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Mendeliome v0.5422 CDKAL1 Naomi Baker reviewed gene: CDKAL1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Skeletal Dysplasia_Fetal v0.40 CRTAP Zornitza Stark Marked gene: CRTAP as ready
Skeletal Dysplasia_Fetal v0.40 CRTAP Zornitza Stark Gene: crtap has been classified as Green List (High Evidence).
Skeletal Dysplasia_Fetal v0.40 CRTAP Zornitza Stark Phenotypes for gene: CRTAP were changed from to Osteogenesis imperfecta, type VII MIM#610682
Skeletal Dysplasia_Fetal v0.39 CRTAP Zornitza Stark Publications for gene: CRTAP were set to
Mendeliome v0.5422 SMARCA1 Naomi Baker reviewed gene: SMARCA1: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 26740508, 26539891, 29249292.; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Skeletal Dysplasia_Fetal v0.38 CRTAP Zornitza Stark Mode of inheritance for gene: CRTAP was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Skeletal Dysplasia_Fetal v0.37 CRTAP Zornitza Stark reviewed gene: CRTAP: Rating: GREEN; Mode of pathogenicity: None; Publications: 21955071, 19846465, 17192541; Phenotypes: Osteogenesis imperfecta, type VII MIM#610682; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Osteogenesis Imperfecta and Osteoporosis v0.51 CRTAP Zornitza Stark Marked gene: CRTAP as ready
Osteogenesis Imperfecta and Osteoporosis v0.51 CRTAP Zornitza Stark Gene: crtap has been classified as Green List (High Evidence).
Osteogenesis Imperfecta and Osteoporosis v0.51 CRTAP Zornitza Stark Phenotypes for gene: CRTAP were changed from to Osteogenesis imperfecta, type VII MIM#610682
Osteogenesis Imperfecta and Osteoporosis v0.50 CRTAP Zornitza Stark Publications for gene: CRTAP were set to
Osteogenesis Imperfecta and Osteoporosis v0.49 CRTAP Zornitza Stark Mode of inheritance for gene: CRTAP was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5422 CRTAP Zornitza Stark Marked gene: CRTAP as ready
Mendeliome v0.5422 CRTAP Zornitza Stark Gene: crtap has been classified as Green List (High Evidence).
Mendeliome v0.5422 CRTAP Zornitza Stark Phenotypes for gene: CRTAP were changed from to Osteogenesis imperfecta, type VII MIM#610682
Mendeliome v0.5421 CRTAP Zornitza Stark Publications for gene: CRTAP were set to
Mendeliome v0.5420 CRTAP Zornitza Stark Mode of inheritance for gene: CRTAP was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3208 USP9X Zornitza Stark Marked gene: USP9X as ready
Intellectual disability syndromic and non-syndromic v0.3208 USP9X Zornitza Stark Gene: usp9x has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3208 USP9X Zornitza Stark Phenotypes for gene: USP9X were changed from to Mental retardation, X-linked 99, XLR (MIM#300919) and XLD (MIM#300968)
Intellectual disability syndromic and non-syndromic v0.3207 USP9X Zornitza Stark Publications for gene: USP9X were set to
Intellectual disability syndromic and non-syndromic v0.3206 USP9X Zornitza Stark Mode of inheritance for gene: USP9X 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)
Mendeliome v0.5419 USP9X Zornitza Stark Marked gene: USP9X as ready
Mendeliome v0.5419 USP9X Zornitza Stark Gene: usp9x has been classified as Green List (High Evidence).
Mendeliome v0.5419 USP9X Zornitza Stark Phenotypes for gene: USP9X were changed from to Mental retardation, X-linked 99, XLR (MIM#300919) and XLD (MIM#300968)
Mendeliome v0.5418 USP9X Zornitza Stark Publications for gene: USP9X were set to
Mendeliome v0.5417 USP9X Zornitza Stark Mode of inheritance for gene: USP9X 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)
Regression v0.210 ALG6 Zornitza Stark Marked gene: ALG6 as ready
Regression v0.210 ALG6 Zornitza Stark Gene: alg6 has been classified as Red List (Low Evidence).
Regression v0.210 ALG6 Zornitza Stark Phenotypes for gene: ALG6 were changed from to Congenital disorder of glycosylation, type Ic (MIM#603147)
Regression v0.209 ALG6 Zornitza Stark Publications for gene: ALG6 were set to
Regression v0.208 ALG6 Zornitza Stark Mode of inheritance for gene: ALG6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Regression v0.207 ALG6 Zornitza Stark Classified gene: ALG6 as Red List (low evidence)
Regression v0.207 ALG6 Zornitza Stark Gene: alg6 has been classified as Red List (Low Evidence).
Regression v0.206 ALG6 Zornitza Stark reviewed gene: ALG6: Rating: RED; Mode of pathogenicity: None; Publications: 10914684, 27498540; Phenotypes: Congenital disorder of glycosylation, type Ic (MIM#603147); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Callosome v0.227 ALG6 Zornitza Stark Marked gene: ALG6 as ready
Callosome v0.227 ALG6 Zornitza Stark Gene: alg6 has been classified as Red List (Low Evidence).
Callosome v0.227 ALG6 Zornitza Stark Phenotypes for gene: ALG6 were changed from to Congenital disorder of glycosylation, type Ic (MIM#603147)
Callosome v0.226 ALG6 Zornitza Stark Publications for gene: ALG6 were set to
Callosome v0.225 ALG6 Zornitza Stark Mode of inheritance for gene: ALG6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Callosome v0.224 ALG6 Zornitza Stark Classified gene: ALG6 as Red List (low evidence)
Callosome v0.224 ALG6 Zornitza Stark Gene: alg6 has been classified as Red List (Low Evidence).
Callosome v0.223 ALG6 Zornitza Stark reviewed gene: ALG6: Rating: RED; Mode of pathogenicity: None; Publications: 10914684, 27498540; Phenotypes: Congenital disorder of glycosylation, type Ic (MIM#603147); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Autism v0.120 ALG6 Zornitza Stark Marked gene: ALG6 as ready
Autism v0.120 ALG6 Zornitza Stark Gene: alg6 has been classified as Green List (High Evidence).
Autism v0.120 ALG6 Zornitza Stark Phenotypes for gene: ALG6 were changed from to Congenital disorder of glycosylation, type Ic (MIM#603147)
Autism v0.119 ALG6 Zornitza Stark Publications for gene: ALG6 were set to
Autism v0.118 ALG6 Zornitza Stark Mode of inheritance for gene: ALG6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Autism v0.117 ALG6 Zornitza Stark reviewed gene: ALG6: Rating: GREEN; Mode of pathogenicity: None; Publications: 10914684, 27498540; Phenotypes: Congenital disorder of glycosylation, type Ic (MIM#603147); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3205 ALG6 Zornitza Stark Marked gene: ALG6 as ready
Intellectual disability syndromic and non-syndromic v0.3205 ALG6 Zornitza Stark Gene: alg6 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3205 ALG6 Zornitza Stark Phenotypes for gene: ALG6 were changed from to Congenital disorder of glycosylation, type Ic (MIM#603147)
Intellectual disability syndromic and non-syndromic v0.3204 ALG6 Zornitza Stark Publications for gene: ALG6 were set to
Intellectual disability syndromic and non-syndromic v0.3203 ALG6 Zornitza Stark Mode of inheritance for gene: ALG6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3202 ALG6 Zornitza Stark reviewed gene: ALG6: Rating: GREEN; Mode of pathogenicity: None; Publications: 10914684, 27498540; Phenotypes: Congenital disorder of glycosylation, type Ic (MIM#603147); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.915 ALG6 Zornitza Stark Marked gene: ALG6 as ready
Genetic Epilepsy v0.915 ALG6 Zornitza Stark Gene: alg6 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.915 ALG6 Zornitza Stark Phenotypes for gene: ALG6 were changed from to Congenital disorder of glycosylation, type Ic (MIM#603147)
Genetic Epilepsy v0.914 ALG6 Zornitza Stark Publications for gene: ALG6 were set to
Genetic Epilepsy v0.913 ALG6 Zornitza Stark Mode of inheritance for gene: ALG6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.912 ALG6 Zornitza Stark reviewed gene: ALG6: Rating: GREEN; Mode of pathogenicity: None; Publications: 10914684, 27498540; Phenotypes: Congenital disorder of glycosylation, type Ic (MIM#603147); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5416 ALG6 Zornitza Stark Marked gene: ALG6 as ready
Mendeliome v0.5416 ALG6 Zornitza Stark Gene: alg6 has been classified as Green List (High Evidence).
Mendeliome v0.5416 ALG6 Zornitza Stark Phenotypes for gene: ALG6 were changed from to Congenital disorder of glycosylation, type Ic (MIM#603147)
Mendeliome v0.5415 ALG6 Zornitza Stark Publications for gene: ALG6 were set to
Mendeliome v0.5414 ALG6 Zornitza Stark Mode of inheritance for gene: ALG6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5413 ALG6 Zornitza Stark reviewed gene: ALG6: Rating: GREEN; Mode of pathogenicity: None; Publications: 10914684, 27498540; Phenotypes: Congenital disorder of glycosylation, type Ic (MIM#603147); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Disorders of Glycosylation v0.192 ALG6 Zornitza Stark Marked gene: ALG6 as ready
Congenital Disorders of Glycosylation v0.192 ALG6 Zornitza Stark Gene: alg6 has been classified as Green List (High Evidence).
Congenital Disorders of Glycosylation v0.192 ALG6 Zornitza Stark Phenotypes for gene: ALG6 were changed from to Congenital disorder of glycosylation, type Ic (MIM#603147)
Congenital Disorders of Glycosylation v0.191 ALG6 Zornitza Stark Publications for gene: ALG6 were set to
Congenital Disorders of Glycosylation v0.190 ALG6 Zornitza Stark reviewed gene: ALG6: Rating: GREEN; Mode of pathogenicity: None; Publications: 27498540; Phenotypes: Congenital disorder of glycosylation, type Ic (MIM#603147); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Disorders of Glycosylation v0.190 ALG6 Zornitza Stark Mode of inheritance for gene: ALG6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Dystonia and Chorea v0.155 MOGS Zornitza Stark Marked gene: MOGS as ready
Dystonia and Chorea v0.155 MOGS Zornitza Stark Gene: mogs has been classified as Red List (Low Evidence).
Dystonia and Chorea v0.155 MOGS Zornitza Stark gene: MOGS was added
gene: MOGS was added to Dystonia - complex. Sources: Expert Review
Mode of inheritance for gene: MOGS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MOGS were set to 33058492
Phenotypes for gene: MOGS were set to Congenital disorder of glycosylation, type IIb, MIM# 606056
Review for gene: MOGS was set to RED
Added comment: 7 individuals from 6 unrelated families reported with CDGIIb. Of these, one had prominent dystonia, with forced posture of the head and of both hands, as well as a hyperkinetic movement disorder.
Sources: Expert Review
Mackenzie's Mission_Reproductive Carrier Screening v0.49 MOGS Zornitza Stark gene: MOGS was added
gene: MOGS was added to Mackenzie's Mission_Reproductive Carrier Screening. Sources: Expert Review
Mode of inheritance for gene: MOGS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MOGS were set to 31925597; 30587846; 33058492
Phenotypes for gene: MOGS were set to Congenital disorder of glycosylation, type IIb, MIM# 606056
Review for gene: MOGS was set to GREEN
Added comment: Six unrelated families reported. Common features include: hypotonia, global developmental delay, feeding problems, seizures, movement disorder, hypogammaglobulinaemia, variable problems with cardiac, dysmorpholology overlapping fingers, short palpebral fissures, micrognathia, can have upsweeping hair at front.
Sources: Expert Review
Intellectual disability syndromic and non-syndromic v0.3202 MOGS Zornitza Stark Marked gene: MOGS as ready
Intellectual disability syndromic and non-syndromic v0.3202 MOGS Zornitza Stark Gene: mogs has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3202 MOGS Zornitza Stark Phenotypes for gene: MOGS were changed from to Congenital disorder of glycosylation, type IIb, MIM# 606056
Intellectual disability syndromic and non-syndromic v0.3201 MOGS Zornitza Stark Publications for gene: MOGS were set to
Intellectual disability syndromic and non-syndromic v0.3200 MOGS Zornitza Stark Mode of inheritance for gene: MOGS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3199 MOGS Zornitza Stark reviewed gene: MOGS: Rating: GREEN; Mode of pathogenicity: None; Publications: 31925597, 30587846, 33058492; Phenotypes: Congenital disorder of glycosylation, type IIb, MIM# 606056; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Predominantly Antibody Deficiency v0.61 MOGS Zornitza Stark Marked gene: MOGS as ready
Predominantly Antibody Deficiency v0.61 MOGS Zornitza Stark Gene: mogs has been classified as Green List (High Evidence).
Predominantly Antibody Deficiency v0.61 MOGS Zornitza Stark Phenotypes for gene: MOGS were changed from to Congenital disorder of glycosylation, type IIb, MIM# 606056
Predominantly Antibody Deficiency v0.60 MOGS Zornitza Stark Publications for gene: MOGS were set to
Predominantly Antibody Deficiency v0.59 MOGS Zornitza Stark Mode of inheritance for gene: MOGS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Predominantly Antibody Deficiency v0.58 MOGS Zornitza Stark reviewed gene: MOGS: Rating: GREEN; Mode of pathogenicity: None; Publications: 31925597, 30587846, 33058492; Phenotypes: Congenital disorder of glycosylation, type IIb, MIM# 606056; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.912 MOGS Zornitza Stark Marked gene: MOGS as ready
Genetic Epilepsy v0.912 MOGS Zornitza Stark Gene: mogs has been classified as Green List (High Evidence).
Genetic Epilepsy v0.912 MOGS Zornitza Stark Phenotypes for gene: MOGS were changed from to Congenital disorder of glycosylation, type IIb, MIM# 606056
Genetic Epilepsy v0.911 MOGS Zornitza Stark Publications for gene: MOGS were set to
Genetic Epilepsy v0.910 MOGS Zornitza Stark Mode of inheritance for gene: MOGS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.909 MOGS Zornitza Stark reviewed gene: MOGS: Rating: GREEN; Mode of pathogenicity: None; Publications: 31925597, 30587846, 33058492; Phenotypes: Congenital disorder of glycosylation, type IIb, MIM# 606056; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5413 MOGS Zornitza Stark Publications for gene: MOGS were set to 31925597
Mendeliome v0.5412 MOGS Zornitza Stark reviewed gene: MOGS: Rating: GREEN; Mode of pathogenicity: None; Publications: 31925597, 30587846, 33058492; Phenotypes: Congenital disorder of glycosylation, type IIb, MIM# 606056; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Disorders of Glycosylation v0.189 MOGS Zornitza Stark Publications for gene: MOGS were set to 31925597; 30587846
Congenital Disorders of Glycosylation v0.188 MOGS Zornitza Stark edited their review of gene: MOGS: Added comment: Six unrelated families reported.; Changed publications: 31925597, 33058492
Congenital Disorders of Glycosylation v0.188 MOGS Zornitza Stark Publications for gene: MOGS were set to 31925597
Congenital Disorders of Glycosylation v0.187 NGLY1 Zornitza Stark Phenotypes for gene: NGLY1 were changed from Congenital disorder of deglycosylation, MIM# 615273 to Congenital disorder of deglycosylation, MIM# 615273; alacrima, movement disorder, microcephaly, abnormal LFTs
Congenital Disorders of Glycosylation v0.186 NGLY1 Zornitza Stark Publications for gene: NGLY1 were set to 24651605; 27388694; 32259258
Additional findings_Paediatric v0.160 GATA3 Zornitza Stark Marked gene: GATA3 as ready
Additional findings_Paediatric v0.160 GATA3 Zornitza Stark Gene: gata3 has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.160 GATA3 Zornitza Stark Classified gene: GATA3 as Green List (high evidence)
Additional findings_Paediatric v0.160 GATA3 Zornitza Stark Gene: gata3 has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.159 FOXI1 Zornitza Stark Marked gene: FOXI1 as ready
Additional findings_Paediatric v0.159 FOXI1 Zornitza Stark Gene: foxi1 has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.159 FOXI1 Zornitza Stark Classified gene: FOXI1 as Green List (high evidence)
Additional findings_Paediatric v0.159 FOXI1 Zornitza Stark Gene: foxi1 has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.158 EPS8L2 Zornitza Stark Marked gene: EPS8L2 as ready
Additional findings_Paediatric v0.158 EPS8L2 Zornitza Stark Gene: eps8l2 has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.158 EPS8L2 Zornitza Stark Classified gene: EPS8L2 as Green List (high evidence)
Additional findings_Paediatric v0.158 EPS8L2 Zornitza Stark Gene: eps8l2 has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.157 EPS8 Zornitza Stark Marked gene: EPS8 as ready
Additional findings_Paediatric v0.157 EPS8 Zornitza Stark Gene: eps8 has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.157 EPS8 Zornitza Stark Classified gene: EPS8 as Green List (high evidence)
Additional findings_Paediatric v0.157 EPS8 Zornitza Stark Gene: eps8 has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.156 EDNRB Zornitza Stark Marked gene: EDNRB as ready
Additional findings_Paediatric v0.156 EDNRB Zornitza Stark Gene: ednrb has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.156 EDNRB Zornitza Stark Phenotypes for gene: EDNRB were changed from Hirschsprung disease; Waardenburg syndrome to Waardenburg syndrome, type 4A, MIM# 277580
Additional findings_Paediatric v0.155 EDNRB Zornitza Stark Mode of inheritance for gene: EDNRB was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Additional findings_Paediatric v0.154 EDNRB Zornitza Stark Classified gene: EDNRB as Green List (high evidence)
Additional findings_Paediatric v0.154 EDNRB Zornitza Stark Gene: ednrb has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.153 COL9A2 Zornitza Stark Marked gene: COL9A2 as ready
Additional findings_Paediatric v0.153 COL9A2 Zornitza Stark Gene: col9a2 has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.153 COL9A2 Zornitza Stark Phenotypes for gene: COL9A2 were changed from Stickler syndrome to Stickler syndrome, type V, MIM# 614284
Additional findings_Paediatric v0.152 COL9A2 Zornitza Stark Classified gene: COL9A2 as Green List (high evidence)
Additional findings_Paediatric v0.152 COL9A2 Zornitza Stark Gene: col9a2 has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.151 COL9A1 Zornitza Stark Marked gene: COL9A1 as ready
Additional findings_Paediatric v0.151 COL9A1 Zornitza Stark Gene: col9a1 has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.151 COL9A1 Zornitza Stark Phenotypes for gene: COL9A1 were changed from Stickler syndrome to Stickler syndrome, type IV, MIM#614134
Additional findings_Paediatric v0.150 COL9A1 Zornitza Stark Classified gene: COL9A1 as Green List (high evidence)
Additional findings_Paediatric v0.150 COL9A1 Zornitza Stark Gene: col9a1 has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.149 EDN3 Zornitza Stark Marked gene: EDN3 as ready
Additional findings_Paediatric v0.149 EDN3 Zornitza Stark Gene: edn3 has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.149 EDN3 Zornitza Stark Phenotypes for gene: EDN3 were changed from Hirschsprung disease; Waardenburg syndrome to Waardenburg syndrome
Additional findings_Paediatric v0.148 EDN3 Zornitza Stark Mode of inheritance for gene: EDN3 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BIALLELIC, autosomal or pseudoautosomal
Additional findings_Paediatric v0.147 EDN3 Zornitza Stark Classified gene: EDN3 as Green List (high evidence)
Additional findings_Paediatric v0.147 EDN3 Zornitza Stark Gene: edn3 has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.146 DIAPH1 Zornitza Stark Marked gene: DIAPH1 as ready
Additional findings_Paediatric v0.146 DIAPH1 Zornitza Stark Gene: diaph1 has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.146 DIAPH1 Zornitza Stark Phenotypes for gene: DIAPH1 were changed from Hearing loss to Deafness, autosomal dominant 1, with or without thrombocytopenia MIM#124900
Additional findings_Paediatric v0.145 DIAPH1 Zornitza Stark Classified gene: DIAPH1 as Green List (high evidence)
Additional findings_Paediatric v0.145 DIAPH1 Zornitza Stark Gene: diaph1 has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.144 CCDC50 Zornitza Stark Marked gene: CCDC50 as ready
Additional findings_Paediatric v0.144 CCDC50 Zornitza Stark Gene: ccdc50 has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.144 CCDC50 Zornitza Stark Phenotypes for gene: CCDC50 were changed from Hearing loss to childhood onset deafness, progressive
Additional findings_Paediatric v0.143 CCDC50 Zornitza Stark Mode of inheritance for gene: CCDC50 was changed from BIALLELIC, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Additional findings_Paediatric v0.142 CCDC50 Zornitza Stark Classified gene: CCDC50 as Green List (high evidence)
Additional findings_Paediatric v0.142 CCDC50 Zornitza Stark Gene: ccdc50 has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.141 DMXL2 Zornitza Stark Marked gene: DMXL2 as ready
Additional findings_Paediatric v0.141 DMXL2 Zornitza Stark Gene: dmxl2 has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.141 DMXL2 Zornitza Stark Classified gene: DMXL2 as Green List (high evidence)
Additional findings_Paediatric v0.141 DMXL2 Zornitza Stark Gene: dmxl2 has been classified as Green List (High Evidence).
Mendeliome v0.5412 RORB Zornitza Stark Marked gene: RORB as ready
Mendeliome v0.5412 RORB Zornitza Stark Gene: rorb has been classified as Green List (High Evidence).
Mendeliome v0.5412 RORB Zornitza Stark Phenotypes for gene: RORB were changed from to {Epilepsy, idiopathic generalized, susceptibility to, 15} (MIM#618357), AD; Genetic generalized epilepsy (GGE); Photosensitive generalized and occipital epilepsy
Mendeliome v0.5411 RORB Zornitza Stark Publications for gene: RORB were set to
Mendeliome v0.5410 RORB Zornitza Stark Mode of inheritance for gene: RORB was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5409 RORB Zornitza Stark reviewed gene: RORB: Rating: GREEN; Mode of pathogenicity: None; Publications: 27352968, 32162308; Phenotypes: {Epilepsy, idiopathic generalized, susceptibility to, 15} (MIM#618357), AD, Genetic generalized epilepsy (GGE), Photosensitive generalized and occipital epilepsy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.909 RORB Zornitza Stark Marked gene: RORB as ready
Genetic Epilepsy v0.909 RORB Zornitza Stark Gene: rorb has been classified as Green List (High Evidence).
Genetic Epilepsy v0.909 RORB Zornitza Stark Phenotypes for gene: RORB were changed from to {Epilepsy, idiopathic generalized, susceptibility to, 15} (MIM#618357), AD; Genetic generalized epilepsy (GGE); Photosensitive generalized and occipital epilepsy
Genetic Epilepsy v0.908 RORB Zornitza Stark Publications for gene: RORB were set to
Genetic Epilepsy v0.907 RORB Zornitza Stark Mode of inheritance for gene: RORB was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5409 MYL9 Zornitza Stark Marked gene: MYL9 as ready
Mendeliome v0.5409 MYL9 Zornitza Stark Gene: myl9 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5409 MYL9 Zornitza Stark Classified gene: MYL9 as Amber List (moderate evidence)
Mendeliome v0.5409 MYL9 Zornitza Stark Gene: myl9 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5408 MYL9 Zornitza Stark gene: MYL9 was added
gene: MYL9 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MYL9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MYL9 were set to 29453416; 33031641
Phenotypes for gene: MYL9 were set to Megacystis-microcolon-intestinal hypoperistalsis syndrome
Review for gene: MYL9 was set to AMBER
Added comment: Two unrelated families reported.
Sources: Literature
Gastrointestinal neuromuscular disease v0.32 MYL9 Zornitza Stark Publications for gene: MYL9 were set to 29453416
Gastrointestinal neuromuscular disease v0.31 MYL9 Zornitza Stark Classified gene: MYL9 as Amber List (moderate evidence)
Gastrointestinal neuromuscular disease v0.31 MYL9 Zornitza Stark Gene: myl9 has been classified as Amber List (Moderate Evidence).
Gastrointestinal neuromuscular disease v0.30 MYL9 Zornitza Stark reviewed gene: MYL9: Rating: AMBER; Mode of pathogenicity: None; Publications: 33031641; Phenotypes: Megacystis-microcolon-intestinal hypoperistalsis syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Gastrointestinal neuromuscular disease v0.30 MYLK Zornitza Stark Marked gene: MYLK as ready
Gastrointestinal neuromuscular disease v0.30 MYLK Zornitza Stark Gene: mylk has been classified as Amber List (Moderate Evidence).
Gastrointestinal neuromuscular disease v0.30 MYLK Zornitza Stark Publications for gene: MYLK were set to
Gastrointestinal neuromuscular disease v0.29 MYLK Zornitza Stark Classified gene: MYLK as Amber List (moderate evidence)
Gastrointestinal neuromuscular disease v0.29 MYLK Zornitza Stark Gene: mylk has been classified as Amber List (Moderate Evidence).
Osteogenesis Imperfecta and Osteoporosis v0.48 CRTAP Paul De Fazio reviewed gene: CRTAP: Rating: GREEN; Mode of pathogenicity: None; Publications: 21955071, 19846465, 17192541; Phenotypes: Osteogenesis imperfecta, type VII MIM#610682; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.5407 CRTAP Paul De Fazio reviewed gene: CRTAP: Rating: GREEN; Mode of pathogenicity: None; Publications: 21955071, 19846465, 17192541; Phenotypes: Osteogenesis imperfecta, type VII MIM#610682; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.3199 USP9X Paul De Fazio reviewed gene: USP9X: Rating: GREEN; Mode of pathogenicity: None; Publications: 31443933, 26833328; Phenotypes: Mental retardation, X-linked 99, XLR (MIM#300919) and XLD (MIM#300968); Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males); Current diagnostic: yes
Mendeliome v0.5407 USP9X Paul De Fazio reviewed gene: USP9X: Rating: GREEN; Mode of pathogenicity: None; Publications: 31443933, 26833328; Phenotypes: Mental retardation, X-linked 99, XLR (MIM#300919) and XLD (MIM#300968); Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males); Current diagnostic: yes
Congenital Disorders of Glycosylation v0.185 ALG6 Melanie Marty reviewed gene: ALG6: Rating: GREEN; Mode of pathogenicity: None; Publications: 10914684; Phenotypes: Congenital disorder of glycosylation, type Ic (MIM#603147); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Disorders of Glycosylation v0.185 MOGS Sarah Donoghue reviewed gene: MOGS: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 30587846, PMID: 31925597,; Phenotypes: hypotonia, global developmental delay, feeding problems, seizures, hypogammaglobulinaemia, variable problems with cardiac, dysmorpholology overlapping fingers, short palpebral fissures, micrognathia, can have upsweeping hair at front. MRI may be normal, but can have generalised atrophy. Transferrin isoforms may be normal - look at urine Gl4 (tetrasaccharide) increased in cases; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Congenital Disorders of Glycosylation v0.185 NGLY1 Sarah Donoghue reviewed gene: NGLY1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 29550355; Phenotypes: alacrima, movement disorder, microcephaly, abnormal LFT's; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Additional findings_Paediatric v0.140 GATA3 Lilian Downie gene: GATA3 was added
gene: GATA3 was added to Additional findings_Paediatric. Sources: Expert list
Mode of inheritance for gene: GATA3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: GATA3 were set to Hypoparathyroidism, sensorineural deafness, and renal dysplasia, MIM# 146255
Review for gene: GATA3 was set to GREEN
Added comment: Sources: Expert list
Additional findings_Paediatric v0.140 FOXI1 Lilian Downie gene: FOXI1 was added
gene: FOXI1 was added to Additional findings_Paediatric. Sources: Expert list
Mode of inheritance for gene: FOXI1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: FOXI1 were set to sensorineural deafness and distal renal tubular acidosis
Review for gene: FOXI1 was set to GREEN
Added comment: Sources: Expert list
Additional findings_Paediatric v0.140 EPS8L2 Lilian Downie gene: EPS8L2 was added
gene: EPS8L2 was added to Additional findings_Paediatric. Sources: Expert list
Mode of inheritance for gene: EPS8L2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: EPS8L2 were set to Deafness, MIM#617637
Review for gene: EPS8L2 was set to GREEN
Added comment: Sources: Expert list
Additional findings_Paediatric v0.140 EPS8 Lilian Downie gene: EPS8 was added
gene: EPS8 was added to Additional findings_Paediatric. Sources: Expert list
Mode of inheritance for gene: EPS8 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: EPS8 were set to deafness MIM#600205
Review for gene: EPS8 was set to GREEN
Added comment: Sources: Expert list
Additional findings_Paediatric v0.140 EDNRB Lilian Downie reviewed gene: EDNRB: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Waardenburg syndrome, type 4A, MIM# 277580; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Additional findings_Paediatric v0.140 COL9A2 Lilian Downie reviewed gene: COL9A2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Stickler syndrome, type V, MIM# 614284; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Additional findings_Paediatric v0.140 COL9A1 Lilian Downie reviewed gene: COL9A1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Stickler syndrome, type IV, MIM#614134; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Additional findings_Paediatric v0.140 EDN3 Lilian Downie reviewed gene: EDN3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Waardenburg syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Additional findings_Paediatric v0.140 DIAPH1 Lilian Downie reviewed gene: DIAPH1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Deafness, autosomal dominant 1, with or without thrombocytopenia MIM#124900; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Additional findings_Paediatric v0.140 CCDC50 Lilian Downie reviewed gene: CCDC50: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: childhood onset deafness, progressive; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Additional findings_Paediatric v0.140 DMXL2 Lilian Downie gene: DMXL2 was added
gene: DMXL2 was added to Additional findings_Paediatric. Sources: Expert list
Mode of inheritance for gene: DMXL2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: DMXL2 were set to Developmental and epileptic encephalopathy 81, MIM#618663
Review for gene: DMXL2 was set to GREEN
Added comment: EE and deafness
Sources: Expert list
Genetic Epilepsy v0.906 RORB Kristin Rigbye reviewed gene: RORB: Rating: GREEN; Mode of pathogenicity: None; Publications: 27352968, 32162308; Phenotypes: {Epilepsy, idiopathic generalized, susceptibility to, 15} (MIM#618357), AD, Genetic generalized epilepsy (GGE), Photosensitive generalized and occipital epilepsy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Gastrointestinal neuromuscular disease v0.28 MYLK Ain Roesley reviewed gene: MYLK: Rating: AMBER; Mode of pathogenicity: None; Publications: 28602422; Phenotypes: Megacystis-microcolon-intestinal hypoperistalsis syndrome, 249210; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5407 M1AP Zornitza Stark Phenotypes for gene: M1AP were changed from non-obstructive azoospermia (NOA); severe spermatogenic failure; male infertility to Spermatogenic failure 48, MIM# 619108; non-obstructive azoospermia (NOA); severe spermatogenic failure; male infertility
Mendeliome v0.5406 M1AP Zornitza Stark reviewed gene: M1AP: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Spermatogenic failure 48, MIM# 619108; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Neuropathy v0.92 NEMF Zornitza Stark Phenotypes for gene: NEMF were changed from Intellectual disability; neuropathy to Intellectual developmental disorder with speech delay and axonal peripheral neuropathy, MIM# 619099; Intellectual disability; neuropathy
Hereditary Neuropathy v0.91 NEMF Zornitza Stark edited their review of gene: NEMF: Changed phenotypes: Intellectual developmental disorder with speech delay and axonal peripheral neuropathy, MIM# 619099, Intellectual disability, neuropathy
Intellectual disability syndromic and non-syndromic v0.3199 NEMF Zornitza Stark Phenotypes for gene: NEMF were changed from Intellectual disability; neuropathy to Intellectual developmental disorder with speech delay and axonal peripheral neuropathy, MIM# 619099; Intellectual disability; neuropathy
Intellectual disability syndromic and non-syndromic v0.3198 NEMF Zornitza Stark edited their review of gene: NEMF: Changed phenotypes: Intellectual developmental disorder with speech delay and axonal peripheral neuropathy, MIM# 619099, Intellectual disability, neuropathy
Mendeliome v0.5406 NEMF Zornitza Stark Phenotypes for gene: NEMF were changed from Intellectual disability; neuropathy to Intellectual developmental disorder with speech delay and axonal peripheral neuropathy, MIM# 619099; Intellectual disability; neuropathy
Mendeliome v0.5405 NEMF Zornitza Stark edited their review of gene: NEMF: Changed phenotypes: Intellectual developmental disorder with speech delay and axonal peripheral neuropathy, MIM# 619099, Intellectual disability, neuropathy
Mendeliome v0.5405 PHYKPL Zornitza Stark Marked gene: PHYKPL as ready
Mendeliome v0.5405 PHYKPL Zornitza Stark Gene: phykpl has been classified as Red List (Low Evidence).
Mendeliome v0.5405 PHYKPL Zornitza Stark Phenotypes for gene: PHYKPL were changed from to [?Phosphohydroxylysinuria] 615011
Mendeliome v0.5404 PHYKPL Zornitza Stark Publications for gene: PHYKPL were set to
Mendeliome v0.5403 PHYKPL Zornitza Stark Mode of inheritance for gene: PHYKPL was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5402 PHYKPL Zornitza Stark Classified gene: PHYKPL as Red List (low evidence)
Mendeliome v0.5402 PHYKPL Zornitza Stark Gene: phykpl has been classified as Red List (Low Evidence).
Mackenzie's Mission_Reproductive Carrier Screening v0.48 EDA Sarah Righetti reviewed gene: EDA: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Ectodermal dysplasia 1, hypohidrotic, X-linked MIM#305100; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.5401 MTCL1 Bryony Thompson Classified gene: MTCL1 as Green List (high evidence)
Mendeliome v0.5401 MTCL1 Bryony Thompson Gene: mtcl1 has been classified as Green List (High Evidence).
Mendeliome v0.5400 MTCL1 Bryony Thompson edited their review of gene: MTCL1: Added comment: A new report of another case with a homozygous loss of function variant and a similar phenotype to the previously reported early onset homozygous Polish case (2 independent cases), and the supporting null mouse model.; Changed rating: GREEN; Changed publications: 30548255, 28283581, 32961396; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia v0.266 MTCL1 Bryony Thompson Classified gene: MTCL1 as Green List (high evidence)
Ataxia v0.266 MTCL1 Bryony Thompson Gene: mtcl1 has been classified as Green List (High Evidence).
Ataxia v0.265 MTCL1 Bryony Thompson edited their review of gene: MTCL1: Added comment: A new report of another case with a homozygous loss of function variant and a similar phenotype to the previously reported early onset homozygous Polish case (2 independent cases), and the supporting null mouse model.; Changed rating: GREEN; Changed publications: 30548255, 28283581, 32961396; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5400 PHYKPL Elena Savva reviewed gene: PHYKPL: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 23242558; Phenotypes: [?Phosphohydroxylysinuria] 615011; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5400 POLE Zornitza Stark Marked gene: POLE as ready
Mendeliome v0.5400 POLE Zornitza Stark Gene: pole has been classified as Green List (High Evidence).
Mendeliome v0.5400 POLE Zornitza Stark Phenotypes for gene: POLE were changed from to FILS syndrome, 615139; IMAGE-I syndrome, 618336; {Colorectal cancer, susceptibility to, 12}, 615083
Mendeliome v0.5399 POLE Zornitza Stark Publications for gene: POLE were set to
Mendeliome v0.5398 POLE Zornitza Stark Mode of pathogenicity for gene: POLE was changed from to Other
Mendeliome v0.5397 POLE Zornitza Stark Mode of inheritance for gene: POLE was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.5396 POLE Zornitza Stark Tag deep intronic tag was added to gene: POLE.
Mendeliome v0.5396 OFD1 Zornitza Stark Marked gene: OFD1 as ready
Mendeliome v0.5396 OFD1 Zornitza Stark Gene: ofd1 has been classified as Green List (High Evidence).
Mendeliome v0.5396 OFD1 Zornitza Stark Phenotypes for gene: OFD1 were changed from to Joubert syndrome 10, 300804; Simpson-Golabi-Behmel syndrome, type 2, 300209; Orofaciodigital syndrome I, 311200; Retinitis pigmentosa 23, 300424
Mendeliome v0.5395 OFD1 Zornitza Stark Publications for gene: OFD1 were set to
Mendeliome v0.5394 OFD1 Zornitza Stark Mode of inheritance for gene: OFD1 was changed from Unknown to Other
Additional findings_Paediatric v0.140 COL9A3 Zornitza Stark Marked gene: COL9A3 as ready
Additional findings_Paediatric v0.140 COL9A3 Zornitza Stark Gene: col9a3 has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.140 COL9A3 Zornitza Stark Classified gene: COL9A3 as Green List (high evidence)
Additional findings_Paediatric v0.140 COL9A3 Zornitza Stark Gene: col9a3 has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.139 CEP78 Zornitza Stark Marked gene: CEP78 as ready
Additional findings_Paediatric v0.139 CEP78 Zornitza Stark Gene: cep78 has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.139 CEP78 Zornitza Stark Classified gene: CEP78 as Green List (high evidence)
Additional findings_Paediatric v0.139 CEP78 Zornitza Stark Gene: cep78 has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.138 CDC14A Zornitza Stark Marked gene: CDC14A as ready
Additional findings_Paediatric v0.138 CDC14A Zornitza Stark Gene: cdc14a has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.138 CDC14A Zornitza Stark Classified gene: CDC14A as Green List (high evidence)
Additional findings_Paediatric v0.138 CDC14A Zornitza Stark Gene: cdc14a has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.137 CABP2 Zornitza Stark Marked gene: CABP2 as ready
Additional findings_Paediatric v0.137 CABP2 Zornitza Stark Gene: cabp2 has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.137 CABP2 Zornitza Stark Classified gene: CABP2 as Green List (high evidence)
Additional findings_Paediatric v0.137 CABP2 Zornitza Stark Gene: cabp2 has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.136 ATP2B2 Zornitza Stark Marked gene: ATP2B2 as ready
Additional findings_Paediatric v0.136 ATP2B2 Zornitza Stark Gene: atp2b2 has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.136 ATP2B2 Zornitza Stark Classified gene: ATP2B2 as Green List (high evidence)
Additional findings_Paediatric v0.136 ATP2B2 Zornitza Stark Gene: atp2b2 has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.135 ADGRV1 Zornitza Stark Marked gene: ADGRV1 as ready
Additional findings_Paediatric v0.135 ADGRV1 Zornitza Stark Gene: adgrv1 has been classified as Green List (High Evidence).
Additional findings_Paediatric v0.135 ADGRV1 Zornitza Stark Classified gene: ADGRV1 as Green List (high evidence)
Additional findings_Paediatric v0.135 ADGRV1 Zornitza Stark Gene: adgrv1 has been classified as Green List (High Evidence).
Mendeliome v0.5393 POLE Elena Savva reviewed gene: POLE: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 30503519, 23230001; Phenotypes: FILS syndrome, 615139, IMAGE-I syndrome, 618336, {Colorectal cancer, susceptibility to, 12}, 615083; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.5393 OFD1 Elena Savva reviewed gene: OFD1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31373179, 23033313, 16783569; Phenotypes: ?Retinitis pigmentosa 23, 300424, Joubert syndrome 10, 300804, Simpson-Golabi-Behmel syndrome, type 2, 300209, Orofaciodigital syndrome I, 311200; Mode of inheritance: Other
Additional findings_Paediatric v0.134 COL9A3 Lilian Downie gene: COL9A3 was added
gene: COL9A3 was added to Additional findings_Paediatric. Sources: Expert list
Mode of inheritance for gene: COL9A3 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: COL9A3 were set to Stickler syndrome
Review for gene: COL9A3 was set to GREEN
Added comment: Sources: Expert list
Additional findings_Paediatric v0.134 CEP78 Lilian Downie gene: CEP78 was added
gene: CEP78 was added to Additional findings_Paediatric. Sources: Expert list
Mode of inheritance for gene: CEP78 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CEP78 were set to Cone-rod dystrophy and hearing loss
Review for gene: CEP78 was set to GREEN
Added comment: Sources: Expert list
Additional findings_Paediatric v0.134 CDC14A Lilian Downie gene: CDC14A was added
gene: CDC14A was added to Additional findings_Paediatric. Sources: Expert list
Mode of inheritance for gene: CDC14A was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CDC14A were set to Deafness, autosomal recessive 32, with or without immotile sperm, MIM# 608653
Review for gene: CDC14A was set to GREEN
Added comment: Sources: Expert list
Additional findings_Paediatric v0.134 CABP2 Lilian Downie gene: CABP2 was added
gene: CABP2 was added to Additional findings_Paediatric. Sources: Expert list
Mode of inheritance for gene: CABP2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CABP2 were set to Deafness, autosomal recessive 93, MIM# 614899
Additional findings_Paediatric v0.134 ATP2B2 Lilian Downie gene: ATP2B2 was added
gene: ATP2B2 was added to Additional findings_Paediatric. Sources: Expert list
Mode of inheritance for gene: ATP2B2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: ATP2B2 were set to Deafness, childhood onset
Review for gene: ATP2B2 was set to GREEN
Added comment: Sources: Expert list
Additional findings_Paediatric v0.134 ADGRV1 Lilian Downie gene: ADGRV1 was added
gene: ADGRV1 was added to Additional findings_Paediatric. Sources: Expert list
Mode of inheritance for gene: ADGRV1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ADGRV1 were set to Usher syndrome, type 2C
Added comment: Added from deafness gene list
Sources: Expert list
Hereditary Neuropathy v0.91 NARS Zornitza Stark Phenotypes for gene: NARS were changed from Abnormal muscle tone; Microcephaly; Global developmental delay; Intellectual disability; Seizures; Ataxia; Abnormality of the face; Demyelinating peripheral neuropathy to Neurodevelopmental disorder with microcephaly, impaired language, and gait abnormalities (NEDMILG), MIM#619091; Neurodevelopmental disorder with microcephaly, impaired language, epilepsy, and gait abnormalities (NEDMILEG), MIM#619092; Abnormal muscle tone; Microcephaly; Global developmental delay; Intellectual disability; Seizures; Ataxia; Abnormality of the face; Demyelinating peripheral neuropathy
Hereditary Neuropathy v0.90 NARS Zornitza Stark edited their review of gene: NARS: Changed phenotypes: Neurodevelopmental disorder with microcephaly, impaired language, and gait abnormalities (NEDMILG), MIM#619091, Neurodevelopmental disorder with microcephaly, impaired language, epilepsy, and gait abnormalities (NEDMILEG), MIM#619092, Abnormal muscle tone, Microcephaly, Global developmental delay, Intellectual disability, Seizures, Ataxia, Abnormality of the face, Demyelinating peripheral neuropathy
Intellectual disability syndromic and non-syndromic v0.3198 NARS Zornitza Stark Phenotypes for gene: NARS were changed from Neurodevelopmental disorder with microcephaly, impaired language, and gait abnormalities (NEDMILG), MIM#619091; Neurodevelopmental disorder with microcephaly, impaired language, epilepsy, and gait abnormalities (NEDMILEG), MIM#619092; Abnormal muscle tone; Microcephaly; Global developmental delay; Intellectual disability; Seizures; Ataxia; Abnormality of the face; Demyelinating peripheral neuropathy to Neurodevelopmental disorder with microcephaly, impaired language, and gait abnormalities (NEDMILG), MIM#619091; Neurodevelopmental disorder with microcephaly, impaired language, epilepsy, and gait abnormalities (NEDMILEG), MIM#619092; Abnormal muscle tone; Microcephaly; Global developmental delay; Intellectual disability; Seizures; Ataxia; Abnormality of the face; Demyelinating peripheral neuropathy
Intellectual disability syndromic and non-syndromic v0.3197 NARS Zornitza Stark Phenotypes for gene: NARS were changed from Abnormal muscle tone; Microcephaly; Global developmental delay; Intellectual disability; Seizures; Ataxia; Abnormality of the face; Demyelinating peripheral neuropathy to Neurodevelopmental disorder with microcephaly, impaired language, and gait abnormalities (NEDMILG), MIM#619091; Neurodevelopmental disorder with microcephaly, impaired language, epilepsy, and gait abnormalities (NEDMILEG), MIM#619092; Abnormal muscle tone; Microcephaly; Global developmental delay; Intellectual disability; Seizures; Ataxia; Abnormality of the face; Demyelinating peripheral neuropathy
Intellectual disability syndromic and non-syndromic v0.3196 NARS Zornitza Stark reviewed gene: NARS: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with microcephaly, impaired language, and gait abnormalities (NEDMILG), MIM#619091, Neurodevelopmental disorder with microcephaly, impaired language, epilepsy, and gait abnormalities (NEDMILEG), MIM#619092, Abnormal muscle tone, Microcephaly, Global developmental delay, Intellectual disability, Seizures, Ataxia, Abnormality of the face, Demyelinating peripheral neuropathy; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genetic Epilepsy v0.906 NARS Zornitza Stark Phenotypes for gene: NARS were changed from Abnormal muscle tone; Microcephaly; Global developmental delay; Intellectual disability; Seizures; Ataxia; Abnormality of the face; Demyelinating peripheral neuropathy to Neurodevelopmental disorder with microcephaly, impaired language, and gait abnormalities (NEDMILG), MIM#619091; Neurodevelopmental disorder with microcephaly, impaired language, epilepsy, and gait abnormalities (NEDMILEG), MIM#619092; Abnormal muscle tone; Microcephaly; Global developmental delay; Intellectual disability; Seizures; Ataxia; Abnormality of the face; Demyelinating peripheral neuropathy
Genetic Epilepsy v0.905 NARS Zornitza Stark reviewed gene: NARS: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with microcephaly, impaired language, and gait abnormalities (NEDMILG), MIM#619091, Neurodevelopmental disorder with microcephaly, impaired language, epilepsy, and gait abnormalities (NEDMILEG), MIM#619092, Abnormal muscle tone, Microcephaly, Global developmental delay, Intellectual disability, Seizures, Ataxia, Abnormality of the face, Demyelinating peripheral neuropathy; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.5393 NARS Zornitza Stark Phenotypes for gene: NARS were changed from Abnormal muscle tone; Microcephaly; Global developmental delay; Intellectual disability; Seizures; Ataxia; Abnormality of the face; Demyelinating peripheral neuropathy to Neurodevelopmental disorder with microcephaly, impaired language, and gait abnormalities (NEDMILG), MIM#619091; Neurodevelopmental disorder with microcephaly, impaired language, epilepsy, and gait abnormalities (NEDMILEG), MIM#619092; Abnormal muscle tone; Microcephaly; Global developmental delay; Intellectual disability; Seizures; Ataxia; Abnormality of the face; Demyelinating peripheral neuropathy
Mendeliome v0.5392 NARS Zornitza Stark Tag new gene name tag was added to gene: NARS.
Mendeliome v0.5392 NARS Zornitza Stark edited their review of gene: NARS: Changed phenotypes: Neurodevelopmental disorder with microcephaly, impaired language, and gait abnormalities (NEDMILG), MIM#619091, Neurodevelopmental disorder with microcephaly, impaired language, epilepsy, and gait abnormalities (NEDMILEG), MIM#619092, Abnormal muscle tone, Microcephaly, Global developmental delay, Intellectual disability, Seizures, Ataxia, Abnormality of the face, Demyelinating peripheral neuropathy
Lipodystrophy_Lipoatrophy v0.14 OTULIN Zornitza Stark Marked gene: OTULIN as ready
Lipodystrophy_Lipoatrophy v0.14 OTULIN Zornitza Stark Gene: otulin has been classified as Green List (High Evidence).
Lipodystrophy_Lipoatrophy v0.14 OTULIN Zornitza Stark Classified gene: OTULIN as Green List (high evidence)
Lipodystrophy_Lipoatrophy v0.14 OTULIN Zornitza Stark Gene: otulin has been classified as Green List (High Evidence).
Lipodystrophy_Lipoatrophy v0.13 OTULIN Zornitza Stark gene: OTULIN was added
gene: OTULIN was added to Lipodystrophy_Lipoatrophy. Sources: Expert list
Mode of inheritance for gene: OTULIN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: OTULIN were set to 27523608; 27559085
Phenotypes for gene: OTULIN were set to Autoinflammation, panniculitis, and dermatosis syndrome, MIM# 617099
Review for gene: OTULIN was set to GREEN
Added comment: Autoinflammatory disease characterized by neonatal onset of recurrent fever, erythematous rash with painful nodules, painful joints, and lipodystrophy. Additional features may include diarrhea, increased serum C-reactive protein, leukocytosis, and neutrophilia in the absence of any infection.

