EMC1: Rating: ; Mode of pathogenicity: None; Publications: 35234901, 26942288; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Hereditary Neuropathy - complex v0.237 SLC52A2 Sangavi Sivagnanasundram reviewed gene: SLC52A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 22740598, 24253200; Phenotypes: Brown-Vialetto-van Laere syndrome 2 (BVVLS2) (MONDO:0013867); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Neuropathy - complex v0.237 SCYL1 Sangavi Sivagnanasundram reviewed gene: SCYL1: Rating: GREEN; Mode of pathogenicity: None; Publications: 26581903, 30531813; Phenotypes: Spinocerebellar ataxia, autosomal recessive 21 (MIM#616719), acute infantile liver failure-cerebellar ataxia-peripheral sensory motor neuropathy syndrome (MONDO:0014744); Mode of inheritance: None
BabyScreen+ newborn screening v1.0 Zornitza Stark promoted panel to version 1.0
Hereditary Neuropathy - complex v0.237 SACS Sangavi Sivagnanasundram reviewed gene: SACS: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301432, 20876471; Phenotypes: Charlevoix-Saguenay spastic ataxia (MONDO:0010041, MIM#270550); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Neuropathy - complex v0.237 PTRH2 Sangavi Sivagnanasundram reviewed gene: PTRH2: Rating: GREEN; Mode of pathogenicity: None; Publications: 25574476, 27129381, 28328138; Phenotypes: Infantile multisystem neurologic, endocrine, and pancreatic disease (IMNPED) (MIM#616263); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebral Palsy v1.186 SYNE1 Zornitza Stark reviewed gene: SYNE1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Arthrogryposis multiplex congenita 3, myogenic type MIM#618484, Emery-Dreifuss muscular dystrophy 4, autosomal dominant MIM#612998, Spinocerebellar ataxia, autosomal recessive 8 MIM#610743; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Systemic Autoinflammatory Disease_Periodic Fever v1.12 RELA Zornitza Stark Marked gene: RELA as ready
Systemic Autoinflammatory Disease_Periodic Fever v1.12 RELA Zornitza Stark Gene: rela has been classified as Green List (High Evidence).
Systemic Autoinflammatory Disease_Periodic Fever v1.12 RELA Zornitza Stark Phenotypes for gene: RELA were changed from periodic fever, inflammatory bowel disease, JIA to Mucocutaneous ulceration, chronic, MIM# 618287; periodic fever, inflammatory bowel disease, JIA
Systemic Autoinflammatory Disease_Periodic Fever v1.11 RELA Zornitza Stark Classified gene: RELA as Green List (high evidence)
Systemic Autoinflammatory Disease_Periodic Fever v1.11 RELA Zornitza Stark Gene: rela has been classified as Green List (High Evidence).
Systemic Autoinflammatory Disease_Periodic Fever v1.10 RELA Zornitza Stark reviewed gene: RELA: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Mucocutaneous ulceration, chronic, MIM# 618287; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Combined Immunodeficiency v1.43 RELA Zornitza Stark Publications for gene: RELA were set to 28600438; 29305315
Combined Immunodeficiency v1.42 RELA Zornitza Stark Classified gene: RELA as Green List (high evidence)
Combined Immunodeficiency v1.42 RELA Zornitza Stark Gene: rela has been classified as Green List (High Evidence).
Combined Immunodeficiency v1.41 RELA Zornitza Stark edited their review of gene: RELA: Added comment: Additional 6 individuals from five families reported.; Changed rating: GREEN; Changed publications: 28600438, 29305315, 37273177; Changed phenotypes: Mucocutaneous ulceration, chronic, MIM# 618287, Impaired NFkB activation, reduced production of inflammatory cytokines, autoimmune cytopaenias
Mendeliome v1.1101 RELA Zornitza Stark Publications for gene: RELA were set to 28600438; 29305315
Mendeliome v1.1100 RELA Zornitza Stark Classified gene: RELA as Green List (high evidence)
Mendeliome v1.1100 RELA Zornitza Stark Gene: rela has been classified as Green List (High Evidence).
Inflammatory bowel disease v0.105 RELA Zornitza Stark changed review comment from: Additional 6 individuals from two families reported.; to: Additional 6 individuals from five families reported.
Mendeliome v1.1099 RELA Zornitza Stark changed review comment from: Additional 6 individuals from two families reported.; to: Additional 6 individuals from five families reported.
Mendeliome v1.1099 RELA Zornitza Stark edited their review of gene: RELA: Added comment: Additional 6 individuals from two families reported.; Changed rating: GREEN; Changed publications: 28600438, 29305315, 37273177; Changed phenotypes: Mucocutaneous ulceration, chronic, MIM# 618287, Impaired NFkB activation, reduced production of inflammatory cytokines, autoimmune cytopaenias
Inflammatory bowel disease v0.105 RELA Zornitza Stark Marked gene: RELA as ready
Inflammatory bowel disease v0.105 RELA Zornitza Stark Gene: rela has been classified as Green List (High Evidence).
Inflammatory bowel disease v0.105 RELA Zornitza Stark Phenotypes for gene: RELA were changed from Inflammatory bowel disease to Mucocutaneous ulceration, chronic, MIM# 618287; Inflammatory bowel disease
Inflammatory bowel disease v0.104 RELA Zornitza Stark Classified gene: RELA as Green List (high evidence)
Inflammatory bowel disease v0.104 RELA Zornitza Stark Gene: rela has been classified as Green List (High Evidence).
Inflammatory bowel disease v0.103 RELA Zornitza Stark edited their review of gene: RELA: Added comment: Additional 6 individuals from two families reported.; Changed rating: GREEN; Changed publications: 37273177
Inflammatory bowel disease v0.103 RELA Zornitza Stark reviewed gene: RELA: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Mucocutaneous ulceration, chronic, MIM# 618287; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary Neuropathy - complex v0.237 NGLY1 Zornitza Stark Marked gene: NGLY1 as ready
Hereditary Neuropathy - complex v0.237 NGLY1 Zornitza Stark Gene: ngly1 has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v0.237 NGLY1 Zornitza Stark Phenotypes for gene: NGLY1 were changed from Developmental delay, choreoathetosis, alacrimia, seizures, microcephaly, transaminitis, neuropathy to Congenital disorder of deglycosylation 1 (CDDG1) (MIM#615273); Developmental delay, choreoathetosis, alacrimia, seizures, microcephaly, transaminitis, neuropathy
Hereditary Neuropathy - complex v0.236 NGLY1 Zornitza Stark Publications for gene: NGLY1 were set to
Hereditary Neuropathy - complex v0.235 OPA1 Zornitza Stark Marked gene: OPA1 as ready
Hereditary Neuropathy - complex v0.235 OPA1 Zornitza Stark Gene: opa1 has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v0.235 OPA1 Zornitza Stark Phenotypes for gene: OPA1 were changed from Optic atrophy plus syndrome, 125250; Optic atrophy 1, 165500; HMSN to Optic atrophy plus syndrome (MIM#125250)
Hereditary Neuropathy - complex v0.234 OPA1 Zornitza Stark Publications for gene: OPA1 were set to
Hereditary Neuropathy - complex v0.233 PDYN Zornitza Stark Marked gene: PDYN as ready
Hereditary Neuropathy - complex v0.233 PDYN Zornitza Stark Gene: pdyn has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v0.233 PDYN Zornitza Stark Phenotypes for gene: PDYN were changed from Cerebellar ataxia, sensory-motor axonal neuropathy; Spinocerebellar ataxia 23 to Spinocerebellar ataxia 23 (MIM#610245); Cerebellar ataxia, sensory-motor axonal neuropathy; Spinocerebellar ataxia 23
Hereditary Neuropathy - complex v0.232 PDYN Zornitza Stark Publications for gene: PDYN were set to
Hereditary Neuropathy - complex v0.231 PDYN Zornitza Stark reviewed gene: PDYN: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Spinocerebellar ataxia 23 (MIM#610245); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary Neuropathy - complex v0.231 PEX7 Zornitza Stark Marked gene: PEX7 as ready
Hereditary Neuropathy - complex v0.231 PEX7 Zornitza Stark Gene: pex7 has been classified as Red List (Low Evidence).
Hereditary Neuropathy - complex v0.231 PEX7 Zornitza Stark Publications for gene: PEX7 were set to
Hereditary Neuropathy - complex v0.230 PEX7 Zornitza Stark Classified gene: PEX7 as Red List (low evidence)
Hereditary Neuropathy - complex v0.230 PEX7 Zornitza Stark Gene: pex7 has been classified as Red List (Low Evidence).
Hereditary Neuropathy - complex v0.229 PHYH Zornitza Stark Marked gene: PHYH as ready
Hereditary Neuropathy - complex v0.229 PHYH Zornitza Stark Gene: phyh has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v0.229 PHYH Zornitza Stark Phenotypes for gene: PHYH were changed from Refsum disease; Phytanic acid storage disease to Refsum Disease MIM#266500
Hereditary Neuropathy - complex v0.228 PHYH Zornitza Stark Publications for gene: PHYH were set to
Hereditary Neuropathy - complex v0.227 PHYH Zornitza Stark reviewed gene: PHYH: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Refsum Disease MIM#266500; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Neuropathy - complex v0.227 PLA2G6 Zornitza Stark Marked gene: PLA2G6 as ready
Hereditary Neuropathy - complex v0.227 PLA2G6 Zornitza Stark Gene: pla2g6 has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v0.227 PLA2G6 Zornitza Stark Phenotypes for gene: PLA2G6 were changed from Infantile-onset, progressive neurodegeneration (tetraplegia, dementia, visual loss) and axonal sensory-motor neuropathy, globus pallidus iron deposition on MRI to Infantile neuroaxonal dystrophy 1 (MIM#256600); Neurodegeneration with brain iron accumulation 2B (MIM#610217)
Hereditary Neuropathy - complex v0.226 PLA2G6 Zornitza Stark Publications for gene: PLA2G6 were set to
Hereditary Neuropathy - complex v0.225 PLA2G6 Zornitza Stark reviewed gene: PLA2G6: Rating: GREEN; Mode of pathogenicity: None; Publications: 29859652; Phenotypes: Infantile neuroaxonal dystrophy 1 (MIM#256600), Neurodegeneration with brain iron accumulation 2B (MIM#610217), Parkinson disease 14, autosomal recessive (MIM#612953); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1099 DPP9 Zornitza Stark Phenotypes for gene: DPP9 were changed from Autoinflammatory syndrome MONDO:0019751, DPP9-related; recurrent fevers; repeated infections; herpes susceptibility; cytopenias to Hatipoglu immunodeficiency syndrome MIM#620331; Autoinflammatory syndrome MONDO:0019751, DPP9-related; recurrent fevers; repeated infections; herpes susceptibility; cytopenias
Mendeliome v1.1098 DPP9 Zornitza Stark Phenotypes for gene: DPP9 were changed from Autoinflammatory syndrome MONDO:0019751, DPP9-related; recurrent fevers; repeated infections; herpes susceptibility; cytopenias to Autoinflammatory syndrome MONDO:0019751, DPP9-related; recurrent fevers; repeated infections; herpes susceptibility; cytopenias
Mendeliome v1.1097 DPP9 Zornitza Stark Publications for gene: DPP9 were set to 36112693
Mendeliome v1.1096 DPP9 Zornitza Stark Mode of inheritance for gene: DPP9 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.1095 DPP9 Zornitza Stark edited their review of gene: DPP9: Added comment: Amber for mono-allelic association:

de novo monoallelic dominant-negative mutation in DPP9 (c.755G>C, R252P) presenting with HLH at ~2m. Functional data supporting dominant negative mechanism.; Changed publications: 36112693, 37544411; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Systemic Autoinflammatory Disease_Periodic Fever v1.10 DPP9 Zornitza Stark Mode of inheritance for gene: DPP9 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hereditary Neuropathy - complex v0.225 PLP1 Zornitza Stark Marked gene: PLP1 as ready
Hereditary Neuropathy - complex v0.225 PLP1 Zornitza Stark Gene: plp1 has been classified as Amber List (Moderate Evidence).
Hereditary Neuropathy - complex v0.225 PLP1 Zornitza Stark Phenotypes for gene: PLP1 were changed from Pelizaeus-Merzbacher disease; Infantile-onset, nystagmus, cognitive impairment, spasticity and ataxia, leukodystrophy on MRI, mild multifocal SNCV neuropathy seen with null mutations and more mild phenotype of mild spasticity and ataxia; HMSN to Pelizaeus-Merzbacher disease (MIM#312080)
Hereditary Neuropathy - complex v0.224 PLP1 Zornitza Stark Publications for gene: PLP1 were set to
Hereditary Neuropathy - complex v0.223 PLP1 Zornitza Stark Classified gene: PLP1 as Amber List (moderate evidence)
Hereditary Neuropathy - complex v0.223 PLP1 Zornitza Stark Gene: plp1 has been classified as Amber List (Moderate Evidence).
Hereditary Neuropathy - complex v0.222 PNKP Zornitza Stark Marked gene: PNKP as ready
Hereditary Neuropathy - complex v0.222 PNKP Zornitza Stark Gene: pnkp has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v0.222 PNKP Zornitza Stark Phenotypes for gene: PNKP were changed from Ataxia-oculomotor apraxia 4, 616267; Microcephaly, global developmental delay, progressive cerebellar ataxia and atrophy, sensory-motor axonal neuropathy; Microcephaly, seizures, and developmental delay, 613402; HMSN to Charcot-Marie-Tooth disease, axonal, type 2B2 (MIM#605589); Ataxia-oculomotor apraxia 4 (MIM#616267)
Hereditary Neuropathy - complex v0.221 PNKP Zornitza Stark Publications for gene: PNKP were set to
Hereditary Neuropathy - complex v0.220 PNPLA6 Zornitza Stark Marked gene: PNPLA6 as ready
Hereditary Neuropathy - complex v0.220 PNPLA6 Zornitza Stark Gene: pnpla6 has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v0.220 PNPLA6 Zornitza Stark Phenotypes for gene: PNPLA6 were changed from progressive distal motor neuropathy beginning in early through late adolescence; Hereditary Neuropathies; Childhood onset of slowly progressive spastic paraplegia to Laurence-Moon Syndrome (LMS) MIM#245800; Spastic Paraplegia Type 39 MIM#612020
Hereditary Neuropathy - complex v0.219 PNPLA6 Zornitza Stark Publications for gene: PNPLA6 were set to
Cerebral Palsy v1.186 ADNP Zornitza Stark Classified gene: ADNP as Green List (high evidence)
Cerebral Palsy v1.186 ADNP Zornitza Stark Gene: adnp has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v0.218 PRNP Sangavi Sivagnanasundram changed review comment from: Neuropathy not an established feature of CAA - only one reported family.
PMID: 24224623
Multigenerational British family with symptoms of mixed neuropathy (predominantly sensory and autonomic) with a Y163X truncation mutation with the M129V polymorphism.; to: Neuropathy not an established feature of PRNP-related CAA - only one reported family.
PMID: 24224623
Multigenerational British family with symptoms of mixed neuropathy (predominantly sensory and autonomic) with a Y163X truncation mutation with the M129V polymorphism.
Hereditary Neuropathy - complex v0.218 POLG Zornitza Stark Marked gene: POLG as ready
Hereditary Neuropathy - complex v0.218 POLG Zornitza Stark Gene: polg has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v0.218 POLG Zornitza Stark Phenotypes for gene: POLG were changed from Mitochondrial DNA depletion syndrome 4B (MNGIE type); Mitochondrial DNA depletion syndrome 4A (Alpers type); Mitochondrial recessive ataxia syndrome (includes SANDO and SCAE); Progressive external ophthalmoplegia, autosomal dominant 1; Progressive external ophthalmoplegia, autosomal recessive 1; Cardiomyopathy; sensory ataxia neuropathy dysarthria and ophthalmoplegia (SANDO); HMSN to Mitochondrial recessive ataxia syndrome (includes SANDO and SCAE) 607459
Hereditary Neuropathy - complex v0.217 POLG Zornitza Stark Publications for gene: POLG were set to
Hereditary Neuropathy - complex v0.216 PRNP Sangavi Sivagnanasundram reviewed gene: PRNP: Rating: RED; Mode of pathogenicity: None; Publications: 24224623; Phenotypes: Inherited prion disease, Cerebral amyloid angiopathy, PRNP-related (MIM#137440); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Hereditary Neuropathy - complex v0.216 POLG Zornitza Stark Mode of inheritance for gene: POLG was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Pulmonary Arterial Hypertension v1.35 SOX17 Zornitza Stark Phenotypes for gene: SOX17 were changed from Vesicoureteral reflux 3 MIM#613674; Pulmonary arterial hypertension to Heritable pulmonary arterial hypertension, MONDO:0017148, SOX17-related
Pulmonary Arterial Hypertension v1.33 SMAD4 Zornitza Stark Phenotypes for gene: SMAD4 were changed from Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome MIM#175050; Pulmonary arterial hypertension to Pulmonary arterial hypertension MONDO:0015924, SMAD4-related
Pulmonary Arterial Hypertension v1.32 SMAD4 Zornitza Stark Tag disputed tag was added to gene: SMAD4.
Pulmonary Arterial Hypertension v1.32 SMAD4 Zornitza Stark reviewed gene: SMAD4: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Pulmonary arterial hypertension MONDO:0015924, SMAD4-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Pulmonary Arterial Hypertension v1.32 SMAD1 Zornitza Stark Tag disputed tag was added to gene: SMAD1.
Pulmonary Arterial Hypertension v1.32 SMAD1 Zornitza Stark Phenotypes for gene: SMAD1 were changed from Pulmonary arterial hypertension to Pulmonary arterial hypertension MONDO:0015924, SMAD1-related
Pulmonary Arterial Hypertension v1.31 SMAD1 Zornitza Stark reviewed gene: SMAD1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Pulmonary arterial hypertension MONDO:0015924, SMAD1-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Pulmonary Arterial Hypertension v1.31 NOTCH3 Zornitza Stark Phenotypes for gene: NOTCH3 were changed from Pulmonary arterial hypertension, MONDO:0015924 to Pulmonary arterial hypertension MONDO:0015924, NOTCH3-related
Pulmonary Arterial Hypertension v1.30 NOTCH3 Zornitza Stark Tag disputed tag was added to gene: NOTCH3.
Pulmonary Arterial Hypertension v1.30 NOTCH3 Zornitza Stark reviewed gene: NOTCH3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Pulmonary arterial hypertension MONDO:0015924, NOTCH3-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Pulmonary Arterial Hypertension v1.30 BMPR1B Zornitza Stark Tag disputed tag was added to gene: BMPR1B.
Pulmonary Arterial Hypertension v1.30 BMPR1B Zornitza Stark reviewed gene: BMPR1B: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Pulmonary arterial hypertension MONDO:0015924, BMPR1B-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.1095 PDGFD Zornitza Stark Marked gene: PDGFD as ready
Mendeliome v1.1095 PDGFD Zornitza Stark Gene: pdgfd has been classified as Red List (Low Evidence).
Mendeliome v1.1095 PDGFD Zornitza Stark gene: PDGFD was added
gene: PDGFD was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: PDGFD was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PDGFD were set to 33187088; 33971972
Phenotypes for gene: PDGFD were set to Pulmonary arterial hypertension MONDO:0015924, PDGFD-related
Review for gene: PDGFD was set to RED
Added comment: Rated as LIMITED by ClinGen. 10 unique variants (all missense) that have been reported in 10 probands in 2 publications (PMIDs: 33187088, 33971972) are included in this curation. 9 of these variants were observed in a cohort of 1647 idiopathic pulmonary arterial hypertension (IPAH) patients of European Ancestry as part of a case-control study. Variant aggregation analysis revealed a significant burden (p=0.0000172) of likely gene damaging PDGFD variants in the IPAH cohort as compared to a group of 18,819 European controls (PMID:33971972). Gelinas et al. also reported a missense PDGFD variant in a proband with IPAH (PMID:33187088). There is currently no functional evidence demonstrating a damaging effect of any of the reported PDGFD variants in humans.
Sources: Expert list
Pulmonary Arterial Hypertension v1.30 PDGFD Zornitza Stark Marked gene: PDGFD as ready
Pulmonary Arterial Hypertension v1.30 PDGFD Zornitza Stark Gene: pdgfd has been classified as Red List (Low Evidence).
Pulmonary Arterial Hypertension v1.30 PDGFD Zornitza Stark gene: PDGFD was added
gene: PDGFD was added to Pulmonary Arterial Hypertension. Sources: Expert list
Mode of inheritance for gene: PDGFD was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PDGFD were set to 33187088; 33971972
Phenotypes for gene: PDGFD were set to Pulmonary arterial hypertension MONDO:0015924, PDGFD-related
Review for gene: PDGFD was set to RED
Added comment: Rated as LIMITED by ClinGen.