At least 3 unrelated families reported.
Sources: Expert list
Lipodystrophy_Lipoatrophy v0.12 PSMB4 Zornitza Stark Marked gene: PSMB4 as ready
Lipodystrophy_Lipoatrophy v0.12 PSMB4 Zornitza Stark Gene: psmb4 has been classified as Amber List (Moderate Evidence).
Lipodystrophy_Lipoatrophy v0.12 PSMB4 Zornitza Stark Classified gene: PSMB4 as Amber List (moderate evidence)
Lipodystrophy_Lipoatrophy v0.12 PSMB4 Zornitza Stark Gene: psmb4 has been classified as Amber List (Moderate Evidence).
Lipodystrophy_Lipoatrophy v0.11 PSMB4 Zornitza Stark gene: PSMB4 was added
gene: PSMB4 was added to Lipodystrophy_Lipoatrophy. Sources: Expert list
Mode of inheritance for gene: PSMB4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PSMB4 were set to 26524591
Phenotypes for gene: PSMB4 were set to Proteasome-associated autoinflammatory syndrome 3 and digenic forms, MIM# 617591
Review for gene: PSMB4 was set to AMBER
Added comment: Proteasome-associated autoinflammatory syndrome-3 is an autosomal recessive syndrome with onset in early infancy. Affected individuals present with nodular dermatitis, recurrent fever, myositis, panniculitis-induced lipodystrophy, lymphadenopathy, and dysregulation of the immune response, particularly associated with abnormal type I interferon-induced gene expression patterns. Additional features are highly variable, but may include joint contractures, hepatosplenomegaly, anaemia, thrombocytopaenia, recurrent infections, autoantibodies, and hypergammaglobulinaemia. Some may have intracranial calcifications.

One individual with bi-allelic variants, and two others with mono-allelic variants in PSMB4 as well as variants in PSMB9 or PSMB8, digenic model proposed.
Sources: Expert list
Cataract v0.243 ANAPC1 Zornitza Stark Tag deep intronic tag was added to gene: ANAPC1.
Cataract v0.243 ANAPC1 Zornitza Stark reviewed gene: ANAPC1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Rothmund Thomson syndrome type 1, OMIM 618625; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5392 ANAPC1 Zornitza Stark Tag deep intronic tag was added to gene: ANAPC1.
Mendeliome v0.5392 ANAPC1 Zornitza Stark reviewed gene: ANAPC1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Rothmund-Thomson syndrome, type 1 618625; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5392 DZIP1 Zornitza Stark Phenotypes for gene: DZIP1 were changed from Mitral valve prolapse, MIM#610840 to Mitral valve prolapse, MIM#610840; Spermatogenic failure 47, MIM# 619102
Mendeliome v0.5391 DZIP1 Zornitza Stark Publications for gene: DZIP1 were set to 31118289
Mendeliome v0.5390 DZIP1 Zornitza Stark Mode of inheritance for gene: DZIP1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.5389 DZIP1 Zornitza Stark changed review comment from: One large 4-generation family reported, where missense variant segregated with disease. Two additional individuals identified from a cohort. All variants present at low frequency in population databases. Mouse model recapitulated phenotype.
Sources: Literature; to: Association with MVP: One large 4-generation family reported, where missense variant segregated with disease. Two additional individuals identified from a cohort. All variants present at low frequency in population databases. Mouse model recapitulated phenotype.
Sources: Literature
Mendeliome v0.5389 DZIP1 Zornitza Stark edited their review of gene: DZIP1: Added comment: Two individuals reported in PMID 32051257 with bi-allelic variants and spermatogenic failure.; Changed publications: 31118289, 32051257; Changed phenotypes: Mitral valve prolapse, MIM#610840, Spermatogenic failure 47, MIM# 619102; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.5389 DZIP1 Zornitza Stark Marked gene: DZIP1 as ready
Mendeliome v0.5389 DZIP1 Zornitza Stark Gene: dzip1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5389 DZIP1 Zornitza Stark Phenotypes for gene: DZIP1 were changed from Mitral valve prolapse to Mitral valve prolapse, MIM#610840
Mendeliome v0.5388 DZIP1 Zornitza Stark Classified gene: DZIP1 as Amber List (moderate evidence)
Mendeliome v0.5388 DZIP1 Zornitza Stark Gene: dzip1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5387 DZIP1 Zornitza Stark edited their review of gene: DZIP1: Changed phenotypes: Mitral valve prolapse, MIM#610840
Mendeliome v0.5387 DZIP1 Zornitza Stark gene: DZIP1 was added
gene: DZIP1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: DZIP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DZIP1 were set to 31118289
Phenotypes for gene: DZIP1 were set to Mitral valve prolapse
Review for gene: DZIP1 was set to AMBER
Added comment: One large 4-generation family reported, where missense variant segregated with disease. Two additional individuals identified from a cohort. All variants present at low frequency in population databases. Mouse model recapitulated phenotype.
Sources: Literature
Bone Marrow Failure v0.171 ADH5 Zornitza Stark Marked gene: ADH5 as ready
Bone Marrow Failure v0.171 ADH5 Zornitza Stark Gene: adh5 has been classified as Green List (High Evidence).
Mendeliome v0.5386 ADH5 Zornitza Stark Marked gene: ADH5 as ready
Mendeliome v0.5386 ADH5 Zornitza Stark Gene: adh5 has been classified as Green List (High Evidence).
Mendeliome v0.5386 ADH5 Zornitza Stark Classified gene: ADH5 as Green List (high evidence)
Mendeliome v0.5386 ADH5 Zornitza Stark Gene: adh5 has been classified as Green List (High Evidence).
Mendeliome v0.5385 ADH5 Zornitza Stark gene: ADH5 was added
gene: ADH5 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ADH5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADH5 were set to 33147438
Phenotypes for gene: ADH5 were set to Aplastic anaemia; myelodysplasia; short stature
Review for gene: ADH5 was set to GREEN
Added comment: 7 individuals reported with bi-allelic variants in this gene and a Fanconi syndrome-like phenotype. All had aplastic anaemia, 4 developed a myelodysplastic syndrome, and one developed AML. Short stature and abnormal skin pigmentation were additional features.

Note, all also had the ALDH2*2 allele, which is common in East Asian populations, and may be contributory.

Extensive experimental data.
Sources: Literature
Bone Marrow Failure v0.171 ADH5 Zornitza Stark Classified gene: ADH5 as Green List (high evidence)
Bone Marrow Failure v0.171 ADH5 Zornitza Stark Gene: adh5 has been classified as Green List (High Evidence).
Bone Marrow Failure v0.170 ADH5 Zornitza Stark gene: ADH5 was added
gene: ADH5 was added to Bone Marrow Failure. Sources: Literature
Mode of inheritance for gene: ADH5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADH5 were set to 33147438
Phenotypes for gene: ADH5 were set to Aplastic anaemia; myelodysplasia; short stature
Review for gene: ADH5 was set to GREEN
Added comment: 7 individuals reported with bi-allelic variants in this gene and a Fanconi syndrome-like phenotype. All had aplastic anaemia, 4 developed a myelodysplastic syndrome, and one developed AML. Short stature and abnormal skin pigmentation were additional features.

Note, all also had the ALDH2*2 allele, which is common in East Asian populations, and may be contributory.

Extensive experimental data.
Sources: Literature
Malignant Hyperthermia Susceptibility v1.0 Bryony Thompson promoted panel to version 1.0
Vascular Malformations_Somatic v1.0 Bryony Thompson promoted panel to version 1.0
Vascular Malformations_Somatic v0.16 Bryony Thompson Panel types changed to Victorian Clinical Genetics Services; Royal Melbourne Hospital; Rare Disease
Hereditary Neuropathy v0.90 RFC1 Bryony Thompson Classified gene: RFC1 as No list
Hereditary Neuropathy v0.90 RFC1 Bryony Thompson Added comment: Comment on list classification: STR is the only reported cause of condition. It is present under the STRs in this panel.
Hereditary Neuropathy v0.90 RFC1 Bryony Thompson Gene: rfc1 has been removed from the panel.
Hereditary Neuropathy v0.89 CANVAS Bryony Thompson Classified STR: CANVAS as Green List (high evidence)
Hereditary Neuropathy v0.89 CANVAS Bryony Thompson Str: canvas has been classified as Green List (High Evidence).
Hereditary Neuropathy v0.88 CANVAS Bryony Thompson STR: CANVAS was added
STR: CANVAS was added to Hereditary Neuropathy - complex. Sources: Expert list
STR tags were added to STR: CANVAS.
Mode of inheritance for STR: CANVAS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for STR: CANVAS were set to 30926972
Phenotypes for STR: CANVAS were set to Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome MIM#614575
Review for STR: CANVAS was set to GREEN
STR: CANVAS was marked as clinically relevant
STR: CANVAS was marked as current diagnostic
Added comment: Simple tandem repeat (AAAAG)11 replaced with (AAGGG)n in intron 2 of RFC1. Loss of function is not the mechanism of disease.
Sources: Expert list
Incidentalome v0.51 SNCA Zornitza Stark Marked gene: SNCA as ready
Incidentalome v0.51 SNCA Zornitza Stark Gene: snca has been classified as Green List (High Evidence).
Incidentalome v0.51 SNCA Zornitza Stark Phenotypes for gene: SNCA were changed from to Dementia, Lewy body (MIM#127750); Parkinson disease 1 (MIM#168601); Parkinson disease 4 (MIM#605543)
Incidentalome v0.50 SNCA Zornitza Stark Publications for gene: SNCA were set to
Incidentalome v0.49 SNCA Zornitza Stark Mode of inheritance for gene: SNCA was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
Incidentalome v0.48 SNCA Zornitza Stark Tag SV/CNV tag was added to gene: SNCA.
Incidentalome v0.48 SNCA Zornitza Stark reviewed gene: SNCA: Rating: GREEN; Mode of pathogenicity: None; Publications: 32849182, 26858591, 32740728; Phenotypes: Dementia, Lewy body (MIM#127750), Parkinson disease 1 (MIM#168601), Parkinson disease 4 (MIM#605543); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Dementia v0.130 SNCA Zornitza Stark Marked gene: SNCA as ready
Early-onset Dementia v0.130 SNCA Zornitza Stark Gene: snca has been classified as Green List (High Evidence).
Early-onset Dementia v0.130 SNCA Zornitza Stark Phenotypes for gene: SNCA were changed from to Dementia, Lewy body (MIM#127750); Parkinson disease 1 (MIM#168601); Parkinson disease 4 (MIM#605543)
Early-onset Dementia v0.129 SNCA Zornitza Stark Publications for gene: SNCA were set to
Early-onset Dementia v0.128 SNCA Zornitza Stark Mode of inheritance for gene: SNCA was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Dementia v0.127 SNCA Zornitza Stark reviewed gene: SNCA: Rating: GREEN; Mode of pathogenicity: None; Publications: 32849182, 26858591, 32740728; Phenotypes: Dementia, Lewy body (MIM#127750), Parkinson disease 1 (MIM#168601), Parkinson disease 4 (MIM#605543); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.92 SNCA Zornitza Stark Marked gene: SNCA as ready
Early-onset Parkinson disease v0.92 SNCA Zornitza Stark Gene: snca has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.92 SNCA Zornitza Stark Phenotypes for gene: SNCA were changed from to Dementia, Lewy body (MIM#127750); Parkinson disease 1 (MIM#168601); Parkinson disease 4 (MIM#605543)
Early-onset Parkinson disease v0.91 SNCA Zornitza Stark Publications for gene: SNCA were set to
Early-onset Parkinson disease v0.90 SNCA Zornitza Stark Mode of inheritance for gene: SNCA was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.89 SNCA Zornitza Stark Tag SV/CNV tag was added to gene: SNCA.
Early-onset Parkinson disease v0.89 SNCA Ain Roesley reviewed gene: SNCA: Rating: GREEN; Mode of pathogenicity: None; Publications: 32849182, 26858591, 32740728; Phenotypes: Dementia, Lewy body (MIM#127750), Parkinson disease 1 (MIM#168601), Parkinson disease 4 (MIM#605543); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Proteinuria v0.148 NPHS2 Zornitza Stark Marked gene: NPHS2 as ready
Proteinuria v0.148 NPHS2 Zornitza Stark Gene: nphs2 has been classified as Green List (High Evidence).
Proteinuria v0.148 NPHS2 Zornitza Stark Phenotypes for gene: NPHS2 were changed from to Nephrotic syndrome, type 2 (MIM#600995), AR
Proteinuria v0.147 NPHS2 Zornitza Stark Publications for gene: NPHS2 were set to
Proteinuria v0.146 NPHS2 Zornitza Stark Mode of inheritance for gene: NPHS2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Proteinuria v0.145 NPHS2 Zornitza Stark reviewed gene: NPHS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 32467597, 30260545, 24509478; Phenotypes: Nephrotic syndrome, type 2 (MIM#600995), AR; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5384 NPHS2 Zornitza Stark Marked gene: NPHS2 as ready
Mendeliome v0.5384 NPHS2 Zornitza Stark Gene: nphs2 has been classified as Green List (High Evidence).
Mendeliome v0.5384 NPHS2 Zornitza Stark Phenotypes for gene: NPHS2 were changed from to Nephrotic syndrome, type 2 (MIM#600995), AR
Mendeliome v0.5383 NPHS2 Zornitza Stark Publications for gene: NPHS2 were set to
Mendeliome v0.5382 NPHS2 Zornitza Stark Mode of inheritance for gene: NPHS2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5381 NPHS2 Chern Lim reviewed gene: NPHS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 32467597, 30260545, 24509478; Phenotypes: Nephrotic syndrome, type 2 (MIM#600995), AR; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Congenital ophthalmoplegia v0.66 RYR1 Zornitza Stark Marked gene: RYR1 as ready
Congenital ophthalmoplegia v0.66 RYR1 Zornitza Stark Gene: ryr1 has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.66 RYR1 Zornitza Stark Classified gene: RYR1 as Green List (high evidence)
Congenital ophthalmoplegia v0.66 RYR1 Zornitza Stark Gene: ryr1 has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.65 POLG Zornitza Stark Marked gene: POLG as ready
Congenital ophthalmoplegia v0.65 POLG Zornitza Stark Gene: polg has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.65 POLG Zornitza Stark Classified gene: POLG as Green List (high evidence)
Congenital ophthalmoplegia v0.65 POLG Zornitza Stark Gene: polg has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.64 MYH2 Zornitza Stark Marked gene: MYH2 as ready
Congenital ophthalmoplegia v0.64 MYH2 Zornitza Stark Gene: myh2 has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.64 MYH2 Zornitza Stark Phenotypes for gene: MYH2 were changed from to Proximal myopathy and ophthalmoplegia, MIM# 605637
Congenital ophthalmoplegia v0.63 MYH2 Zornitza Stark Classified gene: MYH2 as Green List (high evidence)
Congenital ophthalmoplegia v0.63 MYH2 Zornitza Stark Gene: myh2 has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.62 MYH2 Zornitza Stark reviewed gene: MYH2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Proximal myopathy and ophthalmoplegia, MIM# 605637; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Congenital ophthalmoplegia v0.62 TYMP Zornitza Stark reviewed gene: TYMP: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Mitochondrial DNA depletion syndrome 1 (MNGIE type) 603041; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital ophthalmoplegia v0.62 TYMP Zornitza Stark Marked gene: TYMP as ready
Congenital ophthalmoplegia v0.62 TYMP Zornitza Stark Gene: tymp has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.62 TYMP Zornitza Stark Classified gene: TYMP as Green List (high evidence)
Congenital ophthalmoplegia v0.62 TYMP Zornitza Stark Gene: tymp has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.61 NPC1 Zornitza Stark Marked gene: NPC1 as ready
Congenital ophthalmoplegia v0.61 NPC1 Zornitza Stark Gene: npc1 has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.61 NPC1 Zornitza Stark Classified gene: NPC1 as Green List (high evidence)
Congenital ophthalmoplegia v0.61 NPC1 Zornitza Stark Gene: npc1 has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.60 TWNK Zornitza Stark Marked gene: TWNK as ready
Congenital ophthalmoplegia v0.60 TWNK Zornitza Stark Gene: twnk has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.60 TWNK Zornitza Stark Classified gene: TWNK as Green List (high evidence)
Congenital ophthalmoplegia v0.60 TWNK Zornitza Stark Gene: twnk has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.59 TWNK Shannon LeBlanc gene: TWNK was added
gene: TWNK was added to Congenital ophthalmoplegia. Sources: Literature
Mode of inheritance for gene: TWNK was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: TWNK were set to PMID 17921179; 32234020
Phenotypes for gene: TWNK were set to Mitochondrial DNA depletion syndrome 7 (hepatocerebral type) 271245; Perrault syndrome 5 616138; Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 609286
Review for gene: TWNK was set to GREEN
Added comment: Mitochondrial DNA depletion syndrome-7: biallelic, severe neurodegenerative disorder characterized primarily by hypotonia, ataxia, ophthalmoplegia, hearing loss, seizures, and sensory axonal neuropathy. Infantile onset

PMID: 32234020: Fig 1 shows the variant distribution for various phenotypes
Sources: Literature
Congenital ophthalmoplegia v0.59 NPC1 Shannon LeBlanc gene: NPC1 was added
gene: NPC1 was added to Congenital ophthalmoplegia. Sources: Literature
Mode of inheritance for gene: NPC1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NPC1 were set to Niemann-Pick disease, type C, 257220
Review for gene: NPC1 was set to GREEN
Added comment: Well established gene-disease association.

Vertical supranuclear gaze palsy is an early manifestation in childhood-onset type.
Sources: Literature
Congenital ophthalmoplegia v0.59 TYMP Shannon LeBlanc gene: TYMP was added
gene: TYMP was added to Congenital ophthalmoplegia. Sources: Literature
Mode of inheritance for gene: TYMP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TYMP were set to PMID: 21933806; 30775048
Phenotypes for gene: TYMP were set to Mitochondrial DNA depletion syndrome 1 (MNGIE type) 603041
Added comment: Ophthalmoplegia is a common feature.

age of onset range 5 months to 35 years); however, the majority of patients reported the first symptoms before the age of 12 years.

Garone 2011: 92 patients with biallelic variants
Sources: Literature
Congenital ophthalmoplegia v0.59 MYH2 Shannon LeBlanc gene: MYH2 was added
gene: MYH2 was added to Congenital ophthalmoplegia. Sources: Literature
Mode of inheritance for gene: MYH2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: MYH2 were set to PMID 24193343; 32578970; 11114175; 23489661
Added comment: childhood consent ophthalmoplegia and progressive proximal limb weakness. Either slowly progressive or non-progressive.

> 10 families reported with balletic variants
monoallelic variants: two missense variants reported
Sources: Literature
Congenital ophthalmoplegia v0.59 POLG Shannon LeBlanc gene: POLG was added
gene: POLG was added to Congenital ophthalmoplegia. Sources: Literature
Mode of inheritance for gene: POLG was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: POLG were set to Mitochondrial DNA depletion syndrome 4A (Alpers type) MIM#203700; Mitochondrial DNA depletion syndrome 4B (MNGIE type) MIM#613662; Mitochondrial recessive ataxia syndrome (includes SANDO and SCAE) MIM#607459; Progressive external ophthalmoplegia, autosomal recessive 1 MIM#258450
Review for gene: POLG was set to GREEN
Added comment: Well established gene-disease associaition. Variable age of onset of ophthalmoplegia, including infancy and early childhood.
Sources: Literature
Congenital ophthalmoplegia v0.59 RYR1 Shannon LeBlanc gene: RYR1 was added
gene: RYR1 was added to Congenital ophthalmoplegia. Sources: Literature
Mode of inheritance for gene: RYR1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: RYR1 were set to Minicore myopathy with external ophthalmoplegia 255320
Review for gene: RYR1 was set to GREEN
Added comment: ophthalmoplegia is a common features. Also presents with congenital myopathy, including neonatal hypotonia, delayed motor development, and generalized muscle weakness and amyotrophy,
Sources: Literature
Congenital ophthalmoplegia v0.59 CHRNE Zornitza Stark Marked gene: CHRNE as ready
Congenital ophthalmoplegia v0.59 CHRNE Zornitza Stark Gene: chrne has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.59 CHRNE Zornitza Stark Classified gene: CHRNE as Green List (high evidence)
Congenital ophthalmoplegia v0.59 CHRNE Zornitza Stark Gene: chrne has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.58 CHRNE Zornitza Stark gene: CHRNE was added
gene: CHRNE was added to Congenital ophthalmoplegia. Sources: Expert list
Mode of inheritance for gene: CHRNE was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CHRNE were set to Myasthenic syndrome, congenital, 4B, fast-channel, MIM# 616324
Review for gene: CHRNE was set to GREEN
Added comment: Ophthalmoplegia is a feature.
Sources: Expert list
Congenital ophthalmoplegia v0.57 CHRNB1 Zornitza Stark Marked gene: CHRNB1 as ready
Congenital ophthalmoplegia v0.57 CHRNB1 Zornitza Stark Gene: chrnb1 has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.57 CHRNB1 Zornitza Stark Classified gene: CHRNB1 as Green List (high evidence)
Congenital ophthalmoplegia v0.57 CHRNB1 Zornitza Stark Gene: chrnb1 has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.56 CHRNB1 Zornitza Stark gene: CHRNB1 was added
gene: CHRNB1 was added to Congenital ophthalmoplegia. Sources: Expert list
Mode of inheritance for gene: CHRNB1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CHRNB1 were set to Myasthenic syndrome, congenital, 2A, slow-channel, MIM# 616313
Review for gene: CHRNB1 was set to GREEN
Added comment: Ophthalmoplegia is a feature.
Sources: Expert list
Congenital ophthalmoplegia v0.55 MFF Zornitza Stark Marked gene: MFF as ready
Congenital ophthalmoplegia v0.55 MFF Zornitza Stark Gene: mff has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.55 MFF Zornitza Stark Classified gene: MFF as Green List (high evidence)
Congenital ophthalmoplegia v0.55 MFF Zornitza Stark Gene: mff has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.54 MFF Zornitza Stark gene: MFF was added
gene: MFF was added to Congenital ophthalmoplegia. Sources: Expert list
Mode of inheritance for gene: MFF was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MFF were set to 26783368
Phenotypes for gene: MFF were set to Encephalopathy due to defective mitochondrial and peroxisomal fission 2, MIM# 617086
Review for gene: MFF was set to GREEN
Added comment: Ophthalmoplegia is a feature along with severe hypotonia with inability to walk, microcephaly, and abnormal signals in the basal ganglia.
Sources: Expert list
Congenital ophthalmoplegia v0.53 MUSK Zornitza Stark Marked gene: MUSK as ready
Congenital ophthalmoplegia v0.53 MUSK Zornitza Stark Gene: musk has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.53 MUSK Zornitza Stark Classified gene: MUSK as Green List (high evidence)
Congenital ophthalmoplegia v0.53 MUSK Zornitza Stark Gene: musk has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.52 MUSK Zornitza Stark gene: MUSK was added
gene: MUSK was added to Congenital ophthalmoplegia. Sources: Expert list
Mode of inheritance for gene: MUSK was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: MUSK were set to Myasthenic syndrome, congenital, 9, associated with acetylcholine receptor deficiency, MIM# 616325
Review for gene: MUSK was set to GREEN
Added comment: Ophthalmoplegia is a feature.
Sources: Expert list
Congenital ophthalmoplegia v0.51 NDUFV1 Zornitza Stark Marked gene: NDUFV1 as ready
Congenital ophthalmoplegia v0.51 NDUFV1 Zornitza Stark Gene: ndufv1 has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.51 NDUFV1 Zornitza Stark Classified gene: NDUFV1 as Green List (high evidence)
Congenital ophthalmoplegia v0.51 NDUFV1 Zornitza Stark Gene: ndufv1 has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.50 NDUFV1 Zornitza Stark gene: NDUFV1 was added
gene: NDUFV1 was added to Congenital ophthalmoplegia. Sources: Expert list
Mode of inheritance for gene: NDUFV1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NDUFV1 were set to Mitochondrial complex I deficiency, nuclear type 4, MIM# 618225
Review for gene: NDUFV1 was set to GREEN
Added comment: Ophthalmoplegia is a reported feature.
Sources: Expert list
Congenital ophthalmoplegia v0.49 MTM1 Zornitza Stark Marked gene: MTM1 as ready
Congenital ophthalmoplegia v0.49 MTM1 Zornitza Stark Gene: mtm1 has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.49 MTM1 Zornitza Stark Classified gene: MTM1 as Green List (high evidence)
Congenital ophthalmoplegia v0.49 MTM1 Zornitza Stark Gene: mtm1 has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.48 MTM1 Zornitza Stark gene: MTM1 was added
gene: MTM1 was added to Congenital ophthalmoplegia. Sources: Expert list
Mode of inheritance for gene: MTM1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: MTM1 were set to Myotubular myopathy, X-linked, MIM# 310400
Review for gene: MTM1 was set to GREEN
Added comment: External ophthalmoplegia is a prominent feature.
Sources: Expert list
Mendeliome v0.5381 LRIF1 Bryony Thompson changed review comment from: A single consanguineous case with a homozygous truncating variant. DZ4Z hypomethylation and increased DUX expression was present in patient cells. siRNA-mediated depletion of LRIF1L in immortalized myoblasts derepressed the DUX4 locus.
Sources: Literature; to: A single consanguineous case with a homozygous truncating variant, and D4Z4 repeat of 13 units on a 4qA haplotype (permissive haplotype). DZ4Z hypomethylation and increased DUX expression was present in patient cells. siRNA-mediated depletion of LRIF1L in immortalized myoblasts derepressed the DUX4 locus.
Sources: Literature
Mendeliome v0.5381 LRIF1 Bryony Thompson Classified gene: LRIF1 as Amber List (moderate evidence)
Mendeliome v0.5381 LRIF1 Bryony Thompson Gene: lrif1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5380 LRIF1 Bryony Thompson gene: LRIF1 was added
gene: LRIF1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: LRIF1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LRIF1 were set to 32467133
Phenotypes for gene: LRIF1 were set to Facioscapulohumeral muscular dystrophy
Review for gene: LRIF1 was set to AMBER
Added comment: A single consanguineous case with a homozygous truncating variant. DZ4Z hypomethylation and increased DUX expression was present in patient cells. siRNA-mediated depletion of LRIF1L in immortalized myoblasts derepressed the DUX4 locus.
Sources: Literature
Ciliary Dyskinesia v1.2 DNAH8 Zornitza Stark Phenotypes for gene: DNAH8 were changed from Asthenozoospermia; primary ciliary dyskinesia to Spermatogenic failure 46, MIM#619095; Asthenozoospermia; primary ciliary dyskinesia
Mendeliome v0.5379 DNAH8 Zornitza Stark Phenotypes for gene: DNAH8 were changed from Asthenozoospermia; primary ciliary dyskinesia to Spermatogenic failure 46, MIM#619095; Asthenozoospermia; primary ciliary dyskinesia
Mendeliome v0.5378 DNAH8 Zornitza Stark edited their review of gene: DNAH8: Changed phenotypes: Spermatogenic failure 46, MIM#619095, Asthenozoospermia, primary ciliary dyskinesia
Anophthalmia_Microphthalmia_Coloboma v0.69 C16orf62 Zornitza Stark Tag new gene name tag was added to gene: C16orf62.
Congenital diaphragmatic hernia v0.32 TRRAP Zornitza Stark Marked gene: TRRAP as ready
Congenital diaphragmatic hernia v0.32 TRRAP Zornitza Stark Gene: trrap has been classified as Red List (Low Evidence).
Congenital diaphragmatic hernia v0.32 TRRAP Zornitza Stark gene: TRRAP was added
gene: TRRAP was added to Congenital diaphragmatic hernia. Sources: Expert list
Mode of inheritance for gene: TRRAP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TRRAP were set to 30827496
Phenotypes for gene: TRRAP were set to Developmental delay with or without dysmorphic facies and autism, MIM# 618454
Review for gene: TRRAP was set to RED
Added comment: Developmental delay with or without dysmorphic facies and autism (DEDDFA) is a complex neurodevelopmental disorder apparent from infancy or early childhood and associated with variably impaired intellectual development. Some patients may be severely affected with no speech and inability to walk, whereas others may be able to attend special schools or have normal intellectual function associated with autism spectrum disorder and mild speech delay. Genetic analysis has suggested that the phenotype can be broadly categorized into 2 main groups. Patients with TRRAP mutations affecting residues 1031-1159 have a more severe disorder, often with multisystem involvement, including renal, cardiac, and genitourinary systems, as well as structural brain abnormalities. Patients with mutations outside of that region tend to have a less severe phenotype with a higher incidence of autism and usually no systemic involvement. Patients in both groups usually have somewhat similar dysmorphic facial features, such as upslanting palpebral fissures, hypertelorism, low-set ears, and broad or depressed nasal bridge, although these features are highly variable.

One of 13 individuals had CDH in PMID 30827496.
Sources: Expert list
Congenital diaphragmatic hernia v0.31 EFEMP2 Zornitza Stark Marked gene: EFEMP2 as ready
Congenital diaphragmatic hernia v0.31 EFEMP2 Zornitza Stark Gene: efemp2 has been classified as Green List (High Evidence).
Congenital diaphragmatic hernia v0.31 EFEMP2 Zornitza Stark Classified gene: EFEMP2 as Green List (high evidence)
Congenital diaphragmatic hernia v0.31 EFEMP2 Zornitza Stark Gene: efemp2 has been classified as Green List (High Evidence).
Congenital diaphragmatic hernia v0.30 EFEMP2 Zornitza Stark gene: EFEMP2 was added
gene: EFEMP2 was added to Congenital diaphragmatic hernia. Sources: Expert list
Mode of inheritance for gene: EFEMP2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EFEMP2 were set to 30140196; 21563328
Phenotypes for gene: EFEMP2 were set to Cutis laxa, autosomal recessive, type IB, MIM# 614437
Review for gene: EFEMP2 was set to GREEN
Added comment: Autosomal recessive cutis laxa type IB (ARCL1B) is characterized by the presence of severe systemic connective tissue abnormalities, including emphysema, cardiopulmonary insufficiency, birth fractures, arachnodactyly, and fragility of blood vessels.