10 unique variants (all missense) that have been reported in 10 probands in 2 publications (PMIDs: 33187088, 33971972) are included in this curation. 9 of these variants were observed in a cohort of 1647 idiopathic pulmonary arterial hypertension (IPAH) patients of European Ancestry as part of a case-control study. Variant aggregation analysis revealed a significant burden (p=0.0000172) of likely gene damaging PDGFD variants in the IPAH cohort as compared to a group of 18,819 European controls (PMID:33971972). Gelinas et al. also reported a missense PDGFD variant in a proband with IPAH (PMID:33187088). There is currently no functional evidence demonstrating a damaging effect of any of the reported PDGFD variants in humans.
Sources: Expert list
Mendeliome v1.1094 KLF2 Zornitza Stark Phenotypes for gene: KLF2 were changed from Pulmonary arterial hypertension to Pulmonary arterial hypertension MONDO:0015924, KLF2-related
Mendeliome v1.1093 KLF2 Zornitza Stark edited their review of gene: KLF2: Changed phenotypes: Pulmonary arterial hypertension MONDO:0015924, KLF2-related
Pulmonary Arterial Hypertension v1.29 KLF2 Zornitza Stark Phenotypes for gene: KLF2 were changed from Pulmonary arterial hypertension to Pulmonary arterial hypertension MONDO:0015924, KLF2-related
Pulmonary Arterial Hypertension v1.28 KLF2 Zornitza Stark reviewed gene: KLF2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Pulmonary arterial hypertension MONDO:0015924, KLF2-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.1093 FBLN2 Zornitza Stark Marked gene: FBLN2 as ready
Mendeliome v1.1093 FBLN2 Zornitza Stark Gene: fbln2 has been classified as Red List (Low Evidence).
Mendeliome v1.1093 FBLN2 Zornitza Stark gene: FBLN2 was added
gene: FBLN2 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: FBLN2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FBLN2 were set to 33971972
Phenotypes for gene: FBLN2 were set to Pulmonary arterial hypertension MONDO:0015924, FBLN2-related
Review for gene: FBLN2 was set to RED
Added comment: LIMITED by ClinGen. Out of a cohort of 1647 idiopathic PAH cases, 3 rare predicted deleterious missense variants were identified in 6 unrelated individuals with one variant recurrent in four individuals. Gene-disease association also supported by tissue expression data.
Sources: Expert list
Pulmonary Arterial Hypertension v1.28 FBLN2 Zornitza Stark Marked gene: FBLN2 as ready
Pulmonary Arterial Hypertension v1.28 FBLN2 Zornitza Stark Gene: fbln2 has been classified as Red List (Low Evidence).
Pulmonary Arterial Hypertension v1.28 FBLN2 Zornitza Stark gene: FBLN2 was added
gene: FBLN2 was added to Pulmonary Arterial Hypertension. Sources: Expert list
Mode of inheritance for gene: FBLN2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FBLN2 were set to 33971972
Phenotypes for gene: FBLN2 were set to Pulmonary arterial hypertension MONDO:0015924, FBLN2-related
Review for gene: FBLN2 was set to RED
Added comment: LIMITED by ClinGen. Out of a cohort of 1647 idiopathic PAH cases, 3 rare predicted deleterious missense variants were identified in 6 unrelated individuals with one variant recurrent in four individuals. Gene-disease association also supported by tissue expression data.
Sources: Expert list
Pulmonary Arterial Hypertension v1.27 BMP10 Zornitza Stark Phenotypes for gene: BMP10 were changed from Pulmonary arterial hypertension to Pulmonary arterial hypertension MONDO:0015924, BMP10-related
Pulmonary Arterial Hypertension v1.26 BMP10 Zornitza Stark Publications for gene: BMP10 were set to 30578383
Pulmonary Arterial Hypertension v1.25 BMP10 Zornitza Stark reviewed gene: BMP10: Rating: AMBER; Mode of pathogenicity: None; Publications: 29843651, 33187088, 31661308, 30578383; Phenotypes: Pulmonary arterial hypertension MONDO:0015924, BMP10-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.1092 AQP1 Zornitza Stark Phenotypes for gene: AQP1 were changed from Pulmonary arterial hypertension to Pulmonary arterial hypertension MONDO:0015924, AQP1-related
Mendeliome v1.1091 AQP1 Zornitza Stark Publications for gene: AQP1 were set to PMID:22683574; 29650961
Mendeliome v1.1090 AQP1 Zornitza Stark Classified gene: AQP1 as Amber List (moderate evidence)
Mendeliome v1.1090 AQP1 Zornitza Stark Gene: aqp1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1089 AQP1 Zornitza Stark reviewed gene: AQP1: Rating: AMBER; Mode of pathogenicity: None; Publications: 37007933, 35627312; Phenotypes: Pulmonary arterial hypertension MONDO:0015924, AQP1-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Pulmonary Arterial Hypertension v1.25 AQP1 Zornitza Stark Phenotypes for gene: AQP1 were changed from Pulmonary arterial hypertension MONDO:0015924, AQP2-related to Pulmonary arterial hypertension MONDO:0015924, AQP1-related
Pulmonary Arterial Hypertension v1.24 AQP1 Zornitza Stark edited their review of gene: AQP1: Changed phenotypes: Pulmonary arterial hypertension MONDO:0015924, AQP1-related
Pulmonary Arterial Hypertension v1.24 AQP1 Zornitza Stark Phenotypes for gene: AQP1 were changed from Pulmonary arterial hypertension to Pulmonary arterial hypertension MONDO:0015924, AQP2-related
Pulmonary Arterial Hypertension v1.23 AQP1 Zornitza Stark Publications for gene: AQP1 were set to 22683574; 29650961
Pulmonary Arterial Hypertension v1.22 AQP1 Zornitza Stark Classified gene: AQP1 as Amber List (moderate evidence)
Pulmonary Arterial Hypertension v1.22 AQP1 Zornitza Stark Gene: aqp1 has been classified as Amber List (Moderate Evidence).
Pulmonary Arterial Hypertension v1.21 AQP1 Zornitza Stark reviewed gene: AQP1: Rating: AMBER; Mode of pathogenicity: None; Publications: 37007933, 35627312; Phenotypes: Pulmonary arterial hypertension MONDO:0015924, AQP2-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.1089 TET2 Zornitza Stark Phenotypes for gene: TET2 were changed from Dementia; Lymphoma/myeloid malignancy; Immunodeficiency-75 (IMD75), MIM#619126 to Dementia; Lymphoma/myeloid malignancy; Immunodeficiency-75 (IMD75), MIM#619126; Pulmonary arterial hypertension MONDO:0015924, TET2-related
Mendeliome v1.1088 TET2 Zornitza Stark Publications for gene: TET2 were set to 30890702; 31827242; 32330418
Mendeliome v1.1087 TET2 Zornitza Stark changed review comment from: Association with PAH:
MODERATE by ClinGen. TET2 was first reported in relation to autosomal dominant pulmonary arterial hypertension (PAH) in 2020 (Potus et al., PMID: 32192357). Out of a cohort of 2572 cases from the PAH biobank, 6 rare predicted deleterious likely germline variants including missense, nonsense, and frameshift variants were identified in 6 unrelated individuals. The relationship between TET2 and PAH is also supported by experimental evidence including tissue expression in controls and patients, biochemical function as a negative regulator of a proinflammatory response, and knock out TET2 mice exhibiting a PH phenotype.; to: Association with PAH:
MODERATE by ClinGen/Amber rating here. TET2 was first reported in relation to autosomal dominant pulmonary arterial hypertension (PAH) in 2020 (Potus et al., PMID: 32192357). Out of a cohort of 2572 cases from the PAH biobank, 6 rare predicted deleterious likely germline variants including missense, nonsense, and frameshift variants were identified in 6 unrelated individuals. The relationship between TET2 and PAH is also supported by experimental evidence including tissue expression in controls and patients, biochemical function as a negative regulator of a proinflammatory response, and knock out TET2 mice exhibiting a PH phenotype.
Mendeliome v1.1087 TET2 Zornitza Stark edited their review of gene: TET2: Added comment: Association with PAH:
MODERATE by ClinGen. TET2 was first reported in relation to autosomal dominant pulmonary arterial hypertension (PAH) in 2020 (Potus et al., PMID: 32192357). Out of a cohort of 2572 cases from the PAH biobank, 6 rare predicted deleterious likely germline variants including missense, nonsense, and frameshift variants were identified in 6 unrelated individuals. The relationship between TET2 and PAH is also supported by experimental evidence including tissue expression in controls and patients, biochemical function as a negative regulator of a proinflammatory response, and knock out TET2 mice exhibiting a PH phenotype.; Changed publications: 30890702, 31827242, 32330418, 32518946, 32192357; Changed phenotypes: Dementia, Lymphoma/myeloid malignancy, Immunodeficiency-75 (IMD75), MIM#619126, Pulmonary arterial hypertension MONDO:0015924, TET2-related
Pulmonary Arterial Hypertension v1.21 TET2 Zornitza Stark Marked gene: TET2 as ready
Pulmonary Arterial Hypertension v1.21 TET2 Zornitza Stark Gene: tet2 has been classified as Amber List (Moderate Evidence).
Pulmonary Arterial Hypertension v1.21 TET2 Zornitza Stark Classified gene: TET2 as Amber List (moderate evidence)
Pulmonary Arterial Hypertension v1.21 TET2 Zornitza Stark Gene: tet2 has been classified as Amber List (Moderate Evidence).
Pulmonary Arterial Hypertension v1.20 TET2 Zornitza Stark edited their review of gene: TET2: Changed rating: AMBER
Pulmonary Arterial Hypertension v1.20 TET2 Zornitza Stark gene: TET2 was added
gene: TET2 was added to Pulmonary Arterial Hypertension. Sources: Expert list
Mode of inheritance for gene: TET2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TET2 were set to 32192357
Phenotypes for gene: TET2 were set to Pulmonary arterial hypertension MONDO:0015924, TET2-related
Added comment: MODERATE by ClinGen.