Diaphragmatic hypoplasia and hernia are features in 25-90%.
Sources: Expert list
Congenital diaphragmatic hernia v0.29 PORCN Zornitza Stark Marked gene: PORCN as ready
Congenital diaphragmatic hernia v0.29 PORCN Zornitza Stark Added comment: Comment when marking as ready: XLD.
Congenital diaphragmatic hernia v0.29 PORCN Zornitza Stark Gene: porcn has been classified as Green List (High Evidence).
Congenital diaphragmatic hernia v0.29 PORCN Zornitza Stark Phenotypes for gene: PORCN were changed from to Focal dermal hypoplasia, MIM# 305600
Congenital diaphragmatic hernia v0.28 PORCN Zornitza Stark Publications for gene: PORCN were set to
Congenital diaphragmatic hernia v0.27 PORCN Zornitza Stark Mode of inheritance for gene: PORCN was changed from Unknown to Other
Congenital diaphragmatic hernia v0.26 PORCN Zornitza Stark reviewed gene: PORCN: Rating: GREEN; Mode of pathogenicity: None; Publications: 25026905; Phenotypes: Focal dermal hypoplasia, MIM# 305600; Mode of inheritance: Other
Mendeliome v0.5378 MYRF Zornitza Stark Phenotypes for gene: MYRF were changed from Nanophthalmos; High hyperopia to Nanophthalmos and high hyperopia; Cardiac-urogenital syndrome, MIM# 618280; Encephalitis/encephalopathy, mild, with reversible myelin vacuolization, MIM# 618113
Mendeliome v0.5377 MYRF Zornitza Stark Publications for gene: MYRF were set to 31048900; 31172260; 31266062; 31700225
Mendeliome v0.5376 MYRF Zornitza Stark edited their review of gene: MYRF: Added comment: Association with Encephalitis/encephalopathy, mild, with reversible myelin vacuolization 618113: limited evidence, two multiplex families with same missense variant (likely founder effect) reported (p.Gln403Arg); Changed publications: 31048900, 31172260, 31266062, 31700225, 29446546, 29446546, 30532227, 31069960, 29265453; Changed phenotypes: Nanophthalmos and high hyperopia, Cardiac-urogenital syndrome, MIM# 618280, Encephalitis/encephalopathy, mild, with reversible myelin vacuolization, MIM# 618113
Mendeliome v0.5376 MYRF Zornitza Stark changed review comment from: Cardiac-urogenital syndrome is characterized by partial anomalous pulmonary venous return in association with tracheal anomalies, pulmonary hypoplasia, congenital diaphragmatic hernia, thyroid fibrosis, thymic involution, cleft spleen, penoscrotal hypospadias, and cryptorchidism. More than 10 unrelated individuals reported.; to: Cardiac-urogenital syndrome MIM# 618280 is characterized by partial anomalous pulmonary venous return in association with tracheal anomalies, pulmonary hypoplasia, congenital diaphragmatic hernia, thyroid fibrosis, thymic involution, cleft spleen, penoscrotal hypospadias, and cryptorchidism. More than 10 unrelated individuals reported.
Mendeliome v0.5376 MYRF Zornitza Stark edited their review of gene: MYRF: Added comment: Cardiac-urogenital syndrome is characterized by partial anomalous pulmonary venous return in association with tracheal anomalies, pulmonary hypoplasia, congenital diaphragmatic hernia, thyroid fibrosis, thymic involution, cleft spleen, penoscrotal hypospadias, and cryptorchidism. More than 10 unrelated individuals reported.; Changed publications: 31048900, 31172260, 31266062, 31700225, 29446546, 29446546, 30532227, 31069960; Changed phenotypes: Nanophthalmos and high hyperopia, Cardiac-urogenital syndrome, MIM# 618280
Mendeliome v0.5376 MYRF Zornitza Stark changed review comment from: Multiple affected individuals reported.
Sources: Expert list; to: Multiple affected individuals reported with nanophthalmos and high hyperopia and C-terminal frameshift variants, with or without dextrocardia or congenital diaphragmatic hernia.
Sources: Expert list
Congenital diaphragmatic hernia v0.26 MYRF Zornitza Stark Marked gene: MYRF as ready
Congenital diaphragmatic hernia v0.26 MYRF Zornitza Stark Gene: myrf has been classified as Green List (High Evidence).
Congenital diaphragmatic hernia v0.26 MYRF Zornitza Stark Classified gene: MYRF as Green List (high evidence)
Congenital diaphragmatic hernia v0.26 MYRF Zornitza Stark Gene: myrf has been classified as Green List (High Evidence).
Congenital diaphragmatic hernia v0.25 MYRF Zornitza Stark gene: MYRF was added
gene: MYRF was added to Congenital diaphragmatic hernia. Sources: Expert list
Mode of inheritance for gene: MYRF was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MYRF were set to 29446546; 29446546; 30532227; 31069960
Phenotypes for gene: MYRF were set to Cardiac-urogenital syndrome, MIM# 618280
Review for gene: MYRF was set to GREEN
Added comment: Cardiac-urogenital syndrome is characterized by partial anomalous pulmonary venous return in association with tracheal anomalies, pulmonary hypoplasia, congenital diaphragmatic hernia, thyroid fibrosis, thymic involution, cleft spleen, penoscrotal hypospadias, and cryptorchidism.

More than 10 unrelated individuals reported.
Sources: Expert list
Congenital diaphragmatic hernia v0.24 NR2F2 Zornitza Stark Marked gene: NR2F2 as ready
Congenital diaphragmatic hernia v0.24 NR2F2 Zornitza Stark Gene: nr2f2 has been classified as Green List (High Evidence).
Congenital diaphragmatic hernia v0.24 NR2F2 Zornitza Stark Classified gene: NR2F2 as Green List (high evidence)
Congenital diaphragmatic hernia v0.24 NR2F2 Zornitza Stark Gene: nr2f2 has been classified as Green List (High Evidence).
Congenital diaphragmatic hernia v0.23 NR2F2 Zornitza Stark gene: NR2F2 was added
gene: NR2F2 was added to Congenital diaphragmatic hernia. Sources: Expert list
Mode of inheritance for gene: NR2F2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NR2F2 were set to 29570242; 29966037; 27363585
Phenotypes for gene: NR2F2 were set to Congenital heart defects, multiple types, 4, MIM# 615779
Review for gene: NR2F2 was set to GREEN
Added comment: The multiple types of congenital heart defects observed in CHTD4 include atrial, ventricular, and atrioventricular septal defects, double-outlet right ventricle, tetralogy of Fallot, hypoplastic left heart syndrome, aortic stenosis, and coarctation of the aorta. Intrafamilial variability and incomplete penetrance has been reported. Some exhibit syndromic features such as developmental delay, congenital diaphragmatic hernia, and severe gastro-oesophageal reflux.

CDH reported in more than 3 unrelated individuals.
Sources: Expert list
Congenital diaphragmatic hernia v0.22 GATA6 Zornitza Stark Marked gene: GATA6 as ready
Congenital diaphragmatic hernia v0.22 GATA6 Zornitza Stark Gene: gata6 has been classified as Green List (High Evidence).
Congenital diaphragmatic hernia v0.22 GATA6 Zornitza Stark Classified gene: GATA6 as Green List (high evidence)
Congenital diaphragmatic hernia v0.22 GATA6 Zornitza Stark Gene: gata6 has been classified as Green List (High Evidence).
Congenital diaphragmatic hernia v0.21 GATA6 Zornitza Stark gene: GATA6 was added
gene: GATA6 was added to Congenital diaphragmatic hernia. Sources: Expert list
Mode of inheritance for gene: GATA6 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GATA6 were set to 31301121
Phenotypes for gene: GATA6 were set to Pancreatic agenesis and congenital heart defects, MIM# 600001
Review for gene: GATA6 was set to GREEN
Added comment: Recent review of 78 published cases: most common phenotypes were structural cardiac and pancreatic abnormalities, with a penetrance of 87 and 60%, respectively. Other common malformations were gallbladder agenesis, congenital diaphragmatic hernia, and neurocognitive abnormalities, mostly developmental delay. Approximately half were inherited, variable expressivity.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.3196 RLIM Zornitza Stark Marked gene: RLIM as ready
Intellectual disability syndromic and non-syndromic v0.3196 RLIM Zornitza Stark Gene: rlim has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3196 RLIM Zornitza Stark Phenotypes for gene: RLIM were changed from to Tonne-Kalscheuer syndrome, MIM# 300978
Intellectual disability syndromic and non-syndromic v0.3195 RLIM Zornitza Stark Publications for gene: RLIM were set to
Intellectual disability syndromic and non-syndromic v0.3194 RLIM Zornitza Stark Mode of inheritance for gene: RLIM was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.3193 RLIM Zornitza Stark reviewed gene: RLIM: Rating: GREEN; Mode of pathogenicity: None; Publications: 29728705, 25735484, 25644381; Phenotypes: Tonne-Kalscheuer syndrome, MIM# 300978; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.5376 RLIM Zornitza Stark Marked gene: RLIM as ready
Mendeliome v0.5376 RLIM Zornitza Stark Gene: rlim has been classified as Green List (High Evidence).
Mendeliome v0.5376 RLIM Zornitza Stark Phenotypes for gene: RLIM were changed from to Tonne-Kalscheuer syndrome, MIM# 300978
Mendeliome v0.5375 RLIM Zornitza Stark Publications for gene: RLIM were set to
Mendeliome v0.5374 RLIM Zornitza Stark Mode of inheritance for gene: RLIM was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.5373 RLIM Zornitza Stark reviewed gene: RLIM: Rating: GREEN; Mode of pathogenicity: None; Publications: 29728705, 25735484, 25644381; Phenotypes: Tonne-Kalscheuer syndrome, MIM# 300978; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Congenital diaphragmatic hernia v0.20 RLIM Zornitza Stark Marked gene: RLIM as ready
Congenital diaphragmatic hernia v0.20 RLIM Zornitza Stark Gene: rlim has been classified as Green List (High Evidence).
Congenital diaphragmatic hernia v0.20 RLIM Zornitza Stark Classified gene: RLIM as Green List (high evidence)
Congenital diaphragmatic hernia v0.20 RLIM Zornitza Stark Gene: rlim has been classified as Green List (High Evidence).
Congenital diaphragmatic hernia v0.19 RLIM Zornitza Stark gene: RLIM was added
gene: RLIM was added to Congenital diaphragmatic hernia. Sources: Expert list
Mode of inheritance for gene: RLIM was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: RLIM were set to 29728705; 25735484; 25644381
Phenotypes for gene: RLIM were set to Tonne-Kalscheuer syndrome, MIM# 300978
Review for gene: RLIM was set to GREEN
Added comment: Eight unrelated families and a zebrafish model.

Most individuals exhibit global developmental delay apparent from early infancy, impaired intellectual development, speech delay, behavioural abnormalities, and abnormal gait. Affected individuals also have dysmorphic facial features that evolve with age, anomalies of the hands, feet, and nails, and urogenital abnormalities with hypogenitalism. A subset of more severely affected males develop congenital diaphragmatic hernia in utero, which may result in perinatal or premature death. Carrier females may have very mild skeletal or hormonal abnormalities
Sources: Expert list
Congenital diaphragmatic hernia v0.18 RARB Zornitza Stark Marked gene: RARB as ready
Congenital diaphragmatic hernia v0.18 RARB Zornitza Stark Gene: rarb has been classified as Green List (High Evidence).
Congenital diaphragmatic hernia v0.18 RARB Zornitza Stark Classified gene: RARB as Green List (high evidence)
Congenital diaphragmatic hernia v0.18 RARB Zornitza Stark Gene: rarb has been classified as Green List (High Evidence).
Congenital diaphragmatic hernia v0.17 RARB Zornitza Stark gene: RARB was added
gene: RARB was added to Congenital diaphragmatic hernia. Sources: Expert list
Mode of inheritance for gene: RARB was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: RARB were set to 24075189; 22686418
Phenotypes for gene: RARB were set to Microphthalmia, syndromic 12, MIM# 615524
Review for gene: RARB was set to GREEN
Added comment: Both mono allelic and bi-allelic variants associated with bilateral microphthalmia, pulmonary hypoplasia, and diaphragmatic hernia.
Sources: Expert list
Congenital diaphragmatic hernia v0.16 ZFPM2 Zornitza Stark Marked gene: ZFPM2 as ready
Congenital diaphragmatic hernia v0.16 ZFPM2 Zornitza Stark Gene: zfpm2 has been classified as Green List (High Evidence).
Congenital diaphragmatic hernia v0.16 ZFPM2 Zornitza Stark Classified gene: ZFPM2 as Green List (high evidence)
Congenital diaphragmatic hernia v0.16 ZFPM2 Zornitza Stark Gene: zfpm2 has been classified as Green List (High Evidence).
Congenital diaphragmatic hernia v0.15 ZFPM2 Zornitza Stark gene: ZFPM2 was added
gene: ZFPM2 was added to Congenital diaphragmatic hernia. Sources: Expert list
Mode of inheritance for gene: ZFPM2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ZFPM2 were set to 16103912; 17568391; 24702427
Phenotypes for gene: ZFPM2 were set to Diaphragmatic hernia 3, MIM# 610187
Review for gene: ZFPM2 was set to GREEN
Added comment: More than 5 unrelated families reported with variants in this gene and CDH. Note variants in this gene are also linked to CHD and sex reversal.
Sources: Expert list
Congenital diaphragmatic hernia v0.14 STRA6 Zornitza Stark Marked gene: STRA6 as ready
Congenital diaphragmatic hernia v0.14 STRA6 Zornitza Stark Gene: stra6 has been classified as Green List (High Evidence).
Congenital diaphragmatic hernia v0.14 STRA6 Zornitza Stark Phenotypes for gene: STRA6 were changed from to Microphthalmia, syndromic 9, MIM# 601186
Congenital diaphragmatic hernia v0.13 STRA6 Zornitza Stark Publications for gene: STRA6 were set to
Congenital diaphragmatic hernia v0.12 STRA6 Zornitza Stark Mode of inheritance for gene: STRA6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Congenital diaphragmatic hernia v0.11 STRA6 Zornitza Stark reviewed gene: STRA6: Rating: GREEN; Mode of pathogenicity: None; Publications: 26373900, 22686418]; Phenotypes: Microphthalmia, syndromic 9, MIM# 601186; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Angelman Rett like syndromes v0.46 ADSL Zornitza Stark Marked gene: ADSL as ready
Angelman Rett like syndromes v0.46 ADSL Zornitza Stark Gene: adsl has been classified as Green List (High Evidence).
Angelman Rett like syndromes v0.46 ADSL Zornitza Stark Phenotypes for gene: ADSL were changed from to Adenylosuccinase deficiency, MIM# 103050
Angelman Rett like syndromes v0.45 ADSL Zornitza Stark Mode of inheritance for gene: ADSL was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Angelman Rett like syndromes v0.44 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
Angelman Rett like syndromes v0.44 ACTL6B Zornitza Stark Marked gene: ACTL6B as ready
Angelman Rett like syndromes v0.44 ACTL6B Zornitza Stark Gene: actl6b has been classified as Green List (High Evidence).
Angelman Rett like syndromes v0.44 ACTL6B Zornitza Stark Classified gene: ACTL6B as Green List (high evidence)
Angelman Rett like syndromes v0.44 ACTL6B Zornitza Stark Gene: actl6b has been classified as Green List (High Evidence).
Angelman Rett like syndromes v0.43 ACTL6B Zornitza Stark gene: ACTL6B was added
gene: ACTL6B was added to Angelman Rett like syndromes. Sources: Expert Review
Mode of inheritance for gene: ACTL6B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ACTL6B were set to 31031012
Phenotypes for gene: ACTL6B were set to Intellectual developmental disorder with severe speech and ambulation defects, MIM# 618470
Review for gene: ACTL6B was set to GREEN
Added comment: Ten individuals reported with de novo heterozygous variants and intellectual disability, ambulation deficits, severe language impairment, hypotonia, Rett-like stereotypies, and minor facial dysmorphisms (wide mouth, diastema, bulbous nose). Nine of these ten unrelated individuals had the identical de novo c.1027G>A (p.Gly343Arg) variant.

Note bi-allelic variants cause a neurodevelopmental disorder characterised by epilepsy and spasticity.
Sources: Expert Review
Mackenzie's Mission_Reproductive Carrier Screening v0.48 NTNG2 Zornitza Stark gene: NTNG2 was added
gene: NTNG2 was added to Mackenzie's Mission_Reproductive Carrier Screening. Sources: Expert Review
Mode of inheritance for gene: NTNG2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NTNG2 were set to 31668703; 31692205
Phenotypes for gene: NTNG2 were set to Neurodevelopmental disorder with behavioral abnormalities, absent speech, and hypotonia, MIM# 618718
Review for gene: NTNG2 was set to GREEN
Added comment: Neurodevelopmental disorder with behavioral abnormalities, absent speech, and hypotonia (NEDBASH) is an autosomal recessive disorder characterized by severely impaired intellectual and motor development, axial and peripheral hypotonia usually with inability to walk, and significant behavioral abnormalities consistent with autism spectrum disorder and reminiscent of Rett syndrome, such as poor communication, stereotypic or repetitive behaviours, hand-wringing, bruxism, and sleep disturbances. Other features include poor overall growth, and joint hypermobility. Rare features include seizures, dystonia, spasticity, and nonspecific brain abnormalities.

More than 8 families reported.
Sources: Expert Review
Angelman Rett like syndromes v0.42 NTNG2 Zornitza Stark Marked gene: NTNG2 as ready
Angelman Rett like syndromes v0.42 NTNG2 Zornitza Stark Gene: ntng2 has been classified as Green List (High Evidence).
Angelman Rett like syndromes v0.42 NTNG2 Zornitza Stark Classified gene: NTNG2 as Green List (high evidence)
Angelman Rett like syndromes v0.42 NTNG2 Zornitza Stark Gene: ntng2 has been classified as Green List (High Evidence).
Angelman Rett like syndromes v0.41 NTNG2 Zornitza Stark gene: NTNG2 was added
gene: NTNG2 was added to Angelman Rett like syndromes. Sources: Literature
Mode of inheritance for gene: NTNG2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NTNG2 were set to 31668703; 31692205
Phenotypes for gene: NTNG2 were set to Neurodevelopmental disorder with behavioral abnormalities, absent speech, and hypotonia, MIM# 618718
Review for gene: NTNG2 was set to GREEN
Added comment: Neurodevelopmental disorder with behavioral abnormalities, absent speech, and hypotonia (NEDBASH) is an autosomal recessive disorder characterized by severely impaired intellectual and motor development, axial and peripheral hypotonia usually with inability to walk, and significant behavioral abnormalities consistent with autism spectrum disorder and reminiscent of Rett syndrome, such as poor communication, stereotypic or repetitive behaviours, hand-wringing, bruxism, and sleep disturbances. Other features include poor overall growth, and joint hypermobility. Rare features include seizures, dystonia, spasticity, and nonspecific brain abnormalities.

More than 8 families reported.
Sources: Literature
Angelman Rett like syndromes v0.40 GRIN2B Zornitza Stark Marked gene: GRIN2B as ready
Angelman Rett like syndromes v0.40 GRIN2B Zornitza Stark Gene: grin2b has been classified as Green List (High Evidence).
Angelman Rett like syndromes v0.40 GRIN2B Zornitza Stark Classified gene: GRIN2B as Green List (high evidence)
Angelman Rett like syndromes v0.40 GRIN2B Zornitza Stark Gene: grin2b has been classified as Green List (High Evidence).
Angelman Rett like syndromes v0.39 GRIN2B Zornitza Stark gene: GRIN2B was added
gene: GRIN2B was added to Angelman Rett like syndromes. Sources: Expert list
Mode of inheritance for gene: GRIN2B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GRIN2B were set to 31409060; 28734458
Phenotypes for gene: GRIN2B were set to Mental retardation, autosomal dominant 6, MIM# 613970; Developmental and epileptic encephalopathy 27, MIM# 616139
Review for gene: GRIN2B was set to GREEN
Added comment: More than 3 individuals reported as part of Rett-like cohorts.
Sources: Expert list
Mendeliome v0.5373 GABBR2 Zornitza Stark commented on gene: GABBR2: At least 3 unrelated individuals reported with DEE 59, MIM# 617904. Neurodevelopmental disorder with poor language and loss of hand skills, MIM# 617903 is an allelic disorder, which is less severe. The two may represent a spectrum.
Genetic Epilepsy v0.905 GABBR2 Zornitza Stark Marked gene: GABBR2 as ready
Genetic Epilepsy v0.905 GABBR2 Zornitza Stark Gene: gabbr2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.905 GABBR2 Zornitza Stark Phenotypes for gene: GABBR2 were changed from to Developmental and epileptic encephalopathy 59, MIM# 617904
Mendeliome v0.5373 GABBR2 Zornitza Stark edited their review of gene: GABBR2: Changed publications: 29100083, 28061363, 28135719, 28856709, 29369404, 29377213, 25262651, 28856709; Changed phenotypes: Neurodevelopmental disorder with poor language and loss of hand skills, 617903, Developmental and epileptic encephalopathy 59, MIM# 617904
Genetic Epilepsy v0.904 GABBR2 Zornitza Stark Publications for gene: GABBR2 were set to
Genetic Epilepsy v0.903 GABBR2 Zornitza Stark Mode of inheritance for gene: GABBR2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.902 GABBR2 Zornitza Stark reviewed gene: GABBR2: Rating: GREEN; Mode of pathogenicity: None; Publications: 29100083, 25262651, 28856709; Phenotypes: Developmental and epileptic encephalopathy 59, MIM# 617904; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Angelman Rett like syndromes v0.38 GABBR2 Zornitza Stark Marked gene: GABBR2 as ready
Angelman Rett like syndromes v0.38 GABBR2 Zornitza Stark Gene: gabbr2 has been classified as Green List (High Evidence).
Angelman Rett like syndromes v0.38 GABBR2 Zornitza Stark Classified gene: GABBR2 as Green List (high evidence)
Angelman Rett like syndromes v0.38 GABBR2 Zornitza Stark Gene: gabbr2 has been classified as Green List (High Evidence).
Angelman Rett like syndromes v0.37 GABBR2 Zornitza Stark gene: GABBR2 was added
gene: GABBR2 was added to Angelman Rett like syndromes. Sources: Expert list
Mode of inheritance for gene: GABBR2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GABBR2 were set to 28856709; 26740508; 29369404
Phenotypes for gene: GABBR2 were set to Neurodevelopmental disorder with poor language and loss of hand skills, MIM# 617903
Review for gene: GABBR2 was set to GREEN
Added comment: NDPLHS is an autosomal dominant disorder characterized by developmental stagnation or regression apparent in the first years of life and manifest as loss of purposeful hand movements, loss of language, and intellectual disability. Additional features may include stereotypic movements, dystonia, gait abnormalities, sleep disturbances, and small hands and feet. The phenotype is reminiscent of Rett syndrome.

At least 5 unrelated individuals reported.
Sources: Expert list
Angelman Rett like syndromes v0.36 SMC1A Zornitza Stark Marked gene: SMC1A as ready
Angelman Rett like syndromes v0.36 SMC1A Zornitza Stark Gene: smc1a has been classified as Green List (High Evidence).
Angelman Rett like syndromes v0.36 SMC1A Zornitza Stark Classified gene: SMC1A as Green List (high evidence)
Angelman Rett like syndromes v0.36 SMC1A Zornitza Stark Gene: smc1a has been classified as Green List (High Evidence).
Angelman Rett like syndromes v0.35 SMC1A Zornitza Stark gene: SMC1A was added
gene: SMC1A was added to Angelman Rett like syndromes. Sources: Expert list
Mode of inheritance for gene: SMC1A was set to Other
Publications for gene: SMC1A were set to 29023665; 31409060
Phenotypes for gene: SMC1A were set to Cornelia de Lange syndrome 2, MIM# 300590; Epileptic encephalopathy, early infantile, 85, with or without midline brain defects, MIM# 301044
Review for gene: SMC1A was set to GREEN
Added comment: At least 4 unrelated individuals identified in Rett-like cohorts.
Sources: Expert list
Mendeliome v0.5373 DNAH2 Zornitza Stark Marked gene: DNAH2 as ready
Mendeliome v0.5373 DNAH2 Zornitza Stark Gene: dnah2 has been classified as Green List (High Evidence).
Mendeliome v0.5373 DNAH2 Zornitza Stark Classified gene: DNAH2 as Green List (high evidence)
Mendeliome v0.5373 DNAH2 Zornitza Stark Gene: dnah2 has been classified as Green List (High Evidence).
Mendeliome v0.5372 DNAH2 Zornitza Stark gene: DNAH2 was added
gene: DNAH2 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: DNAH2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DNAH2 were set to 30811583
Phenotypes for gene: DNAH2 were set to Spermatogenic failure 45, MIM# 619094
Review for gene: DNAH2 was set to GREEN
Added comment: Three unrelated families reported.
Sources: Expert list
Mendeliome v0.5371 CLDN9 Zornitza Stark Phenotypes for gene: CLDN9 were changed from Deafness, autosomal recessive to Deafness, autosomal recessive 116, MIM#619093
Mendeliome v0.5370 CLDN9 Zornitza Stark edited their review of gene: CLDN9: Changed phenotypes: Deafness, autosomal recessive 116, MIM#619093
Deafness_IsolatedAndComplex v1.17 CLDN9 Zornitza Stark Phenotypes for gene: CLDN9 were changed from Deafness, autosomal recessive to Deafness, autosomal recessive 116, MIM#619093
Deafness_IsolatedAndComplex v1.16 CLDN9 Zornitza Stark edited their review of gene: CLDN9: Changed phenotypes: Deafness, autosomal recessive 116, MIM#619093
Autoinflammatory Disorders v0.98 UBA1 Zornitza Stark Phenotypes for gene: UBA1 were changed from Autoinflammatory disease, adult onset; VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) to Autoinflammatory disease, adult onset; VEXAS syndrome (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic), MIM#301054
Autoinflammatory Disorders v0.97 UBA1 Zornitza Stark Publications for gene: UBA1 were set to
Autoinflammatory Disorders v0.96 UBA1 Zornitza Stark edited their review of gene: UBA1: Changed phenotypes: Autoinflammatory disease, adult onset, VEXAS syndrome (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic), MIM#301054
Mendeliome v0.5370 UBA1 Zornitza Stark Phenotypes for gene: UBA1 were changed from Spinal muscular atrophy, X-linked 2, infantile, MIM# 301830; Autoinflammatory disease, adult onset: VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) to Spinal muscular atrophy, X-linked 2, infantile, MIM# 301830; Autoinflammatory disease, adult onset: VEXAS syndrome (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) #301054
Mendeliome v0.5369 UBA1 Zornitza Stark edited their review of gene: UBA1: Changed phenotypes: Spinal muscular atrophy, X-linked 2, infantile, MIM# 301830, Autoinflammatory disease, adult onset: VEXAS syndrome (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) #301054
Angelman Rett like syndromes v0.34 WDR45 Zornitza Stark Marked gene: WDR45 as ready
Angelman Rett like syndromes v0.34 WDR45 Zornitza Stark Gene: wdr45 has been classified as Green List (High Evidence).
Angelman Rett like syndromes v0.34 WDR45 Zornitza Stark Classified gene: WDR45 as Green List (high evidence)
Angelman Rett like syndromes v0.34 WDR45 Zornitza Stark Gene: wdr45 has been classified as Green List (High Evidence).
Angelman Rett like syndromes v0.33 WDR45 Zornitza Stark gene: WDR45 was added
gene: WDR45 was added to Angelman Rett like syndromes. Sources: Expert list
Mode of inheritance for gene: WDR45 was set to Other
Publications for gene: WDR45 were set to 26790960; 31409060
Phenotypes for gene: WDR45 were set to Neurodegeneration with brain iron accumulation 5, MIM# 300894
Review for gene: WDR45 was set to GREEN
Added comment: XLD.