TET2 was first reported in relation to autosomal dominant pulmonary arterial hypertension (PAH) in 2020 (Potus et al., PMID: 32192357). Out of a cohort of 2572 cases from the PAH biobank, 6 rare predicted deleterious likely germline variants including missense, nonsense, and frameshift variants were identified in 6 unrelated individuals. The relationship between TET2 and PAH is also supported by experimental evidence including tissue expression in controls and patients, biochemical function as a negative regulator of a proinflammatory response, and knock out TET2 mice exhibiting a PH phenotype.
Sources: Expert list
Pulmonary Arterial Hypertension v1.19 GGCX Zornitza Stark reviewed gene: GGCX: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: pulmonary arterial hypertension MONDO:0015924; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Pulmonary Arterial Hypertension v1.19 ABCC8 Zornitza Stark reviewed gene: ABCC8: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: pulmonary arterial hypertension MONDO:0015924, ABCC8-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Pulmonary Arterial Hypertension v1.19 SOX17 Zornitza Stark reviewed gene: SOX17: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Heritable pulmonary arterial hypertension, MONDO:0017148, SOX17-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Pulmonary Arterial Hypertension v1.19 SMAD9 Zornitza Stark reviewed gene: SMAD9: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Pulmonary hypertension, primary, 2 MIM#615342; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Pulmonary Arterial Hypertension v1.19 KDR Zornitza Stark commented on gene: KDR: DEFINITIVE by ClinGen.
Pulmonary Arterial Hypertension v1.19 KCNK3 Zornitza Stark reviewed gene: KCNK3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Pulmonary hypertension, primary, 4 MIM#615344; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Pulmonary Arterial Hypertension v1.19 GDF2 Zornitza Stark reviewed gene: GDF2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Telangiectasia, hereditary hemorrhagic, type 5 MIM#615506, Pulmonary arterial hypertension; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary Neuropathy - complex v0.215 POLG Sangavi Sivagnanasundram reviewed gene: POLG: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301791; Phenotypes: Mitochondrial recessive ataxia syndrome (includes SANDO and SCAE) 607459; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebral Palsy v1.185 ADNP Luisa Weiss edited their review of gene: ADNP: Added comment: In addition to the previous cases, there is one case report of a boy with the full phenotypic picture of Helsmoortel-van der Aa syndrome and hypotonic cerebral palsy. Note that hypotonia is one feature of Helsmoortel-van der Aa syndrome, but hypotonic cerebral palsy seems to be rare.; Changed rating: GREEN; Changed publications: 29780943; Changed phenotypes: Helsmoortel-van der Aa syndrome MIM#615873
Pulmonary Arterial Hypertension v1.19 CAV1 Zornitza Stark reviewed gene: CAV1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Pulmonary hypertension, primary, 3 MIM#615343; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Pulmonary Arterial Hypertension v1.19 BMPR2 Zornitza Stark reviewed gene: BMPR2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Pulmonary hypertension, familial primary, 1, with or without HHT MIM#178600, Pulmonary hypertension, primary, fenfluramine or dexfenfluramine-associated MIM#178600; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Pulmonary Arterial Hypertension v1.19 ATP13A3 Zornitza Stark commented on gene: ATP13A3: DEFINITIVE by ClinGen.
Hereditary Neuropathy - complex v0.215 PNPLA6 Sangavi Sivagnanasundram reviewed gene: PNPLA6: Rating: GREEN; Mode of pathogenicity: None; Publications: 25299038, 18313024; Phenotypes: Laurence-Moon Syndrome (LMS) MIM#245800, Spastic Paraplegia Type 39 MIM#612020; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Neuropathy - complex v0.215 PNKP Sangavi Sivagnanasundram reviewed gene: PNKP: Rating: GREEN; Mode of pathogenicity: None; Publications: 30039206, 27066567, 25728773; Phenotypes: Charcot-Marie-Tooth disease, axonal, type 2B2 (MIM#605589), Ataxia-oculomotor apraxia 4 (MIM#616267); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Neuropathy - complex v0.215 PLP1 Sangavi Sivagnanasundram reviewed gene: PLP1: Rating: AMBER; Mode of pathogenicity: None; Publications: 20301361, 11872612; Phenotypes: Pelizaeus-Merzbacher disease (MIM#312080); Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Systemic Autoinflammatory Disease_Periodic Fever v1.9 DPP9 Peter McNaughton edited their review of gene: DPP9: Added comment: de novo monoallelic dominant-negative mutation in DPP9 (c.755G>C, R252P) presenting with HLH at ~2m. Functional data supporting dominant negative mechanism.; Changed publications: PMID: 37544411; Changed phenotypes: HLH; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hereditary Neuropathy - complex v0.215 PLA2G6 Sangavi Sivagnanasundram reviewed gene: PLA2G6: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Infantile neuroaxonal dystrophy 1 (MIM#256600), Neurodegeneration with brain iron accumulation 2B (MIM#610217), Parkinson disease 14, autosomal recessive (MIM#612953); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Neuropathy - complex v0.215 PHYH Sangavi Sivagnanasundram reviewed gene: PHYH: Rating: AMBER; Mode of pathogenicity: None; Publications: 2433405, 20301527; Phenotypes: Adult Refsum Disease MIM#266500; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Neuropathy - complex v0.215 PEX7 Sangavi Sivagnanasundram reviewed gene: PEX7: Rating: RED; Mode of pathogenicity: None; Publications: 20301447, 12325024; Phenotypes: Peroxisome biogenesis disorder 9B (MIM#614879); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Neuropathy - complex v0.215 PDYN Sangavi Sivagnanasundram reviewed gene: PDYN: Rating: AMBER; Mode of pathogenicity: None; Publications: 21035104; Phenotypes: Spinocerebellar ataxia 23 (MIM#610245); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Hereditary Neuropathy - complex v0.215 OPA1 Sangavi Sivagnanasundram reviewed gene: OPA1: Rating: GREEN; Mode of pathogenicity: None; Publications: 16240368, 18065439, 20157015, 21112924; Phenotypes: Optic atrophy plus syndrome (MIM#125250); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Hereditary Neuropathy - complex v0.215 NGLY1 Sangavi Sivagnanasundram reviewed gene: NGLY1: Rating: GREEN; Mode of pathogenicity: None; Publications: 22581936, 27388694, 29419975; Phenotypes: Congenital disorder of deglycosylation 1 (CDDG1) (MIM#615273); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Inflammatory bowel disease v0.103 RELA Peter McNaughton gene: RELA was added
gene: RELA was added to Inflammatory bowel disease. Sources: Literature
Mode of inheritance for gene: RELA was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: RELA were set to PMID: 37273177
Phenotypes for gene: RELA were set to Inflammatory bowel disease
Review for gene: RELA was set to GREEN
Added comment: Patients with RELA DN mutations additionally presented periodic fever, inflammatory bowel diseases (IBDs), juvenile idiopathic arthritis (JIA), and skin involvement. Complete penetrance was observed for IBD
Sources: Literature
Systemic Autoinflammatory Disease_Periodic Fever v1.9 RELA Peter McNaughton gene: RELA was added
gene: RELA was added to Systemic Autoinflammatory Disease_Periodic Fever. Sources: Literature
Mode of inheritance for gene: RELA was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: RELA were set to PMID: 37273177
Phenotypes for gene: RELA were set to periodic fever, inflammatory bowel disease, JIA
Review for gene: RELA was set to GREEN
Added comment: Dominant negative RELA mutations in six patients from five unrelated families. Phenotypic overlap with RELA haploinsufficiency - chronic mucocutaneous ulcerations and autoimmune hematological disorders such as immune thrombocytopenia (ITP) and neutropenia. Patients with RELA DN mutations additionally presented periodic fever, inflammatory bowel diseases (IBDs), juvenile idiopathic arthritis (JIA), and skin involvement.
Sources: Literature
Cerebral Palsy v1.185 SYNE1 Luisa Weiss Deleted their comment
Cerebral Palsy v1.185 SYNE1 Luisa Weiss edited their review of gene: SYNE1: Added comment: Two cases each in two larger CP cohort studies, one with ataxic and one with spastic CP, with biallelic SYNE1 mutations.
In addition, one case report of an 18-year-old girl with CP and a heterozygous SYNE1-mutation. Not that this patient had a history of perinatal distress and asphyxia. The SYNE1 mutation was discovered at the age of 18 years due to a hypertrophic cardiomyopathy. It is uncertain whether the SYNE1 mutation is the cause for the CP.; Changed rating: GREEN; Changed publications: 34321325, 34816117, 31110749; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Congenital ophthalmoplegia v1.8 HNRNPA2B1 Zornitza Stark Phenotypes for gene: HNRNPA2B1 were changed from oculopharyngeal muscular dystrophy, MONDO:0008116 to oculopharyngeal muscular dystrophy, MONDO:0008116, OMIM#620460
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.22 HNRNPA2B1 Zornitza Stark Phenotypes for gene: HNRNPA2B1 were changed from inclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia 2 MONDO:0014178; oculopharyngeal muscular dystrophy, MONDO:0008116 to oculopharyngeal muscular dystrophy, MONDO:0008116, OMIM#620460
Mendeliome v1.1087 HNRNPA2B1 Zornitza Stark Phenotypes for gene: HNRNPA2B1 were changed from oculopharyngeal muscular dystrophy, MONDO:0008116; Inclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia 2 MIM#615422 to oculopharyngeal muscular dystrophy, MONDO:0008116, OMIM#620460; Inclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia 2 MIM#615422
Hereditary Neuropathy - complex v0.215 SURF1 Sangavi Sivagnanasundram reviewed gene: SURF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 9843204, 9837813; Phenotypes: Charcot-Marie-Tooth disease, type 4K (MIM#616684, MONDO:0014733); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Neuropathy - complex v0.215 TECPR2 Sangavi Sivagnanasundram reviewed gene: TECPR2: Rating: GREEN; Mode of pathogenicity: None; Publications: 36137062, 26542466, 23176824; Phenotypes: Neuropathy, hereditary sensory and autonomic, type IX, with developmental delay (HSAN) (MIM#615031); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Neuropathy - complex v0.215 TYMP Sangavi Sivagnanasundram reviewed gene: TYMP: Rating: AMBER; Mode of pathogenicity: Other; Publications: 20301358, 14757860; Phenotypes: Mitochondrial DNA depletion syndrome 1 (MNGIE type) MIM#603041; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1086 AGAP1 Zornitza Stark Phenotypes for gene: AGAP1 were changed from Cerebral palsy to Cerebral palsy, MONDO:0006497, AGAP1-related
Mendeliome v1.1085 AGAP1 Zornitza Stark edited their review of gene: AGAP1: Changed phenotypes: Cerebral palsy, MONDO:0006497, AGAP1-related
Cerebral Palsy v1.184 AGAP1 Zornitza Stark Phenotypes for gene: AGAP1 were changed from Neurodevelopmental disorder, MONDO:0700092, AGAP1-related to Cerebral palsy, MONDO:0006497, AGAP1-related
Cerebral Palsy v1.183 AGAP1 Zornitza Stark Phenotypes for gene: AGAP1 were changed from Cerebral palsy to Neurodevelopmental disorder, MONDO:0700092, AGAP1-related
Cerebral Palsy v1.182 AGAP1 Zornitza Stark Publications for gene: AGAP1 were set to 31700678; 25666757; 30472483
Cerebral Palsy v1.181 AGAP1 Zornitza Stark Tag SV/CNV tag was added to gene: AGAP1.
Cerebral Palsy v1.181 HPDL Zornitza Stark Publications for gene: HPDL were set to 33634263
Cerebral Palsy v1.180 HPDL Zornitza Stark Classified gene: HPDL as Green List (high evidence)
Cerebral Palsy v1.180 HPDL Zornitza Stark Gene: hpdl has been classified as Green List (High Evidence).
Cerebral Palsy v1.179 MAP2K1 Zornitza Stark Marked gene: MAP2K1 as ready
Cerebral Palsy v1.179 MAP2K1 Zornitza Stark Gene: map2k1 has been classified as Green List (High Evidence).
Cerebral Palsy v1.179 MAP2K1 Zornitza Stark Classified gene: MAP2K1 as Green List (high evidence)
Cerebral Palsy v1.179 MAP2K1 Zornitza Stark Gene: map2k1 has been classified as Green List (High Evidence).
Mendeliome v1.1085 PRDM10 Zornitza Stark Phenotypes for gene: PRDM10 were changed from Fibrofolliculoma, HP:0030436; lipomatosis, MONDO:0006574; renal cell carcinoma, MONDO:0005086 to Birt-Hogg-Dube syndrome 2, MIM# 620459
Mendeliome v1.1084 PRDM10 Zornitza Stark reviewed gene: PRDM10: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Birt-Hogg-Dube syndrome 2, MIM# 620459; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v1.136 PLCB4 Zornitza Stark Phenotypes for gene: PLCB4 were changed from Auriculocondylar syndrome 2, MIM# 614669 to Auriculocondylar syndrome 2A, MIM# 614669; Auriculocondylar syndrome 2B, MIM# 620458
Fetal anomalies v1.135 PLCB4 Zornitza Stark reviewed gene: PLCB4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Auriculocondylar syndrome 2A, MIM# 614669, Auriculocondylar syndrome 2B, MIM# 620458; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Clefting disorders v0.240 PLCB4 Zornitza Stark Phenotypes for gene: PLCB4 were changed from Auriculocondylar syndrome 2, MIM# 614669; Cleft palate to Auriculocondylar syndrome 2A, MIM# 614669; Auriculocondylar syndrome 2B, MIM# 620458; Cleft palate
Clefting disorders v0.239 PLCB4 Zornitza Stark edited their review of gene: PLCB4: Changed phenotypes: AAuriculocondylar syndrome 2A, MIM# 614669, Auriculocondylar syndrome 2B, MIM# 620458
Pierre Robin Sequence v0.47 PLCB4 Zornitza Stark edited their review of gene: PLCB4: Changed phenotypes: Auriculocondylar syndrome 2A, MIM# 614669, Auriculocondylar syndrome 2B, MIM# 620458
Pierre Robin Sequence v0.47 PLCB4 Zornitza Stark Phenotypes for gene: PLCB4 were changed from Auriculocondylar syndrome 2, MIM# 614669 to Auriculocondylar syndrome 2A, MIM# 614669; Auriculocondylar syndrome 2B, MIM# 620458
Mendeliome v1.1084 PLCB4 Zornitza Stark Phenotypes for gene: PLCB4 were changed from Auriculocondylar syndrome 2, MIM# 614669 to Auriculocondylar syndrome 2A, MIM# 614669; Auriculocondylar syndrome 2B, MIM# 620458
Mendeliome v1.1083 PLCB4 Zornitza Stark edited their review of gene: PLCB4: Changed phenotypes: Auriculocondylar syndrome 2A, MIM# 614669, Auriculocondylar syndrome 2B, MIM# 620458
Mandibulofacial Acrofacial dysostosis v1.9 PLCB4 Zornitza Stark Phenotypes for gene: PLCB4 were changed from Auriculocondylar syndrome 2, MIM# 614669 to Auriculocondylar syndrome 2A, MIM# 614669; Auriculocondylar syndrome 2B, MIM# 620458
Mandibulofacial Acrofacial dysostosis v1.8 PLCB4 Zornitza Stark edited their review of gene: PLCB4: Changed phenotypes: Auriculocondylar syndrome 2A, MIM# 614669, Auriculocondylar syndrome 2B, MIM# 620458
Cardiomyopathy_Paediatric v0.166 TBX5 Zornitza Stark Marked gene: TBX5 as ready
Cardiomyopathy_Paediatric v0.166 TBX5 Zornitza Stark Gene: tbx5 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v0.166 TBX5 Zornitza Stark Classified gene: TBX5 as Green List (high evidence)
Cardiomyopathy_Paediatric v0.166 TBX5 Zornitza Stark Gene: tbx5 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v0.165 TBX5 Zornitza Stark gene: TBX5 was added
gene: TBX5 was added to Cardiomyopathy_Paediatric. Sources: Expert Review
Mode of inheritance for gene: TBX5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TBX5 were set to 32449309; 32236096; 25963046; 25725155
Phenotypes for gene: TBX5 were set to Holt-Oram syndrome, MIM# 142900; Dilated cardiomyopathy
Review for gene: TBX5 was set to GREEN
Added comment: DCM is a feature of this congenital disorder.
Sources: Expert Review
Cardiomyopathy_Paediatric v0.164 TBX20 Zornitza Stark Marked gene: TBX20 as ready
Cardiomyopathy_Paediatric v0.164 TBX20 Zornitza Stark Gene: tbx20 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v0.164 TBX20 Zornitza Stark Classified gene: TBX20 as Green List (high evidence)
Cardiomyopathy_Paediatric v0.164 TBX20 Zornitza Stark Gene: tbx20 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v0.163 TBX20 Zornitza Stark gene: TBX20 was added
gene: TBX20 was added to Cardiomyopathy_Paediatric. Sources: Literature
Mode of inheritance for gene: TBX20 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TBX20 were set to 26118961; 17668378; 27510170; 35282022
Phenotypes for gene: TBX20 were set to Dilated cardiomyopathy, MONDO:0005021, TBX20-related
Review for gene: TBX20 was set to GREEN
Added comment: Multiple reports in literature, including of children. Also aware of additional four families identified internally, publication pending.
Sources: Literature
Dilated Cardiomyopathy v1.22 TBX20 Zornitza Stark Phenotypes for gene: TBX20 were changed from Dilated cardiomyopathy to Dilated cardiomyopathy, MONDO:0005021, TBX20-related
Dilated Cardiomyopathy v1.21 TBX20 Zornitza Stark Publications for gene: TBX20 were set to 26118961; 17668378; 27510170
Dilated Cardiomyopathy v1.20 TBX20 Zornitza Stark Mode of inheritance for gene: TBX20 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Dilated Cardiomyopathy v1.19 TBX20 Zornitza Stark Classified gene: TBX20 as Green List (high evidence)
Dilated Cardiomyopathy v1.19 TBX20 Zornitza Stark Gene: tbx20 has been classified as Green List (High Evidence).
Dilated Cardiomyopathy v1.18 TBX20 Zornitza Stark reviewed gene: TBX20: Rating: GREEN; Mode of pathogenicity: None; Publications: 35282022; Phenotypes: Dilated cardiomyopathy, MONDO:0005021, TBX20-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cardiomyopathy_Paediatric v0.162 PRDM16 Zornitza Stark Marked gene: PRDM16 as ready
Cardiomyopathy_Paediatric v0.162 PRDM16 Zornitza Stark Gene: prdm16 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v0.162 PRDM16 Zornitza Stark Classified gene: PRDM16 as Green List (high evidence)
Cardiomyopathy_Paediatric v0.162 PRDM16 Zornitza Stark Gene: prdm16 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v0.161 PRDM16 Zornitza Stark gene: PRDM16 was added
gene: PRDM16 was added to Cardiomyopathy_Paediatric. Sources: Expert Review
Mode of inheritance for gene: PRDM16 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PRDM16 were set to 29367541; 29447731; 30847666; 33082984; 32183154; 33500567; 34540771; 34350506; 34935411
Phenotypes for gene: PRDM16 were set to Cardiomyopathy, dilated, 1LL MIM#615373; Left ventricular noncompaction 8 MIM#615373
Review for gene: PRDM16 was set to GREEN
Added comment: Paediatric onset reported.
Sources: Expert Review
Motor Neurone Disease v0.192 LRP12-ALS_CGG Zornitza Stark Marked STR: LRP12-ALS_CGG as ready
Motor Neurone Disease v0.192 LRP12-ALS_CGG Zornitza Stark Str: lrp12-als_cgg has been classified as Green List (High Evidence).
Motor Neurone Disease v0.192 LRP12-ALS_CGG Zornitza Stark Phenotypes for STR: LRP12-ALS_CGG were changed from Amyotrophic lateral sclerosis MONDO:0004976 to Amyotrophic lateral sclerosis MONDO:0004976; Amyotrophic lateral sclerosis 28, MIM# 620452
Mendeliome v1.1083 IL1R1 Zornitza Stark Marked gene: IL1R1 as ready
Mendeliome v1.1083 IL1R1 Zornitza Stark Gene: il1r1 has been classified as Red List (Low Evidence).
Mendeliome v1.1083 IL1R1 Zornitza Stark gene: IL1R1 was added
gene: IL1R1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: IL1R1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: IL1R1 were set to 37315560
Phenotypes for gene: IL1R1 were set to Chronic recurrent multifocal osteomyelitis 3, MIM# 259680
Review for gene: IL1R1 was set to RED
Added comment: Single individual reported with de novo missense variant in this gene and a phenotype of chronic recurrent multifocal osteomyelitis, auto inflammatory in nature. Some functional data presented.
Sources: Literature
Systemic Autoinflammatory Disease_Periodic Fever v1.9 IL1R1 Zornitza Stark Marked gene: IL1R1 as ready
Systemic Autoinflammatory Disease_Periodic Fever v1.9 IL1R1 Zornitza Stark Gene: il1r1 has been classified as Red List (Low Evidence).
Systemic Autoinflammatory Disease_Periodic Fever v1.9 IL1R1 Zornitza Stark gene: IL1R1 was added
gene: IL1R1 was added to Systemic Autoinflammatory Disease_Periodic Fever. Sources: Literature
Mode of inheritance for gene: IL1R1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: IL1R1 were set to 37315560
Phenotypes for gene: IL1R1 were set to Chronic recurrent multifocal osteomyelitis 3, MIM# 259680
Review for gene: IL1R1 was set to RED
Added comment: Single individual reported with de novo missense variant in this gene and a phenotype of chronic recurrent multifocal osteomyelitis, auto inflammatory in nature. Some functional data presented.
Sources: Literature
Mendeliome v1.1082 STAB1 Zornitza Stark Marked gene: STAB1 as ready
Mendeliome v1.1082 STAB1 Zornitza Stark Gene: stab1 has been classified as Green List (High Evidence).
Mendeliome v1.1082 STAB1 Zornitza Stark Classified gene: STAB1 as Green List (high evidence)
Mendeliome v1.1082 STAB1 Zornitza Stark Gene: stab1 has been classified as Green List (High Evidence).
Mendeliome v1.1081 RINT1 Zornitza Stark Phenotypes for gene: RINT1 were changed from Recurrent acute liver failure to Infantile liver failure syndrome 3, MIM# 618641
Hereditary Spastic Paraplegia - paediatric v1.68 RINT1 Zornitza Stark Marked gene: RINT1 as ready
Hereditary Spastic Paraplegia - paediatric v1.68 RINT1 Zornitza Stark Gene: rint1 has been classified as Amber List (Moderate Evidence).
Hereditary Spastic Paraplegia - paediatric v1.68 RINT1 Zornitza Stark Phenotypes for gene: RINT1 were changed from Hereditary spastic paraplegia, MONDO:0019064, RINT1-related to Infantile liver failure syndrome 3, MIM# 618641; Hereditary spastic paraplegia, MONDO:0019064, RINT1-related
Hereditary Spastic Paraplegia - paediatric v1.67 RINT1 Zornitza Stark Classified gene: RINT1 as Amber List (moderate evidence)
Hereditary Spastic Paraplegia - paediatric v1.67 RINT1 Zornitza Stark Gene: rint1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1080 SMARCA4 Zornitza Stark Phenotypes for gene: SMARCA4 were changed from Coffin-Siris syndrome 4, MIM# 614609 to Coffin-Siris syndrome 4, MIM# 614609; Otosclerosis MONDO:0005349, SMARCA4-related
Mendeliome v1.1079 SMARCA4 Zornitza Stark Publications for gene: SMARCA4 were set to 22426308
Deafness_Isolated v1.47 SMARCA4 Zornitza Stark Marked gene: SMARCA4 as ready
Deafness_Isolated v1.47 SMARCA4 Zornitza Stark Gene: smarca4 has been classified as Amber List (Moderate Evidence).
Deafness_Isolated v1.47 SMARCA4 Zornitza Stark Classified gene: SMARCA4 as Amber List (moderate evidence)
Deafness_Isolated v1.47 SMARCA4 Zornitza Stark Gene: smarca4 has been classified as Amber List (Moderate Evidence).
Congenital anomalies of the kidney and urinary tract (CAKUT) Nonsyndromic v0.115 TBC1D31 Zornitza Stark Marked gene: TBC1D31 as ready
Congenital anomalies of the kidney and urinary tract (CAKUT) Nonsyndromic v0.115 TBC1D31 Zornitza Stark Gene: tbc1d31 has been classified as Red List (Low Evidence).
Congenital anomalies of the kidney and urinary tract (CAKUT) Nonsyndromic v0.115 TBC1D31 Zornitza Stark gene: TBC1D31 was added
gene: TBC1D31 was added to Congenital anomalies of the kidney and urinary tract (CAKUT) Nonsyndromic. Sources: Literature
Mode of inheritance for gene: TBC1D31 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TBC1D31 were set to 37468454
Phenotypes for gene: TBC1D31 were set to congenital anomaly of kidney and urinary tract MONDO:0019719, TBC1D31-related
Review for gene: TBC1D31 was set to RED
Added comment: Single paper with homozygous mutations in 3 sibs with CAKUT from consanguineous family
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5324 SLC4A10 Krithika Murali Classified gene: SLC4A10 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5324 SLC4A10 Krithika Murali Gene: slc4a10 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5323 SLC4A10 Krithika Murali Marked gene: SLC4A10 as ready
Intellectual disability syndromic and non-syndromic v0.5323 SLC4A10 Krithika Murali Gene: slc4a10 has been classified as Red List (Low Evidence).
Mendeliome v1.1078 TBC1D31 Zornitza Stark Marked gene: TBC1D31 as ready
Mendeliome v1.1078 TBC1D31 Zornitza Stark Gene: tbc1d31 has been classified as Red List (Low Evidence).
Mendeliome v1.1078 TBC1D31 Zornitza Stark Classified gene: TBC1D31 as Red List (low evidence)
Mendeliome v1.1078 TBC1D31 Zornitza Stark Gene: tbc1d31 has been classified as Red List (Low Evidence).
Leukodystrophy - paediatric v0.296 AQP4 Zornitza Stark Marked gene: AQP4 as ready
Leukodystrophy - paediatric v0.296 AQP4 Zornitza Stark Gene: aqp4 has been classified as Amber List (Moderate Evidence).
Leukodystrophy - paediatric v0.296 AQP4 Zornitza Stark Classified gene: AQP4 as Amber List (moderate evidence)
Leukodystrophy - paediatric v0.296 AQP4 Zornitza Stark Gene: aqp4 has been classified as Amber List (Moderate Evidence).
Leukodystrophy - paediatric v0.295 AQP4 Zornitza Stark gene: AQP4 was added
gene: AQP4 was added to Leukodystrophy - paediatric. Sources: Literature
Mode of inheritance for gene: AQP4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AQP4 were set to 37143309
Phenotypes for gene: AQP4 were set to Megalencephalic leukoencephalopathy with subcortical cysts 4, remitting MIM#620448
Review for gene: AQP4 was set to AMBER
Added comment: Borderline Amber/Red.