Multiple individuals reported as part of Rett-like cohorts.
Sources: Expert list
Angelman Rett like syndromes v0.32 SYNGAP1 Zornitza Stark Marked gene: SYNGAP1 as ready
Angelman Rett like syndromes v0.32 SYNGAP1 Zornitza Stark Gene: syngap1 has been classified as Green List (High Evidence).
Angelman Rett like syndromes v0.32 SYNGAP1 Zornitza Stark Classified gene: SYNGAP1 as Green List (high evidence)
Angelman Rett like syndromes v0.32 SYNGAP1 Zornitza Stark Gene: syngap1 has been classified as Green List (High Evidence).
Angelman Rett like syndromes v0.31 SYNGAP1 Zornitza Stark gene: SYNGAP1 was added
gene: SYNGAP1 was added to Angelman Rett like syndromes. Sources: Expert list
Mode of inheritance for gene: SYNGAP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SYNGAP1 were set to 31105003
Phenotypes for gene: SYNGAP1 were set to Mental retardation, autosomal dominant 5, MIM# 612621
Review for gene: SYNGAP1 was set to GREEN
Added comment: More than 3 unrelated individuals reported as part of Rett-like cohorts.
Sources: Expert list
Angelman Rett like syndromes v0.30 KCNQ2 Zornitza Stark Marked gene: KCNQ2 as ready
Angelman Rett like syndromes v0.30 KCNQ2 Zornitza Stark Gene: kcnq2 has been classified as Green List (High Evidence).
Angelman Rett like syndromes v0.30 KCNQ2 Zornitza Stark Classified gene: KCNQ2 as Green List (high evidence)
Angelman Rett like syndromes v0.30 KCNQ2 Zornitza Stark Gene: kcnq2 has been classified as Green List (High Evidence).
Angelman Rett like syndromes v0.29 KCNQ2 Zornitza Stark gene: KCNQ2 was added
gene: KCNQ2 was added to Angelman Rett like syndromes. Sources: Expert list
Mode of inheritance for gene: KCNQ2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KCNQ2 were set to 31105003; 33134511
Phenotypes for gene: KCNQ2 were set to Epileptic encephalopathy, early infantile, 7, MIM# 613720
Review for gene: KCNQ2 was set to GREEN
Added comment: More than 3 unrelated individuals identified as part of Rett-like cohorts.
Sources: Expert list
Angelman Rett like syndromes v0.28 SCN2A Zornitza Stark Marked gene: SCN2A as ready
Angelman Rett like syndromes v0.28 SCN2A Zornitza Stark Gene: scn2a has been classified as Green List (High Evidence).
Angelman Rett like syndromes v0.28 SCN2A Zornitza Stark Classified gene: SCN2A as Green List (high evidence)
Angelman Rett like syndromes v0.28 SCN2A Zornitza Stark Gene: scn2a has been classified as Green List (High Evidence).
Angelman Rett like syndromes v0.27 SCN2A Zornitza Stark gene: SCN2A was added
gene: SCN2A was added to Angelman Rett like syndromes. Sources: Expert list
Mode of inheritance for gene: SCN2A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SCN2A were set to 31105003
Phenotypes for gene: SCN2A were set to Developmental and epileptic encephalopathy 11, MIM# 613721; Rett-like
Review for gene: SCN2A was set to GREEN
Added comment: More than 5 unrelated individuals reported in Rett-like cohorts.
Sources: Expert list
Mendeliome v0.5369 FGFR1 Zornitza Stark Marked gene: FGFR1 as ready
Mendeliome v0.5369 FGFR1 Zornitza Stark Gene: fgfr1 has been classified as Green List (High Evidence).
Mendeliome v0.5369 FGFR1 Zornitza Stark Tag somatic tag was added to gene: FGFR1.
Mendeliome v0.5369 FGFR1 Zornitza Stark Phenotypes for gene: FGFR1 were changed from to Encephalocraniocutaneous lipomatosis, somatic mosaic 613001; Hartsfield syndrome 615465; Hypogonadotropic hypogonadism 2 with or without anosmia 147950; Jackson-Weiss syndrome 123150; Osteoglophonic dysplasia 166250; Pfeiffer syndrome 101600; Trigonocephaly 1 190440
Mendeliome v0.5368 FGFR1 Zornitza Stark Publications for gene: FGFR1 were set to
Mendeliome v0.5367 FGFR1 Zornitza Stark Mode of pathogenicity for gene: FGFR1 was changed from to Other
Mendeliome v0.5366 FGFR1 Zornitza Stark Mode of inheritance for gene: FGFR1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Congenital Disorders of Glycosylation v0.185 B4GALT7 Zornitza Stark Marked gene: B4GALT7 as ready
Congenital Disorders of Glycosylation v0.185 B4GALT7 Zornitza Stark Gene: b4galt7 has been classified as Green List (High Evidence).
Congenital Disorders of Glycosylation v0.185 B4GALT7 Zornitza Stark Phenotypes for gene: B4GALT7 were changed from to Ehlers-Danlos syndrome, spondylodysplastic type, 1, 130070
Congenital Disorders of Glycosylation v0.184 B4GALT7 Zornitza Stark Publications for gene: B4GALT7 were set to
Congenital Disorders of Glycosylation v0.183 B4GALT7 Zornitza Stark Mode of inheritance for gene: B4GALT7 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Congenital Disorders of Glycosylation v0.182 B4GALT7 Zornitza Stark Tag founder tag was added to gene: B4GALT7.
Congenital Disorders of Glycosylation v0.182 B4GALT7 Zornitza Stark reviewed gene: B4GALT7: Rating: GREEN; Mode of pathogenicity: None; Publications: 23956117, 24755949, 31278392, 31614862, 31862401; Phenotypes: Ehlers-Danlos syndrome, spondylodysplastic type, 1, 130070; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3193 B4GALT7 Zornitza Stark Marked gene: B4GALT7 as ready
Intellectual disability syndromic and non-syndromic v0.3193 B4GALT7 Zornitza Stark Gene: b4galt7 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3193 B4GALT7 Zornitza Stark Phenotypes for gene: B4GALT7 were changed from to Ehlers-Danlos syndrome, spondylodysplastic type, 1, MIM# 130070
Intellectual disability syndromic and non-syndromic v0.3192 B4GALT7 Zornitza Stark Publications for gene: B4GALT7 were set to
Intellectual disability syndromic and non-syndromic v0.3191 B4GALT7 Zornitza Stark Mode of inheritance for gene: B4GALT7 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3190 B4GALT7 Zornitza Stark reviewed gene: B4GALT7: Rating: AMBER; Mode of pathogenicity: None; Publications: 23956117, 24755949, 31278392, 31614862, 31862401; Phenotypes: Ehlers-Danlos syndrome, spondylodysplastic type, 1, MIM# 130070; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5365 B4GALT7 Zornitza Stark Marked gene: B4GALT7 as ready
Mendeliome v0.5365 B4GALT7 Zornitza Stark Gene: b4galt7 has been classified as Green List (High Evidence).
Mendeliome v0.5365 B4GALT7 Zornitza Stark Phenotypes for gene: B4GALT7 were changed from to Ehlers-Danlos syndrome, spondylodysplastic type, 1, MIM# 130070
Mendeliome v0.5364 B4GALT7 Zornitza Stark Publications for gene: B4GALT7 were set to
Mendeliome v0.5363 B4GALT7 Zornitza Stark Mode of inheritance for gene: B4GALT7 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5362 B4GALT7 Zornitza Stark Tag founder tag was added to gene: B4GALT7.
Mendeliome v0.5362 B4GALT7 Zornitza Stark reviewed gene: B4GALT7: Rating: GREEN; Mode of pathogenicity: None; Publications: 23956117, 24755949; Phenotypes: Ehlers-Danlos syndrome, spondylodysplastic type, 1, MIM# 130070; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal Dysplasia_Fetal v0.37 TBX6 Zornitza Stark Marked gene: TBX6 as ready
Skeletal Dysplasia_Fetal v0.37 TBX6 Zornitza Stark Gene: tbx6 has been classified as Green List (High Evidence).
Skeletal Dysplasia_Fetal v0.37 TBX6 Zornitza Stark Phenotypes for gene: TBX6 were changed from to Spondylocostal dysostosis 5, 122600
Skeletal Dysplasia_Fetal v0.36 TBX6 Zornitza Stark Publications for gene: TBX6 were set to
Skeletal Dysplasia_Fetal v0.35 TBX6 Zornitza Stark Mode of inheritance for gene: TBX6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Skeletal Dysplasia_Fetal v0.34 TBX6 Zornitza Stark reviewed gene: TBX6: Rating: GREEN; Mode of pathogenicity: None; Publications: 8954725, 20503311, 23335591, 25564734, 31015262, 30307510, 31015262; Phenotypes: Spondylocostal dysostosis 5, 122600; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5362 TBX6 Zornitza Stark Phenotypes for gene: TBX6 were changed from Skeletal dysplasia; spondylocostal dysostosis; congenital scoliosis to Spondylocostal dysostosis 5, 122600
Skeletal dysplasia v0.64 TBX6 Zornitza Stark Marked gene: TBX6 as ready
Skeletal dysplasia v0.64 TBX6 Zornitza Stark Gene: tbx6 has been classified as Green List (High Evidence).
Skeletal dysplasia v0.64 TBX6 Zornitza Stark Phenotypes for gene: TBX6 were changed from Spondylocostal dysostosis 5 122600; Spondylocostal dysostosis 5 122600 to Spondylocostal dysostosis 5 122600
Skeletal dysplasia v0.63 TBX6 Zornitza Stark Publications for gene: TBX6 were set to
Skeletal dysplasia v0.62 TBX6 Zornitza Stark Mode of inheritance for gene: TBX6 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v0.61 TBX6 Zornitza Stark reviewed gene: TBX6: Rating: GREEN; Mode of pathogenicity: None; Publications: 33058178, 31015262, 30636772, 28054739, 23335591, 30307510; Phenotypes: Spondylocostal dysostosis 5, 122600; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.902 KCNQ2 Zornitza Stark Marked gene: KCNQ2 as ready
Genetic Epilepsy v0.902 KCNQ2 Zornitza Stark Gene: kcnq2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.902 KCNQ2 Zornitza Stark Phenotypes for gene: KCNQ2 were changed from to Epileptic encephalopathy, early infantile, 7, 613720; Seizures, benign neonatal, 1, 121200
Genetic Epilepsy v0.901 KCNQ2 Zornitza Stark Publications for gene: KCNQ2 were set to
Genetic Epilepsy v0.900 KCNQ2 Zornitza Stark Mode of pathogenicity for gene: KCNQ2 was changed from to Other
Genetic Epilepsy v0.899 KCNQ2 Zornitza Stark Mode of inheritance for gene: KCNQ2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.898 KCNQ2 Zornitza Stark reviewed gene: KCNQ2: Rating: GREEN; Mode of pathogenicity: Other; Publications: 25959266, 32917465, 24318194; Phenotypes: Epileptic encephalopathy, early infantile, 7, 613720, Seizures, benign neonatal, 1, 121200; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5361 KCNQ2 Zornitza Stark edited their review of gene: KCNQ2: Changed rating: GREEN
Mendeliome v0.5361 KCNQ2 Zornitza Stark Marked gene: KCNQ2 as ready
Mendeliome v0.5361 KCNQ2 Zornitza Stark Gene: kcnq2 has been classified as Green List (High Evidence).
Mendeliome v0.5361 KCNQ2 Zornitza Stark Phenotypes for gene: KCNQ2 were changed from to Epileptic encephalopathy, early infantile, 7, 613720; Seizures, benign neonatal, 1, 121200; Myokymia, 121200
Mendeliome v0.5360 KCNQ2 Zornitza Stark Publications for gene: KCNQ2 were set to
Mendeliome v0.5359 KCNQ2 Zornitza Stark Mode of pathogenicity for gene: KCNQ2 was changed from to Other
Mendeliome v0.5358 KCNQ2 Zornitza Stark Mode of inheritance for gene: KCNQ2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5357 KCNQ2 Elena Savva reviewed gene: KCNQ2: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID 25959266, 32917465, 24318194; Phenotypes: Epileptic encephalopathy, early infantile, 7, 613720, Seizures, benign neonatal, 1, 121200, Myokymia, 121200; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Mendeliome v0.5357 B4GALT7 Elena Savva reviewed gene: B4GALT7: Rating: GREEN; Mode of pathogenicity: None; Publications: Ehlers-Danlos syndrome, spondylodysplastic type, 1, 130070; Phenotypes: PMID: 31278392, 31614862, 31862401; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5357 FGFR1 Elena Savva reviewed gene: FGFR1: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 18034870, 23812909, 26942290; Phenotypes: Encephalocraniocutaneous lipomatosis, somatic mosaic 613001, Hartsfield syndrome 615465, Hypogonadotropic hypogonadism 2 with or without anosmia 147950, Jackson-Weiss syndrome 123150, Osteoglophonic dysplasia 166250, Pfeiffer syndrome 101600, Trigonocephaly 1 190440; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Autonomic neuropathy v0.42 LIFR Alison Yeung Marked gene: LIFR as ready
Autonomic neuropathy v0.42 LIFR Alison Yeung Gene: lifr has been classified as Green List (High Evidence).
Autonomic neuropathy v0.42 LIFR Alison Yeung Classified gene: LIFR as Green List (high evidence)
Autonomic neuropathy v0.42 LIFR Alison Yeung Gene: lifr has been classified as Green List (High Evidence).
Autonomic neuropathy v0.41 LIFR Alison Yeung gene: LIFR was added
gene: LIFR was added to Autonomic neuropathy. Sources: Literature
Mode of inheritance for gene: LIFR was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: LIFR were set to OMIM# 601559 STUVE-WIEDEMANN SYNDROME; STWS
gene: LIFR was marked as current diagnostic
Added comment: Dysautonomia a common feature
Sources: Literature
Angelman Rett like syndromes v0.26 KIF1A Zornitza Stark Marked gene: KIF1A as ready
Angelman Rett like syndromes v0.26 KIF1A Zornitza Stark Gene: kif1a has been classified as Green List (High Evidence).
Angelman Rett like syndromes v0.26 KIF1A Zornitza Stark Classified gene: KIF1A as Green List (high evidence)
Angelman Rett like syndromes v0.26 KIF1A Zornitza Stark Gene: kif1a has been classified as Green List (High Evidence).
Angelman Rett like syndromes v0.25 KIF1A Zornitza Stark gene: KIF1A was added
gene: KIF1A was added to Angelman Rett like syndromes. Sources: Literature
Mode of inheritance for gene: KIF1A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KIF1A were set to 31512412; 32652677
Phenotypes for gene: KIF1A were set to NESCAV syndrome, MIM# 614255; Rett-like syndrome
Review for gene: KIF1A was set to GREEN
Added comment: Individuals identified in Rett and Rett-like cohorts.
Sources: Literature
Tuberous Sclerosis_Focal Cortical Dysplasia_Hemimegalencephaly v0.27 TSC1 Zornitza Stark Marked gene: TSC1 as ready
Tuberous Sclerosis_Focal Cortical Dysplasia_Hemimegalencephaly v0.27 TSC1 Zornitza Stark Gene: tsc1 has been classified as Green List (High Evidence).
Tuberous Sclerosis_Focal Cortical Dysplasia_Hemimegalencephaly v0.27 TSC1 Zornitza Stark Phenotypes for gene: TSC1 were changed from to Tuberous sclerosis-1, 191100; Autosomal dominant Focal cortical dysplasia, type II, somatic, 607341
Tuberous Sclerosis_Focal Cortical Dysplasia_Hemimegalencephaly v0.26 TSC1 Zornitza Stark Publications for gene: TSC1 were set to 32917966
Tuberous Sclerosis_Focal Cortical Dysplasia_Hemimegalencephaly v0.25 TSC1 Zornitza Stark Publications for gene: TSC1 were set to
Tuberous Sclerosis_Focal Cortical Dysplasia_Hemimegalencephaly v0.24 TSC1 Zornitza Stark Mode of inheritance for gene: TSC1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Tuberous Sclerosis_Focal Cortical Dysplasia_Hemimegalencephaly v0.23 TSC1 Zornitza Stark Tag SV/CNV tag was added to gene: TSC1.
Tuberous Sclerosis_Focal Cortical Dysplasia_Hemimegalencephaly v0.23 TSC1 Elena Savva reviewed gene: TSC1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 32917966; Phenotypes: Tuberous sclerosis-1, 191100, Autosomal dominant Focal cortical dysplasia, type II, somatic, 607341, Lymphangioleiomyomatosis, 606690; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mackenzie's Mission_Reproductive Carrier Screening v0.47 NHS Sarah Righetti reviewed gene: NHS: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Mackenzie's Mission_Reproductive Carrier Screening v0.47 COL4A5 Sarah Righetti reviewed gene: COL4A5: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Congenital ophthalmoplegia v0.47 CHRNA1 Zornitza Stark Marked gene: CHRNA1 as ready
Congenital ophthalmoplegia v0.47 CHRNA1 Zornitza Stark Gene: chrna1 has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.47 CHRNA1 Zornitza Stark Classified gene: CHRNA1 as Green List (high evidence)
Congenital ophthalmoplegia v0.47 CHRNA1 Zornitza Stark Gene: chrna1 has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.46 CHRNA1 Zornitza Stark gene: CHRNA1 was added
gene: CHRNA1 was added to Congenital ophthalmoplegia. Sources: Expert list
Mode of inheritance for gene: CHRNA1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: CHRNA1 were set to Myasthenic syndrome, congenital, 1A, slow-channel, MIM# 601462
Review for gene: CHRNA1 was set to GREEN
Added comment: Ophthalmoplegia is a feature of this condition.
Sources: Expert list
Dilated Cardiomyopathy v0.89 FKRP Zornitza Stark Marked gene: FKRP as ready
Dilated Cardiomyopathy v0.89 FKRP Zornitza Stark Gene: fkrp has been classified as Green List (High Evidence).
Dilated Cardiomyopathy v0.89 FKRP Zornitza Stark Phenotypes for gene: FKRP were changed from Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 5, 607155; Muscular dystrophy-dystroglycanopathy (congenital with or without mental retardation), type B, 5, 606612; Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 5, 613153 to Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 5, 607155
Dilated Cardiomyopathy v0.88 FKRP Zornitza Stark Classified gene: FKRP as Green List (high evidence)
Dilated Cardiomyopathy v0.88 FKRP Zornitza Stark Gene: fkrp has been classified as Green List (High Evidence).
Dilated Cardiomyopathy v0.87 FKRP Elena Savva gene: FKRP was added
gene: FKRP was added to Dilated Cardiomyopathy. Sources: Literature
Mode of inheritance for gene: FKRP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FKRP were set to PMID: 32914449
Phenotypes for gene: FKRP were set to Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 5, 607155; Muscular dystrophy-dystroglycanopathy (congenital with or without mental retardation), type B, 5, 606612; Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 5, 613153
Review for gene: FKRP was set to GREEN
Added comment: PMID: 32914449 - reviewed 56 patients w/ LGMD R9 and biallelic FKRP mutations. Dilated cardiomyopathy detected in 45% of patients with a median age of 54 years for patients homozygous for the common founder c.826C>A, compared to 18 years of age for other genotypes.
Sources: Literature
Congenital ophthalmoplegia v0.45 CHAT Zornitza Stark Marked gene: CHAT as ready
Congenital ophthalmoplegia v0.45 CHAT Zornitza Stark Gene: chat has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.45 CHAT Zornitza Stark Classified gene: CHAT as Green List (high evidence)
Congenital ophthalmoplegia v0.45 CHAT Zornitza Stark Gene: chat has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.44 CHAT Zornitza Stark gene: CHAT was added
gene: CHAT was added to Congenital ophthalmoplegia. Sources: Expert list
Mode of inheritance for gene: CHAT was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CHAT were set to Myasthenic syndrome, congenital, 6, presynaptic, MIM# 254210
Review for gene: CHAT was set to GREEN
Added comment: Ophthalmoparesis and strabismus are a feature.
Sources: Expert list
Congenital ophthalmoplegia v0.43 OPA1 Zornitza Stark Marked gene: OPA1 as ready
Congenital ophthalmoplegia v0.43 OPA1 Zornitza Stark Gene: opa1 has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.43 OPA1 Zornitza Stark Classified gene: OPA1 as Green List (high evidence)
Congenital ophthalmoplegia v0.43 OPA1 Zornitza Stark Gene: opa1 has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.42 OPA1 Zornitza Stark gene: OPA1 was added
gene: OPA1 was added to Congenital ophthalmoplegia. Sources: Expert list
Mode of inheritance for gene: OPA1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: OPA1 were set to Optic atrophy plus syndrome, MIM# 125250
Review for gene: OPA1 was set to GREEN
Added comment: Childhood onset disorder, characterised by optic atrophy, but progressive external ophthalmoplegia can be a feature.
Sources: Expert list
Congenital ophthalmoplegia v0.41 PIEZO2 Zornitza Stark Marked gene: PIEZO2 as ready
Congenital ophthalmoplegia v0.41 PIEZO2 Zornitza Stark Gene: piezo2 has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.41 PIEZO2 Zornitza Stark Classified gene: PIEZO2 as Green List (high evidence)
Congenital ophthalmoplegia v0.41 PIEZO2 Zornitza Stark Gene: piezo2 has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.40 PIEZO2 Zornitza Stark gene: PIEZO2 was added
gene: PIEZO2 was added to Congenital ophthalmoplegia. Sources: Expert list
Mode of inheritance for gene: PIEZO2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: PIEZO2 were set to Arthrogryposis, distal, type 5, MIM# 108145; Arthrogryposis, distal, type 3, MIM# 114300
Review for gene: PIEZO2 was set to GREEN
Added comment: Ophthalmoplegia is an associated feature.
Sources: Expert list
Congenital ophthalmoplegia v0.39 NDUFS1 Zornitza Stark Marked gene: NDUFS1 as ready
Congenital ophthalmoplegia v0.39 NDUFS1 Zornitza Stark Gene: ndufs1 has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.39 NDUFS1 Zornitza Stark Classified gene: NDUFS1 as Green List (high evidence)
Congenital ophthalmoplegia v0.39 NDUFS1 Zornitza Stark Gene: ndufs1 has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.38 NDUFS1 Zornitza Stark gene: NDUFS1 was added
gene: NDUFS1 was added to Congenital ophthalmoplegia. Sources: Expert list
Mode of inheritance for gene: NDUFS1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NDUFS1 were set to Mitochondrial complex I deficiency, nuclear type 5, MIM# 618226
Review for gene: NDUFS1 was set to GREEN
Added comment: Nystagmus, strabismus and ophthalmoplegia are features.
Sources: Expert list
Congenital ophthalmoplegia v0.37 MGME1 Zornitza Stark Marked gene: MGME1 as ready
Congenital ophthalmoplegia v0.37 MGME1 Zornitza Stark Gene: mgme1 has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.37 MGME1 Zornitza Stark Classified gene: MGME1 as Green List (high evidence)
Congenital ophthalmoplegia v0.37 MGME1 Zornitza Stark Gene: mgme1 has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.36 MGME1 Zornitza Stark gene: MGME1 was added
gene: MGME1 was added to Congenital ophthalmoplegia. Sources: Expert list
Mode of inheritance for gene: MGME1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: MGME1 were set to Mitochondrial DNA depletion syndrome 11, MIM#615084
Review for gene: MGME1 was set to GREEN
Added comment: Onset in the first decade, and progressive external ophthalmoplegia is a prominent feature.
Sources: Expert list
Congenital ophthalmoplegia v0.35 SLC9A6 Zornitza Stark Marked gene: SLC9A6 as ready
Congenital ophthalmoplegia v0.35 SLC9A6 Zornitza Stark Gene: slc9a6 has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.35 SLC9A6 Zornitza Stark Classified gene: SLC9A6 as Green List (high evidence)
Congenital ophthalmoplegia v0.35 SLC9A6 Zornitza Stark Gene: slc9a6 has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.34 SLC9A6 Zornitza Stark gene: SLC9A6 was added
gene: SLC9A6 was added to Congenital ophthalmoplegia. Sources: Expert list
Mode of inheritance for gene: SLC9A6 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Phenotypes for gene: SLC9A6 were set to Mental retardation, X-linked syndromic, Christianson type, MIM# 300243
Review for gene: SLC9A6 was set to GREEN
Added comment: Impaired eye movements including ophthalmoplegia are a feature.
Sources: Expert list
Autonomic neuropathy v0.39 DBH Alison Yeung Marked gene: DBH as ready
Autonomic neuropathy v0.39 DBH Alison Yeung Gene: dbh has been classified as Green List (High Evidence).
Autonomic neuropathy v0.39 DBH Alison Yeung Classified gene: DBH as Green List (high evidence)
Autonomic neuropathy v0.39 DBH Alison Yeung Gene: dbh has been classified as Green List (High Evidence).
Autonomic neuropathy v0.38 DBH Alison Yeung gene: DBH was added
gene: DBH was added to Autonomic neuropathy. Sources: Literature
Mode of inheritance for gene: DBH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DBH were set to 21209083; 11857564
Phenotypes for gene: DBH were set to OMIM# 223360 ORTHOSTATIC HYPOTENSION 1; ORTHYP1
Review for gene: DBH was set to GREEN
Added comment: Two unrelated families reported and functional studies
Sources: Literature
Congenital ophthalmoplegia v0.33 PDHB Zornitza Stark Marked gene: PDHB as ready
Congenital ophthalmoplegia v0.33 PDHB Zornitza Stark Gene: pdhb has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.33 PDHB Zornitza Stark Classified gene: PDHB as Green List (high evidence)
Congenital ophthalmoplegia v0.33 PDHB Zornitza Stark Gene: pdhb has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.32 PDHB Zornitza Stark gene: PDHB was added
gene: PDHB was added to Congenital ophthalmoplegia. Sources: Expert list
Mode of inheritance for gene: PDHB was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PDHB were set to Pyruvate dehydrogenase E1-beta deficiency, MIM# 614111
Review for gene: PDHB was set to GREEN
Added comment: Well established gene disease association, strabismus and abnormal eye movements are a feature in addition to lactic acidosis and hypotonia.
Sources: Expert list
Congenital ophthalmoplegia v0.31 COLQ Zornitza Stark Marked gene: COLQ as ready
Congenital ophthalmoplegia v0.31 COLQ Zornitza Stark Gene: colq has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.31 COLQ Zornitza Stark Classified gene: COLQ as Green List (high evidence)
Congenital ophthalmoplegia v0.31 COLQ Zornitza Stark Gene: colq has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.30 COLQ Zornitza Stark gene: COLQ was added
gene: COLQ was added to Congenital ophthalmoplegia. Sources: Expert list
Mode of inheritance for gene: COLQ was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: COLQ were set to Myasthenic syndrome, congenital, 5, MIM# 603034
Review for gene: COLQ was set to GREEN
Added comment: Well established gene-disease association. Ophthalmoparesis is a feature.
Sources: Expert list
Autonomic neuropathy v0.37 LMNB1 Alison Yeung Marked gene: LMNB1 as ready
Autonomic neuropathy v0.37 LMNB1 Alison Yeung Gene: lmnb1 has been classified as Green List (High Evidence).
Autonomic neuropathy v0.37 LMNB1 Alison Yeung Classified gene: LMNB1 as Green List (high evidence)
Autonomic neuropathy v0.37 LMNB1 Alison Yeung Gene: lmnb1 has been classified as Green List (High Evidence).
Autonomic neuropathy v0.36 LMNB1 Alison Yeung gene: LMNB1 was added
gene: LMNB1 was added to Autonomic neuropathy. Sources: Literature
Mode of inheritance for gene: LMNB1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: LMNB1 were set to OMIM# 169500 LEUKODYSTROPHY, DEMYELINATING, ADULT-ONSET, AUTOSOMAL DOMINANT; ADLD
Review for gene: LMNB1 was set to GREEN
gene: LMNB1 was marked as current diagnostic
Added comment: Autonomic dysfunction a common feature
Sources: Literature
Autonomic neuropathy v0.35 MADD Alison Yeung Marked gene: MADD as ready
Autonomic neuropathy v0.35 MADD Alison Yeung Gene: madd has been classified as Green List (High Evidence).
Autonomic neuropathy v0.35 MADD Alison Yeung Classified gene: MADD as Green List (high evidence)
Autonomic neuropathy v0.35 MADD Alison Yeung Gene: madd has been classified as Green List (High Evidence).
Autonomic neuropathy v0.34 MADD Alison Yeung gene: MADD was added
gene: MADD was added to Autonomic neuropathy. Sources: Literature
Mode of inheritance for gene: MADD was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: MADD were set to OMIM# 619004 DEEAH SYNDROME; DEEAH
Review for gene: MADD was set to GREEN
gene: MADD was marked as current diagnostic
Added comment: Sources: Literature
Autonomic neuropathy v0.33 PHOX2B Alison Yeung Marked gene: PHOX2B as ready
Autonomic neuropathy v0.33 PHOX2B Alison Yeung Gene: phox2b has been classified as Green List (High Evidence).
Autonomic neuropathy v0.33 PHOX2B Alison Yeung Classified gene: PHOX2B as Green List (high evidence)
Autonomic neuropathy v0.33 PHOX2B Alison Yeung Gene: phox2b has been classified as Green List (High Evidence).
Autonomic neuropathy v0.32 PHOX2B Alison Yeung gene: PHOX2B was added
gene: PHOX2B was added to Autonomic neuropathy. Sources: Literature
Mode of inheritance for gene: PHOX2B was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: PHOX2B were set to OMIM# 209880 CENTRAL HYPOVENTILATION SYNDROME, CONGENITAL; CCHS
Review for gene: PHOX2B was set to GREEN
gene: PHOX2B was marked as current diagnostic
Added comment: Sources: Literature
Autonomic neuropathy v0.31 SCN9A Alison Yeung Marked gene: SCN9A as ready
Autonomic neuropathy v0.31 SCN9A Alison Yeung Gene: scn9a has been classified as Green List (High Evidence).
Autonomic neuropathy v0.31 SCN9A Alison Yeung Classified gene: SCN9A as Green List (high evidence)
Autonomic neuropathy v0.31 SCN9A Alison Yeung Gene: scn9a has been classified as Green List (High Evidence).
Autonomic neuropathy v0.30 SCN9A Alison Yeung gene: SCN9A was added
gene: SCN9A was added to Autonomic neuropathy. Sources: Literature
Mode of inheritance for gene: SCN9A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SCN9A were set to 23596073
Phenotypes for gene: SCN9A were set to OMIM# 243000 NEUROPATHY, HEREDITARY SENSORY AND AUTONOMIC, TYPE IID, INCLUDED; HSAN2D,
Review for gene: SCN9A was set to GREEN
Added comment: Two unrelated Japanese families reported
Sources: Literature
Autonomic neuropathy v0.29 GMPPA Alison Yeung Marked gene: GMPPA as ready
Autonomic neuropathy v0.29 GMPPA Alison Yeung Gene: gmppa has been classified as Green List (High Evidence).
Autonomic neuropathy v0.29 GMPPA Alison Yeung Classified gene: GMPPA as Green List (high evidence)
Autonomic neuropathy v0.29 GMPPA Alison Yeung Gene: gmppa has been classified as Green List (High Evidence).
Autonomic neuropathy v0.28 GMPPA Alison Yeung gene: GMPPA was added
gene: GMPPA was added to Autonomic neuropathy. Sources: Literature
Mode of inheritance for gene: GMPPA was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: GMPPA were set to # 615510 ALACRIMA, ACHALASIA, AND MENTAL RETARDATION SYNDROME; AAMR
Review for gene: GMPPA was set to GREEN
gene: GMPPA was marked as current diagnostic
Added comment: Sources: Literature
Autonomic neuropathy v0.27 AAAS Alison Yeung Marked gene: AAAS as ready
Autonomic neuropathy v0.27 AAAS Alison Yeung Gene: aaas has been classified as Green List (High Evidence).
Autonomic neuropathy v0.27 AAAS Alison Yeung Classified gene: AAAS as Green List (high evidence)
Autonomic neuropathy v0.27 AAAS Alison Yeung Gene: aaas has been classified as Green List (High Evidence).
Autonomic neuropathy v0.26 AAAS Alison Yeung gene: AAAS was added
gene: AAAS was added to Autonomic neuropathy. Sources: Literature
Mode of inheritance for gene: AAAS was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: AAAS were set to OMIM# 231550 ACHALASIA-ADDISONIANISM-ALACRIMA SYNDROME; AAAS
Review for gene: AAAS was set to GREEN
gene: AAAS was marked as current diagnostic
Added comment: Sources: Literature
Autonomic neuropathy v0.25 WNK1 Alison Yeung Marked gene: WNK1 as ready
Autonomic neuropathy v0.25 WNK1 Alison Yeung Gene: wnk1 has been classified as Green List (High Evidence).
Autonomic neuropathy v0.25 WNK1 Alison Yeung Classified gene: WNK1 as Green List (high evidence)
Autonomic neuropathy v0.25 WNK1 Alison Yeung Gene: wnk1 has been classified as Green List (High Evidence).
Autonomic neuropathy v0.24 WNK1 Alison Yeung gene: WNK1 was added
gene: WNK1 was added to Autonomic neuropathy. Sources: Literature
Mode of inheritance for gene: WNK1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: WNK1 were set to # 201300 NEUROPATHY, HEREDITARY SENSORY AND AUTONOMIC, TYPE IIA; HSAN2A
Review for gene: WNK1 was set to GREEN
gene: WNK1 was marked as current diagnostic
Added comment: Sources: Literature
Autonomic neuropathy v0.23 ATL3 Alison Yeung Phenotypes for gene: ATL3 were changed from OMIM# 201300 NEUROPATHY, HEREDITARY SENSORY AND AUTONOMIC, TYPE IIA; HSAN2A to # 615632 NEUROPATHY, HEREDITARY SENSORY, TYPE IF; HSN1F
Autonomic neuropathy v0.22 ATL3 Alison Yeung Classified gene: ATL3 as Red List (low evidence)
Autonomic neuropathy v0.22 ATL3 Alison Yeung Gene: atl3 has been classified as Red List (Low Evidence).
Autonomic neuropathy v0.21 ATL3 Alison Yeung commented on gene: ATL3: Incorrect OMIM phenotype entered in previous review. ATL3 variants not associated with autonomic dysfunction.
Autonomic neuropathy v0.21 ATL3 Alison Yeung reviewed gene: ATL3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: # 615632 NEUROPATHY, HEREDITARY SENSORY, TYPE IF, HSN1F; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Autonomic neuropathy v0.21 ATL3 Alison Yeung Deleted their review
Autonomic neuropathy v0.21 SPTLC2 Alison Yeung Marked gene: SPTLC2 as ready
Autonomic neuropathy v0.21 SPTLC2 Alison Yeung Gene: sptlc2 has been classified as Green List (High Evidence).
Autonomic neuropathy v0.21 SPTLC2 Alison Yeung Classified gene: SPTLC2 as Green List (high evidence)
Autonomic neuropathy v0.21 SPTLC2 Alison Yeung Gene: sptlc2 has been classified as Green List (High Evidence).
Autonomic neuropathy v0.20 SPTLC2 Alison Yeung gene: SPTLC2 was added
gene: SPTLC2 was added to Autonomic neuropathy. Sources: Literature
Mode of inheritance for gene: SPTLC2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: SPTLC2 were set to OMIM# 613640 NEUROPATHY, HEREDITARY SENSORY AND AUTONOMIC, TYPE IC; HSAN1C
Review for gene: SPTLC2 was set to GREEN
gene: SPTLC2 was marked as current diagnostic
Added comment: Sources: Literature
Autonomic neuropathy v0.19 ATL3 Alison Yeung Marked gene: ATL3 as ready
Autonomic neuropathy v0.19 ATL3 Alison Yeung Gene: atl3 has been classified as Green List (High Evidence).
Autonomic neuropathy v0.19 ATL3 Alison Yeung Classified gene: ATL3 as Green List (high evidence)
Autonomic neuropathy v0.19 ATL3 Alison Yeung Gene: atl3 has been classified as Green List (High Evidence).
Autonomic neuropathy v0.18 ATL3 Alison Yeung gene: ATL3 was added
gene: ATL3 was added to Autonomic neuropathy. Sources: Literature
Mode of inheritance for gene: ATL3 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ATL3 were set to OMIM# 201300 NEUROPATHY, HEREDITARY SENSORY AND AUTONOMIC, TYPE IIA; HSAN2A
Review for gene: ATL3 was set to GREEN
gene: ATL3 was marked as current diagnostic
Added comment: Sources: Literature
Autonomic neuropathy v0.17 PRDM12 Alison Yeung Marked gene: PRDM12 as ready
Autonomic neuropathy v0.17 PRDM12 Alison Yeung Gene: prdm12 has been classified as Green List (High Evidence).
Autonomic neuropathy v0.17 PRDM12 Alison Yeung Classified gene: PRDM12 as Green List (high evidence)
Autonomic neuropathy v0.17 PRDM12 Alison Yeung Gene: prdm12 has been classified as Green List (High Evidence).
Autonomic neuropathy v0.16 PRDM12 Alison Yeung gene: PRDM12 was added
gene: PRDM12 was added to Autonomic neuropathy. Sources: Literature
Mode of inheritance for gene: PRDM12 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PRDM12 were set to OMIM# 616488 NEUROPATHY, HEREDITARY SENSORY AND AUTONOMIC, TYPE VIII; HSAN8
Review for gene: PRDM12 was set to GREEN
gene: PRDM12 was marked as current diagnostic
Added comment: Sources: Literature
Autonomic neuropathy v0.15 ELP1 Alison Yeung Classified gene: ELP1 as Green List (high evidence)
Autonomic neuropathy v0.15 ELP1 Alison Yeung Gene: elp1 has been classified as Green List (High Evidence).
Autonomic neuropathy v0.14 ELP1 Alison Yeung Marked gene: ELP1 as ready
Autonomic neuropathy v0.14 ELP1 Alison Yeung Gene: elp1 has been classified as Red List (Low Evidence).
Autonomic neuropathy v0.14 ELP1 Alison Yeung gene: ELP1 was added
gene: ELP1 was added to Autonomic neuropathy. Sources: Literature
Mode of inheritance for gene: ELP1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ELP1 were set to OMIM# 223900 NEUROPATHY, HEREDITARY SENSORY AND AUTONOMIC, TYPE III; HSAN3
Review for gene: ELP1 was set to GREEN
gene: ELP1 was marked as current diagnostic
Added comment: Sources: Literature
Autonomic neuropathy v0.13 SPTLC1 Alison Yeung Marked gene: SPTLC1 as ready
Autonomic neuropathy v0.13 SPTLC1 Alison Yeung Gene: sptlc1 has been classified as Green List (High Evidence).
Autonomic neuropathy v0.13 SPTLC1 Alison Yeung Classified gene: SPTLC1 as Green List (high evidence)
Autonomic neuropathy v0.13 SPTLC1 Alison Yeung Gene: sptlc1 has been classified as Green List (High Evidence).
Autonomic neuropathy v0.12 SPTLC1 Alison Yeung gene: SPTLC1 was added
gene: SPTLC1 was added to Autonomic neuropathy. Sources: Literature
Mode of inheritance for gene: SPTLC1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: SPTLC1 were set to OMIM# 162400 NEUROPATHY, HEREDITARY SENSORY AND AUTONOMIC, TYPE IA; HSAN1A
Review for gene: SPTLC1 was set to GREEN
gene: SPTLC1 was marked as current diagnostic
Added comment: Sources: Literature
Autonomic neuropathy v0.11 DST Alison Yeung Marked gene: DST as ready
Autonomic neuropathy v0.11 DST Alison Yeung Added comment: Comment when marking as ready: Single family reported 2012
Autonomic neuropathy v0.11 DST Alison Yeung Gene: dst has been classified as Red List (Low Evidence).
Autonomic neuropathy v0.11 DST Alison Yeung Classified gene: DST as Red List (low evidence)
Autonomic neuropathy v0.11 DST Alison Yeung Gene: dst has been classified as Red List (Low Evidence).
Autonomic neuropathy v0.10 DST Alison Yeung gene: DST was added
gene: DST was added to Autonomic neuropathy. Sources: Literature
Mode of inheritance for gene: DST was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: DST were set to OMIM# 614653 NEUROPATHY, HEREDITARY SENSORY AND AUTONOMIC, TYPE VI; HSAN6
Review for gene: DST was set to AMBER
gene: DST was marked as current diagnostic
Added comment: single consanguineous family reported
Sources: Literature
Autonomic neuropathy v0.9 RETREG1 Alison Yeung Marked gene: RETREG1 as ready
Autonomic neuropathy v0.9 RETREG1 Alison Yeung Gene: retreg1 has been classified as Green List (High Evidence).
Autonomic neuropathy v0.9 RETREG1 Alison Yeung Classified gene: RETREG1 as Green List (high evidence)
Autonomic neuropathy v0.9 RETREG1 Alison Yeung Gene: retreg1 has been classified as Green List (High Evidence).
Autonomic neuropathy v0.8 RETREG1 Alison Yeung gene: RETREG1 was added
gene: RETREG1 was added to Autonomic neuropathy. Sources: Literature
Mode of inheritance for gene: RETREG1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: RETREG1 were set to OMIM# 613115 NEUROPATHY, HEREDITARY SENSORY AND AUTONOMIC, TYPE IIB; HSAN2B
Review for gene: RETREG1 was set to GREEN
gene: RETREG1 was marked as current diagnostic
Added comment: Sources: Literature
Autonomic neuropathy v0.7 SCN11A Alison Yeung Classified gene: SCN11A as Green List (high evidence)
Autonomic neuropathy v0.7 SCN11A Alison Yeung Gene: scn11a has been classified as Green List (High Evidence).
Autonomic neuropathy v0.6 SCN11A Alison Yeung Marked gene: SCN11A as ready
Autonomic neuropathy v0.6 SCN11A Alison Yeung Gene: scn11a has been classified as Red List (Low Evidence).
Autonomic neuropathy v0.6 SCN11A Alison Yeung gene: SCN11A was added
gene: SCN11A was added to Autonomic neuropathy. Sources: Literature
Mode of inheritance for gene: SCN11A was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: SCN11A were set to OMIM# 615548 NEUROPATHY, HEREDITARY SENSORY AND AUTONOMIC, TYPE VII; HSAN7
Review for gene: SCN11A was set to GREEN
gene: SCN11A was marked as current diagnostic
Added comment: Sources: Literature
Autonomic neuropathy v0.5 NTRK1 Alison Yeung Marked gene: NTRK1 as ready
Autonomic neuropathy v0.5 NTRK1 Alison Yeung Gene: ntrk1 has been classified as Green List (High Evidence).
Autonomic neuropathy v0.5 NTRK1 Alison Yeung Classified gene: NTRK1 as Green List (high evidence)
Autonomic neuropathy v0.5 NTRK1 Alison Yeung Gene: ntrk1 has been classified as Green List (High Evidence).
Autonomic neuropathy v0.4 NTRK1 Alison Yeung gene: NTRK1 was added
gene: NTRK1 was added to Autonomic neuropathy. Sources: Literature
Mode of inheritance for gene: NTRK1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NTRK1 were set to OMIM# 191315 NEUROTROPHIC TYROSINE KINASE, RECEPTOR, TYPE 1; NTRK1
Review for gene: NTRK1 was set to GREEN
Added comment: Sources: Literature
Autonomic neuropathy v0.3 NGF Alison Yeung Classified gene: NGF as Green List (high evidence)
Autonomic neuropathy v0.3 NGF Alison Yeung Gene: ngf has been classified as Green List (High Evidence).
Autonomic neuropathy v0.2 NGF Alison Yeung gene: NGF was added
gene: NGF was added to Autonomic neuropathy. Sources: Literature
Mode of inheritance for gene: NGF was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NGF were set to OMIM #608654 NEUROPATHY, HEREDITARY SENSORY AND AUTONOMIC, TYPE V; HSAN5
Review for gene: NGF was set to GREEN
gene: NGF was marked as current diagnostic
Added comment: Sources: Literature
Autonomic neuropathy v0.1 Alison Yeung Panel status changed from internal to public
Autonomic neuropathy v0.0 Alison Yeung Added Panel Autonomic neuropathy
Set panel types to: Victorian Clinical Genetics Services; Rare Disease
Mendeliome v0.5357 ADAR Zornitza Stark Marked gene: ADAR as ready
Mendeliome v0.5357 ADAR Zornitza Stark Gene: adar has been classified as Green List (High Evidence).
Mendeliome v0.5357 ADAR Zornitza Stark Phenotypes for gene: ADAR were changed from to Aicardi-Goutieres syndrome 6, MIM# 615010; Dyschromatosis symmetrica hereditaria, MIM# 127400
Mendeliome v0.5356 ADAR Zornitza Stark Mode of inheritance for gene: ADAR was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.5355 ADAR Zornitza Stark reviewed gene: ADAR: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Aicardi-Goutieres syndrome 6, MIM# 615010, Dyschromatosis symmetrica hereditaria, MIM# 127400; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Brain Calcification v0.64 ADAR Zornitza Stark Mode of inheritance for gene: ADAR was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Brain Calcification v0.63 ADAR Zornitza Stark edited their review of gene: ADAR: Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Congenital ophthalmoplegia v0.29 SLC19A3 Zornitza Stark Marked gene: SLC19A3 as ready
Congenital ophthalmoplegia v0.29 SLC19A3 Zornitza Stark Gene: slc19a3 has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.29 SLC19A3 Zornitza Stark Classified gene: SLC19A3 as Green List (high evidence)
Congenital ophthalmoplegia v0.29 SLC19A3 Zornitza Stark Gene: slc19a3 has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.28 SLC19A3 Zornitza Stark gene: SLC19A3 was added
gene: SLC19A3 was added to Congenital ophthalmoplegia. Sources: Expert list
Mode of inheritance for gene: SLC19A3 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SLC19A3 were set to Thiamine metabolism dysfunction syndrome 2 (biotin- or thiamine-responsive encephalopathy type 2), MIM# 607483
Review for gene: SLC19A3 was set to GREEN
Added comment: Well established gene-disease association, treatable condition. External ophthalmoplegia is a feature.
Sources: Expert list
Congenital ophthalmoplegia v0.27 GBA Zornitza Stark Marked gene: GBA as ready
Congenital ophthalmoplegia v0.27 GBA Zornitza Stark Gene: gba has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.27 GBA Zornitza Stark Classified gene: GBA as Green List (high evidence)
Congenital ophthalmoplegia v0.27 GBA Zornitza Stark Gene: gba has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.26 GBA Zornitza Stark gene: GBA was added
gene: GBA was added to Congenital ophthalmoplegia. Sources: Expert list
Mode of inheritance for gene: GBA was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: GBA were set to Gaucher disease, type II, MIM# 230900
Review for gene: GBA was set to GREEN
Added comment: Well established gene-disease association. Cranial nerve involvement is common and can manifest as convergent squint, strabismus, ocular paresis, oculomotor apraxia.
Sources: Expert list
Congenital ophthalmoplegia v0.24 Zornitza Stark Panel name changed from Congenital fibrosis of the extraocular muscles to Congenital ophthalmoplegia
Mitochondrial disease v0.555 NDUFB10 Zornitza Stark Publications for gene: NDUFB10 were set to 28040730; 32025618
Mendeliome v0.5355 NDUFB10 Zornitza Stark Classified gene: NDUFB10 as Green List (high evidence)
Mendeliome v0.5355 NDUFB10 Zornitza Stark Gene: ndufb10 has been classified as Green List (High Evidence).
Mendeliome v0.5354 NDUFB10 Zornitza Stark Publications for gene: NDUFB10 were set to 28040730; 32025618
Mendeliome v0.5353 NDUFB10 Zornitza Stark edited their review of gene: NDUFB10: Added comment: Second family reported, functional data, upgrade to Green.; Changed rating: GREEN; Changed publications: 28040730, 32025618, 33169436
Mitochondrial disease v0.554 NDUFB10 Zornitza Stark Classified gene: NDUFB10 as Green List (high evidence)
Mitochondrial disease v0.554 NDUFB10 Zornitza Stark Gene: ndufb10 has been classified as Green List (High Evidence).
Mitochondrial disease v0.553 NDUFB10 Zornitza Stark edited their review of gene: NDUFB10: Added comment: Second family reported, functional data, upgrade to Green.; Changed rating: GREEN; Changed publications: 33169436
Cerebral vascular malformations v0.6 RNF213 Daniel Flanagan reviewed gene: RNF213: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 28635953; Phenotypes: susceptibility to Moyamoya disease 2, (MIM# 607151); Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Neurodegeneration with brain iron accumulation v0.3 SCP2 Bryony Thompson Marked gene: SCP2 as ready
Neurodegeneration with brain iron accumulation v0.3 SCP2 Bryony Thompson Gene: scp2 has been classified as Red List (Low Evidence).
Neurodegeneration with brain iron accumulation v0.3 SCP2 Bryony Thompson gene: SCP2 was added
gene: SCP2 was added to Neuroferritinopathies. Sources: Literature
Mode of inheritance for gene: SCP2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SCP2 were set to 26497993
Phenotypes for gene: SCP2 were set to Neurodegeneration with brain iron accumulation; ataxia
Review for gene: SCP2 was set to RED
Added comment: A single case with biallelic variants has been reported with neurodegeneration with brain iron accumulation and ataxia.
Sources: Literature
Neurodegeneration with brain iron accumulation v0.2 PSEN1 Bryony Thompson Marked gene: PSEN1 as ready
Neurodegeneration with brain iron accumulation v0.2 PSEN1 Bryony Thompson Gene: psen1 has been classified as Red List (Low Evidence).
Neurodegeneration with brain iron accumulation v0.2 PSEN1 Bryony Thompson gene: PSEN1 was added
gene: PSEN1 was added to Neuroferritinopathies. Sources: Literature
Mode of inheritance for gene: PSEN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PSEN1 were set to 28664294
Phenotypes for gene: PSEN1 were set to Neurodegeneration with brain iron accumulation; Frontotemporal dementia, MIM# 600274
Review for gene: PSEN1 was set to RED
Added comment: A single case has been reported with a de novo variant and iron accumulation in the brain.
Sources: Literature
Neurodegeneration with brain iron accumulation v0.1 Bryony Thompson Panel status changed from internal to public
Panel types changed to Royal Melbourne Hospital; Rare Disease
Neurodegeneration with brain iron accumulation v0.0 WDR45 Bryony Thompson gene: WDR45 was added
gene: WDR45 was added to Neuroferritinopathies. Sources: Expert Review Green,GeneReviews
Mode of inheritance for gene: WDR45 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Phenotypes for gene: WDR45 were set to Beta-propeller protein-associated neurodegeneration (BPAN)
Neurodegeneration with brain iron accumulation v0.0 PLA2G6 Bryony Thompson gene: PLA2G6 was added
gene: PLA2G6 was added to Neuroferritinopathies. Sources: Expert Review Green,GeneReviews
Mode of inheritance for gene: PLA2G6 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PLA2G6 were set to PLA2G6-associated neurodegeneration (PLAN)
Neurodegeneration with brain iron accumulation v0.0 PANK2 Bryony Thompson gene: PANK2 was added
gene: PANK2 was added to Neuroferritinopathies. Sources: Expert Review Green,GeneReviews
Mode of inheritance for gene: PANK2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PANK2 were set to Pantothenate kinase-associated neurodegeneration (PKAN)
Neurodegeneration with brain iron accumulation v0.0 FTL Bryony Thompson gene: FTL was added
gene: FTL was added to Neuroferritinopathies. Sources: Expert Review Green,GeneReviews
Mode of inheritance for gene: FTL was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: FTL were set to Neuroferritinopathy
Neurodegeneration with brain iron accumulation v0.0 FA2H Bryony Thompson gene: FA2H was added
gene: FA2H was added to Neuroferritinopathies. Sources: Expert Review Green,GeneReviews
Mode of inheritance for gene: FA2H was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: FA2H were set to Fatty acid hydroxylase-associated neurodegeneration (FAHN)
Neurodegeneration with brain iron accumulation v0.0 DCAF17 Bryony Thompson gene: DCAF17 was added
gene: DCAF17 was added to Neuroferritinopathies. Sources: Expert Review Green,GeneReviews
Mode of inheritance for gene: DCAF17 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: DCAF17 were set to Woodhouse-Sakati syndrome
Neurodegeneration with brain iron accumulation v0.0 CP Bryony Thompson gene: CP was added
gene: CP was added to Neuroferritinopathies. Sources: Expert Review Green,GeneReviews
Mode of inheritance for gene: CP was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CP were set to Aceruloplasminemia
Neurodegeneration with brain iron accumulation v0.0 COASY Bryony Thompson gene: COASY was added
gene: COASY was added to Neuroferritinopathies. Sources: Expert Review Green,GeneReviews
Mode of inheritance for gene: COASY was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: COASY were set to OMIM 618266); COASY protein-associated neurodegeneration (CoPAN
Neurodegeneration with brain iron accumulation v0.0 C19orf12 Bryony Thompson gene: C19orf12 was added
gene: C19orf12 was added to Neuroferritinopathies. Sources: Expert Review Green,GeneReviews
Mode of inheritance for gene: C19orf12 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: C19orf12 were set to Mitochondrial membrane protein-associated neurodegeneration (MPAN)
Neurodegeneration with brain iron accumulation v0.0 ATP13A2 Bryony Thompson gene: ATP13A2 was added
gene: ATP13A2 was added to Neuroferritinopathies. Sources: Expert Review Green,GeneReviews
Mode of inheritance for gene: ATP13A2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ATP13A2 were set to Kufor-Rakeb syndrome (OMIM 606693)
Neurodegeneration with brain iron accumulation v0.0 Bryony Thompson Added panel Neuroferritinopathies
Mendeliome v0.5353 FOXJ1 Zornitza Stark Phenotypes for gene: FOXJ1 were changed from hydrocephalus; chronic destructive airway disease; randomization of left/right body asymmetry to Ciliary dyskinesia, primary, 43, MIM#618699; hydrocephalus; chronic destructive airway disease; randomization of left/right body asymmetry
Mendeliome v0.5352 FOXJ1 Zornitza Stark edited their review of gene: FOXJ1: Changed phenotypes: Ciliary dyskinesia, primary, 43, MIM#618699, hydrocephalus, chronic destructive airway disease, randomization of left/right body asymmetry
Hydrocephalus_Ventriculomegaly v0.71 FOXJ1 Zornitza Stark Phenotypes for gene: FOXJ1 were changed from Congenital hydrocephalus to Congenital hydrocephalus; Ciliary dyskinesia, primary, 43, MIM#618699
Hydrocephalus_Ventriculomegaly v0.70 FOXJ1 Zornitza Stark edited their review of gene: FOXJ1: Changed phenotypes: Congenital hydrocephalus, Ciliary dyskinesia, primary, 43, MIM#618699
Heterotaxy v1.1 FOXJ1 Zornitza Stark Phenotypes for gene: FOXJ1 were changed from Hydrocephalus; chronic destructive airway disease; randomization of left/right body asymmetry to Ciliary dyskinesia, primary, 43, MIM#618699; Hydrocephalus; chronic destructive airway disease; randomization of left/right body asymmetry
Heterotaxy v1.0 FOXJ1 Zornitza Stark edited their review of gene: FOXJ1: Changed rating: GREEN; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Heterotaxy v1.0 FOXJ1 Zornitza Stark reviewed gene: FOXJ1: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Ciliary dyskinesia, primary, 43, MIM#618699; Mode of inheritance: None
Ciliary Dyskinesia v1.1 FOXJ1 Zornitza Stark Phenotypes for gene: FOXJ1 were changed from hydrocephalus; chronic destructive airway disease; randomization of left/right body asymmetry to Ciliary dyskinesia, primary, 43, MIM# 618699; hydrocephalus; chronic destructive airway disease; randomization of left/right body asymmetry
Ciliary Dyskinesia v1.0 FOXJ1 Zornitza Stark edited their review of gene: FOXJ1: Changed phenotypes: Ciliary dyskinesia, primary, 43, MIM# 618699, hydrocephalus, chronic destructive airway disease, randomization of left/right body asymmetry
Intellectual disability syndromic and non-syndromic v0.3190 MAPK1 Zornitza Stark Phenotypes for gene: MAPK1 were changed from Global developmental delay; Intellectual disability; Behavioral abnormality; Growth delay; Abnormality of the face; Abnormality of the neck; Abnormality of the cardiovascular system; Abnormality of the skin to Noonan syndrome 13, MIM#619087; Global developmental delay; Intellectual disability; Behavioral abnormality; Growth delay; Abnormality of the face; Abnormality of the neck; Abnormality of the cardiovascular system; Abnormality of the skin
Intellectual disability syndromic and non-syndromic v0.3189 MAPK1 Zornitza Stark reviewed gene: MAPK1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Noonan syndrome 13, MIM#619087, Global developmental delay, Intellectual disability, Behavioral abnormality, Growth delay, Abnormality of the face, Abnormality of the neck, Abnormality of the cardiovascular system, Abnormality of the skin; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Rasopathy v0.90 MAPK1 Zornitza Stark Phenotypes for gene: MAPK1 were changed from Global developmental delay; Intellectual disability; Behavioral abnormality; Growth delay; Abnormality of the face; Abnormality of the neck; Abnormality of the cardiovascular system; Abnormality of the skin to Noonan syndrome 13, MIM#619087; Global developmental delay; Intellectual disability; Behavioral abnormality; Growth delay; Abnormality of the face; Abnormality of the neck; Abnormality of the cardiovascular system; Abnormality of the skin
Rasopathy v0.89 MAPK1 Zornitza Stark edited their review of gene: MAPK1: Changed phenotypes: Noonan syndrome 13, MIM#619087, Global developmental delay, Intellectual disability, Behavioral abnormality, Growth delay, Abnormality of the face, Abnormality of the neck, Abnormality of the cardiovascular system, Abnormality of the skin
Mendeliome v0.5352 MAPK1 Zornitza Stark Phenotypes for gene: MAPK1 were changed from Global developmental delay; Intellectual disability; Behavioral abnormality; Growth delay; Abnormality of the face; Abnormality of the neck; Abnormality of the cardiovascular system; Abnormality of the skin to Noonan syndrome 13, MIM#619087; Global developmental delay; Intellectual disability; Behavioral abnormality; Growth delay; Abnormality of the face; Abnormality of the neck; Abnormality of the cardiovascular system; Abnormality of the skin
Mendeliome v0.5351 MAPK1 Zornitza Stark edited their review of gene: MAPK1: Changed phenotypes: Noonan syndrome 13, MIM# 619087, Global developmental delay, Intellectual disability, Behavioral abnormality, Growth delay, Abnormality of the face, Abnormality of the neck, Abnormality of the cardiovascular system, Abnormality of the skin
Mendeliome v0.5351 SCD5 Zornitza Stark Marked gene: SCD5 as ready