PMID: 37143309 Missense variant in AQP4 seen homozygous in 2 siblings and het in the parents. Patients had macrocephaly, developmental delay, hypotonia, epilepsy, and cognitive deficit.

Western blots on generated MDCK cell lines showed no detectable expression of AQP4 protein from the cells with the patients variant. Immunofluorescence also showed no membrane expression. Overexpression studies in HEK293T cells showed WT was seen as mainly monomers or dimers where as variant protein formed large aggregates- likely due to the saturation of protein degradation pathways because of the overexpression.
Sources: Literature
Early-onset Parkinson disease v0.243 PTPA Zornitza Stark Publications for gene: PTPA were set to 36073231
Early-onset Parkinson disease v0.242 PTPA Zornitza Stark Mode of inheritance for gene: PTPA was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5323 AQP4 Zornitza Stark Marked gene: AQP4 as ready
Intellectual disability syndromic and non-syndromic v0.5323 AQP4 Zornitza Stark Gene: aqp4 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5323 AQP4 Zornitza Stark Phenotypes for gene: AQP4 were changed from ?Megalencephalic leukoencephalopathy with subcortical cysts 4, remitting MIM#620448 to Megalencephalic leukoencephalopathy with subcortical cysts 4, remitting MIM#620448
Intellectual disability syndromic and non-syndromic v0.5322 AQP4 Zornitza Stark Classified gene: AQP4 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.5322 AQP4 Zornitza Stark Gene: aqp4 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1077 AQP4 Zornitza Stark Marked gene: AQP4 as ready
Mendeliome v1.1077 AQP4 Zornitza Stark Gene: aqp4 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1077 AQP4 Zornitza Stark Phenotypes for gene: AQP4 were changed from ?Megalencephalic leukoencephalopathy with subcortical cysts 4, remitting MIM#620448 to Megalencephalic leukoencephalopathy with subcortical cysts 4, remitting MIM#620448
Mendeliome v1.1076 AQP4 Zornitza Stark Classified gene: AQP4 as Amber List (moderate evidence)
Mendeliome v1.1076 AQP4 Zornitza Stark Gene: aqp4 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.1879 AQP4 Zornitza Stark Marked gene: AQP4 as ready
Genetic Epilepsy v0.1879 AQP4 Zornitza Stark Gene: aqp4 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.1879 AQP4 Zornitza Stark Phenotypes for gene: AQP4 were changed from ?Megalencephalic leukoencephalopathy with subcortical cysts 4, remitting MIM#620448 to Megalencephalic leukoencephalopathy with subcortical cysts 4, remitting MIM#620448
Genetic Epilepsy v0.1878 AQP4 Zornitza Stark Classified gene: AQP4 as Amber List (moderate evidence)
Genetic Epilepsy v0.1878 AQP4 Zornitza Stark Gene: aqp4 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.1877 AQP4 Zornitza Stark reviewed gene: AQP4: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Megalencephalic leukoencephalopathy with subcortical cysts 4, remitting MIM#620448; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1075 EZH1 Zornitza Stark Marked gene: EZH1 as ready
Mendeliome v1.1075 EZH1 Zornitza Stark Gene: ezh1 has been classified as Green List (High Evidence).
Mendeliome v1.1075 EZH1 Zornitza Stark Classified gene: EZH1 as Green List (high evidence)
Mendeliome v1.1075 EZH1 Zornitza Stark Gene: ezh1 has been classified as Green List (High Evidence).
Mendeliome v1.1074 EZH1 Zornitza Stark gene: EZH1 was added
gene: EZH1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: EZH1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: EZH1 were set to 37433783
Phenotypes for gene: EZH1 were set to Neurodevelopmental disorder (MONDO:0700092), EZH1-related
Review for gene: EZH1 was set to GREEN
Added comment: PMID: 37433783
Variants were identified 19 individuals from 14 unrelated families, all sharing a clinical phenotype of a neurodevelopmental disorder manifested early in life as global motor, speech and cognitive delay leading to intellectual disability, usually non-progressive and co-occurring with dysmorphic facial features.