Mendeliome v0.5351 SCD5 Zornitza Stark Gene: scd5 has been classified as Red List (Low Evidence).
Mendeliome v0.5351 SCD5 Zornitza Stark gene: SCD5 was added
gene: SCD5 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: SCD5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SCD5 were set to 31972369
Phenotypes for gene: SCD5 were set to Deafness, autosomal dominant 79, MIM#619086
Review for gene: SCD5 was set to RED
Added comment: Single 5-generation family reported with a missense variant segregating in 19 affected individuals. Variant is found at a low frequency in ExAC.
Sources: Expert list
Deafness_IsolatedAndComplex v1.16 SCD5 Zornitza Stark Marked gene: SCD5 as ready
Deafness_IsolatedAndComplex v1.16 SCD5 Zornitza Stark Gene: scd5 has been classified as Red List (Low Evidence).
Deafness_IsolatedAndComplex v1.16 SCD5 Zornitza Stark gene: SCD5 was added
gene: SCD5 was added to Deafness_IsolatedAndComplex. Sources: Expert list
Mode of inheritance for gene: SCD5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SCD5 were set to 31972369
Phenotypes for gene: SCD5 were set to Deafness, autosomal dominant 79, MIM#619086
Review for gene: SCD5 was set to RED
Added comment: Single 5-generation family reported with a missense variant segregating in 19 affected individuals. Variant is found at a low frequency in ExAC.
Sources: Expert list
Mendeliome v0.5350 SLC12A2 Zornitza Stark Phenotypes for gene: SLC12A2 were changed from Kilquist syndrome, MIM#619080; deafness, intellectual disability, dysmorphic features, absent salivation; Deafness, autosomal dominant 78, MIM#619081; Congenital, severe to profound hearing loss to Delpire-McNeill syndrome, MIM# 619083; Kilquist syndrome, MIM#619080; deafness, intellectual disability, dysmorphic features, absent salivation; Deafness, autosomal dominant 78, MIM#619081; Congenital, severe to profound hearing loss
Mendeliome v0.5349 SLC12A2 Zornitza Stark edited their review of gene: SLC12A2: Changed phenotypes: Delpire-McNeill syndrome, MIM#619083, Kilquist syndrome, MIM#619080, deafness, intellectual disability, dysmorphic features, absent salivation, ectodermal dysplasia, constipation, intestinal malrotation, multiple congenital anomalies, Deafness, autosomal dominant 78, MIM# 619081
Intellectual disability syndromic and non-syndromic v0.3189 SLC12A2 Zornitza Stark Phenotypes for gene: SLC12A2 were changed from Kilquist syndrome, MIM#619080; deafness; intellectual disability; dysmorphic features; absent salivation; ectodermal dysplasia; constipation; intestinal malrotation; multiple congenital anomalies to Delpire-McNeill syndrome, MIM# 619083; Kilquist syndrome, MIM#619080; deafness; intellectual disability; dysmorphic features; absent salivation; ectodermal dysplasia; constipation; intestinal malrotation; multiple congenital anomalies
Intellectual disability syndromic and non-syndromic v0.3188 SLC12A2 Zornitza Stark edited their review of gene: SLC12A2: Changed phenotypes: Delpire-McNeill syndrome, MIM# 619083, Kilquist syndrome, MIM#619080, deafness, intellectual disability, dysmorphic features, absent salivation, ectodermal dysplasia, constipation, intestinal malrotation, multiple congenital anomalies
Deafness_IsolatedAndComplex v1.15 SLC12A2 Zornitza Stark Phenotypes for gene: SLC12A2 were changed from Kilquist syndrome, MIM#619080; deafness, intellectual disability, dysmorphic features, absent salivation; Congenital, severe to profound hearing loss; minor motor developmental delay to Kilquist syndrome, MIM#619080; deafness, intellectual disability, dysmorphic features, absent salivation; Congenital, severe to profound hearing loss; minor motor developmental delay; Deafness, autosomal dominant 78, MIM# 619081
Deafness_IsolatedAndComplex v1.14 SLC12A2 Zornitza Stark edited their review of gene: SLC12A2: Changed phenotypes: Kilquist syndrome, MIM#619080, deafness, intellectual disability, dysmorphic features, absent salivation, ectodermal dysplasia, constipation, intestinal malrotation, multiple congenital anomalies, Deafness, autosomal dominant 78, MIM# 619081
Mendeliome v0.5349 SLC12A2 Zornitza Stark Phenotypes for gene: SLC12A2 were changed from Kilquist syndrome, MIM#619080; deafness, intellectual disability, dysmorphic features, absent salivation; Congenital, severe to profound hearing loss to Kilquist syndrome, MIM#619080; deafness, intellectual disability, dysmorphic features, absent salivation; Deafness, autosomal dominant 78, MIM#619081; Congenital, severe to profound hearing loss
Mendeliome v0.5348 SLC12A2 Zornitza Stark edited their review of gene: SLC12A2: Changed phenotypes: Kilquist syndrome, MIM#619080, deafness, intellectual disability, dysmorphic features, absent salivation, ectodermal dysplasia, constipation, intestinal malrotation, multiple congenital anomalies, Deafness, autosomal dominant 78, MIM# 619081
Intellectual disability syndromic and non-syndromic v0.3188 SLC12A2 Zornitza Stark Phenotypes for gene: SLC12A2 were changed from Kilquist syndrome; deafness; intellectual disability; dysmorphic features; absent salivation; ectodermal dysplasia; constipation; intestinal malrotation; multiple congenital anomalies to Kilquist syndrome, MIM#619080; deafness; intellectual disability; dysmorphic features; absent salivation; ectodermal dysplasia; constipation; intestinal malrotation; multiple congenital anomalies
Intellectual disability syndromic and non-syndromic v0.3187 SLC12A2 Zornitza Stark edited their review of gene: SLC12A2: Changed phenotypes: Kilquist syndrome, MIM#619080, deafness, intellectual disability, dysmorphic features, absent salivation, ectodermal dysplasia, constipation, intestinal malrotation, multiple congenital anomalies
Deafness_IsolatedAndComplex v1.14 SLC12A2 Zornitza Stark Phenotypes for gene: SLC12A2 were changed from Kilquist syndrome: deafness, intellectual disability, dysmorphic features, absent salivation; Congenital, severe to profound hearing loss; minor motor developmental delay to Kilquist syndrome, MIM#619080; deafness, intellectual disability, dysmorphic features, absent salivation; Congenital, severe to profound hearing loss; minor motor developmental delay
Deafness_IsolatedAndComplex v1.13 SLC12A2 Zornitza Stark edited their review of gene: SLC12A2: Changed phenotypes: Kilquist syndrome, MIM#619080, deafness, intellectual disability, dysmorphic features, absent salivation, ectodermal dysplasia, constipation, intestinal malrotation, multiple congenital anomalies
Mendeliome v0.5348 SLC12A2 Zornitza Stark Phenotypes for gene: SLC12A2 were changed from Kilquist syndrome: deafness, intellectual disability, dysmorphic features, absent salivation; Congenital, severe to profound hearing loss to Kilquist syndrome, MIM#619080; deafness, intellectual disability, dysmorphic features, absent salivation; Congenital, severe to profound hearing loss
Mendeliome v0.5347 SLC12A2 Zornitza Stark edited their review of gene: SLC12A2: Changed phenotypes: Kilquist syndrome, MIM#619080, deafness, intellectual disability, dysmorphic features, absent salivation, ectodermal dysplasia, constipation, intestinal malrotation, multiple congenital anomalies
Brain Calcification v0.63 CTC1 Zornitza Stark Marked gene: CTC1 as ready
Brain Calcification v0.63 CTC1 Zornitza Stark Gene: ctc1 has been classified as Green List (High Evidence).
Brain Calcification v0.63 CTC1 Zornitza Stark Phenotypes for gene: CTC1 were changed from to Cerebroretinal microangiopathy with calcifications and cysts, MIM# 612199
Brain Calcification v0.62 CTC1 Zornitza Stark Publications for gene: CTC1 were set to
Brain Calcification v0.61 CTC1 Zornitza Stark Mode of inheritance for gene: CTC1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Brain Calcification v0.60 CTC1 Zornitza Stark reviewed gene: CTC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 22267198, 22387016; Phenotypes: Cerebroretinal microangiopathy with calcifications and cysts, MIM# 612199; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5347 OCLN Zornitza Stark Marked gene: OCLN as ready
Mendeliome v0.5347 OCLN Zornitza Stark Gene: ocln has been classified as Green List (High Evidence).
Mendeliome v0.5347 OCLN Zornitza Stark Phenotypes for gene: OCLN were changed from to Pseudo-TORCH syndrome 1, MIM#251290
Mendeliome v0.5346 OCLN Zornitza Stark Publications for gene: OCLN were set to
Mendeliome v0.5345 OCLN Zornitza Stark Mode of inheritance for gene: OCLN was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Brain Calcification v0.60 OCLN Zornitza Stark Marked gene: OCLN as ready
Brain Calcification v0.60 OCLN Zornitza Stark Gene: ocln has been classified as Green List (High Evidence).
Mendeliome v0.5344 OCLN Zornitza Stark reviewed gene: OCLN: Rating: GREEN; Mode of pathogenicity: None; Publications: 20727516, 32240828, 29192239, 28386946; Phenotypes: Pseudo-TORCH syndrome 1, MIM#251290; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Brain Calcification v0.60 OCLN Zornitza Stark Phenotypes for gene: OCLN were changed from to Pseudo-TORCH syndrome 1, MIM#251290
Brain Calcification v0.59 OCLN Zornitza Stark Publications for gene: OCLN were set to
Brain Calcification v0.58 OCLN Zornitza Stark Mode of inheritance for gene: OCLN was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Brain Calcification v0.57 OCLN Zornitza Stark reviewed gene: OCLN: Rating: GREEN; Mode of pathogenicity: None; Publications: 20727516, 32240828, 29192239, 28386946; Phenotypes: Pseudo-TORCH syndrome 1, MIM#251290; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Brain Calcification v0.57 ERCC6 Zornitza Stark Marked gene: ERCC6 as ready
Brain Calcification v0.57 ERCC6 Zornitza Stark Gene: ercc6 has been classified as Green List (High Evidence).
Brain Calcification v0.57 ERCC6 Zornitza Stark Phenotypes for gene: ERCC6 were changed from to Cockayne syndrome, type B, MIM#133540
Brain Calcification v0.56 ERCC6 Zornitza Stark Mode of inheritance for gene: ERCC6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Brain Calcification v0.55 ERCC6 Zornitza Stark reviewed gene: ERCC6: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cockayne syndrome, type B, MIM#133540; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3187 JAM3 Zornitza Stark Marked gene: JAM3 as ready
Intellectual disability syndromic and non-syndromic v0.3187 JAM3 Zornitza Stark Gene: jam3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3187 JAM3 Zornitza Stark Phenotypes for gene: JAM3 were changed from to Hemorrhagic destruction of the brain, subependymal calcification, and cataracts, MIM# 613730
Intellectual disability syndromic and non-syndromic v0.3186 JAM3 Zornitza Stark Publications for gene: JAM3 were set to
Intellectual disability syndromic and non-syndromic v0.3185 JAM3 Zornitza Stark Mode of inheritance for gene: JAM3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3184 JAM3 Zornitza Stark reviewed gene: JAM3: Rating: GREEN; Mode of pathogenicity: None; Publications: 23255084, 21109224; Phenotypes: Hemorrhagic destruction of the brain, subependymal calcification, and cataracts, MIM# 613730; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5344 JAM3 Zornitza Stark Marked gene: JAM3 as ready
Mendeliome v0.5344 JAM3 Zornitza Stark Gene: jam3 has been classified as Green List (High Evidence).
Mendeliome v0.5344 JAM3 Zornitza Stark Phenotypes for gene: JAM3 were changed from to Hemorrhagic destruction of the brain, subependymal calcification, and cataracts, MIM# 613730
Mendeliome v0.5343 JAM3 Zornitza Stark Publications for gene: JAM3 were set to
Mendeliome v0.5342 JAM3 Zornitza Stark Mode of inheritance for gene: JAM3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5341 JAM3 Zornitza Stark reviewed gene: JAM3: Rating: GREEN; Mode of pathogenicity: None; Publications: 23255084, 21109224; Phenotypes: Hemorrhagic destruction of the brain, subependymal calcification, and cataracts, MIM# 613730; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cataract v0.243 JAM3 Zornitza Stark Marked gene: JAM3 as ready
Cataract v0.243 JAM3 Zornitza Stark Gene: jam3 has been classified as Green List (High Evidence).
Cataract v0.243 JAM3 Zornitza Stark Phenotypes for gene: JAM3 were changed from to Hemorrhagic destruction of the brain, subependymal calcification, and cataracts, MIM# 613730
Cataract v0.242 JAM3 Zornitza Stark Publications for gene: JAM3 were set to
Cataract v0.241 JAM3 Zornitza Stark Mode of inheritance for gene: JAM3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Cataract v0.240 JAM3 Zornitza Stark reviewed gene: JAM3: Rating: GREEN; Mode of pathogenicity: None; Publications: 23255084, 21109224; Phenotypes: Hemorrhagic destruction of the brain, subependymal calcification, and cataracts, MIM# 613730; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Brain Calcification v0.55 JAM3 Zornitza Stark Marked gene: JAM3 as ready
Brain Calcification v0.55 JAM3 Zornitza Stark Gene: jam3 has been classified as Green List (High Evidence).
Brain Calcification v0.55 JAM3 Zornitza Stark Phenotypes for gene: JAM3 were changed from to Hemorrhagic destruction of the brain, subependymal calcification, and cataracts, MIM# 613730
Brain Calcification v0.54 JAM3 Zornitza Stark Publications for gene: JAM3 were set to
Brain Calcification v0.53 JAM3 Zornitza Stark Mode of inheritance for gene: JAM3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Brain Calcification v0.52 JAM3 Zornitza Stark reviewed gene: JAM3: Rating: GREEN; Mode of pathogenicity: None; Publications: 23255084, 21109224; Phenotypes: Hemorrhagic destruction of the brain, subependymal calcification, and cataracts, MIM# 613730; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Brain Calcification v0.52 IFIH1 Zornitza Stark Marked gene: IFIH1 as ready
Brain Calcification v0.52 IFIH1 Zornitza Stark Gene: ifih1 has been classified as Green List (High Evidence).
Brain Calcification v0.52 IFIH1 Zornitza Stark Phenotypes for gene: IFIH1 were changed from to Aicardi-Goutieres syndrome 7, MIM#615846
Brain Calcification v0.51 IFIH1 Zornitza Stark Publications for gene: IFIH1 were set to
Brain Calcification v0.50 IFIH1 Zornitza Stark Mode of inheritance for gene: IFIH1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Brain Calcification v0.49 IFIH1 Zornitza Stark reviewed gene: IFIH1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24686847; Phenotypes: Aicardi-Goutieres syndrome 7, MIM#615846; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Brain Calcification v0.49 ADAR Zornitza Stark Marked gene: ADAR as ready
Brain Calcification v0.49 ADAR Zornitza Stark Gene: adar has been classified as Green List (High Evidence).
Brain Calcification v0.49 ADAR Zornitza Stark Phenotypes for gene: ADAR were changed from to Aicardi-Goutieres syndrome 6, MIM#615010
Brain Calcification v0.48 ADAR Zornitza Stark Publications for gene: ADAR were set to
Brain Calcification v0.47 ADAR Zornitza Stark Mode of inheritance for gene: ADAR was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Brain Calcification v0.46 ADAR Zornitza Stark reviewed gene: ADAR: Rating: GREEN; Mode of pathogenicity: None; Publications: 23001123, 24262145; Phenotypes: Aicardi-Goutieres syndrome 6, MIM#615010; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Bardet Biedl syndrome v1.0 Zornitza Stark promoted panel to version 1.0
Microcephaly v0.498 POLE Zornitza Stark edited their review of gene: POLE: Changed rating: GREEN
Microcephaly v0.498 POLE Zornitza Stark Marked gene: POLE as ready
Microcephaly v0.498 POLE Zornitza Stark Added comment: Comment when marking as ready: The association with microcephaly relates to IMAGE-I syndrome.
Microcephaly v0.498 POLE Zornitza Stark Gene: pole has been classified as Green List (High Evidence).
Microcephaly v0.498 POLE Zornitza Stark Phenotypes for gene: POLE were changed from FILS syndrome 615139; IMAGE-I syndrome 618336 to IMAGE-I syndrome, MIM# 618336
Microcephaly v0.497 POLE Zornitza Stark Classified gene: POLE as Green List (high evidence)
Microcephaly v0.497 POLE Zornitza Stark Gene: pole has been classified as Green List (High Evidence).
Microcephaly v0.496 POLE Elena Savva gene: POLE was added
gene: POLE was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: POLE was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POLE were set to PMID: 30503519
Phenotypes for gene: POLE were set to FILS syndrome 615139; IMAGE-I syndrome 618336
Review for gene: POLE was set to GREEN
Added comment: PMID: 30503519 - microcephaly reported in multiple patients with biallelic LOF variants
Sources: Literature
Autism v0.117 NCKAP1 Zornitza Stark Marked gene: NCKAP1 as ready
Autism v0.117 NCKAP1 Zornitza Stark Gene: nckap1 has been classified as Green List (High Evidence).
Autism v0.117 NCKAP1 Zornitza Stark Phenotypes for gene: NCKAP1 were changed from to Intellectual disability; autism
Autism v0.116 NCKAP1 Zornitza Stark Publications for gene: NCKAP1 were set to
Autism v0.115 NCKAP1 Zornitza Stark Mode of inheritance for gene: NCKAP1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Autism v0.114 NCKAP1 Zornitza Stark reviewed gene: NCKAP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 33157009; Phenotypes: Intellectual disability, autism; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5341 NCKAP1 Zornitza Stark Marked gene: NCKAP1 as ready
Mendeliome v0.5341 NCKAP1 Zornitza Stark Gene: nckap1 has been classified as Green List (High Evidence).
Mendeliome v0.5341 NCKAP1 Zornitza Stark Phenotypes for gene: NCKAP1 were changed from to Intellectual disability; autism
Mendeliome v0.5340 NCKAP1 Zornitza Stark Publications for gene: NCKAP1 were set to
Mendeliome v0.5339 NCKAP1 Zornitza Stark Mode of inheritance for gene: NCKAP1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5338 NCKAP1 Zornitza Stark reviewed gene: NCKAP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 33157009; Phenotypes: Intellectual disability, autism; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.3184 NCKAP1 Zornitza Stark Marked gene: NCKAP1 as ready
Intellectual disability syndromic and non-syndromic v0.3184 NCKAP1 Zornitza Stark Gene: nckap1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3184 NCKAP1 Zornitza Stark Phenotypes for gene: NCKAP1 were changed from to Intellectual disability; autism
Intellectual disability syndromic and non-syndromic v0.3183 NCKAP1 Zornitza Stark Publications for gene: NCKAP1 were set to
Intellectual disability syndromic and non-syndromic v0.3182 NCKAP1 Zornitza Stark Mode of inheritance for gene: NCKAP1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.3181 NCKAP1 Zornitza Stark reviewed gene: NCKAP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 33157009; Phenotypes: Intellectual disability, autism; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome_PREGEN_DRAFT v0.1 Zornitza Stark Panel types changed to New South Wales Health Pathology
Incidentalome_PREGEN_DRAFT v0.0 ZBTB16 Zornitza Stark gene: ZBTB16 was added
gene: ZBTB16 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: ZBTB16 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 VHL Zornitza Stark gene: VHL was added
gene: VHL was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: VHL was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 TRIM33 Zornitza Stark gene: TRIM33 was added
gene: TRIM33 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: TRIM33 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 TRIM27 Zornitza Stark gene: TRIM27 was added
gene: TRIM27 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: TRIM27 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 TRIM24 Zornitza Stark gene: TRIM24 was added
gene: TRIM24 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: TRIM24 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 TPR Zornitza Stark gene: TPR was added
gene: TPR was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: TPR was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 TP53 Zornitza Stark gene: TP53 was added
gene: TP53 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: TP53 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 TGFBR2 Zornitza Stark gene: TGFBR2 was added
gene: TGFBR2 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: TGFBR2 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 TFG Zornitza Stark gene: TFG was added
gene: TFG was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: TFG was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 TET2 Zornitza Stark gene: TET2 was added
gene: TET2 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: TET2 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 TCF12 Zornitza Stark gene: TCF12 was added
gene: TCF12 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: TCF12 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 TBL1XR1 Zornitza Stark gene: TBL1XR1 was added
gene: TBL1XR1 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: TBL1XR1 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 TAF15 Zornitza Stark gene: TAF15 was added
gene: TAF15 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: TAF15 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 TACC3 Zornitza Stark gene: TACC3 was added
gene: TACC3 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: TACC3 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 TACC1 Zornitza Stark gene: TACC1 was added
gene: TACC1 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: TACC1 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 SUFU Zornitza Stark gene: SUFU was added
gene: SUFU was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: SUFU was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 STAT5B Zornitza Stark gene: STAT5B was added
gene: STAT5B was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: STAT5B was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 SRD5A2 Zornitza Stark gene: SRD5A2 was added
gene: SRD5A2 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: SRD5A2 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 SMAD4 Zornitza Stark gene: SMAD4 was added
gene: SMAD4 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: SMAD4 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 SDHD Zornitza Stark gene: SDHD was added
gene: SDHD was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: SDHD was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 SDHC Zornitza Stark gene: SDHC was added
gene: SDHC was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: SDHC was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 SDHB Zornitza Stark gene: SDHB was added
gene: SDHB was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: SDHB was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 SDHAF2 Zornitza Stark gene: SDHAF2 was added
gene: SDHAF2 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: SDHAF2 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 SDHA Zornitza Stark gene: SDHA was added
gene: SDHA was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: SDHA was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 RUNX1 Zornitza Stark gene: RUNX1 was added
gene: RUNX1 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: RUNX1 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 RPS20 Zornitza Stark gene: RPS20 was added
gene: RPS20 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: RPS20 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 RPS14 Zornitza Stark gene: RPS14 was added
gene: RPS14 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: RPS14 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 RNASEL Zornitza Stark gene: RNASEL was added
gene: RNASEL was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: RNASEL was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 RET Zornitza Stark gene: RET was added
gene: RET was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: RET was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 RARA Zornitza Stark gene: RARA was added
gene: RARA was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: RARA was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 PTPN3 Zornitza Stark gene: PTPN3 was added
gene: PTPN3 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: PTPN3 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 PTEN Zornitza Stark gene: PTEN was added
gene: PTEN was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: PTEN was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 PRLR Zornitza Stark gene: PRLR was added
gene: PRLR was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: PRLR was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 PRKAR1A Zornitza Stark gene: PRKAR1A was added
gene: PRKAR1A was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: PRKAR1A was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 PPARG Zornitza Stark gene: PPARG was added
gene: PPARG was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: PPARG was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 POT1 Zornitza Stark gene: POT1 was added
gene: POT1 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: POT1 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 PMS2 Zornitza Stark gene: PMS2 was added
gene: PMS2 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: PMS2 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 PMS1 Zornitza Stark gene: PMS1 was added
gene: PMS1 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: PMS1 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 PML Zornitza Stark gene: PML was added
gene: PML was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: PML was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 PIK3CA Zornitza Stark gene: PIK3CA was added
gene: PIK3CA was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: PIK3CA was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 PDGFRB Zornitza Stark gene: PDGFRB was added
gene: PDGFRB was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: PDGFRB was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 PDGFRA Zornitza Stark gene: PDGFRA was added
gene: PDGFRA was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: PDGFRA was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 PCM1 Zornitza Stark gene: PCM1 was added
gene: PCM1 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: PCM1 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 PALB2 Zornitza Stark gene: PALB2 was added
gene: PALB2 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: PALB2 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 NUMA1 Zornitza Stark gene: NUMA1 was added
gene: NUMA1 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: NUMA1 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 NTRK1 Zornitza Stark gene: NTRK1 was added
gene: NTRK1 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: NTRK1 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 NR4A3 Zornitza Stark gene: NR4A3 was added
gene: NR4A3 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: NR4A3 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 NPM1 Zornitza Stark gene: NPM1 was added
gene: NPM1 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: NPM1 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 NLRP7 Zornitza Stark gene: NLRP7 was added
gene: NLRP7 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: NLRP7 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 NKX2-1 Zornitza Stark gene: NKX2-1 was added
gene: NKX2-1 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: NKX2-1 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 NFKBIA Zornitza Stark gene: NFKBIA was added
gene: NFKBIA was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: NFKBIA was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 NF2 Zornitza Stark gene: NF2 was added
gene: NF2 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: NF2 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 NDUFA13 Zornitza Stark gene: NDUFA13 was added
gene: NDUFA13 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: NDUFA13 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 NCOA4 Zornitza Stark gene: NCOA4 was added
gene: NCOA4 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: NCOA4 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 NBN Zornitza Stark gene: NBN was added
gene: NBN was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: NBN was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 NABP1 Zornitza Stark gene: NABP1 was added
gene: NABP1 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: NABP1 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 MUTYH Zornitza Stark gene: MUTYH was added
gene: MUTYH was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: MUTYH was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 MSR1 Zornitza Stark gene: MSR1 was added
gene: MSR1 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: MSR1 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 MSMB Zornitza Stark gene: MSMB was added
gene: MSMB was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: MSMB was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 MSH6 Zornitza Stark gene: MSH6 was added
gene: MSH6 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: MSH6 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 MSH2 Zornitza Stark gene: MSH2 was added
gene: MSH2 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: MSH2 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 MLH3 Zornitza Stark gene: MLH3 was added
gene: MLH3 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: MLH3 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 MLH1 Zornitza Stark gene: MLH1 was added
gene: MLH1 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: MLH1 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 MGMT Zornitza Stark gene: MGMT was added
gene: MGMT was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: MGMT was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 MET Zornitza Stark gene: MET was added
gene: MET was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: MET was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 MEN1 Zornitza Stark gene: MEN1 was added
gene: MEN1 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: MEN1 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 MDM2 Zornitza Stark gene: MDM2 was added
gene: MDM2 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: MDM2 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 MANF Zornitza Stark gene: MANF was added
gene: MANF was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: MANF was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 MALT1 Zornitza Stark gene: MALT1 was added
gene: MALT1 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: MALT1 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 LZTR1 Zornitza Stark gene: LZTR1 was added
gene: LZTR1 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: LZTR1 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 LRRFIP2 Zornitza Stark gene: LRRFIP2 was added
gene: LRRFIP2 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: LRRFIP2 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 KRAS Zornitza Stark gene: KRAS was added
gene: KRAS was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: KRAS was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 KIT Zornitza Stark gene: KIT was added
gene: KIT was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: KIT was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 KHDC3L Zornitza Stark gene: KHDC3L was added
gene: KHDC3L was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: KHDC3L was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 IGHV4-34 Zornitza Stark gene: IGHV4-34 was added
gene: IGHV4-34 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: IGHV4-34 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 IGHV3-21 Zornitza Stark gene: IGHV3-21 was added
gene: IGHV3-21 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: IGHV3-21 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 IGHG1 Zornitza Stark gene: IGHG1 was added
gene: IGHG1 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: IGHG1 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 IDH2 Zornitza Stark gene: IDH2 was added
gene: IDH2 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: IDH2 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 IDH1 Zornitza Stark gene: IDH1 was added
gene: IDH1 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: IDH1 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 HOXB13 Zornitza Stark gene: HOXB13 was added
gene: HOXB13 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: HOXB13 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 HNF1B Zornitza Stark gene: HNF1B was added
gene: HNF1B was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: HNF1B was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 HMGA2 Zornitza Stark gene: HMGA2 was added
gene: HMGA2 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: HMGA2 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 HLA-DRB1 Zornitza Stark gene: HLA-DRB1 was added
gene: HLA-DRB1 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: HLA-DRB1 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 GOLGA5 Zornitza Stark gene: GOLGA5 was added
gene: GOLGA5 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: GOLGA5 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 FUS Zornitza Stark gene: FUS was added
gene: FUS was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: FUS was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 FOXP1 Zornitza Stark gene: FOXP1 was added
gene: FOXP1 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: FOXP1 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 FOXE1 Zornitza Stark gene: FOXE1 was added
gene: FOXE1 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: FOXE1 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 FLT3 Zornitza Stark gene: FLT3 was added
gene: FLT3 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: FLT3 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 FLCN Zornitza Stark gene: FLCN was added
gene: FLCN was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: FLCN was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 FIP1L1 Zornitza Stark gene: FIP1L1 was added
gene: FIP1L1 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: FIP1L1 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 FGFR3 Zornitza Stark gene: FGFR3 was added
gene: FGFR3 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: FGFR3 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 FGFR1 Zornitza Stark gene: FGFR1 was added
gene: FGFR1 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: FGFR1 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 EWSR1 Zornitza Stark gene: EWSR1 was added
gene: EWSR1 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: EWSR1 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 ETV6 Zornitza Stark gene: ETV6 was added
gene: ETV6 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: ETV6 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 ERC1 Zornitza Stark gene: ERC1 was added
gene: ERC1 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: ERC1 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 EPHB2 Zornitza Stark gene: EPHB2 was added
gene: EPHB2 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: EPHB2 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 EPCAM Zornitza Stark gene: EPCAM was added
gene: EPCAM was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: EPCAM was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 ELAC2 Zornitza Stark gene: ELAC2 was added
gene: ELAC2 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: ELAC2 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 EGFR Zornitza Stark gene: EGFR was added
gene: EGFR was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: EGFR was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 DIRC3 Zornitza Stark gene: DIRC3 was added
gene: DIRC3 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: DIRC3 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 DDIT3 Zornitza Stark gene: DDIT3 was added
gene: DDIT3 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: DDIT3 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 CSF3R Zornitza Stark gene: CSF3R was added
gene: CSF3R was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: CSF3R was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 CREB3L2 Zornitza Stark gene: CREB3L2 was added
gene: CREB3L2 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: CREB3L2 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 CREB3L1 Zornitza Stark gene: CREB3L1 was added
gene: CREB3L1 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: CREB3L1 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 CHEK2 Zornitza Stark gene: CHEK2 was added
gene: CHEK2 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: CHEK2 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 CDKN2A Zornitza Stark gene: CDKN2A was added
gene: CDKN2A was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: CDKN2A was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 CDK4 Zornitza Stark gene: CDK4 was added
gene: CDK4 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: CDK4 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 CDH1 Zornitza Stark gene: CDH1 was added
gene: CDH1 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: CDH1 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 CCND1 Zornitza Stark gene: CCND1 was added
gene: CCND1 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: CCND1 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 CCDC6 Zornitza Stark gene: CCDC6 was added
gene: CCDC6 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: CCDC6 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 BRAF Zornitza Stark gene: BRAF was added
gene: BRAF was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: BRAF was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 BMPR1A Zornitza Stark gene: BMPR1A was added
gene: BMPR1A was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: BMPR1A was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 BIRC3 Zornitza Stark gene: BIRC3 was added
gene: BIRC3 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: BIRC3 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 BCR Zornitza Stark gene: BCR was added
gene: BCR was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: BCR was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 BCL6 Zornitza Stark gene: BCL6 was added
gene: BCL6 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: BCL6 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 BCL2 Zornitza Stark gene: BCL2 was added
gene: BCL2 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: BCL2 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 BAP1 Zornitza Stark gene: BAP1 was added
gene: BAP1 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: BAP1 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 ATM Zornitza Stark gene: ATM was added
gene: ATM was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: ATM was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 ARL11 Zornitza Stark gene: ARL11 was added
gene: ARL11 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: ARL11 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 APC Zornitza Stark gene: APC was added
gene: APC was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: APC was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 ABL1 Zornitza Stark gene: ABL1 was added
gene: ABL1 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: ABL1 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 CACNA1S Zornitza Stark gene: CACNA1S was added
gene: CACNA1S was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: CACNA1S was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 RYR1 Zornitza Stark gene: RYR1 was added
gene: RYR1 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: RYR1 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 TGFBR1 Zornitza Stark gene: TGFBR1 was added
gene: TGFBR1 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: TGFBR1 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 SMAD3 Zornitza Stark gene: SMAD3 was added
gene: SMAD3 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: SMAD3 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 MYH11 Zornitza Stark gene: MYH11 was added
gene: MYH11 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: MYH11 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 FBN1 Zornitza Stark gene: FBN1 was added
gene: FBN1 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: FBN1 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 COL3A1 Zornitza Stark gene: COL3A1 was added
gene: COL3A1 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: COL3A1 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 ACTA2 Zornitza Stark gene: ACTA2 was added
gene: ACTA2 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: ACTA2 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 TPM1 Zornitza Stark gene: TPM1 was added
gene: TPM1 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: TPM1 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 TNNT2 Zornitza Stark gene: TNNT2 was added
gene: TNNT2 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: TNNT2 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 TNNI3 Zornitza Stark gene: TNNI3 was added
gene: TNNI3 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: TNNI3 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 TMEM43 Zornitza Stark gene: TMEM43 was added
gene: TMEM43 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: TMEM43 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 SCN5A Zornitza Stark gene: SCN5A was added
gene: SCN5A was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: SCN5A was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 RYR2 Zornitza Stark gene: RYR2 was added
gene: RYR2 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: RYR2 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 PRKAG2 Zornitza Stark gene: PRKAG2 was added
gene: PRKAG2 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: PRKAG2 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 PKP2 Zornitza Stark gene: PKP2 was added
gene: PKP2 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: PKP2 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 LMNA Zornitza Stark gene: LMNA was added
gene: LMNA was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: LMNA was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 MYH7 Zornitza Stark gene: MYH7 was added
gene: MYH7 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: MYH7 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 MYL3 Zornitza Stark gene: MYL3 was added
gene: MYL3 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: MYL3 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 MYL2 Zornitza Stark gene: MYL2 was added
gene: MYL2 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: MYL2 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 MYBPC3 Zornitza Stark gene: MYBPC3 was added
gene: MYBPC3 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: MYBPC3 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 KCNH2 Zornitza Stark gene: KCNH2 was added
gene: KCNH2 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: KCNH2 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 KCNQ1 Zornitza Stark gene: KCNQ1 was added
gene: KCNQ1 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: KCNQ1 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 GLA Zornitza Stark gene: GLA was added
gene: GLA was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: GLA was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 DSP Zornitza Stark gene: DSP was added
gene: DSP was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: DSP was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 DSG2 Zornitza Stark gene: DSG2 was added
gene: DSG2 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: DSG2 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 DSC2 Zornitza Stark gene: DSC2 was added
gene: DSC2 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: DSC2 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 ACTC1 Zornitza Stark gene: ACTC1 was added
gene: ACTC1 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: ACTC1 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 WT1 Zornitza Stark gene: WT1 was added
gene: WT1 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: WT1 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 STK11 Zornitza Stark gene: STK11 was added
gene: STK11 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: STK11 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 RB1 Zornitza Stark gene: RB1 was added
gene: RB1 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: RB1 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 BRCA2 Zornitza Stark gene: BRCA2 was added
gene: BRCA2 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: BRCA2 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 BRCA1 Zornitza Stark gene: BRCA1 was added
gene: BRCA1 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: BRCA1 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 ATP7B Zornitza Stark gene: ATP7B was added
gene: ATP7B was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: ATP7B was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 GBA Zornitza Stark gene: GBA was added
gene: GBA was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: GBA was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 SNCB Zornitza Stark gene: SNCB was added
gene: SNCB was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: SNCB was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 SNCA Zornitza Stark gene: SNCA was added
gene: SNCA was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: SNCA was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 TARDBP Zornitza Stark gene: TARDBP was added
gene: TARDBP was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: TARDBP was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 CHMP2B Zornitza Stark gene: CHMP2B was added
gene: CHMP2B was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: CHMP2B was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 C9orf72 Zornitza Stark gene: C9orf72 was added
gene: C9orf72 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: C9orf72 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 GRN Zornitza Stark gene: GRN was added
gene: GRN was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: GRN was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 MAPT Zornitza Stark gene: MAPT was added
gene: MAPT was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: MAPT was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 ITM2B Zornitza Stark gene: ITM2B was added
gene: ITM2B was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: ITM2B was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 CST3 Zornitza Stark gene: CST3 was added
gene: CST3 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: CST3 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 NOTCH3 Zornitza Stark gene: NOTCH3 was added
gene: NOTCH3 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: NOTCH3 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 SQSTM1 Zornitza Stark gene: SQSTM1 was added
gene: SQSTM1 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: SQSTM1 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 VCP Zornitza Stark gene: VCP was added
gene: VCP was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: VCP was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 TYROBP Zornitza Stark gene: TYROBP was added
gene: TYROBP was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: TYROBP was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 TREM2 Zornitza Stark gene: TREM2 was added
gene: TREM2 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: TREM2 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 PSEN2 Zornitza Stark gene: PSEN2 was added
gene: PSEN2 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: PSEN2 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 PSEN1 Zornitza Stark gene: PSEN1 was added
gene: PSEN1 was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: PSEN1 was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 APP Zornitza Stark gene: APP was added
gene: APP was added to Incidentalome_NSW. Sources: Expert Review Green,NSW Health Pathology
Mode of inheritance for gene: APP was set to Unknown
Incidentalome_PREGEN_DRAFT v0.0 Zornitza Stark Added panel Incidentalome_NSW
Cardiomyopathy_Paediatric v0.41 ATAD3A Zornitza Stark Marked gene: ATAD3A as ready
Cardiomyopathy_Paediatric v0.41 ATAD3A Zornitza Stark Gene: atad3a has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v0.41 ATAD3A Zornitza Stark Phenotypes for gene: ATAD3A were changed from 618810 to Harel-Yoon syndrome, MIM# 617183; Pontocerebellar hypoplasia, hypotonia, and respiratory insufficiency syndrome, neonatal lethal (PHRINL SYNDROME), MIM# 618810; perinatal cardiomyopathy; cataracts; corneal clouding
Cardiomyopathy_Paediatric v0.40 ATAD3A Zornitza Stark Publications for gene: ATAD3A were set to PMID: 32004445
Cardiomyopathy_Paediatric v0.39 ATAD3A Zornitza Stark Tag SV/CNV tag was added to gene: ATAD3A.
Cardiomyopathy_Paediatric v0.39 ATAD3A Zornitza Stark Classified gene: ATAD3A as Green List (high evidence)
Cardiomyopathy_Paediatric v0.39 ATAD3A Zornitza Stark Gene: atad3a has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v0.38 ATAD3A John Christodoulou reviewed gene: ATAD3A: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 32004445, PMID: 27640307, PMID: 28549128, also Frazier et al, Med (in press); Phenotypes: Harel-Yoon syndrome, MIM# 617183, Pontocerebellar hypoplasia, hypotonia, and respiratory insufficiency syndrome, neonatal lethal (PHRINL SYNDROME), MIM# 618810, perinatal cardiomyopathy, cataracts, corneal clouding; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.5338 ACAD9 Zornitza Stark Marked gene: ACAD9 as ready
Mendeliome v0.5338 ACAD9 Zornitza Stark Gene: acad9 has been classified as Green List (High Evidence).
Mendeliome v0.5338 ACAD9 Zornitza Stark Phenotypes for gene: ACAD9 were changed from to Mitochondrial complex I deficiency, nuclear type 20 MIM#611126
Mendeliome v0.5337 ACAD9 Zornitza Stark Publications for gene: ACAD9 were set to
Mendeliome v0.5336 ACAD9 Zornitza Stark Mode of inheritance for gene: ACAD9 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5335 ACAD9 Zornitza Stark reviewed gene: ACAD9: Rating: GREEN; Mode of pathogenicity: None; Publications: 30025539; Phenotypes: Mitochondrial complex I deficiency, nuclear type 20 MIM#611126; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5335 CNP Zornitza Stark Phenotypes for gene: CNP were changed from Hypomyelinating leukodystrophy to Leukodystrophy, hypomyelinating, 20, MIM# 619071
Mendeliome v0.5334 CNP Zornitza Stark reviewed gene: CNP: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Leukodystrophy, hypomyelinating, 20, MIM# 619071; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Leukodystrophy v0.208 CNP Zornitza Stark Phenotypes for gene: CNP were changed from Hypomyelinating leukodystrophy to Leukodystrophy, hypomyelinating, 20, MIM# 619071
Leukodystrophy v0.207 CNP Zornitza Stark reviewed gene: CNP: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Leukodystrophy, hypomyelinating, 20, MIM# 619071; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v0.38 ATAD3A John Christodoulou gene: ATAD3A was added
gene: ATAD3A was added to Cardiomyopathy_Paediatric. Sources: Literature,Expert Review
Mode of inheritance for gene: ATAD3A was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: ATAD3A were set to PMID: 32004445
Phenotypes for gene: ATAD3A were set to 618810
Penetrance for gene: ATAD3A were set to Complete
Mitochondrial disease v0.553 ACAD9 Zornitza Stark Marked gene: ACAD9 as ready
Mitochondrial disease v0.553 ACAD9 Zornitza Stark Gene: acad9 has been classified as Green List (High Evidence).
Mitochondrial disease v0.553 ACAD9 Zornitza Stark Phenotypes for gene: ACAD9 were changed from to Mitochondrial complex I deficiency, nuclear type 20 MIM#611126
Mitochondrial disease v0.552 ACAD9 Zornitza Stark Publications for gene: ACAD9 were set to
Mitochondrial disease v0.551 ACAD9 Zornitza Stark Mode of inheritance for gene: ACAD9 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disease v0.550 ACAD9 Zornitza Stark reviewed gene: ACAD9: Rating: GREEN; Mode of pathogenicity: None; Publications: 30025539; Phenotypes: Mitochondrial complex I deficiency, nuclear type 20 MIM#611126; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3181 ACAD9 Zornitza Stark Marked gene: ACAD9 as ready
Intellectual disability syndromic and non-syndromic v0.3181 ACAD9 Zornitza Stark Gene: acad9 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3181 ACAD9 Zornitza Stark Phenotypes for gene: ACAD9 were changed from to Mitochondrial complex I deficiency, nuclear type 20 MIM#611126
Intellectual disability syndromic and non-syndromic v0.3180 ACAD9 Zornitza Stark Publications for gene: ACAD9 were set to
Intellectual disability syndromic and non-syndromic v0.3179 ACAD9 Zornitza Stark Mode of inheritance for gene: ACAD9 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3178 ACAD9 Zornitza Stark reviewed gene: ACAD9: Rating: GREEN; Mode of pathogenicity: None; Publications: 30025539; Phenotypes: Mitochondrial complex I deficiency, nuclear type 20 MIM#611126; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mackenzie's Mission_Reproductive Carrier Screening v0.47 NEXMIF Sarah Righetti reviewed gene: NEXMIF: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Mental retardation, X-linked 98, MIM #300912; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Mackenzie's Mission_Reproductive Carrier Screening v0.47 CLCN4 Sarah Righetti reviewed gene: CLCN4: Rating: GREEN; Mode of pathogenicity: None; Publications: 27550844; Phenotypes: Raynaud-Claes syndrome, MIM #300114; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Mackenzie's Mission_Reproductive Carrier Screening v0.47 NYX Sarah Righetti Deleted their comment
Mackenzie's Mission_Reproductive Carrier Screening v0.47 NYX Sarah Righetti edited their review of gene: NYX: Added comment: Clinical summary: Function of rods disrupted - difficulty seeing in low light. Other vision problems including reduced acuity (20/30 to 20/200) which is considered mild-moderate visual impairment or reduced-low vision. 20/40 is Australian legal driving limit. Myopia - can range from low to high. May have nystagmus/strabismus. Color vision not affected. Non-progressive, present at birth.