Functional studies have shown that some missense EZH1 variants lead to GOF with increased methyltransferase activity and recessive variants impair EZH1 expression causing loss of function effects.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5321 EZH1 Zornitza Stark Marked gene: EZH1 as ready
Intellectual disability syndromic and non-syndromic v0.5321 EZH1 Zornitza Stark Gene: ezh1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5321 EZH1 Zornitza Stark Phenotypes for gene: EZH1 were changed from to Neurodevelopmental disorder (MONDO:0700092), EZH1-related
Intellectual disability syndromic and non-syndromic v0.5320 EZH1 Zornitza Stark Publications for gene: EZH1 were set to
Intellectual disability syndromic and non-syndromic v0.5319 EZH1 Zornitza Stark Classified gene: EZH1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5319 EZH1 Zornitza Stark Gene: ezh1 has been classified as Green List (High Evidence).
Hereditary Spastic Paraplegia - paediatric v1.66 RINT1 Chern Lim gene: RINT1 was added
gene: RINT1 was added to Hereditary Spastic Paraplegia - paediatric. Sources: Literature
Mode of inheritance for gene: RINT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RINT1 were set to 37463447
Phenotypes for gene: RINT1 were set to Hereditary spastic paraplegia, MONDO:0019064, RINT1-related
Review for gene: RINT1 was set to AMBER
gene: RINT1 was marked as current diagnostic
Added comment: PMID: 37463447
- 3 individuals from 2 unrelated families with biallelic LoF variants - hom canonical spice variant in 1 family, chet stopgain+canonical splice variants in another family.
- Affected individuals presented with early onset spastic paraplegia, ataxia, optic nerve hypoplasia, and dysmorphic features, broadening the previously described phenotype.
- One of the individual died at 14 months due to acute liver failure, probably before the development of a neurological phenotype. The episodic liver dysfunction two other patients was very similar to that previously reported in PMID: 31204009.
- RNA studies showed the splice variants result in aberrant splicing. Other functional and lipidomic analyses supportive of pathogenicity.
Sources: Literature
Mendeliome v1.1073 GPRC5B Zornitza Stark Marked gene: GPRC5B as ready
Mendeliome v1.1073 GPRC5B Zornitza Stark Gene: gprc5b has been classified as Green List (High Evidence).
Mendeliome v1.1073 GPRC5B Zornitza Stark Classified gene: GPRC5B as Green List (high evidence)
Mendeliome v1.1073 GPRC5B Zornitza Stark Gene: gprc5b has been classified as Green List (High Evidence).
Ataxia - adult onset v1.4 RFC1 Dean Phelan Deleted their review
Ataxia - adult onset v1.4 CANVAS Dean Phelan reviewed STR: CANVAS: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 37450567; Phenotypes: Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (MIM:614575); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1072 PHF5A Zornitza Stark Marked gene: PHF5A as ready
Mendeliome v1.1072 PHF5A Zornitza Stark Gene: phf5a has been classified as Green List (High Evidence).
Mendeliome v1.1072 PHF5A Zornitza Stark Classified gene: PHF5A as Green List (high evidence)
Mendeliome v1.1072 PHF5A Zornitza Stark Gene: phf5a has been classified as Green List (High Evidence).
Mendeliome v1.1071 SMARCA4 Paul De Fazio changed review comment from: Additional phenotype reported:

A single missense variant E1610K (M_001128849.3) was reported in 7 affected members of a family with progressive hearing loss due to otosclerosis and no other clinical features. Variant is absent from gnomAD. Note that unaffected members of the family were not tested.

A mouse CRISPR model with the orthologous variant had a similar phenotype.; to: Additional phenotype reported:

A single missense variant E1610K (M_001128849.3) was reported in 7 affected members of a family with progressive hearing loss due to otosclerosis and no other clinical features. Variant is absent from gnomAD. Note that unaffected members of the family were not tested - some obligate carriers were apparently unaffected, reflecting incomplete penetrance.

A mouse CRISPR model with the orthologous variant had a similar phenotype.
Deafness_Isolated v1.46 SMARCA4 Paul De Fazio changed review comment from: A single missense variant E1610K (M_001128849.3) was reported in 7 affected members of a family with progressive hearing loss due to otosclerosis and no other clinical features. Variant is absent from gnomAD. Note that unaffected members of the family were not tested.

A mouse CRISPR model with the orthologous variant had a similar phenotype.
Sources: Literature; to: A single missense variant E1610K (M_001128849.3) was reported in 7 affected members of a family with progressive hearing loss due to otosclerosis and no other clinical features. Variant is absent from gnomAD. Note that unaffected members of the family were not tested - some obligate carriers were apparently unaffected, reflecting incomplete penetrance.

A mouse CRISPR model with the orthologous variant had a similar phenotype.
Sources: Literature
Mendeliome v1.1071 CANVAS Dean Phelan reviewed STR: CANVAS: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 37450567; Phenotypes: Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (MIM:614575); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5318 PHF5A Zornitza Stark Marked gene: PHF5A as ready
Intellectual disability syndromic and non-syndromic v0.5318 PHF5A Zornitza Stark Gene: phf5a has been classified as Green List (High Evidence).
Mendeliome v1.1071 PHF5A Daniel Flanagan gene: PHF5A was added
gene: PHF5A was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: PHF5A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PHF5A were set to PMID: 37422718
Phenotypes for gene: PHF5A were set to Neurodevelopmental disorder (MONDO#0700092), PHF5A-related
Review for gene: PHF5A was set to GREEN
Added comment: Nine subjects with congenital malformations, including hypospadias, growth abnormalities, and developmental delay who had de novo PHF5A variants. Prenatally, six subjects had intrauterine growth retardation. All subjects had motor and speech delay and developmental delay. Congenital abnormalities comprised hypospadias in three of four male subjects, and heart defects (3/9), inguinal hernia (3/9), and sacral dimple (3/9). Six of the nine subjects had short stature. Craniofacial dysmorphism is variable in the nine subjects, high forehead and preauricular skin tag(s) in five subjects.
Sources: Expert list
Mendeliome v1.1071 TBC1D31 Lilian Downie gene: TBC1D31 was added
gene: TBC1D31 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TBC1D31 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TBC1D31 were set to PMID: 37468454
Phenotypes for gene: TBC1D31 were set to congenital anomaly of kidney and urinary tract MONDO:0019719
Review for gene: TBC1D31 was set to RED
Added comment: Single paper with homozygous mutations in 3 sibs with CAKUT from consanguineous family
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5318 PHF5A Zornitza Stark Classified gene: PHF5A as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5318 PHF5A Zornitza Stark Gene: phf5a has been classified as Green List (High Evidence).
Mendeliome v1.1071 AQP4 Lucy Spencer gene: AQP4 was added
gene: AQP4 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: AQP4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AQP4 were set to 37143309
Phenotypes for gene: AQP4 were set to ?Megalencephalic leukoencephalopathy with subcortical cysts 4, remitting MIM#620448
Review for gene: AQP4 was set to AMBER
Added comment: PMID: 37143309
Cohort of patients with an MRI based diagnosis of megalencephalic leukoencephalopathy with subcortical cysts (MLC). Missense variant in AQP4 seen homozygous in 2 siblings and het in the parents. Patients had macrocephaly, developmental delay, hypotonia, epilepsy, and cognitive deficit.

Western blots on generated MDCK cell lines showed no detectable expression of AQP4 protein from the cells with the patients variant. Immunofluorescence also showed no membrane expression. Overexpression studies in HEK293T cells showed WT was seen as mainly monomers or dimers where as variant protein formed large aggregates- likely due to the saturation of protein degradation pathways because of the overexpression.
Sources: Literature
Fetal anomalies v1.135 PHF5A Zornitza Stark Marked gene: PHF5A as ready
Fetal anomalies v1.135 PHF5A Zornitza Stark Gene: phf5a has been classified as Green List (High Evidence).
Fetal anomalies v1.135 PHF5A Zornitza Stark Phenotypes for gene: PHF5A were changed from PMID: 37422718 to Neurodevelopmental disorder (MONDO#0700092), PHF5A-related
Mitochondrial disease v0.882 COX18 Elena Savva Classified gene: COX18 as Red List (low evidence)
Mitochondrial disease v0.882 COX18 Elena Savva Gene: cox18 has been classified as Red List (Low Evidence).
Mitochondrial disease v0.882 COX18 Elena Savva Classified gene: COX18 as Red List (low evidence)
Mitochondrial disease v0.882 COX18 Elena Savva Gene: cox18 has been classified as Red List (Low Evidence).
Fetal anomalies v1.134 PHF5A Zornitza Stark Publications for gene: PHF5A were set to
Congenital Heart Defect v0.290 CTNNB1 Zornitza Stark Classified gene: CTNNB1 as Green List (high evidence)
Early-onset Parkinson disease v0.241 PTPA Zornitza Stark Mode of inheritance for gene: PTPA was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5317 GPRC5B Ain Roesley Classified gene: GPRC5B as Green List (high evidence)
Congenital Heart Defect v0.290 CTNNB1 Zornitza Stark Gene: ctnnb1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5317 GPRC5B Ain Roesley Gene: gprc5b has been classified as Green List (High Evidence).
Congenital Heart Defect v0.290 CTNNB1 Zornitza Stark Marked gene: CTNNB1 as ready
Congenital Heart Defect v0.290 CTNNB1 Zornitza Stark Gene: ctnnb1 has been classified as Green List (High Evidence).
Mitochondrial disease v0.881 COX18 Elena Savva Classified gene: COX18 as Red List (low evidence)
Mitochondrial disease v0.881 COX18 Elena Savva Gene: cox18 has been classified as Red List (Low Evidence).
Congenital Heart Defect v0.290 CTNNB1 Zornitza Stark Marked gene: CTNNB1 as ready
Congenital Heart Defect v0.290 CTNNB1 Zornitza Stark Gene: ctnnb1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5317 AQP4 Lucy Spencer gene: AQP4 was added
gene: AQP4 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: AQP4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AQP4 were set to 37143309
Phenotypes for gene: AQP4 were set to ?Megalencephalic leukoencephalopathy with subcortical cysts 4, remitting MIM#620448
Review for gene: AQP4 was set to AMBER
Added comment: PMID: 37143309
Cohort patients with an MRI based diagnosis of megalencephalic leukoencephalopathy with subcortical cysts (MLC). Missense variant in AQP4 seen homozygous in 2 siblings and het in the parents. Patients had macrocephaly, developmental delay, hypotonia, epilepsy, and cognitive deficit.