Severe end of phenoypic spectrum meets MM criteria for inclusion - GREEN; Changed mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mackenzie's Mission_Reproductive Carrier Screening v0.47 NYX Sarah Righetti reviewed gene: NYX: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Night blindness, congenital stationary (complete), 1A, X-linked, MIM #310500; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mackenzie's Mission_Reproductive Carrier Screening v0.47 COL2A1 Sarah Righetti Deleted their comment
Mackenzie's Mission_Reproductive Carrier Screening v0.47 COL2A1 Sarah Righetti edited their review of gene: COL2A1: Added comment: Limited evidence for a recessive condition. 8 patients from 5 families, at least 2 mildly affected. Almost all literature dominant.

PMID: 31755234 (Girisha et al. 2020) six patients from 4 families, variability in phenotype.

PMID: 32896647 (Al-Sannaa et al 2020) two sibs from consang family with disproportionate short stature, ocular abnormalities, cleft palate and hearing impairment. Radiographic study showed signs of a spondyloepiphyseal dysplasia, compatible with a type 2 collagen disorder. Both siblings homozygous for c.3111+2T > C p.(Glu1 033Lysfs *5) splice site variant in the COL2A1 gene. Het parents phenotypically normal. cDNA analysis on skin fibroblasts demonstrated abberant splicing.
Created: 6 Nov 2020, 4:59 a.; Changed rating: AMBER
Mackenzie's Mission_Reproductive Carrier Screening v0.47 COL2A1 Sarah Righetti reviewed gene: COL2A1: Rating: RED; Mode of pathogenicity: None; Publications: 31755234, 32896647; Phenotypes: Spondyloperipheral dysplasia, MIM #271700; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mackenzie's Mission_Reproductive Carrier Screening v0.47 MBTPS1 Sarah Righetti gene: MBTPS1 was added
gene: MBTPS1 was added to Mackenzie's Mission_Reproductive Carrier Screening. Sources: Expert Review,Literature
Mode of inheritance for gene: MBTPS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MBTPS1 were set to 32857899; 32420688; 30046013
Phenotypes for gene: MBTPS1 were set to ?Spondyloepiphyseal dysplasia, Kondo-Fu type, MIM #618392
Review for gene: MBTPS1 was set to AMBER
Added comment: Three unrelated individuals reported with bi-allelic variants in this gene and a skeletal dysplasia, one described with SRS-like features. Elevated blood lysosomal enzymes are also a feature.
Sources: Expert Review, Literature
Mackenzie's Mission_Reproductive Carrier Screening v0.47 TBX22 Sarah Righetti gene: TBX22 was added
gene: TBX22 was added to Mackenzie's Mission_Reproductive Carrier Screening. Sources: Expert Review
Mode of inheritance for gene: TBX22 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: TBX22 were set to Cleft palate with ankyloglossia, MIM #303400
Review for gene: TBX22 was set to RED
Added comment: Treatable condition. RED on phenotypic grounds.
Sources: Expert Review
Mackenzie's Mission_Reproductive Carrier Screening v0.47 POLA1 Sarah Righetti reviewed gene: POLA1: Rating: AMBER; Mode of pathogenicity: None; Publications: 27019227, 31006512; Phenotypes: Pigmentary disorder, reticulate, with systemic manifestations, X-linked, MIM#301220, Van Esch-O'Driscoll syndrome, MIM #301030; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mackenzie's Mission_Reproductive Carrier Screening v0.47 POLA1 Sarah Righetti Deleted their review
Mackenzie's Mission_Reproductive Carrier Screening v0.47 POLA1 Sarah Righetti changed review comment from: Immunodeficieny phenotype MIM#301220 has strong gene-disease association but is caused by a specific deep intronic variant that is not detectable by MM ES. See PMID: 27019227.

Van Esch-O'Driscoll syndrome MIM #30103, which is ID, is described in a single paper PMID 31006512. 5 families, 5 variants in 9 patients, AMBER for gene-disease association.; to: Immunodeficieny phenotype MIM#301220 has strong gene-disease association but is caused by a specific deep intronic variant that is not detectable by MM ES. PMID: 27019227.

Van Esch-O'Driscoll syndrome MIM #30103, which is ID, is described in a single paper PMID 31006512. 5 families, 5 variants in 9 patients, AMBER for gene-disease association.
Mackenzie's Mission_Reproductive Carrier Screening v0.47 POLA1 Sarah Righetti reviewed gene: POLA1: Rating: AMBER; Mode of pathogenicity: None; Publications: 27019227; Phenotypes: Pigmentary disorder, reticulate, with systemic manifestations, X-linked, MIM #301220, Van Esch-O'Driscoll syndrome, MIM #301030; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mackenzie's Mission_Reproductive Carrier Screening v0.47 UPB1 Sarah Righetti reviewed gene: UPB1: Rating: RED; Mode of pathogenicity: None; Publications: 24526388; Phenotypes: Beta-ureidopropionase deficiency, MIM #613161; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mackenzie's Mission_Reproductive Carrier Screening v0.47 UPB1 Sarah Righetti Deleted their review
Mackenzie's Mission_Reproductive Carrier Screening v0.47 UPB1 Sarah Righetti changed review comment from: Insufficient evidence that abolition of enzymatic activity is disease-causing. LOF/pathogenic missense alleles at high frequency in general population.In particular, the most frequently reported variant, p.Arg326Gln, is very common among East Asians, with a carrier frequency of 1 in 20 and 1 in 907 being homozygous for the variant. Moreover, published reports (PMID: 24526388) include multiple individuals with mild or no phenotypes. ; to: Insufficient evidence that abolition of enzymatic activity is disease-causing. LOF/pathogenic missense alleles at high frequency in general population.In particular, the most frequently reported variant, p.Arg326Gln, is very common among East Asians, with a carrier frequency of 1 in 20 and 1 in 907 being homozygous for the variant. Moreover, published reports (PMID: 24526388) include multiple individuals with mild or no phenotypes.
Mackenzie's Mission_Reproductive Carrier Screening v0.47 UPB1 Sarah Righetti changed review comment from: Insufficient evidence that abolition of enzymatic activity is disease-causing. LOF/pathogenic missense alleles at high frequency in general population.; to: Insufficient evidence that abolition of enzymatic activity is disease-causing. LOF/pathogenic missense alleles at high frequency in general population.In particular, the most frequently reported variant, p.Arg326Gln, is very common among East Asians, with a carrier frequency of 1 in 20 and 1 in 907 being homozygous for the variant. Moreover, published reports (PMID: 24526388) include multiple individuals with mild or no phenotypes.
Mackenzie's Mission_Reproductive Carrier Screening v0.47 UPB1 Sarah Righetti reviewed gene: UPB1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mackenzie's Mission_Reproductive Carrier Screening v0.47 ERBB3 Seb Lunke Marked gene: ERBB3 as ready
Mackenzie's Mission_Reproductive Carrier Screening v0.47 ERBB3 Seb Lunke Gene: erbb3 has been classified as Amber List (Moderate Evidence).
Mackenzie's Mission_Reproductive Carrier Screening v0.47 ERBB3 Seb Lunke Classified gene: ERBB3 as Amber List (moderate evidence)
Mackenzie's Mission_Reproductive Carrier Screening v0.47 ERBB3 Seb Lunke Added comment: Comment on list classification: Downgraded to Amber due to limited evidence and variable phenotypes described in literature.
Mackenzie's Mission_Reproductive Carrier Screening v0.47 ERBB3 Seb Lunke Gene: erbb3 has been classified as Amber List (Moderate Evidence).
Mackenzie's Mission_Reproductive Carrier Screening v0.46 SLC35A3 Seb Lunke Marked gene: SLC35A3 as ready
Mackenzie's Mission_Reproductive Carrier Screening v0.46 SLC35A3 Seb Lunke Gene: slc35a3 has been classified as Green List (High Evidence).
Mackenzie's Mission_Reproductive Carrier Screening v0.46 SLC35A3 Seb Lunke Publications for gene: SLC35A3 were set to
Mackenzie's Mission_Reproductive Carrier Screening v0.45 SLC35A3 Seb Lunke Phenotypes for gene: SLC35A3 were changed from ?Arthrogryposis, mental retardation, and seizures to Arthrogryposis, mental retardation, and seizures (MIM615553)
Mendeliome v0.5334 ALDOB Zornitza Stark Marked gene: ALDOB as ready
Mendeliome v0.5334 ALDOB Zornitza Stark Gene: aldob has been classified as Green List (High Evidence).
Mendeliome v0.5334 ALDOB Zornitza Stark Phenotypes for gene: ALDOB were changed from to Fructose intolerance, hereditary, 229600
Mendeliome v0.5333 ALDOB Zornitza Stark Publications for gene: ALDOB were set to
Mendeliome v0.5332 ALDOB Zornitza Stark Mode of inheritance for gene: ALDOB was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5331 ALDOB Elena Savva reviewed gene: ALDOB: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 3083321; Phenotypes: Fructose intolerance, hereditary, 229600; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Liver Failure_Paediatric v1.0 Zornitza Stark promoted panel to version 1.0
Liver Failure_Paediatric v0.114 NOTCH2 Zornitza Stark Marked gene: NOTCH2 as ready
Liver Failure_Paediatric v0.114 NOTCH2 Zornitza Stark Gene: notch2 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.114 NOTCH2 Zornitza Stark Classified gene: NOTCH2 as Green List (high evidence)
Liver Failure_Paediatric v0.114 NOTCH2 Zornitza Stark Gene: notch2 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.113 NOTCH2 Zornitza Stark gene: NOTCH2 was added
gene: NOTCH2 was added to Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: NOTCH2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: NOTCH2 were set to Alagille syndrome 2, MIM# 610205
Review for gene: NOTCH2 was set to GREEN
Added comment: Well established gene-disease association.
Sources: Expert list
Liver Failure_Paediatric v0.112 ABCB4 Zornitza Stark Marked gene: ABCB4 as ready
Liver Failure_Paediatric v0.112 ABCB4 Zornitza Stark Gene: abcb4 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.112 ABCB4 Zornitza Stark Classified gene: ABCB4 as Green List (high evidence)
Liver Failure_Paediatric v0.112 ABCB4 Zornitza Stark Gene: abcb4 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.111 ABCB4 Zornitza Stark gene: ABCB4 was added
gene: ABCB4 was added to Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: ABCB4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ABCB4 were set to 17726488
Phenotypes for gene: ABCB4 were set to Cholestasis, progressive familial intrahepatic 3, MIM# 602347
Review for gene: ABCB4 was set to GREEN
Added comment: Well established gene disease association.
Sources: Expert list
Liver Failure_Paediatric v0.110 ABCB11 Zornitza Stark Marked gene: ABCB11 as ready
Liver Failure_Paediatric v0.110 ABCB11 Zornitza Stark Gene: abcb11 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.110 ABCB11 Zornitza Stark Classified gene: ABCB11 as Green List (high evidence)
Liver Failure_Paediatric v0.110 ABCB11 Zornitza Stark Gene: abcb11 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.109 ABCB11 Zornitza Stark gene: ABCB11 was added
gene: ABCB11 was added to Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: ABCB11 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ABCB11 were set to 9806540
Phenotypes for gene: ABCB11 were set to Cholestasis, progressive familial intrahepatic 2, MIM# 601847
Review for gene: ABCB11 was set to GREEN
Added comment: Well established gene-disease association.
Sources: Expert list
Liver Failure_Paediatric v0.108 ATP8B1 Zornitza Stark Marked gene: ATP8B1 as ready
Liver Failure_Paediatric v0.108 ATP8B1 Zornitza Stark Gene: atp8b1 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.108 ATP8B1 Zornitza Stark Classified gene: ATP8B1 as Green List (high evidence)
Liver Failure_Paediatric v0.108 ATP8B1 Zornitza Stark Gene: atp8b1 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.107 ATP8B1 Zornitza Stark gene: ATP8B1 was added
gene: ATP8B1 was added to Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: ATP8B1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATP8B1 were set to 15239083
Phenotypes for gene: ATP8B1 were set to Cholestasis, progressive familial intrahepatic 1, MIM# 211600
Review for gene: ATP8B1 was set to GREEN
Added comment: Well established gene-disease association, early onset of cholestasis that progresses to hepatic fibrosis, cirrhosis, and end-stage liver failure.
Sources: Expert list
Liver Failure_Paediatric v0.106 CPT2 Zornitza Stark Marked gene: CPT2 as ready
Liver Failure_Paediatric v0.106 CPT2 Zornitza Stark Gene: cpt2 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.106 CPT2 Zornitza Stark Classified gene: CPT2 as Green List (high evidence)
Liver Failure_Paediatric v0.106 CPT2 Zornitza Stark Gene: cpt2 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.105 CPT2 Zornitza Stark gene: CPT2 was added
gene: CPT2 was added to Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: CPT2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CPT2 were set to 8651281; 1528846; 12410208
Phenotypes for gene: CPT2 were set to CPT II deficiency, infantile, MIM# 600649
Review for gene: CPT2 was set to GREEN
Added comment: The infantile form usually presents between 6 and 24 months of age with recurrent attacks of hypoketotic hypoglycemia causing loss of consciousness and seizures, liver failure, and transient hepatomegaly. Some children also have heart involvement with cardiomyopathy and arrhythmia. Episodes are triggered by infections, fever, or fasting.
Sources: Expert list
Liver Failure_Paediatric v0.104 CYP7B1 Zornitza Stark Marked gene: CYP7B1 as ready
Liver Failure_Paediatric v0.104 CYP7B1 Zornitza Stark Gene: cyp7b1 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.104 CYP7B1 Zornitza Stark Classified gene: CYP7B1 as Green List (high evidence)
Liver Failure_Paediatric v0.104 CYP7B1 Zornitza Stark Gene: cyp7b1 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.103 CYP7B1 Zornitza Stark gene: CYP7B1 was added
gene: CYP7B1 was added to Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: CYP7B1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CYP7B1 were set to 9802883; 31337596; 21567895; 24658845
Phenotypes for gene: CYP7B1 were set to Bile acid synthesis defect, congenital, 3, MIM# 613812
Review for gene: CYP7B1 was set to GREEN
Added comment: At least 4 unrelated families reported.
Sources: Expert list
Liver Failure_Paediatric v0.102 IARS Zornitza Stark Marked gene: IARS as ready
Liver Failure_Paediatric v0.102 IARS Zornitza Stark Gene: iars has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.102 IARS Zornitza Stark Classified gene: IARS as Green List (high evidence)
Liver Failure_Paediatric v0.102 IARS Zornitza Stark Gene: iars has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.101 IARS Zornitza Stark gene: IARS was added
gene: IARS was added to Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: IARS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IARS were set to 27426735; 27891590
Phenotypes for gene: IARS were set to Growth retardation, impaired intellectual development, hypotonia, and hepatopathy, MIM# 617093
Review for gene: IARS was set to GREEN
Added comment: GRIDHH is an autosomal recessive multisystem disorder characterized by poor overall growth, impaired intellectual development, hypotonia, and variable liver dysfunction. Four unrelated families reported and a zebrafish model.
Sources: Expert list
Liver Failure_Paediatric v0.100 TTC37 Zornitza Stark Marked gene: TTC37 as ready
Liver Failure_Paediatric v0.100 TTC37 Zornitza Stark Gene: ttc37 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.100 TTC37 Zornitza Stark Classified gene: TTC37 as Green List (high evidence)
Liver Failure_Paediatric v0.100 TTC37 Zornitza Stark Gene: ttc37 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.99 TTC37 Zornitza Stark gene: TTC37 was added
gene: TTC37 was added to Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: TTC37 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TTC37 were set to 17318842; 20176027
Phenotypes for gene: TTC37 were set to Trichohepatoenteric syndrome 1, MIM# 222470
Review for gene: TTC37 was set to GREEN
Added comment: Clinical features include intrauterine growth retardation, woolly hair, facial dysmorphism, intractable diarrhoea in infancy requiring total parenteral nutrition, and immunodepression. Hepatic involvement contributes to the poor prognosis of affected patients, cirrhosis reported.

More than 20 unrelated families reported.
Sources: Expert list
Liver Failure_Paediatric v0.98 HSD3B7 Zornitza Stark Marked gene: HSD3B7 as ready
Liver Failure_Paediatric v0.98 HSD3B7 Zornitza Stark Gene: hsd3b7 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.98 HSD3B7 Zornitza Stark Classified gene: HSD3B7 as Green List (high evidence)
Liver Failure_Paediatric v0.98 HSD3B7 Zornitza Stark Gene: hsd3b7 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.97 HSD3B7 Zornitza Stark gene: HSD3B7 was added
gene: HSD3B7 was added to Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: HSD3B7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HSD3B7 were set to 12679481; 11067870
Phenotypes for gene: HSD3B7 were set to Bile acid synthesis defect, congenital, 1, MIM# 607765
Review for gene: HSD3B7 was set to GREEN
Added comment: Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) is an autosomal recessive metabolic disorder characterized by poor growth, intrahepatic cholestasis, and increased serum citrulline. Most individuals show spontaneous improvement by 1 year of age. However, some may have a progressive course with continued failure to thrive and dyslipidemia caused by citrin deficiency (FTTDCD), and some may develop chronic or fatal liver disease.

More than 10 unrelated families reported.
Sources: Expert list
Liver Failure_Paediatric v0.96 CCDC115 Zornitza Stark Marked gene: CCDC115 as ready
Liver Failure_Paediatric v0.96 CCDC115 Zornitza Stark Gene: ccdc115 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.96 CCDC115 Zornitza Stark Classified gene: CCDC115 as Green List (high evidence)
Liver Failure_Paediatric v0.96 CCDC115 Zornitza Stark Gene: ccdc115 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.95 CCDC115 Zornitza Stark gene: CCDC115 was added
gene: CCDC115 was added to Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: CCDC115 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CCDC115 were set to 26833332; 29759592
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: Autosomal recessive metabolic disorder characterized by infantile onset of progressive liver failure, hypotonia, and delayed psychomotor development. Laboratory abnormalities include elevated liver enzymes, coagulation factor deficiencies, hypercholesterolemia, and low ceruloplasmin. Serum isoelectric focusing of proteins shows a combined defect of N- and O-glycosylation, suggestive of a Golgi defect.
Sources: Expert list
Mendeliome v0.5331 ITFG2 Zornitza Stark Publications for gene: ITFG2 were set to 28397838; https://doi.org/10.1038/s41525-020-00150-z
Mendeliome v0.5330 ITFG2 Zornitza Stark edited their review of gene: ITFG2: Changed publications: 28397838, 33083013
Intellectual disability syndromic and non-syndromic v0.3178 ITFG2 Zornitza Stark Publications for gene: ITFG2 were set to 28397838; https://doi.org/10.1038/s41525-020-00150-z
Intellectual disability syndromic and non-syndromic v0.3177 ITFG2 Zornitza Stark edited their review of gene: ITFG2: Changed rating: AMBER; Changed publications: 33083013; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5330 MYO1A Zornitza Stark Marked gene: MYO1A as ready
Mendeliome v0.5330 MYO1A Zornitza Stark Gene: myo1a has been classified as Red List (Low Evidence).
Mendeliome v0.5330 MYO1A Zornitza Stark Classified gene: MYO1A as Red List (low evidence)
Mendeliome v0.5330 MYO1A Zornitza Stark Gene: myo1a has been classified as Red List (Low Evidence).
Mendeliome v0.5329 MYO1A Zornitza Stark reviewed gene: MYO1A: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Motor Neurone Disease v0.116 Bryony Thompson Panel name changed from Motor Neuron Disease to Motor Neurone Disease
Hyperinsulinism v0.29 Zornitza Stark Panel types changed to Victorian Clinical Genetics Services; Royal Melbourne Hospital; Rare Disease
Mendeliome v0.5329 ARL2 Zornitza Stark Marked gene: ARL2 as ready
Mendeliome v0.5329 ARL2 Zornitza Stark Gene: arl2 has been classified as Red List (Low Evidence).
Mendeliome v0.5329 ARL2 Zornitza Stark gene: ARL2 was added
gene: ARL2 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: ARL2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ARL2 were set to 30945270
Phenotypes for gene: ARL2 were set to Microcornea, rod-cone dystrophy, cataract, and posterior staphyloma-1 (MRCS1), MIM#619082
Review for gene: ARL2 was set to RED
Added comment: Single family reported, missense variant segregating with structural eye abnormalities in 4 individuals (father and three daughters).
Sources: Expert list
Cataract v0.240 ARL2 Zornitza Stark Marked gene: ARL2 as ready
Cataract v0.240 ARL2 Zornitza Stark Gene: arl2 has been classified as Red List (Low Evidence).
Cataract v0.240 ARL2 Zornitza Stark gene: ARL2 was added
gene: ARL2 was added to Cataract. Sources: Expert list
Mode of inheritance for gene: ARL2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ARL2 were set to 30945270
Phenotypes for gene: ARL2 were set to Microcornea, rod-cone dystrophy, cataract, and posterior staphyloma-1 (MRCS1), MIM#619082
Review for gene: ARL2 was set to RED
Added comment: Single family reported, missense variant segregating with structural eye abnormalities in 4 individuals (father and three daughters).
Sources: Expert list
Arthrogryposis v0.243 LMX1B Zornitza Stark Phenotypes for gene: LMX1B were changed from Nail-patella syndrome, MIM# 161200 to Nail-patella syndrome, MIM# 161200, MONDO:0008061
Arthrogryposis v0.242 LMX1B Zornitza Stark edited their review of gene: LMX1B: Changed phenotypes: Nail-patella syndrome, MIM# 161200, MONDO:0008061
Arthrogryposis v0.242 LMX1B Zornitza Stark changed review comment from: 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). >300 families reported.; to: 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. >300 families reported.
Arthrogryposis v0.242 LMX1B Zornitza Stark edited their review of gene: LMX1B: 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). >300 families reported.; Changed phenotypes: Nail-patella syndrome, MIM# 161200
Proteinuria v0.145 LMX1B Zornitza Stark Marked gene: LMX1B as ready
Proteinuria v0.145 LMX1B Zornitza Stark Gene: lmx1b has been classified as Green List (High Evidence).
Proteinuria v0.145 LMX1B Zornitza Stark Phenotypes for gene: LMX1B were changed from to Nail-patella syndrome (MIM#161200), MONDO:0008061; LMX1B-related nephropathy
Proteinuria v0.144 LMX1B Zornitza Stark Publications for gene: LMX1B were set to
Proteinuria v0.143 LMX1B Zornitza Stark Mode of inheritance for gene: LMX1B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Proteinuria v0.142 LMX1B Zornitza Stark reviewed gene: LMX1B: Rating: GREEN; Mode of pathogenicity: None; Publications: 27450397, 32457516; Phenotypes: Nail-patella syndrome (MIM#161200), MONDO:0008061, LMX1B-related nephropathy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5328 LMX1B Zornitza Stark Publications for gene: LMX1B were set to 27450397
Mendeliome v0.5327 LMX1B Zornitza Stark commented on gene: LMX1B: 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).

>300 families reported.
Mendeliome v0.5327 LMX1B Zornitza Stark edited their review of gene: LMX1B: Changed publications: 27450397, 32457516
Mendeliome v0.5327 LMX1B Zornitza Stark Phenotypes for gene: LMX1B were changed from Nail-patella syndrome (MIM#161200); LMX1B-related nephropathy to Nail-patella syndrome (MIM#161200), MONDO:0008061; LMX1B-related nephropathy
Mendeliome v0.5326 LMX1B Zornitza Stark reviewed gene: LMX1B: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Nail-patella syndrome (MIM#161200), MONDO:0008061, LMX1B-related nephropathy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Microcephaly v0.496 UNC80 Zornitza Stark Phenotypes for gene: UNC80 were changed from Hypotonia, infantile, with psychomotor retardation and characteristic facies 2 MIM#616801 to Hypotonia, infantile, with psychomotor retardation and characteristic facies 2, MIM# 616801; MONDO:0014777
Microcephaly v0.495 UNC80 Zornitza Stark reviewed gene: UNC80: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Hypotonia, infantile, with psychomotor retardation and characteristic facies 2, MIM# 616801, MONDO:0014777; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Dystonia and Chorea v0.154 UNC80 Zornitza Stark Phenotypes for gene: UNC80 were changed from hypotonia; severe intellectual disability; dyskinesia; dysmorphism to Hypotonia, infantile, with psychomotor retardation and characteristic facies 2, MIM# 616801; MONDO:0014777
Dystonia and Chorea v0.153 UNC80 Zornitza Stark reviewed gene: UNC80: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Hypotonia, infantile, with psychomotor retardation and characteristic facies 2, MIM# 616801, MONDO:0014777; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.898 UNC80 Zornitza Stark Marked gene: UNC80 as ready
Genetic Epilepsy v0.898 UNC80 Zornitza Stark Gene: unc80 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.898 UNC80 Zornitza Stark Phenotypes for gene: UNC80 were changed from to Hypotonia, infantile, with psychomotor retardation and characteristic facies 2, MIM# 616801; MONDO:0014777
Genetic Epilepsy v0.897 UNC80 Zornitza Stark Publications for gene: UNC80 were set to
Genetic Epilepsy v0.896 UNC80 Zornitza Stark Mode of inheritance for gene: UNC80 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.895 UNC80 Zornitza Stark commented on gene: UNC80: UNC80 is part of the NALCN complex, and this is considered a NALCN channelopathy.

More than 20 individuals from more than 5 unrelated families reported with bi-allelic variants in this gene and severe autosomal recessive neurodevelopmental disorder with onset at birth or in early infancy. Affected individuals show severe global developmental delay with poor or absent speech and absent or limited ability to walk. Some have had seizures; brain structure is typically normal.

UNC80 knockout mice are neonatal lethal.
Genetic Epilepsy v0.895 UNC80 Zornitza Stark reviewed gene: UNC80: Rating: GREEN; Mode of pathogenicity: None; Publications: 26708751, 26708753, 26545877, 32620897, 30167850, 30167850; Phenotypes: Hypotonia, infantile, with psychomotor retardation and characteristic facies 2, MIM# 616801, MONDO:0014777; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3177 UNC80 Zornitza Stark Marked gene: UNC80 as ready
Intellectual disability syndromic and non-syndromic v0.3177 UNC80 Zornitza Stark Gene: unc80 has been classified as Green List (High Evidence).
Mendeliome v0.5326 UNC80 Zornitza Stark Marked gene: UNC80 as ready
Mendeliome v0.5326 UNC80 Zornitza Stark Gene: unc80 has been classified as Green List (High Evidence).
Mendeliome v0.5326 UNC80 Zornitza Stark Phenotypes for gene: UNC80 were changed from to Hypotonia, infantile, with psychomotor retardation and characteristic facies 2, MIM# 616801; MONDO:0014777
Mendeliome v0.5325 UNC80 Zornitza Stark Publications for gene: UNC80 were set to
Mendeliome v0.5324 UNC80 Zornitza Stark Mode of inheritance for gene: UNC80 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3177 UNC80 Zornitza Stark Phenotypes for gene: UNC80 were changed from to Hypotonia, infantile, with psychomotor retardation and characteristic facies 2, MIM# 616801; MONDO:0014777
Mendeliome v0.5323 UNC80 Zornitza Stark reviewed gene: UNC80: Rating: GREEN; Mode of pathogenicity: None; Publications: 26708751, 26708753, 26545877, 32620897, 30167850, 30167850; Phenotypes: Hypotonia, infantile, with psychomotor retardation and characteristic facies 2, MIM# 616801, MONDO:0014777; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3176 UNC80 Zornitza Stark Publications for gene: UNC80 were set to 26708751; 26708753; 26545877; 32620897; 30167850; 30167850
Intellectual disability syndromic and non-syndromic v0.3176 UNC80 Zornitza Stark Publications for gene: UNC80 were set to
Intellectual disability syndromic and non-syndromic v0.3175 UNC80 Zornitza Stark edited their review of gene: UNC80: Changed phenotypes: Hypotonia, infantile, with psychomotor retardation and characteristic facies 2, MIM# 616801, MONDO:0014777
Intellectual disability syndromic and non-syndromic v0.3175 UNC80 Zornitza Stark Mode of inheritance for gene: UNC80 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3174 UNC80 Zornitza Stark reviewed gene: UNC80: Rating: GREEN; Mode of pathogenicity: None; Publications: 26708751, 26708753, 26545877, 32620897, 30167850, 30167850; Phenotypes: Hypotonia, infantile, with psychomotor retardation and characteristic facies 2, MIM# 616801; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5323 ZFHX4 Zornitza Stark Tag SV/CNV tag was added to gene: ZFHX4.
Intellectual disability syndromic and non-syndromic v0.3174 ZFHX4 Zornitza Stark Tag SV/CNV tag was added to gene: ZFHX4.
Mendeliome v0.5323 ZFHX4 Zornitza Stark Classified gene: ZFHX4 as Green List (high evidence)
Mendeliome v0.5323 ZFHX4 Zornitza Stark Gene: zfhx4 has been classified as Green List (High Evidence).
Mendeliome v0.5322 ZFHX4 Zornitza Stark reviewed gene: ZFHX4: Rating: GREEN; Mode of pathogenicity: None; Publications: 21802062; Phenotypes: Intellectual disability; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.3174 ZFHX4 Zornitza Stark Classified gene: ZFHX4 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.3174 ZFHX4 Zornitza Stark Gene: zfhx4 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3173 ZFHX4 Zornitza Stark gene: ZFHX4 was added
gene: ZFHX4 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: ZFHX4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ZFHX4 were set to 33057194; 24038936; 21802062
Phenotypes for gene: ZFHX4 were set to Developmental disorders; intellectual disability, dysmorphic features
Review for gene: ZFHX4 was set to GREEN
Added comment: PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 16 de novo variants (5 frameshift, 5 missense, 4 stopgain, 2 synonymous) identified in ~10,000 cases with developmental disorders (no other phenotype info provided).
PMID: 24038936 - a single case with developmental delay, macrocephaly, ventriculomegaly, hypermetropia, recurrent infections, dysmorphism and a de novo deletion of the last 7 exons of the gene.
PMID:21802062 (2011) report 8 individuals with ID and overlapping deletions of 8q21.11 (0.66-13.55 Mb in size); the smallest region of overlap encompasses 3 genes including ZFHX4.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3172 UPF1 Zornitza Stark Marked gene: UPF1 as ready
Intellectual disability syndromic and non-syndromic v0.3172 UPF1 Zornitza Stark Gene: upf1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.3172 UPF1 Zornitza Stark Classified gene: UPF1 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.3172 UPF1 Zornitza Stark Gene: upf1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.3171 UPF1 Zornitza Stark gene: UPF1 was added
gene: UPF1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: UPF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: UPF1 were set to 33057194
Phenotypes for gene: UPF1 were set to Developmental disorders
Review for gene: UPF1 was set to AMBER
Added comment: PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 16 de novo variants (1 frameshift, 11 missense, 4 synonymous) identified in ~10,000 cases with developmental disorders (no other phenotype info provided, hence Amber rating).
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3170 U2AF2 Zornitza Stark Marked gene: U2AF2 as ready
Intellectual disability syndromic and non-syndromic v0.3170 U2AF2 Zornitza Stark Gene: u2af2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.3170 U2AF2 Zornitza Stark Classified gene: U2AF2 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.3170 U2AF2 Zornitza Stark Gene: u2af2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.3169 U2AF2 Zornitza Stark gene: U2AF2 was added
gene: U2AF2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: U2AF2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: U2AF2 were set to 33057194
Phenotypes for gene: U2AF2 were set to Developmental disorders
Review for gene: U2AF2 was set to AMBER
Added comment: PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 10 de novo variants (1 in-frame, 8 missense, 1 synoymous) identified in ~10,000 cases with developmental disorders (no other phenotype info provided, hence Amber rating).
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3168 TCF7L2 Zornitza Stark Marked gene: TCF7L2 as ready
Intellectual disability syndromic and non-syndromic v0.3168 TCF7L2 Zornitza Stark Gene: tcf7l2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.3168 TCF7L2 Zornitza Stark Classified gene: TCF7L2 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.3168 TCF7L2 Zornitza Stark Gene: tcf7l2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.3167 TCF7L2 Zornitza Stark gene: TCF7L2 was added
gene: TCF7L2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: TCF7L2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TCF7L2 were set to 33057194
Phenotypes for gene: TCF7L2 were set to Developmental disorders
Review for gene: TCF7L2 was set to AMBER
Added comment: A diabetes susceptibility locus associated with common SNVs, see OMIM for details.

PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 12 de novo variants (2 frameshift, 6 missense, 1 splice acceptor, 2 stopgain, 1 synonymous) identified in ~10,000 cases with developmental disorders (no other phenotype info provided, hence Amber rating).
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3166 SRRM2 Zornitza Stark Marked gene: SRRM2 as ready
Intellectual disability syndromic and non-syndromic v0.3166 SRRM2 Zornitza Stark Gene: srrm2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.3166 SRRM2 Zornitza Stark Classified gene: SRRM2 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.3166 SRRM2 Zornitza Stark Gene: srrm2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.3165 SRRM2 Zornitza Stark gene: SRRM2 was added
gene: SRRM2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: SRRM2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SRRM2 were set to 33057194
Phenotypes for gene: SRRM2 were set to Developmental disorders
Review for gene: SRRM2 was set to AMBER
Added comment: PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 28 de novo variants (11 frameshift, 7 missense, 1 splice acceptor, 5 stopgain, 4 synonymous) identified in ~10,000 cases with developmental disorders (no other phenotype info provided hence Amber rating).
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3164 SPEN Zornitza Stark Marked gene: SPEN as ready
Intellectual disability syndromic and non-syndromic v0.3164 SPEN Zornitza Stark Gene: spen has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.3164 SPEN Zornitza Stark Classified gene: SPEN as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.3164 SPEN Zornitza Stark Gene: spen has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.3163 SPEN Zornitza Stark gene: SPEN was added
gene: SPEN was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: SPEN was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SPEN were set to 33057194
Phenotypes for gene: SPEN were set to Developmental disorders
Review for gene: SPEN was set to AMBER
Added comment: PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 25 de novo variants (6 frameshift, 1 in-frame, 7 missense, 8 stopgain, 3 synonymous) identified in ~10,000 cases with developmental disorders (no other phenotype info provided hence Amber rating).
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3162 SATB1 Zornitza Stark Marked gene: SATB1 as ready
Intellectual disability syndromic and non-syndromic v0.3162 SATB1 Zornitza Stark Gene: satb1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.3162 SATB1 Zornitza Stark Classified gene: SATB1 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.3162 SATB1 Zornitza Stark Gene: satb1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.3161 SATB1 Zornitza Stark gene: SATB1 was added
gene: SATB1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: SATB1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SATB1 were set to 33057194
Phenotypes for gene: SATB1 were set to Developmental disorders
Review for gene: SATB1 was set to AMBER
Added comment: PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 12 de novo (2 frameshift, 7 missense, 1 stopgain, 2 synonymous) identified in ~10,000 cases with developmental disorders (no other phenotype info provided hence Amber rating).
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3160 RAB14 Zornitza Stark Marked gene: RAB14 as ready
Intellectual disability syndromic and non-syndromic v0.3160 RAB14 Zornitza Stark Gene: rab14 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.3160 RAB14 Zornitza Stark Classified gene: RAB14 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.3160 RAB14 Zornitza Stark Gene: rab14 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.3159 RAB14 Zornitza Stark gene: RAB14 was added
gene: RAB14 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: RAB14 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RAB14 were set to 33057194
Phenotypes for gene: RAB14 were set to Developmental disorders
Review for gene: RAB14 was set to AMBER
Added comment: PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 8 de novo variants (1 in-frame, 7 missense) identified in ~10,000 cases with developmental disorders (no other phenotype info provided hence Amber rating).
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3158 PSMC5 Zornitza Stark Marked gene: PSMC5 as ready
Intellectual disability syndromic and non-syndromic v0.3158 PSMC5 Zornitza Stark Gene: psmc5 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.3158 PSMC5 Zornitza Stark Classified gene: PSMC5 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.3158 PSMC5 Zornitza Stark Gene: psmc5 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.3157 PSMC5 Zornitza Stark gene: PSMC5 was added
gene: PSMC5 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: PSMC5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PSMC5 were set to 33057194
Phenotypes for gene: PSMC5 were set to Developmental disorders
Review for gene: PSMC5 was set to AMBER
Added comment: PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 10 de novo variants (1 in-frame, 9 missense) identified in ~10,000 cases with developmental disorders (no other phenotype info provided hence Amber rating).
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3156 MSL2 Zornitza Stark Marked gene: MSL2 as ready
Intellectual disability syndromic and non-syndromic v0.3156 MSL2 Zornitza Stark Gene: msl2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.3156 MSL2 Zornitza Stark Classified gene: MSL2 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.3156 MSL2 Zornitza Stark Gene: msl2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.3155 MSL2 Zornitza Stark gene: MSL2 was added
gene: MSL2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: MSL2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MSL2 were set to 31332282; 33057194
Phenotypes for gene: MSL2 were set to Developmental disorders; autism
Review for gene: MSL2 was set to AMBER
Added comment: PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 13 de novo variants (9 frameshift, 4 missense) identified in ~10,000 cases with developmental disorders (no other phenotype info provided hence Amber rating).
PMID: 31332282 - candidate gene in a single autism study, with recurrent de novo variants in a potential oligogenic model
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3154 MMGT1 Zornitza Stark Marked gene: MMGT1 as ready
Intellectual disability syndromic and non-syndromic v0.3154 MMGT1 Zornitza Stark Gene: mmgt1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.3154 MMGT1 Zornitza Stark Classified gene: MMGT1 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.3154 MMGT1 Zornitza Stark Gene: mmgt1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.3153 MMGT1 Zornitza Stark gene: MMGT1 was added
gene: MMGT1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: MMGT1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MMGT1 were set to 33057194
Phenotypes for gene: MMGT1 were set to Developmental disorders
Review for gene: MMGT1 was set to AMBER
Added comment: PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 3 de novo missense identified in ~10,000 cases with developmental disorders (no other phenotype info provided hence Amber rating).
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3152 HNRNPD Zornitza Stark Marked gene: HNRNPD as ready
Intellectual disability syndromic and non-syndromic v0.3152 HNRNPD Zornitza Stark Gene: hnrnpd has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.3152 HNRNPD Zornitza Stark Classified gene: HNRNPD as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.3152 HNRNPD Zornitza Stark Gene: hnrnpd has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.3151 HNRNPD Zornitza Stark gene: HNRNPD was added
gene: HNRNPD was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: HNRNPD was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HNRNPD were set to 33057194
Phenotypes for gene: HNRNPD were set to Developmental disorders
Review for gene: HNRNPD was set to AMBER
Added comment: PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 8 de novo variants (5 frameshift, 1 missense, 1 splice acceptor, 1 synonymous) identified in ~10,000 cases with developmental disorders (no other phenotype info provided hence Amber rating).
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3150 GIGYF1 Zornitza Stark Marked gene: GIGYF1 as ready
Intellectual disability syndromic and non-syndromic v0.3150 GIGYF1 Zornitza Stark Gene: gigyf1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.3150 GIGYF1 Zornitza Stark Classified gene: GIGYF1 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.3150 GIGYF1 Zornitza Stark Gene: gigyf1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.3149 GIGYF1 Zornitza Stark gene: GIGYF1 was added
gene: GIGYF1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: GIGYF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GIGYF1 were set to 33057194
Phenotypes for gene: GIGYF1 were set to Developmental disorder
Review for gene: GIGYF1 was set to AMBER
Added comment: PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 14 de novo variants (4 frameshift, 5 missense, 1 splice donor, 3 stopgain, 1 synonymous) identified in ~10,000 cases with developmental disorders (no other phenotype info provided, hence Amber rating).
Sources: Literature
Early-onset Dementia v0.127 STUB1 Bryony Thompson Classified gene: STUB1 as Green List (high evidence)
Early-onset Dementia v0.127 STUB1 Bryony Thompson Gene: stub1 has been classified as Green List (High Evidence).
Early-onset Dementia v0.126 STUB1 Bryony Thompson edited their review of gene: STUB1: Changed phenotypes: Spinocerebellar ataxia 48 MIM#618093, cognitive impairment, Spinocerebellar ataxia, autosomal recessive 16 MIM#615768; Set current diagnostic: yes
Early-onset Dementia v0.126 STUB1 Bryony Thompson gene: STUB1 was added
gene: STUB1 was added to Early-onset Dementia. Sources: Expert list
Mode of inheritance for gene: STUB1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: STUB1 were set to 32713943
Phenotypes for gene: STUB1 were set to Spinocerebellar ataxia 48 MIM#618093; cognitive impairment; Spinocerebellar ataxia, autosomal recessive 16 MIM#615768
Review for gene: STUB1 was set to GREEN
Added comment: Cognitive impairment can be a feature of conditions caused by this gene. Cognitive impairment, mostly dysexecutive, was observed and sometimes predominant in 54% (26/48) of cases with dominant (mainly) or recessive ataxia and pathogenic variants in STUB1. No STUB1 variants were found in 115 patients with FTD.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.3148 AP2S1 Zornitza Stark Marked gene: AP2S1 as ready
Intellectual disability syndromic and non-syndromic v0.3148 AP2S1 Zornitza Stark Gene: ap2s1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.3148 AP2S1 Zornitza Stark Classified gene: AP2S1 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.3148 AP2S1 Zornitza Stark Gene: ap2s1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.3147 AP2S1 Zornitza Stark gene: AP2S1 was added
gene: AP2S1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: AP2S1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: AP2S1 were set to 33057194
Phenotypes for gene: AP2S1 were set to Developmental disorder
Review for gene: AP2S1 was set to AMBER
Added comment: Established hypercalcaemia gene. PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio developmental disorder study. 5 de novo missense identified in ~10,000 cases with developmental disorders (no other phenotype info provided, hence Amber rating).
Sources: Literature
Mendeliome v0.5322 AP2S1 Zornitza Stark Publications for gene: AP2S1 were set to
Intellectual disability syndromic and non-syndromic v0.3146 ARHGAP35 Zornitza Stark Marked gene: ARHGAP35 as ready
Intellectual disability syndromic and non-syndromic v0.3146 ARHGAP35 Zornitza Stark Gene: arhgap35 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5321 AP2S1 Zornitza Stark Marked gene: AP2S1 as ready
Mendeliome v0.5321 AP2S1 Zornitza Stark Gene: ap2s1 has been classified as Green List (High Evidence).
Mendeliome v0.5321 AP2S1 Zornitza Stark Phenotypes for gene: AP2S1 were changed from Hypocalciuric hypercalcemia, type III MIM#600740 to Hypocalciuric hypercalcemia, type III MIM#600740; Developmental disorder
Intellectual disability syndromic and non-syndromic v0.3146 ARHGAP35 Zornitza Stark Classified gene: ARHGAP35 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.3146 ARHGAP35 Zornitza Stark Gene: arhgap35 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.3145 ARHGAP35 Zornitza Stark gene: ARHGAP35 was added
gene: ARHGAP35 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: ARHGAP35 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ARHGAP35 were set to 33057194
Phenotypes for gene: ARHGAP35 were set to Developmental disorder
Review for gene: ARHGAP35 was set to AMBER
Added comment: Has been identified as a gene with significant de novo enrichment in a large trio developmental disorder study. 16 de novo variants (3 frameshift, 2 in-frame, 10 missense, 1 stopgain) identified in ~10,000 cases with developmental disorders (no other phenotype info provided hence Amber rating).
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3144 ATP6V0A1 Zornitza Stark Marked gene: ATP6V0A1 as ready
Intellectual disability syndromic and non-syndromic v0.3144 ATP6V0A1 Zornitza Stark Gene: atp6v0a1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.3144 ATP6V0A1 Zornitza Stark Classified gene: ATP6V0A1 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.3144 ATP6V0A1 Zornitza Stark Gene: atp6v0a1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.3143 ATP6V0A1 Zornitza Stark gene: ATP6V0A1 was added
gene: ATP6V0A1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: ATP6V0A1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ATP6V0A1 were set to 30842224; 33057194
Phenotypes for gene: ATP6V0A1 were set to Developmental disorder; Rett syndrome-like
Review for gene: ATP6V0A1 was set to AMBER
Added comment: PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio developmental disorder study. 11 de novo missense identified in ~10,000 cases with developmental disorders (no other phenotype info provided, hence Amber rating).
PMID: 30842224 - identified a de novo missense variant in a single individual with atypical Rett syndrome phenotype
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3142 DDX23 Zornitza Stark Marked gene: DDX23 as ready
Intellectual disability syndromic and non-syndromic v0.3142 DDX23 Zornitza Stark Gene: ddx23 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.3142 DDX23 Zornitza Stark Classified gene: DDX23 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.3142 DDX23 Zornitza Stark Gene: ddx23 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.3141 DDX23 Zornitza Stark gene: DDX23 was added
gene: DDX23 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: DDX23 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DDX23 were set to 33057194
Phenotypes for gene: DDX23 were set to Developmental disorder
Review for gene: DDX23 was set to AMBER
Added comment: PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio developmental disorder study. 6 de novo missense identified in ~10,000 cases with developmental disorders. Rated Amber as no other phenotype info provided.
Sources: Literature
Mendeliome v0.5320 CARD8 Zornitza Stark Marked gene: CARD8 as ready
Mendeliome v0.5320 CARD8 Zornitza Stark Gene: card8 has been classified as Red List (Low Evidence).
Mendeliome v0.5320 CARD8 Zornitza Stark gene: CARD8 was added
gene: CARD8 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: CARD8 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CARD8 were set to 29408806
Phenotypes for gene: CARD8 were set to Inflammatory bowel disease-30, MIM#619079
Review for gene: CARD8 was set to RED
Added comment: Two individuals from one family reported segregating a missense variant, dominant negative effect postulated.
Sources: Expert list
Inflammatory bowel disease v0.35 CARD8 Zornitza Stark Marked gene: CARD8 as ready
Inflammatory bowel disease v0.35 CARD8 Zornitza Stark Gene: card8 has been classified as Red List (Low Evidence).
Inflammatory bowel disease v0.35 CARD8 Zornitza Stark gene: CARD8 was added
gene: CARD8 was added to Inflammatory bowel disease. Sources: Expert list
Mode of inheritance for gene: CARD8 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CARD8 were set to 29408806
Phenotypes for gene: CARD8 were set to Inflammatory bowel disease-30, MIM#619079
Review for gene: CARD8 was set to RED
Added comment: Two individuals from one family reported segregating a missense variant, dominant negative effect postulated.
Sources: Expert list
Liver Failure_Paediatric v0.94 AMACR Zornitza Stark changed review comment from: Intrahepatic cholestasis and liver failure in infancy.
Sources: Expert list; to: Intrahepatic cholestasis and liver failure in infancy, at least three families and mouse model.
Sources: Expert list
Liver Failure_Paediatric v0.94 AMACR Zornitza Stark Marked gene: AMACR as ready
Liver Failure_Paediatric v0.94 AMACR Zornitza Stark Gene: amacr has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.94 AMACR Zornitza Stark Classified gene: AMACR as Green List (high evidence)
Liver Failure_Paediatric v0.94 AMACR Zornitza Stark Gene: amacr has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.93 AMACR Zornitza Stark gene: AMACR was added
gene: AMACR was added to Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: AMACR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AMACR were set to 31951345; 24735479; 12512044; 10655068
Phenotypes for gene: AMACR were set to Bile acid synthesis defect, congenital, 4, MIM# 214950
Review for gene: AMACR was set to GREEN
Added comment: Intrahepatic cholestasis and liver failure in infancy.
Sources: Expert list
Liver Failure_Paediatric v0.92 HADHB Zornitza Stark Marked gene: HADHB as ready
Liver Failure_Paediatric v0.92 HADHB Zornitza Stark Gene: hadhb has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.92 HADHB Zornitza Stark Classified gene: HADHB as Green List (high evidence)
Liver Failure_Paediatric v0.92 HADHB Zornitza Stark Gene: hadhb has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.91 HADHB Zornitza Stark gene: HADHB was added
gene: HADHB was added to Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: HADHB was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: HADHB were set to Trifunctional protein deficiency, MIM# 609015
Review for gene: HADHB was set to GREEN
Added comment: Trifunctional protein deficiency can be classified into 3 main clinical phenotypes: neonatal onset of a severe, lethal condition resulting in sudden unexplained infant death, infantile onset of a hepatic Reye-like syndrome, and late-adolescent onset of primarily a skeletal myopathy.
Sources: Expert list
Liver Failure_Paediatric v0.90 HADHA Zornitza Stark Marked gene: HADHA as ready
Liver Failure_Paediatric v0.90 HADHA Zornitza Stark Gene: hadha has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.90 HADHA Zornitza Stark Classified gene: HADHA as Green List (high evidence)
Liver Failure_Paediatric v0.90 HADHA Zornitza Stark Gene: hadha has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.89 HADHA Zornitza Stark gene: HADHA was added
gene: HADHA was added to Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: HADHA was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: HADHA were set to Mitochondrial trifunctional protein deficiency, MIM# 609015
Review for gene: HADHA was set to GREEN
Added comment: Trifunctional protein deficiency can be classified into 3 main clinical phenotypes: neonatal onset of a severe, lethal condition resulting in sudden unexplained infant death, infantile onset of a hepatic Reye-like syndrome, and late-adolescent onset of primarily a skeletal myopathy.
Sources: Expert list
Mackenzie's Mission_Reproductive Carrier Screening v0.44 UGT1A1 Sarah Righetti commented on gene: UGT1A1
Mendeliome v0.5319 UBA1 Zornitza Stark Phenotypes for gene: UBA1 were changed from Spinal muscular atrophy, X-linked 2, infantile, MIM# 301830 to Spinal muscular atrophy, X-linked 2, infantile, MIM# 301830; Autoinflammatory disease, adult onset: VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic)
Mendeliome v0.5318 UBA1 Zornitza Stark Publications for gene: UBA1 were set to 18179898; 32181232; 31932168; 29034082; 27699224; 26028276; 23518311
Mendeliome v0.5317 UBA1 Zornitza Stark edited their review of gene: UBA1: Added comment: Association with VEXAS: 25 men reported with somatic mutations affecting methionine-41 (p.Met41) in UBA1, the major E1 enzyme that initiates ubiquitylation, and an often fatal, treatment-refractory inflammatory syndrome develops in late adulthood, with fevers, cytopaenias, characteristic vacuoles in myeloid and erythroid precursor cells, dysplastic bone marrow, neutrophilic cutaneous and pulmonary inflammation, chondritis, and vasculitis.; Changed publications: 18179898, 32181232, 31932168, 29034082, 27699224, 26028276, 23518311, 33108101; Changed phenotypes: Spinal muscular atrophy, X-linked 2, infantile, MIM# 301830, Autoinflammatory disease, adult onset: VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic)
Autoinflammatory Disorders v0.96 UBA1 Zornitza Stark edited their review of gene: UBA1: Changed publications: 33108101
Autoinflammatory Disorders v0.96 UBA1 Zornitza Stark Marked gene: UBA1 as ready
Autoinflammatory Disorders v0.96 UBA1 Zornitza Stark Gene: uba1 has been classified as Green List (High Evidence).
Autoinflammatory Disorders v0.96 UBA1 Zornitza Stark Tag somatic tag was added to gene: UBA1.
Autoinflammatory Disorders v0.96 UBA1 Zornitza Stark Classified gene: UBA1 as Green List (high evidence)
Autoinflammatory Disorders v0.96 UBA1 Zornitza Stark Gene: uba1 has been classified as Green List (High Evidence).
Autoinflammatory Disorders v0.95 UBA1 Zornitza Stark gene: UBA1 was added
gene: UBA1 was added to Systemic Autoinflammatory Disease_Periodic Fever. Sources: Literature
Mode of inheritance for gene: UBA1 was set to Other
Phenotypes for gene: UBA1 were set to Autoinflammatory disease, adult onset; VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic)
Review for gene: UBA1 was set to GREEN
Added comment: 25 men reported with somatic mutations affecting methionine-41 (p.Met41) in UBA1, the major E1 enzyme that initiates ubiquitylation, and an often fatal, treatment-refractory inflammatory syndrome develops in late adulthood, with fevers, cytopaenias, characteristic vacuoles in myeloid and erythroid precursor cells, dysplastic bone marrow, neutrophilic cutaneous and pulmonary inflammation, chondritis, and vasculitis.
Sources: Literature
Liver Failure_Paediatric v0.88 GBE1 Zornitza Stark Marked gene: GBE1 as ready
Liver Failure_Paediatric v0.88 GBE1 Zornitza Stark Gene: gbe1 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.88 GBE1 Zornitza Stark Classified gene: GBE1 as Green List (high evidence)
Liver Failure_Paediatric v0.88 GBE1 Zornitza Stark Gene: gbe1 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.87 GBE1 Zornitza Stark gene: GBE1 was added
gene: GBE1 was added to Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: GBE1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: GBE1 were set to Glycogen storage disease IV, MIM# 232500
Review for gene: GBE1 was set to GREEN
Added comment: Typically presents with liver disease in childhood, progressing to cirrhosis.
Sources: Expert list
Liver Failure_Paediatric v0.86 MRM2 Zornitza Stark Marked gene: MRM2 as ready
Liver Failure_Paediatric v0.86 MRM2 Zornitza Stark Gene: mrm2 has been classified as Amber List (Moderate Evidence).
Liver Failure_Paediatric v0.86 MRM2 Zornitza Stark Classified gene: MRM2 as Amber List (moderate evidence)
Liver Failure_Paediatric v0.86 MRM2 Zornitza Stark Gene: mrm2 has been classified as Amber List (Moderate Evidence).
Liver Failure_Paediatric v0.85 MRM2 Zornitza Stark gene: MRM2 was added
gene: MRM2 was added to Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: MRM2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MRM2 were set to 28973171
Phenotypes for gene: MRM2 were set to Mitochondrial DNA depletion syndrome 17, MIM# 618567
Review for gene: MRM2 was set to AMBER
Added comment: Single individual reported plus functional data. MRM2 encodes an enzyme responsible for 2'-O-methyl modification at position U1369 in the human mitochondrial 16S rRNA.

Recurrent episodes of liver failure were part of the clinical course.
Sources: Expert list
Liver Failure_Paediatric v0.84 ALMS1 Zornitza Stark Marked gene: ALMS1 as ready
Liver Failure_Paediatric v0.84 ALMS1 Zornitza Stark Gene: alms1 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.84 ALMS1 Zornitza Stark Classified gene: ALMS1 as Green List (high evidence)
Liver Failure_Paediatric v0.84 ALMS1 Zornitza Stark Gene: alms1 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.83 ALMS1 Zornitza Stark gene: ALMS1 was added
gene: ALMS1 was added to Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: ALMS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ALMS1 were set to 25296579
Phenotypes for gene: ALMS1 were set to Alstrom syndrome, MIM# 203800
Review for gene: ALMS1 was set to GREEN
Added comment: Autosomal recessive disorder characterized by progressive cone-rod dystrophy leading to blindness, sensorineural hearing loss, childhood obesity associated with hyperinsulinemia, and type 2 diabetes mellitus. Dilated cardiomyopathy occurs in approximately 70% of patients during infancy or adolescence. Renal failure, pulmonary, hepatic, and urologic dysfunction are often observed, and systemic fibrosis develops with age.

Chronic active hepatitis, hepatomegaly, steatosis, and cirrhosis all reported.
Sources: Expert list
Liver Failure_Paediatric v0.82 CYC1 Zornitza Stark Marked gene: CYC1 as ready
Liver Failure_Paediatric v0.82 CYC1 Zornitza Stark Gene: cyc1 has been classified as Red List (Low Evidence).
Liver Failure_Paediatric v0.82 CYC1 Zornitza Stark gene: CYC1 was added
gene: CYC1 was added to Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: CYC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CYC1 were set to 23910460
Phenotypes for gene: CYC1 were set to Mitochondrial complex III deficiency, nuclear type 6, MIM# 615453
Review for gene: CYC1 was set to RED
Added comment: Two families reported, of these episodes of acute liver failure reported in one proband.
Sources: Expert list
Mendeliome v0.5317 ZFHX4 Bryony Thompson Marked gene: ZFHX4 as ready
Mendeliome v0.5317 ZFHX4 Bryony Thompson Gene: zfhx4 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5317 ZFHX4 Bryony Thompson Publications for gene: ZFHX4 were set to 33057194
Mendeliome v0.5316 ZFHX4 Bryony Thompson Classified gene: ZFHX4 as Amber List (moderate evidence)
Mendeliome v0.5316 ZFHX4 Bryony Thompson Gene: zfhx4 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5315 ZFHX4 Bryony Thompson edited their review of gene: ZFHX4: Changed publications: 33057194, 24038936
Mendeliome v0.5315 ZFHX4 Bryony Thompson changed review comment from: PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 16 de novo variants (5 frameshift, 5 missense, 4 stopgain, 2 synonymous) identified in ~10,000 cases with developmental disorders (no other phenotype info provided).
Sources: Literature; to: PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 16 de novo variants (5 frameshift, 5 missense, 4 stopgain, 2 synonymous) identified in ~10,000 cases with developmental disorders (no other phenotype info provided).
PMID: 24038936 - a single case with developmental delay, macrocephaly, ventriculomegaly, hypermetropia, recurrent
infections, dysmorphism and a de novo deletion of the last 7 exons of the gene.
Sources: Literature
Mendeliome v0.5315 ZFHX4 Bryony Thompson edited their review of gene: ZFHX4: Changed phenotypes: Developmental disorders, intellectual disability, dysmorphic features
Mendeliome v0.5315 ZFHX4 Bryony Thompson edited their review of gene: ZFHX4: Changed rating: AMBER
Mendeliome v0.5315 ZFHX4 Bryony Thompson gene: ZFHX4 was added
gene: ZFHX4 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ZFHX4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ZFHX4 were set to 33057194
Phenotypes for gene: ZFHX4 were set to Developmental disorders
Added comment: PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 16 de novo variants (5 frameshift, 5 missense, 4 stopgain, 2 synonymous) identified in ~10,000 cases with developmental disorders (no other phenotype info provided).
Sources: Literature
Mendeliome v0.5314 UPF1 Bryony Thompson Marked gene: UPF1 as ready
Mendeliome v0.5314 UPF1 Bryony Thompson Gene: upf1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5314 UPF1 Bryony Thompson Classified gene: UPF1 as Amber List (moderate evidence)
Mendeliome v0.5314 UPF1 Bryony Thompson Gene: upf1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5313 UPF1 Bryony Thompson gene: UPF1 was added
gene: UPF1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: UPF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: UPF1 were set to 33057194
Phenotypes for gene: UPF1 were set to Developmental disorders
Review for gene: UPF1 was set to AMBER
Added comment: PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 16 de novo variants (1 frameshift, 11 missense, 4 synonymous) identified in ~10,000 cases with developmental disorders (no other phenotype info provided).
Sources: Literature
Mendeliome v0.5312 U2AF2 Bryony Thompson Classified gene: U2AF2 as Amber List (moderate evidence)
Mendeliome v0.5312 U2AF2 Bryony Thompson Gene: u2af2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5311 U2AF2 Bryony Thompson gene: U2AF2 was added
gene: U2AF2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: U2AF2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: U2AF2 were set to 33057194
Phenotypes for gene: U2AF2 were set to Developmental disorders
Review for gene: U2AF2 was set to AMBER
Added comment: PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 10 de novo variants (1 in-frame, 8 missense, 1 synoymous) identified in ~10,000 cases with developmental disorders (no other phenotype info provided).
Sources: Literature
Mendeliome v0.5310 TFE3 Bryony Thompson Publications for gene: TFE3 were set to 30595499; 31833172
Mendeliome v0.5309 TCF7L2 Bryony Thompson Marked gene: TCF7L2 as ready
Mendeliome v0.5309 TCF7L2 Bryony Thompson Gene: tcf7l2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5309 TCF7L2 Bryony Thompson Phenotypes for gene: TCF7L2 were changed from to Developmental disorders
Mendeliome v0.5308 TCF7L2 Bryony Thompson Publications for gene: TCF7L2 were set to
Mendeliome v0.5307 TCF7L2 Bryony Thompson Mode of inheritance for gene: TCF7L2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5306 TCF7L2 Bryony Thompson Classified gene: TCF7L2 as Amber List (moderate evidence)
Mendeliome v0.5306 TCF7L2 Bryony Thompson Gene: tcf7l2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5305 TCF7L2 Bryony Thompson reviewed gene: TCF7L2: Rating: AMBER; Mode of pathogenicity: None; Publications: 33057194; Phenotypes: Developmental disorders; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5305 SRRM2 Bryony Thompson Marked gene: SRRM2 as ready
Mendeliome v0.5305 SRRM2 Bryony Thompson Gene: srrm2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5305 SRRM2 Bryony Thompson Classified gene: SRRM2 as Amber List (moderate evidence)
Mendeliome v0.5305 SRRM2 Bryony Thompson Gene: srrm2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5304 SRRM2 Bryony Thompson gene: SRRM2 was added
gene: SRRM2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SRRM2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SRRM2 were set to 33057194
Phenotypes for gene: SRRM2 were set to Developmental disorders
Review for gene: SRRM2 was set to AMBER
Added comment: PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 28 de novo variants (11 frameshift, 7 missense, 1 splice acceptor, 5 stopgain, 4 synonymous) identified in ~10,000 cases with developmental disorders (no other phenotype info provided).
Sources: Literature
Mendeliome v0.5303 SPEN Bryony Thompson Marked gene: SPEN as ready
Mendeliome v0.5303 SPEN Bryony Thompson Gene: spen has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5303 SPEN Bryony Thompson Classified gene: SPEN as Amber List (moderate evidence)
Mendeliome v0.5303 SPEN Bryony Thompson Gene: spen has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5302 SPEN Bryony Thompson gene: SPEN was added
gene: SPEN was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SPEN was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SPEN were set to 33057194
Phenotypes for gene: SPEN were set to Developmental disorders
Review for gene: SPEN was set to AMBER
Added comment: PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 25 de novo variants (6 frameshift, 1 in-frame, 7 missense, 8 stopgain, 3 synonymous) identified in ~10,000 cases with developmental disorders (no other phenotype info provided).
Sources: Literature
Mendeliome v0.5301 SATB1 Bryony Thompson Marked gene: SATB1 as ready
Mendeliome v0.5301 SATB1 Bryony Thompson Gene: satb1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5301 SATB1 Bryony Thompson Classified gene: SATB1 as Amber List (moderate evidence)
Mendeliome v0.5301 SATB1 Bryony Thompson Gene: satb1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5300 SATB1 Bryony Thompson gene: SATB1 was added
gene: SATB1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SATB1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SATB1 were set to 33057194
Phenotypes for gene: SATB1 were set to Developmental disorders
Review for gene: SATB1 was set to AMBER
Added comment: PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 12 de novo (2 frameshift, 7 missense, 1 stopgain, 2 synonymous) identified in ~10,000 cases with developmental disorders (no other phenotype info provided).
Sources: Literature
Mendeliome v0.5299 RAB14 Bryony Thompson Marked gene: RAB14 as ready
Mendeliome v0.5299 RAB14 Bryony Thompson Gene: rab14 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5299 RAB14 Bryony Thompson Classified gene: RAB14 as Amber List (moderate evidence)
Mendeliome v0.5299 RAB14 Bryony Thompson Gene: rab14 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5298 RAB14 Bryony Thompson gene: RAB14 was added
gene: RAB14 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RAB14 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RAB14 were set to 33057194
Phenotypes for gene: RAB14 were set to Developmental disorders
Review for gene: RAB14 was set to AMBER
Added comment: PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 8 de novo variants (1 in-frame, 7 missense) identified in ~10,000 cases with developmental disorders (no other phenotype info provided).
Sources: Literature
Mendeliome v0.5297 PSMC5 Bryony Thompson Marked gene: PSMC5 as ready
Mendeliome v0.5297 PSMC5 Bryony Thompson Gene: psmc5 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5297 PSMC5 Bryony Thompson Classified gene: PSMC5 as Amber List (moderate evidence)
Mendeliome v0.5297 PSMC5 Bryony Thompson Gene: psmc5 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5296 PSMC5 Bryony Thompson gene: PSMC5 was added
gene: PSMC5 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PSMC5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PSMC5 were set to 33057194
Phenotypes for gene: PSMC5 were set to Developmental disorders
Review for gene: PSMC5 was set to AMBER
Added comment: PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 10 de novo variants (1 in-frame, 9 missense) identified in ~10,000 cases with developmental disorders (no other phenotype info provided).
Sources: Literature
Mendeliome v0.5295 PRPF8 Bryony Thompson Marked gene: PRPF8 as ready
Mendeliome v0.5295 PRPF8 Bryony Thompson Gene: prpf8 has been classified as Green List (High Evidence).
Mendeliome v0.5295 PRPF8 Bryony Thompson Added comment: Comment on phenotypes: Established Retinitis pigmentosa gene.
PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 29 de novo variants (2 frameshift, 19 missense, 1 stopgain, 7 synonymous) identified in ~10,000 cases with developmental disorders (no other phenotype info provided).
Mendeliome v0.5295 PRPF8 Bryony Thompson Phenotypes for gene: PRPF8 were changed from to Retinitis pigmentosa 13, MIM#600059
Mendeliome v0.5294 PRPF8 Bryony Thompson Publications for gene: PRPF8 were set to
Mendeliome v0.5293 PRPF8 Bryony Thompson Mode of inheritance for gene: PRPF8 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5292 MSL2 Bryony Thompson Marked gene: MSL2 as ready
Mendeliome v0.5292 MSL2 Bryony Thompson Gene: msl2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5292 MSL2 Bryony Thompson Classified gene: MSL2 as Amber List (moderate evidence)
Mendeliome v0.5292 MSL2 Bryony Thompson Gene: msl2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5291 PRKAR1B Bryony Thompson Publications for gene: PRKAR1B were set to https://doi.org/10.1101/2020.09.10.20190314; 25414040
Mendeliome v0.5290 MSL2 Bryony Thompson gene: MSL2 was added
gene: MSL2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MSL2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MSL2 were set to 31332282; 33057194
Phenotypes for gene: MSL2 were set to Developmental disorders; autism
Review for gene: MSL2 was set to AMBER
Added comment: PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 13 de novo variants (9 frameshift, 4 missense) identified in ~10,000 cases with developmental disorders (no other phenotype info provided).
PMID: 31332282 - candidate gene in a single autism study, with recurrent de novo variants in a potential oligogenic model
Sources: Literature
Mendeliome v0.5289 MMGT1 Bryony Thompson Classified gene: MMGT1 as Amber List (moderate evidence)
Mendeliome v0.5289 MMGT1 Bryony Thompson Gene: mmgt1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5288 MMGT1 Bryony Thompson gene: MMGT1 was added
gene: MMGT1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MMGT1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MMGT1 were set to 33057194
Phenotypes for gene: MMGT1 were set to Developmental disorders
Review for gene: MMGT1 was set to AMBER
Added comment: PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 3 de novo missense identified in ~10,000 cases with developmental disorders (no other phenotype info provided).
Sources: Literature
Mendeliome v0.5287 MIB1 Bryony Thompson Publications for gene: MIB1 were set to
Mendeliome v0.5286 MIB1 Bryony Thompson Added comment: Comment on phenotypes: Established congenital cardiac disease gene.
PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 11 de novo variants (1 frameshift, 2 missense, 2 splice acceptor, 1 splice donor, 5 stopgain) identified in ~10,000 cases with developmental disorders (no other phenotype info provided).
Mendeliome v0.5286 MIB1 Bryony Thompson Phenotypes for gene: MIB1 were changed from to Left ventricular noncompaction 7 MIM#615092
Mendeliome v0.5285 MIB1 Bryony Thompson Mode of inheritance for gene: MIB1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5284 MFN2 Bryony Thompson Added comment: Comment on phenotypes: Established cause of hereditary neuropathy.
PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 9 de novo variants (8 missense, 1 synonymous) identified in ~10,000 cases with developmental disorders (no other phenotype info provided).
Mendeliome v0.5284 MFN2 Bryony Thompson Phenotypes for gene: MFN2 were changed from to Charcot-Marie-Tooth disease, axonal, type 2A2A, OMIM #609260; Charcot-Marie-Tooth disease, axonal, type 2A2B, OMIM #617087; Hereditary motor and sensory neuropathy VIA, OMIM #601152
Mendeliome v0.5283 MFN2 Bryony Thompson Mode of inheritance for gene: MFN2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.5282 KCNK3 Bryony Thompson Added comment: Comment on phenotypes: Established pulmonary hypertension gene.
PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 8 de novo variants (7 missense, 1 synonymous) identified in ~10,000 cases with developmental disorders (no other phenotype info provided).
Mendeliome v0.5282 KCNK3 Bryony Thompson Phenotypes for gene: KCNK3 were changed from to Pulmonary hypertension, primary, 4 MIM#615344
Mendeliome v0.5281 KCNK3 Bryony Thompson Mode of inheritance for gene: KCNK3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5280 HNRNPD Bryony Thompson Marked gene: HNRNPD as ready
Mendeliome v0.5280 HNRNPD Bryony Thompson Gene: hnrnpd has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5280 HNRNPD Bryony Thompson Classified gene: HNRNPD as Amber List (moderate evidence)
Mendeliome v0.5280 HNRNPD Bryony Thompson Gene: hnrnpd has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5279 HNRNPD Bryony Thompson gene: HNRNPD was added
gene: HNRNPD was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: HNRNPD was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HNRNPD were set to 33057194
Phenotypes for gene: HNRNPD were set to Developmental disorders
Review for gene: HNRNPD was set to AMBER
Added comment: PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 8 de novo variants (5 frameshift, 1 missense, 1 splice acceptor, 1 synonymous) identified in ~10,000 cases with developmental disorders (no other phenotype info provided).
Sources: Literature
Mendeliome v0.5278 H3F3A Bryony Thompson reviewed gene: H3F3A: Rating: AMBER; Mode of pathogenicity: None; Publications: 33057194, 31942419; Phenotypes: Developmental disorders, intellectual disability, microcephaly, severe developmental delay; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cholestasis v0.187 TJP2 Zornitza Stark Mode of inheritance for gene: TJP2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Cholestasis v0.186 TJP2 Zornitza Stark reviewed gene: TJP2: Rating: GREEN; Mode of pathogenicity: None; Publications: 24614073, 25921221, 31696999; Phenotypes: Cholestasis, progressive familial intrahepatic 4, MIM# 615878; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Liver Failure_Paediatric v0.81 TJP2 Zornitza Stark Marked gene: TJP2 as ready
Liver Failure_Paediatric v0.81 TJP2 Zornitza Stark Gene: tjp2 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.81 TJP2 Zornitza Stark Classified gene: TJP2 as Green List (high evidence)
Liver Failure_Paediatric v0.81 TJP2 Zornitza Stark Gene: tjp2 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.80 TJP2 Zornitza Stark gene: TJP2 was added
gene: TJP2 was added to Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: TJP2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TJP2 were set to 24614073; 25921221; 31696999
Phenotypes for gene: TJP2 were set to Cholestasis, progressive familial intrahepatic 4, MIM# 615878
Review for gene: TJP2 was set to GREEN
Added comment: Early childhood onset of severe progressive liver disease. At leat 20 unrelated families reported.
Sources: Expert list
Congenital Disorders of Glycosylation v0.182 ATP6AP2 Zornitza Stark Marked gene: ATP6AP2 as ready
Congenital Disorders of Glycosylation v0.182 ATP6AP2 Zornitza Stark Gene: atp6ap2 has been classified as Green List (High Evidence).
Congenital Disorders of Glycosylation v0.182 ATP6AP2 Zornitza Stark Classified gene: ATP6AP2 as Green List (high evidence)
Congenital Disorders of Glycosylation v0.182 ATP6AP2 Zornitza Stark Gene: atp6ap2 has been classified as Green List (High Evidence).
Congenital Disorders of Glycosylation v0.181 ATP6AP2 Zornitza Stark gene: ATP6AP2 was added
gene: ATP6AP2 was added to Congenital Disorders of Glycosylation. Sources: Expert list
Mode of inheritance for gene: ATP6AP2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATP6AP2 were set to 29127204; 29388887
Phenotypes for gene: ATP6AP2 were set to Congenital disorder of glycosylation, type IIr, MIM# 301045
Review for gene: ATP6AP2 was set to GREEN
Added comment: Congenital disorder of glycosylation type 2R (CDG2R) is an X-linked recessive disorder characterized by infantile onset of liver failure, recurrent infections due to hypogammaglobulinemia, and cutis laxa. Some individuals may also have mild intellectual impairment and dysmorphic features. Laboratory studies showed defective glycosylation of serum transferrin in a type 2 pattern.

Two unrelated families and functional data support gene-disease association. Note gene has also been associated with two other OMIM phenotypes, 300423 and 300911, comprising ID, parkinsonism and spasticity. Unclear whether all of these represent a spectrum of CDG.
Sources: Expert list
Liver Failure_Paediatric v0.79 ATP6AP2 Zornitza Stark Marked gene: ATP6AP2 as ready
Liver Failure_Paediatric v0.79 ATP6AP2 Zornitza Stark Gene: atp6ap2 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.79 ATP6AP2 Zornitza Stark Classified gene: ATP6AP2 as Green List (high evidence)
Liver Failure_Paediatric v0.79 ATP6AP2 Zornitza Stark Gene: atp6ap2 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.78 ATP6AP2 Zornitza Stark edited their review of gene: ATP6AP2: Changed rating: GREEN; Changed phenotypes: Congenital disorder of glycosylation, type IIr, MIM# 301045
Liver Failure_Paediatric v0.78 ATP6AP2 Zornitza Stark gene: ATP6AP2 was added
gene: ATP6AP2 was added to Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: ATP6AP2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: ATP6AP2 were set to 29127204; 29388887
Phenotypes for gene: ATP6AP2 were set to Congenital disorder of glycosylation, type IIr, MIM# 301045
Added comment: Congenital disorder of glycosylation type 2R (CDG2R) is an X-linked recessive disorder characterized by infantile onset of liver failure, recurrent infections due to hypogammaglobulinemia, and cutis laxa. Some individuals may also have mild intellectual impairment and dysmorphic features. Laboratory studies showed defective glycosylation of serum transferrin in a type 2 pattern.