Western blots on generated MDCK cell lines showed no detectable expression of AQP4 protein from the cells with the patients variant. Immunofluorescence also showed no membrane expression. Overexpression studies in HEK293T cells showed WT was seen as mainly monomers or dimers where as variant protein formed large aggregates- likely due to the saturation of protein degradation pathways because of the overexpression.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5317 PHF5A Daniel Flanagan gene: PHF5A was added
gene: PHF5A was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list
Mode of inheritance for gene: PHF5A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PHF5A were set to PMID: 37422718
Phenotypes for gene: PHF5A were set to Neurodevelopmental disorder (MONDO#0700092), PHF5A-related
Review for gene: PHF5A was set to GREEN
Added comment: Nine subjects with congenital malformations, including hypospadias, growth abnormalities, and developmental delay who had de novo PHF5A variants. Prenatally, six subjects had intrauterine growth retardation. All subjects had motor and speech delay and developmental delay. Congenital abnormalities comprised hypospadias in three of four male subjects, and heart defects (3/9), inguinal hernia (3/9), and sacral dimple (3/9). Six of the nine subjects had short stature. Craniofacial dysmorphism is variable in the nine subjects, high forehead and preauricular skin tag(s) in five subjects.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.5317 GPRC5B Ain Roesley Classified gene: GPRC5B as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5317 GPRC5B Ain Roesley Gene: gprc5b has been classified as Green List (High Evidence).
Congenital Heart Defect v0.290 CTNNB1 Zornitza Stark Classified gene: CTNNB1 as Green List (high evidence)
Congenital Heart Defect v0.290 CTNNB1 Zornitza Stark Gene: ctnnb1 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.241 PTPA Zornitza Stark Mode of inheritance for gene: PTPA was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mitochondrial disease v0.881 COX18 Elena Savva Classified gene: COX18 as Red List (low evidence)
Mitochondrial disease v0.881 COX18 Elena Savva Gene: cox18 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.5317 GPRC5B Ain Roesley Marked gene: GPRC5B as ready
Intellectual disability syndromic and non-syndromic v0.5317 GPRC5B Ain Roesley Gene: gprc5b has been classified as Green List (High Evidence).
Fetal anomalies v1.133 PHF5A Zornitza Stark Classified gene: PHF5A as Green List (high evidence)
Fetal anomalies v1.133 PHF5A Zornitza Stark Gene: phf5a has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5317 GPRC5B Ain Roesley Classified gene: GPRC5B as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5317 GPRC5B Ain Roesley Gene: gprc5b has been classified as Green List (High Evidence).
Congenital Heart Defect v0.290 CTNNB1 Zornitza Stark Classified gene: CTNNB1 as Green List (high evidence)
Congenital Heart Defect v0.290 CTNNB1 Zornitza Stark Gene: ctnnb1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1877 GPRC5B Ain Roesley Classified gene: GPRC5B as Green List (high evidence)
Genetic Epilepsy v0.1877 GPRC5B Ain Roesley Gene: gprc5b has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1877 GPRC5B Ain Roesley Marked gene: GPRC5B as ready
Genetic Epilepsy v0.1877 GPRC5B Ain Roesley Gene: gprc5b has been classified as Green List (High Evidence).
Mitochondrial disease v0.881 COX18 Elena Savva Classified gene: COX18 as Red List (low evidence)
Mitochondrial disease v0.881 COX18 Elena Savva Gene: cox18 has been classified as Red List (Low Evidence).
Mendeliome v1.1071 GPRC5B Lucy Spencer gene: GPRC5B was added
gene: GPRC5B was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GPRC5B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GPRC5B were set to 37143309
Phenotypes for gene: GPRC5B were set to Megalencephalic leukoencephalopathy with subcortical cysts 3 620447
Review for gene: GPRC5B was set to GREEN
Added comment: PMID: 37143309
Cohort of 5 patients with an MRI based diagnosis of megalencephalic leukoencephalopathy with subcortical cysts (MLC). 3 unrelated patients had variants in GPRC5B, 2 have the same inframe dup Ile175dup and the third has an in frame dup of Ala177. All 3 were de novo and unaffected siblings did not have the variants. All patients have macrocephaly, delayed motor development, seizures, all had varying degrees of cognitive deficits. 2 also had spasticity, ataxia and dystonia. MRI showed MLC, abnormal and swollen cerebral white matter.

Patient cell lines showed reduced regulatory volume decrease, and western blot showed a strong increase in GRPC5B levels in patient lymphoblasts. Together, these findings indicate disturbed volume regulation in lymphoblasts from patients with GPRC5B variants, potentially due to increased GPRC5B levels. Transfected cells caused increased volume-regulated anion channel activity.
Sources: Literature
Genetic Epilepsy v0.1877 GPRC5B Ain Roesley Classified gene: GPRC5B as Green List (high evidence)
Genetic Epilepsy v0.1877 GPRC5B Ain Roesley Gene: gprc5b has been classified as Green List (High Evidence).
Mendeliome v1.1071 MAMDC2 Elena Savva Marked gene: MAMDC2 as ready
Mendeliome v1.1071 MAMDC2 Elena Savva Gene: mamdc2 has been classified as Amber List (Moderate Evidence).
Mitochondrial disease v0.880 COX18 Elena Savva Marked gene: COX18 as ready
Mitochondrial disease v0.880 COX18 Elena Savva Gene: cox18 has been removed from the panel.
Congenital Heart Defect v0.289 CTNNB1 Zornitza Stark reviewed gene: CTNNB1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with spastic diplegia and visual defects MIM#615075; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.1071 MAMDC2 Elena Savva Classified gene: MAMDC2 as Amber List (moderate evidence)
Mendeliome v1.1071 MAMDC2 Elena Savva Gene: mamdc2 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.1876 AQP4 Lucy Spencer gene: AQP4 was added
gene: AQP4 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: AQP4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AQP4 were set to PMID: 37143309
Phenotypes for gene: AQP4 were set to ?Megalencephalic leukoencephalopathy with subcortical cysts 4, remitting MIM#620448
Review for gene: AQP4 was set to AMBER
Added comment: PMID: 37143309
Cohort of 5 patients with an MRI based diagnosis of megalencephalic leukoencephalopathy with subcortical cysts (MLC). Missense variant in AQP4 seen homozygous in 2 siblings and het in the parents. Patients had macrocephaly, developmental delay, hypotonia, epilepsy, and cognitive deficit.

Western blots on generated MDCK cell lines showed no detectable expression of AQP4 protein from the cells with the patients variant. Immunofluorescence also showed no membrane expression. Overexpression studies in HEK293T cells showed WT was seen as mainly monomers or dimers where as variant protein formed large aggregates- likely due to the saturation of protein degradation pathways because of the overexpression.
Sources: Literature
Mendeliome v1.1070 COX18 Elena Savva Marked gene: COX18 as ready
Mendeliome v1.1070 COX18 Elena Savva Gene: cox18 has been classified as Red List (Low Evidence).
Mendeliome v1.1070 COX18 Elena Savva Classified gene: COX18 as Red List (low evidence)
Mendeliome v1.1070 COX18 Elena Savva Gene: cox18 has been classified as Red List (Low Evidence).
Fetal anomalies v1.132 PHF5A Daniel Flanagan reviewed gene: PHF5A: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 37422718; Phenotypes: Neurodevelopmental disorder (MONDO#0700092), PHF5A-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Leukodystrophy - paediatric v0.294 GPRC5B Ain Roesley Marked gene: GPRC5B as ready
Leukodystrophy - paediatric v0.294 GPRC5B Ain Roesley Gene: gprc5b has been classified as Green List (High Evidence).
Leukodystrophy - paediatric v0.294 GPRC5B Ain Roesley Classified gene: GPRC5B as Green List (high evidence)
Leukodystrophy - paediatric v0.294 GPRC5B Ain Roesley Gene: gprc5b has been classified as Green List (High Evidence).
Mendeliome v1.1068 NAA30 Zornitza Stark Marked gene: NAA30 as ready
Mendeliome v1.1068 NAA30 Zornitza Stark Gene: naa30 has been classified as Red List (Low Evidence).
Mendeliome v1.1069 PTPA Zornitza Stark Publications for gene: PTPA were set to 36073231
Intellectual disability syndromic and non-syndromic v0.5316 EZH1 Dean Phelan reviewed gene: EZH1: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 37433783; Phenotypes: Neurodevelopmental disorder (MONDO:0700092), EZH1-related; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.1068 MAMDC2 Belinda Chong gene: MAMDC2 was added
gene: MAMDC2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MAMDC2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAMDC2 were set to 37503746
Phenotypes for gene: MAMDC2 were set to Muscular Dystrophy MONDO:0020121, MAMDC2-related
Review for gene: MAMDC2 was set to AMBER
Added comment: 17 individuals with an autosomal dominant muscular dystrophy belonging to two unrelated families in which different heterozygous truncating variants in the last exon of MAMDC2 co-segregate correctly with the disease.
Sources: Literature
Macrocephaly_Megalencephaly v0.127 GPRC5B Ain Roesley Classified gene: GPRC5B as Green List (high evidence)
Macrocephaly_Megalencephaly v0.127 GPRC5B Ain Roesley Gene: gprc5b has been classified as Green List (High Evidence).
Macrocephaly_Megalencephaly v0.126 GPRC5B Ain Roesley Marked gene: GPRC5B as ready
Macrocephaly_Megalencephaly v0.126 GPRC5B Ain Roesley Gene: gprc5b has been classified as Green List (High Evidence).
Mendeliome v1.1068 PTPA Zornitza Stark Mode of inheritance for gene: PTPA was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Macrocephaly_Megalencephaly v0.126 GPRC5B Ain Roesley Classified gene: GPRC5B as Green List (high evidence)
Macrocephaly_Megalencephaly v0.126 GPRC5B Ain Roesley Gene: gprc5b has been classified as Green List (High Evidence).
Leukodystrophy - paediatric v0.293 GPRC5B Lucy Spencer gene: GPRC5B was added
gene: GPRC5B was added to Leukodystrophy - paediatric. Sources: Literature
Mode of inheritance for gene: GPRC5B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GPRC5B were set to 37143309
Phenotypes for gene: GPRC5B were set to Megalencephalic leukoencephalopathy with subcortical cysts 3 MIM#620447
Review for gene: GPRC5B was set to GREEN
Added comment: PMID: 37143309
Cohort of 5 patients with an MRI based diagnosis of megalencephalic leukoencephalopathy with subcortical cysts (MLC). 3 unrelated patients had variants in GPRC5B, 2 have the same inframe dup Ile175dup and the third has an in frame dup of Ala177. All 3 were de novo and unaffected siblings did not have the variants. All patients have macrocephaly, delayed motor development, seizures, all had varying degrees of cognitive deficits. 2 also had spasticity, ataxia and dystonia. MRI showed MLC, abnormal and swollen cerebral white matter.

Patient cell lines showed reduced regulatory volume decrease, and western blot showed a strong increase in GRPC5B levels in patient lymphoblasts. Together, these findings indicate disturbed volume regulation in lymphoblasts from patients with GPRC5B variants, potentially due to increased GPRC5B levels. Transfected cells caused increased volume-regulated anion channel activity.
Sources: Literature
Macrocephaly_Megalencephaly v0.126 GPRC5B Ain Roesley Classified gene: GPRC5B as Green List (high evidence)
Macrocephaly_Megalencephaly v0.126 GPRC5B Ain Roesley Gene: gprc5b has been classified as Green List (High Evidence).
Mendeliome v1.1067 NAA30 Zornitza Stark Phenotypes for gene: NAA30 were changed from to neurodevelopmental disorder, MONDO:0700092, NAA30-related