Two unrelated families and functional data support gene-disease association.
Sources: Expert list
Skeletal dysplasia v0.61 PRKG2 Zornitza Stark Marked gene: PRKG2 as ready
Skeletal dysplasia v0.61 PRKG2 Zornitza Stark Gene: prkg2 has been classified as Green List (High Evidence).
Skeletal dysplasia v0.61 PRKG2 Zornitza Stark Classified gene: PRKG2 as Green List (high evidence)
Skeletal dysplasia v0.61 PRKG2 Zornitza Stark Gene: prkg2 has been classified as Green List (High Evidence).
Skeletal dysplasia v0.60 PRKG2 Zornitza Stark gene: PRKG2 was added
gene: PRKG2 was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: PRKG2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PRKG2 were set to 33106379
Phenotypes for gene: PRKG2 were set to Acromesomelic dysplasia
Review for gene: PRKG2 was set to GREEN
Added comment: - PMID: 33106379 (2020) - Distinct homozygous variants in PRKG2 identified in two unrelated individuals, both with a skeletal dysplasia associated with severe short stature due to acromesomelic limb shortening, brachydactyly, mild to moderate platyspondyly and progressively increasing metaphyseal alterations of the long bones. Functional studies showed both variants result in NMD and disrupt the downstream MAPK signalling pathway in response to FGF2. The role of cGKII, encoded by PRKG2, in skeletal growth has been established in several animal models (references provided in paper).
Sources: Literature
Mendeliome v0.5278 PRKG2 Zornitza Stark Marked gene: PRKG2 as ready
Mendeliome v0.5278 PRKG2 Zornitza Stark Gene: prkg2 has been classified as Green List (High Evidence).
Mendeliome v0.5278 PRKG2 Zornitza Stark Classified gene: PRKG2 as Green List (high evidence)
Mendeliome v0.5278 PRKG2 Zornitza Stark Gene: prkg2 has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.23 SALL4 Zornitza Stark Marked gene: SALL4 as ready
Congenital ophthalmoplegia v0.23 SALL4 Zornitza Stark Gene: sall4 has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.23 SALL4 Zornitza Stark Classified gene: SALL4 as Green List (high evidence)
Congenital ophthalmoplegia v0.23 SALL4 Zornitza Stark Gene: sall4 has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.22 ROBO3 Zornitza Stark Marked gene: ROBO3 as ready
Congenital ophthalmoplegia v0.22 ROBO3 Zornitza Stark Gene: robo3 has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.22 ROBO3 Zornitza Stark Classified gene: ROBO3 as Green List (high evidence)
Congenital ophthalmoplegia v0.22 ROBO3 Zornitza Stark Gene: robo3 has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.21 REV3L Zornitza Stark Marked gene: REV3L as ready
Congenital ophthalmoplegia v0.21 REV3L Zornitza Stark Gene: rev3l has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.21 REV3L Zornitza Stark Phenotypes for gene: REV3L were changed from möbius syndrome to Möbius syndrome
Congenital ophthalmoplegia v0.20 REV3L Zornitza Stark Classified gene: REV3L as Green List (high evidence)
Congenital ophthalmoplegia v0.20 REV3L Zornitza Stark Gene: rev3l has been classified as Green List (High Evidence).
Mendeliome v0.5277 PLXND1 Zornitza Stark Marked gene: PLXND1 as ready
Mendeliome v0.5277 PLXND1 Zornitza Stark Gene: plxnd1 has been classified as Green List (High Evidence).
Mendeliome v0.5277 PLXND1 Zornitza Stark Classified gene: PLXND1 as Green List (high evidence)
Mendeliome v0.5277 PLXND1 Zornitza Stark Gene: plxnd1 has been classified as Green List (High Evidence).
Mendeliome v0.5276 PLXND1 Zornitza Stark gene: PLXND1 was added
gene: PLXND1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PLXND1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PLXND1 were set to 26068067
Phenotypes for gene: PLXND1 were set to Möbius syndrome
Review for gene: PLXND1 was set to GREEN
Added comment: De novo variants in 3 unrelated individuals with Moebius syndrome with some functional evidence.
Sources: Literature
Mendeliome v0.5275 ECEL1 Zornitza Stark Marked gene: ECEL1 as ready
Mendeliome v0.5275 ECEL1 Zornitza Stark Gene: ecel1 has been classified as Green List (High Evidence).
Mendeliome v0.5275 ECEL1 Zornitza Stark Phenotypes for gene: ECEL1 were changed from to Arthrogryposis, distal, type 5D, MIM# 615065
Congenital ophthalmoplegia v0.18 PLXND1 Zornitza Stark Marked gene: PLXND1 as ready
Congenital ophthalmoplegia v0.18 PLXND1 Zornitza Stark Gene: plxnd1 has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.18 PLXND1 Zornitza Stark Phenotypes for gene: PLXND1 were changed from möbius syndrome to Möbius syndrome
Congenital ophthalmoplegia v0.17 PLXND1 Zornitza Stark Classified gene: PLXND1 as Green List (high evidence)
Congenital ophthalmoplegia v0.17 PLXND1 Zornitza Stark Gene: plxnd1 has been classified as Green List (High Evidence).
Mendeliome v0.5274 MYMK Zornitza Stark Tag founder tag was added to gene: MYMK.
Mendeliome v0.5274 MYMK Zornitza Stark changed review comment from: Sources: Expert list; to: Carey-Fineman-Ziter syndrome (CFZS) is a multisystem congenital disorder characterized by hypotonia, Moebius sequence (bilateral congenital facial palsy with impairment of ocular abduction), Pierre Robin complex (micrognathia, glossoptosis, and high-arched or cleft palate), delayed motor milestones, and failure to thrive. Intellect has been normal in molecularly confirmed cases. Defect in myoblast fusion. 6 unrelated families reported with CFZ phenotype and bi-allelic MYMK variants. p.Pro91Thr is a common founder variant, which is hypomorphic.
Mendeliome v0.5274 MYMK Zornitza Stark edited their review of gene: MYMK: Changed phenotypes: Carey-Fineman-Ziter syndrome, OMIM #254940
Arthrogryposis v0.242 MYMK Zornitza Stark Tag founder tag was added to gene: MYMK.
Arthrogryposis v0.242 MYMK Zornitza Stark changed review comment from: Distal contractures are part of the phenotype of this muscle disorder.
Sources: Expert list; to: Carey-Fineman-Ziter syndrome (CFZS) is a multisystem congenital disorder characterized by hypotonia, Moebius sequence (bilateral congenital facial palsy with impairment of ocular abduction), Pierre Robin complex (micrognathia, glossoptosis, and high-arched or cleft palate), delayed motor milestones, and failure to thrive. Intellect has been normal in molecularly confirmed cases. Defect in myoblast fusion. 6 unrelated families reported with CFZ phenotype and bi-allelic MYMK variants. p.Pro91Thr is a common founder variant, which is hypomorphic.

Distal contractures are part of the phenotype of this muscle disorder.
Sources: Expert list
Congenital ophthalmoplegia v0.16 MYMK Zornitza Stark Marked gene: MYMK as ready
Congenital ophthalmoplegia v0.16 MYMK Zornitza Stark Gene: mymk has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.16 MYMK Zornitza Stark Tag founder tag was added to gene: MYMK.
Congenital ophthalmoplegia v0.16 MYMK Zornitza Stark Publications for gene: MYMK were set to PMID: 28681861
Congenital ophthalmoplegia v0.15 MYMK Zornitza Stark Classified gene: MYMK as Green List (high evidence)
Congenital ophthalmoplegia v0.15 MYMK Zornitza Stark Gene: mymk has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.14 MYMK Zornitza Stark reviewed gene: MYMK: Rating: GREEN; Mode of pathogenicity: None; Publications: 29560417; Phenotypes: Carey-Fineman-Ziter syndrome, MIM# 254940; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital ophthalmoplegia v0.13 HOXA1 Zornitza Stark Marked gene: HOXA1 as ready
Congenital ophthalmoplegia v0.13 HOXA1 Zornitza Stark Gene: hoxa1 has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.13 HOXA1 Zornitza Stark Classified gene: HOXA1 as Green List (high evidence)
Congenital ophthalmoplegia v0.13 HOXA1 Zornitza Stark Gene: hoxa1 has been classified as Green List (High Evidence).
Mendeliome v0.5274 ECEL1 Zornitza Stark Publications for gene: ECEL1 were set to
Mendeliome v0.5273 ECEL1 Zornitza Stark Mode of inheritance for gene: ECEL1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5272 ECEL1 Zornitza Stark reviewed gene: ECEL1: Rating: GREEN; Mode of pathogenicity: None; Publications: 23261301, 23236030, 25099528, 24782201; Phenotypes: Arthrogryposis, distal, type 5D, MIM# 615065; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.242 ECEL1 Zornitza Stark Marked gene: ECEL1 as ready
Arthrogryposis v0.242 ECEL1 Zornitza Stark Gene: ecel1 has been classified as Green List (High Evidence).
Arthrogryposis v0.242 ECEL1 Zornitza Stark Phenotypes for gene: ECEL1 were changed from to Arthrogryposis, distal, type 5D, MIM# 615065
Arthrogryposis v0.241 ECEL1 Zornitza Stark Publications for gene: ECEL1 were set to
Arthrogryposis v0.240 ECEL1 Zornitza Stark Mode of inheritance for gene: ECEL1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.239 ECEL1 Zornitza Stark reviewed gene: ECEL1: Rating: GREEN; Mode of pathogenicity: None; Publications: 23261301, 23236030, 25099528, 24782201; Phenotypes: Arthrogryposis, distal, type 5D, MIM# 615065; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital ophthalmoplegia v0.11 ECEL1 Zornitza Stark Marked gene: ECEL1 as ready
Congenital ophthalmoplegia v0.11 ECEL1 Zornitza Stark Gene: ecel1 has been classified as Amber List (Moderate Evidence).
Congenital ophthalmoplegia v0.11 ECEL1 Zornitza Stark Classified gene: ECEL1 as Amber List (moderate evidence)
Congenital ophthalmoplegia v0.11 ECEL1 Zornitza Stark Gene: ecel1 has been classified as Amber List (Moderate Evidence).
Congenital ophthalmoplegia v0.10 GRHL2 Zornitza Stark Marked gene: GRHL2 as ready
Congenital ophthalmoplegia v0.10 GRHL2 Zornitza Stark Gene: grhl2 has been classified as Red List (Low Evidence).
Congenital ophthalmoplegia v0.10 GRHL2 Zornitza Stark Tag SV/CNV tag was added to gene: GRHL2.
Congenital ophthalmoplegia v0.10 CHN1 Zornitza Stark Marked gene: CHN1 as ready
Congenital ophthalmoplegia v0.10 CHN1 Zornitza Stark Gene: chn1 has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.10 CHN1 Zornitza Stark Classified gene: CHN1 as Green List (high evidence)
Congenital ophthalmoplegia v0.10 CHN1 Zornitza Stark Gene: chn1 has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.9 TUBB2B Zornitza Stark Marked gene: TUBB2B as ready
Congenital ophthalmoplegia v0.9 TUBB2B Zornitza Stark Gene: tubb2b has been classified as Red List (Low Evidence).
Congenital ophthalmoplegia v0.9 TUBB2B Zornitza Stark Publications for gene: TUBB2B were set to 23001566
Congenital ophthalmoplegia v0.8 TUBB2B Zornitza Stark reviewed gene: TUBB2B: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital ophthalmoplegia v0.8 REV3L Shannon LeBlanc gene: REV3L was added
gene: REV3L was added to Congenital fibrosis of the extraocular muscles. Sources: Literature
Mode of inheritance for gene: REV3L was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: REV3L were set to PMID: 26068067
Phenotypes for gene: REV3L were set to möbius syndrome
Review for gene: REV3L was set to GREEN
Added comment: de novo variants in 3 unrelated individuals with möbius syndrome and some functional evidence
Sources: Literature
Congenital ophthalmoplegia v0.8 PLXND1 Shannon LeBlanc gene: PLXND1 was added
gene: PLXND1 was added to Congenital fibrosis of the extraocular muscles. Sources: Literature
Mode of inheritance for gene: PLXND1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PLXND1 were set to PMID: 26068067
Phenotypes for gene: PLXND1 were set to möbius syndrome
Review for gene: PLXND1 was set to GREEN
Added comment: PMID 26068067 : de novo mutations in 3 unrelated patients with moebius syndrome with some functional evidence.
Sources: Literature
Congenital ophthalmoplegia v0.8 MYMK Shannon LeBlanc gene: MYMK was added
gene: MYMK was added to Congenital fibrosis of the extraocular muscles. Sources: Other
Mode of inheritance for gene: MYMK was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MYMK were set to PMID: 28681861
Phenotypes for gene: MYMK were set to Carey-Fineman-Ziter syndrome, MIM 254940
Review for gene: MYMK was set to GREEN
Added comment: Congenital myopathy due to defect in myoblast fusion. Moebius syndrome / ophthalmoplegia is a common feature.
Sources: Other
Mendeliome v0.5272 PRKG2 Arina Puzriakova gene: PRKG2 was added
gene: PRKG2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PRKG2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PRKG2 were set to 33106379
Phenotypes for gene: PRKG2 were set to Acromesomelic dysplasia
Review for gene: PRKG2 was set to GREEN
Added comment: - PMID: 33106379 (2020) - Distinct homozygous variants in PRKG2 identified in two unrelated individuals, both with a skeletal dysplasia associated with severe short stature due to acromesomelic limb shortening, brachydactyly, mild to moderate platyspondyly and progressively increasing metaphyseal alterations of the long bones.

Functional studies showed both variants result in NMD and disrupt the downstream MAPK signalling pathway in response to FGF2. The role of cGKII, encoded by PRKG2, in skeletal growth has been established in several animal models (references provided in paper).
Sources: Literature
Congenital ophthalmoplegia v0.8 ROBO3 Shannon LeBlanc gene: ROBO3 was added
gene: ROBO3 was added to Congenital fibrosis of the extraocular muscles. Sources: Literature
Mode of inheritance for gene: ROBO3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ROBO3 were set to PMID: 15105459; 16525029
Phenotypes for gene: ROBO3 were set to Gaze palsy, familial horizontal, with progressive scoliosis, 1 (MIM#607313)
Review for gene: ROBO3 was set to GREEN
Added comment: PMID 15105459: 10 patients with homozygous variants (1 nonsense, 1 splice site, 2 frameshift, and 6 missense mutations)

PMID 16525029 - 2 unrelated children with sporadic HGPPS: one patient compound het for 2 different 2-bp deletions, one patient compound het for a missense and a nonsense mutation.
Sources: Literature
Congenital ophthalmoplegia v0.8 HOXA1 Shannon LeBlanc gene: HOXA1 was added
gene: HOXA1 was added to Congenital fibrosis of the extraocular muscles. Sources: Literature
Mode of inheritance for gene: HOXA1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HOXA1 were set to 17875913; 20227628; 18412118
Phenotypes for gene: HOXA1 were set to Athabaskan brainstem dysgenesis syndrome; Bosley-Salih-Alorainy syndrome - 601536
Review for gene: HOXA1 was set to GREEN
Added comment: The HOXA1-related syndrome phenotype is variable. The most common features in affected individuals are limited horizontal gaze (diagnosed as Duane syndrome in BSAS and horizontal gaze palsy in ABDS patients) and sensorineural deafness; facial weakness, mental retardation, autism, motor disabilities, central hypoventilation, carotid artery and/or conotruncal heart defects also occur (PMID 20227628)
Sources: Literature
Congenital ophthalmoplegia v0.8 CHN1 Shannon LeBlanc gene: CHN1 was added
gene: CHN1 was added to Congenital fibrosis of the extraocular muscles. Sources: Literature
Mode of inheritance for gene: CHN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CHN1 were set to PMID 33004823; 18653847; 21555619
Phenotypes for gene: CHN1 were set to Duane retraction syndrome 2, 604356
Review for gene: CHN1 was set to GREEN
Added comment: Gain-of function aetiology: PMID 18653847 - in vitro evidence that gain-of-function heterozygous missense CHN1 mutations in patients with Duane retraction syndrome increase α2-chimaerin RacGAP activity; 21555619 - separate CHN1 mutations 2 families predicted to result in its hyperactivation.
Sources: Literature
Congenital ophthalmoplegia v0.8 SALL4 Shannon LeBlanc gene: SALL4 was added
gene: SALL4 was added to Congenital fibrosis of the extraocular muscles. Sources: Literature
Mode of inheritance for gene: SALL4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: SALL4 were set to Duane-radial ray syndrome, 607323
Review for gene: SALL4 was set to GREEN
Added comment: well documented association with Duane-radial ray syndrome.
Sources: Literature
Congenital ophthalmoplegia v0.8 ECEL1 Shannon LeBlanc gene: ECEL1 was added
gene: ECEL1 was added to Congenital fibrosis of the extraocular muscles. Sources: Literature
Mode of inheritance for gene: ECEL1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ECEL1 were set to PMID: 25173900
Phenotypes for gene: ECEL1 were set to Arthrogryposis, distal, type 5D - 615065; Congenital cranial dysinnervation disorder
Review for gene: ECEL1 was set to AMBER
Added comment: 25173900 described an ocular phenotype consistent with congenital cranial dysinnervation disorder (CCDD) in 3 of 4 siblings with ECEL-1 related distal arthrogryposis. The fourth affected sibling (with the mildest arthrogryposis in the family) had no ocular phenotype. Of 26 other reported recessive ECEL1 mutation cases (14 families), all had arthrogryposis, 19 had documented ptosis, and 4 had documented complex strabismus. One of these cases had both documented ptosis and complex strabismus.
Sources: Literature
Congenital ophthalmoplegia v0.8 GRHL2 Shannon LeBlanc reviewed gene: GRHL2: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 29110737; Phenotypes: Deafness, autosomal dominant 28, Corneal dystrophy, posterior polymorphous, 4; Mode of inheritance: None
Congenital ophthalmoplegia v0.8 TUBB2B Shannon LeBlanc reviewed gene: TUBB2B: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 11425694, 23001566; Phenotypes: Cortical dysplasia, complex, with other brain malformations 7, Fibrosis of extraocular muscles, congenital; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5272 PRKACA Zornitza Stark Phenotypes for gene: PRKACA were changed from Postaxial hand polydactyly; Postaxial foot polydactyly; Common atrium; Atrioventricular canal defect; Narrow chest; Abnormality of the teeth; Intellectual disability to Postaxial hand polydactyly; Postaxial foot polydactyly; Common atrium; Atrioventricular canal defect; Narrow chest; Abnormality of the teeth
Skeletal dysplasia v0.59 Zornitza Stark removed gene:BCAP31 from the panel
Congenital diaphragmatic hernia v0.11 FOXP4 Zornitza Stark edited their review of gene: FOXP4: Changed rating: AMBER
Congenital diaphragmatic hernia v0.11 FOXP4 Zornitza Stark Marked gene: FOXP4 as ready
Congenital diaphragmatic hernia v0.11 FOXP4 Zornitza Stark Gene: foxp4 has been classified as Amber List (Moderate Evidence).
Congenital diaphragmatic hernia v0.11 FOXP4 Zornitza Stark Classified gene: FOXP4 as Amber List (moderate evidence)
Congenital diaphragmatic hernia v0.11 FOXP4 Zornitza Stark Gene: foxp4 has been classified as Amber List (Moderate Evidence).
Congenital diaphragmatic hernia v0.10 FOXP4 Zornitza Stark gene: FOXP4 was added
gene: FOXP4 was added to Congenital diaphragmatic hernia. Sources: Literature
Mode of inheritance for gene: FOXP4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FOXP4 were set to 33110267
Phenotypes for gene: FOXP4 were set to Neurodevelopmental disorder; multiple congenital abnormalities
Review for gene: FOXP4 was set to GREEN
Added comment: Eight unrelated individuals reported, seven de novo missense, and one individual with a truncating variant. Detailed phenotypic information available on 6. Overlapping features included speech and language delays, growth abnormalities, congenital diaphragmatic hernia (2/6), cervical spine abnormalities, and ptosis. Intellectual disability described as mild in 2, some had normal intellect despite the early speech and language delays.
Sources: Literature
Mendeliome v0.5271 FOXP4 Zornitza Stark Marked gene: FOXP4 as ready
Mendeliome v0.5271 FOXP4 Zornitza Stark Gene: foxp4 has been classified as Green List (High Evidence).
Mendeliome v0.5271 FOXP4 Zornitza Stark Classified gene: FOXP4 as Green List (high evidence)
Mendeliome v0.5271 FOXP4 Zornitza Stark Gene: foxp4 has been classified as Green List (High Evidence).
Mendeliome v0.5270 FOXP4 Zornitza Stark gene: FOXP4 was added
gene: FOXP4 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: FOXP4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FOXP4 were set to 33110267
Phenotypes for gene: FOXP4 were set to Neurodevelopmental disorder; multiple congenital abnormalities
Review for gene: FOXP4 was set to GREEN
Added comment: Eight unrelated individuals reported, seven de novo missense, and one individual with a truncating variant. Detailed phenotypic information available on 6. Overlapping features included speech and language delays, growth abnormalities, congenital diaphragmatic hernia (2/6), cervical spine abnormalities, and ptosis. Intellectual disability described as mild in 2, some had normal intellect despite the early speech and language delays.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3140 FOXP4 Zornitza Stark Marked gene: FOXP4 as ready
Intellectual disability syndromic and non-syndromic v0.3140 FOXP4 Zornitza Stark Gene: foxp4 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.3140 FOXP4 Zornitza Stark Classified gene: FOXP4 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.3140 FOXP4 Zornitza Stark Gene: foxp4 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.3139 FOXP4 Zornitza Stark edited their review of gene: FOXP4: Changed rating: AMBER
Intellectual disability syndromic and non-syndromic v0.3139 FOXP4 Zornitza Stark changed review comment from: Eight unrelated individuals reported, seven de novo missense, and one individual with a truncating variant. Detailed phenotypic information available on 6. Overlapping features included speech and language delays, growth abnormalities, congenital diaphragmatic hernia (2/6), cervical spine abnormalities, and ptosis. Intellectual disability described as mild in 2, some had normal intellect despite the early challenges.
Sources: Literature; to: Eight unrelated individuals reported, seven de novo missense, and one individual with a truncating variant. Detailed phenotypic information available on 6. Overlapping features included speech and language delays, growth abnormalities, congenital diaphragmatic hernia (2/6), cervical spine abnormalities, and ptosis. Intellectual disability described as mild in 2, some had normal intellect despite the early speech and language delays.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3139 FOXP4 Zornitza Stark changed review comment from: Six unrelated individuals reported, 5 with missense variants in the forkhead box DNA-binding domain of FOXP4, and one individual with a truncating variant. Overlapping features included speech and language delays, growth abnormalities, congenital diaphragmatic hernia, cervical spine abnormalities, and ptosis.
Sources: Literature; to: Eight unrelated individuals reported, seven de novo missense, and one individual with a truncating variant. Detailed phenotypic information available on 6. Overlapping features included speech and language delays, growth abnormalities, congenital diaphragmatic hernia (2/6), cervical spine abnormalities, and ptosis. Intellectual disability described as mild in 2, some had normal intellect despite the early challenges.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3139 FOXP4 Zornitza Stark gene: FOXP4 was added
gene: FOXP4 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: FOXP4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FOXP4 were set to 33110267
Phenotypes for gene: FOXP4 were set to Neurodevelopmental disorder; multiple congenital abnormalities
Review for gene: FOXP4 was set to GREEN
Added comment: Six unrelated individuals reported, 5 with missense variants in the forkhead box DNA-binding domain of FOXP4, and one individual with a truncating variant. Overlapping features included speech and language delays, growth abnormalities, congenital diaphragmatic hernia, cervical spine abnormalities, and ptosis.
Sources: Literature
Achromatopsia v1.3 Zornitza Stark removed gene:STN1 from the panel
Mendeliome v0.5269 ASAH1 Zornitza Stark Marked gene: ASAH1 as ready
Mendeliome v0.5269 ASAH1 Zornitza Stark Gene: asah1 has been classified as Green List (High Evidence).
Lysosomal Storage Disorder v0.54 ASAH1 Zornitza Stark Marked gene: ASAH1 as ready
Lysosomal Storage Disorder v0.54 ASAH1 Zornitza Stark Gene: asah1 has been classified as Green List (High Evidence).
Lysosomal Storage Disorder v0.54 ASAH1 Zornitza Stark Phenotypes for gene: ASAH1 were changed from to Farber lipogranulomatosis, MIM# 228000
Lysosomal Storage Disorder v0.53 ASAH1 Zornitza Stark Mode of inheritance for gene: ASAH1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Lysosomal Storage Disorder v0.52 ASAH1 Zornitza Stark reviewed gene: ASAH1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Farber lipogranulomatosis, MIM# 228000; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5269 ASAH1 Zornitza Stark Phenotypes for gene: ASAH1 were changed from to Spinal muscular atrophy with progressive myoclonic epilepsy, MIM# 159950; Farber lipogranulomatosis, MIM# 228000
Mendeliome v0.5268 ASAH1 Zornitza Stark Mode of inheritance for gene: ASAH1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5267 ASAH1 Zornitza Stark reviewed gene: ASAH1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Spinal muscular atrophy with progressive myoclonic epilepsy, MIM# 159950, Farber lipogranulomatosis, MIM# 228000; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5267 DHX32 Zornitza Stark Marked gene: DHX32 as ready
Mendeliome v0.5267 DHX32 Zornitza Stark Gene: dhx32 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5267 DHX32 Zornitza Stark Classified gene: DHX32 as Amber List (moderate evidence)
Mendeliome v0.5267 DHX32 Zornitza Stark Gene: dhx32 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.3138 DHX32 Zornitza Stark Marked gene: DHX32 as ready
Intellectual disability syndromic and non-syndromic v0.3138 DHX32 Zornitza Stark Gene: dhx32 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.3138 DHX32 Zornitza Stark Classified gene: DHX32 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.3138 DHX32 Zornitza Stark Gene: dhx32 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5266 TNF Zornitza Stark Marked gene: TNF as ready
Mendeliome v0.5266 TNF Zornitza Stark Gene: tnf has been classified as Red List (Low Evidence).
Mendeliome v0.5266 TNF Zornitza Stark Publications for gene: TNF were set to
Mendeliome v0.5265 TNF Zornitza Stark Classified gene: TNF as Red List (low evidence)
Mendeliome v0.5265 TNF Zornitza Stark Gene: tnf has been classified as Red List (Low Evidence).
Regression v0.206 NHLRC2 Zornitza Stark Marked gene: NHLRC2 as ready
Regression v0.206 NHLRC2 Zornitza Stark Gene: nhlrc2 has been classified as Green List (High Evidence).
Regression v0.206 NHLRC2 Zornitza Stark Classified gene: NHLRC2 as Green List (high evidence)
Regression v0.206 NHLRC2 Zornitza Stark Gene: nhlrc2 has been classified as Green List (High Evidence).
Pulmonary Fibrosis_Interstitial Lung Disease v0.16 NHLRC2 Zornitza Stark Marked gene: NHLRC2 as ready
Pulmonary Fibrosis_Interstitial Lung Disease v0.16 NHLRC2 Zornitza Stark Gene: nhlrc2 has been classified as Green List (High Evidence).
Pulmonary Fibrosis_Interstitial Lung Disease v0.16 NHLRC2 Zornitza Stark Classified gene: NHLRC2 as Green List (high evidence)
Pulmonary Fibrosis_Interstitial Lung Disease v0.16 NHLRC2 Zornitza Stark Gene: nhlrc2 has been classified as Green List (High Evidence).
Pulmonary Fibrosis_Interstitial Lung Disease v0.16 NHLRC2 Zornitza Stark Classified gene: NHLRC2 as Green List (high evidence)
Pulmonary Fibrosis_Interstitial Lung Disease v0.16 NHLRC2 Zornitza Stark Gene: nhlrc2 has been classified as Green List (High Evidence).
Mendeliome v0.5264 ALK Zornitza Stark Marked gene: ALK as ready
Mendeliome v0.5264 ALK Zornitza Stark Gene: alk has been classified as Green List (High Evidence).
Mendeliome v0.5264 ALK Zornitza Stark Phenotypes for gene: ALK were changed from to {Neuroblastoma, susceptibility to, 3} 613014; Spastic-dystonic diplegia
Mendeliome v0.5263 ALK Zornitza Stark Publications for gene: ALK were set to
Mendeliome v0.5262 ALK Zornitza Stark Mode of inheritance for gene: ALK was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5261 ALK Zornitza Stark reviewed gene: ALK: Rating: GREEN; Mode of pathogenicity: None; Publications: 32989326, 18724359; Phenotypes: {Neuroblastoma, susceptibility to, 3} 613014, Spastic-dystonic diplegia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary Spastic Paraplegia v0.156 ALK Zornitza Stark Marked gene: ALK as ready
Hereditary Spastic Paraplegia v0.156 ALK Zornitza Stark Gene: alk has been classified as Amber List (Moderate Evidence).
Hereditary Spastic Paraplegia v0.156 ALK Zornitza Stark Classified gene: ALK as Amber List (moderate evidence)
Hereditary Spastic Paraplegia v0.156 ALK Zornitza Stark Gene: alk has been classified as Amber List (Moderate Evidence).
Dystonia and Chorea v0.153 ALK Zornitza Stark Marked gene: ALK as ready
Dystonia and Chorea v0.153 ALK Zornitza Stark Gene: alk has been classified as Amber List (Moderate Evidence).
Dystonia and Chorea v0.153 ALK Zornitza Stark Classified gene: ALK as Amber List (moderate evidence)
Dystonia and Chorea v0.153 ALK Zornitza Stark Gene: alk has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5261 RHOB Zornitza Stark Marked gene: RHOB as ready
Mendeliome v0.5261 RHOB Zornitza Stark Gene: rhob has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5261 RHOB Zornitza Stark Phenotypes for gene: RHOB were changed from Cerebral Palsy (PMID:32989326) to Cerebral Palsy
Mendeliome v0.5260 RHOB Zornitza Stark Classified gene: RHOB as Amber List (moderate evidence)
Mendeliome v0.5260 RHOB Zornitza Stark Gene: rhob has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v0.54 TUBA1A Zornitza Stark Phenotypes for gene: TUBA1A were changed from Cerebral Palsy (PMID:32989326) to Lissencephaly 3, MIM# 611603; Cerebral palsy
Cerebral Palsy v0.53 TUBA1A Zornitza Stark reviewed gene: TUBA1A: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Lissencephaly 3, MIM# 611603; Mode of inheritance: None
Mendeliome v0.5259 ASAH1 Sue White edited their review of gene: ASAH1: Changed publications: 32875576, 32449975
Intellectual disability syndromic and non-syndromic v0.3137 FBXO31 Zornitza Stark Phenotypes for gene: FBXO31 were changed from Mental retardation, autosomal recessive 45, MIM#615979; Cerebral palsy, intellectual disability, autosomal dominant to Mental retardation, autosomal recessive 45, MIM#615979; Cerebral palsy, intellectual disability, autosomal dominant
Intellectual disability syndromic and non-syndromic v0.3136 FBXO31 Zornitza Stark Phenotypes for gene: FBXO31 were changed from Mental retardation, autosomal recessive 45, MIM#615979 to Mental retardation, autosomal recessive 45, MIM#615979; Cerebral palsy, intellectual disability, autosomal dominant
Intellectual disability syndromic and non-syndromic v0.3135 FBXO31 Zornitza Stark Publications for gene: FBXO31 were set to 24623383
Intellectual disability syndromic and non-syndromic v0.3134 FBXO31 Zornitza Stark Mode of pathogenicity for gene: FBXO31 was changed from to Other
Intellectual disability syndromic and non-syndromic v0.3133 FBXO31 Zornitza Stark Classified gene: FBXO31 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.3133 FBXO31 Zornitza Stark Gene: fbxo31 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5259 FBXO31 Zornitza Stark Phenotypes for gene: FBXO31 were changed from Mental retardation, autosomal recessive 45, MIM#615979 to Mental retardation, autosomal recessive 45, MIM#615979; Cerebral palsy, intellectual disability, autosomal dominant
Mendeliome v0.5258 DHX32 Dean Phelan gene: DHX32 was added
gene: DHX32 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: DHX32 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DHX32 were set to PMID: 32989326
Phenotypes for gene: DHX32 were set to Intellectual disability, spastic diplegia, dystonia, brain abnormalities
Review for gene: DHX32 was set to AMBER
Added comment: PMID: 32989326 - Large cohort study of cerebral palsy cases identified two de novo variants in two unrelated patients with intellectual disability, one with spastic diplegia, and the other characterised as generalised dystonia. Brain abnormalities were identified also.
Sources: Literature
Mendeliome v0.5258 FBXO31 Zornitza Stark Publications for gene: FBXO31 were set to 24623383
Mendeliome v0.5257 ASAH1 Sue White reviewed gene: ASAH1: Rating: ; Mode of pathogenicity: None; Publications: 32875576; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5257 FBXO31 Zornitza Stark Mode of pathogenicity for gene: FBXO31 was changed from None to Other
Intellectual disability syndromic and non-syndromic v0.3132 DHX32 Dean Phelan gene: DHX32 was added
gene: DHX32 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: DHX32 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DHX32 were set to PMID: 32989326
Phenotypes for gene: DHX32 were set to Intellectual disability, spastic diplegia, dystonia, brain abnormalities
Review for gene: DHX32 was set to AMBER
Added comment: PMID: 32989326 - Large cohort study of cerebral palsy cases identified two de novo variants in two unrelated patients with intellectual disability, one with spastic diplegia, and the other characterised as generalised dystonia. Brain abnormalities were identified also.
Sources: Literature
Mendeliome v0.5256 FBXO31 Zornitza Stark Mode of inheritance for gene: FBXO31 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.5255 FBXO31 Zornitza Stark Classified gene: FBXO31 as Amber List (moderate evidence)
Mendeliome v0.5255 FBXO31 Zornitza Stark Gene: fbxo31 has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v0.53 SPAST Zornitza Stark Marked gene: SPAST as ready
Cerebral Palsy v0.53 SPAST Zornitza Stark Added comment: Comment when marking as ready: Gene-disease association with spasticity is well established, individuals identified in a CP cohort.
Cerebral Palsy v0.53 SPAST Zornitza Stark Gene: spast has been classified as Green List (High Evidence).
Cerebral Palsy v0.53 SPAST Zornitza Stark Classified gene: SPAST as Green List (high evidence)
Cerebral Palsy v0.53 SPAST Zornitza Stark Gene: spast has been classified as Green List (High Evidence).
Hereditary Spastic Paraplegia v0.155 ALK Dean Phelan gene: ALK was added
gene: ALK was added to Hereditary Spastic Paraplegia - paediatric. Sources: Literature
Mode of inheritance for gene: ALK was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ALK were set to PMID: 32989326
Phenotypes for gene: ALK were set to Spastic-dystonic diplegia
Review for gene: ALK was set to AMBER
Added comment: PMID: 32989326 - Large cohort study of cerebral palsy cases identified two de novo variants in two patients with spastic diplegia with mild tremor, scattered subcortical hyperintensities and an atrial septal defect; and spastic-dystonic diplegia, white matter abnormalities and epilepsy, respectively, with no evidence of neuroblastoma in either patient
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3132 FBXO31 Kristin Rigbye reviewed gene: FBXO31: Rating: AMBER; Mode of pathogenicity: Other; Publications: PMID: 32989326; Phenotypes: Mental retardation, autosomal recessive 45, MIM#615979, Cerebral palsy; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.5254 TNF Seb Lunke reviewed gene: TNF: Rating: RED; Mode of pathogenicity: None; Publications: 26117714; Phenotypes: ; Mode of inheritance: None
Cerebral Palsy v0.52 DHX32 Zornitza Stark Marked gene: DHX32 as ready
Cerebral Palsy v0.52 DHX32 Zornitza Stark Gene: dhx32 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5254 FBXO31 Kristin Rigbye changed review comment from: 2 unrelated probands with CP harbouring the same de novo missense variant (p.Asp334Asn). The variant affects the cyclin D interaction site, leading to an apparent gain of function of cyclin D degradation, supported by Western blots from patient fibroblasts which showed decreased cyclin D expression.; to: 2 unrelated probands with CP harbouring the same de novo missense variant (p.Asp334Asn). The variant affects the cyclin D interaction site, leading to an apparent gain of function of cyclin D degradation, supported by Western blots from patient fibroblasts which showed decreased cyclin D expression.

Extended patient phenotypes: Spastic diplegia, with esotropia, ID, dysarthria, mixed receptive/expressive language disorder, ADHD, cleft palate, intestinal malrotation and midgut volvulus (patient 1); Spastic paraplegia with ventricular dilation and thin corpus callosum, ID, attention deficit, anxiety, language impairments, strabismus, severe constipation (patient 2).
Cerebral Palsy v0.52 DHX32 Zornitza Stark Classified gene: DHX32 as Amber List (moderate evidence)
Cerebral Palsy v0.52 DHX32 Zornitza Stark Gene: dhx32 has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v0.51 FBXO31 Kristin Rigbye changed review comment from: 2 unrelated probands with CP harbouring the same de novo missense variant (p.Asp334Asn). The variant affects the cyclin D interaction site, leading to an apparent gain of function of cyclin D degradation, supported by Western blots from patient fibroblasts which showed decreased cyclin D expression.

Extended patient phenotypes: Esotropia, ID, dysarthria, mixed receptive/expressive language disorder, ADHD, cleft palate, intestinal malrotation and midgut volvulus (patient 1); Ventricular dilation and thin corpus callosum, ID, attention deficit, anxiety, language impairments, strabismus, severe constipation (patient 2).

Sources: Literature; to: 2 unrelated probands with CP harbouring the same de novo missense variant (p.Asp334Asn). The variant affects the cyclin D interaction site, leading to an apparent gain of function of cyclin D degradation, supported by Western blots from patient fibroblasts which showed decreased cyclin D expression.

Extended patient phenotypes: Spastic diplegia, with esotropia, ID, dysarthria, mixed receptive/expressive language disorder, ADHD, cleft palate, intestinal malrotation and midgut volvulus (patient 1); Spastic paraplegia with ventricular dilation and thin corpus callosum, ID, attention deficit, anxiety, language impairments, strabismus, severe constipation (patient 2).

Sources: Literature
Cerebral Palsy v0.51 FBXO31 Kristin Rigbye changed review comment from: 2 unrelated probands with CP harbouring the same de novo missense variant (p.Asp334Asn). The variant affects the cyclin D interaction site, leading to an apparent gain of function of cyclin D degradation, supported by Western blots from patient fibroblasts which showed decreased cyclin D expression.
Sources: Literature; to: 2 unrelated probands with CP harbouring the same de novo missense variant (p.Asp334Asn). The variant affects the cyclin D interaction site, leading to an apparent gain of function of cyclin D degradation, supported by Western blots from patient fibroblasts which showed decreased cyclin D expression.

Extended patient phenotypes: Esotropia, ID, dysarthria, mixed receptive/expressive language disorder, ADHD, cleft palate, intestinal malrotation and midgut volvulus (patient 1); Ventricular dilation and thin corpus callosum, ID, attention deficit, anxiety, language impairments, strabismus, severe constipation (patient 2).

Sources: Literature
Cerebral Palsy v0.51 SPAST Crystle Lee gene: SPAST was added
gene: SPAST was added to Cerebral Palsy. Sources: Expert list
Mode of inheritance for gene: SPAST was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SPAST were set to 32989326
Phenotypes for gene: SPAST were set to Cerebral Palsy (PMID:32989326)
Review for gene: SPAST was set to AMBER
Added comment: 2 different de novo missense variants reported in CP cohort. Both patients presented with spasticity.
Sources: Expert list
Cerebral Palsy v0.51 ATL1 Zornitza Stark Marked gene: ATL1 as ready
Cerebral Palsy v0.51 ATL1 Zornitza Stark Gene: atl1 has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v0.51 ATL1 Zornitza Stark Classified gene: ATL1 as Amber List (moderate evidence)
Cerebral Palsy v0.51 ATL1 Zornitza Stark Gene: atl1 has been classified as Amber List (Moderate Evidence).
Regression v0.205 NHLRC2 Paul De Fazio gene: NHLRC2 was added
gene: NHLRC2 was added to Regression. Sources: Literature
Mode of inheritance for gene: NHLRC2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NHLRC2 were set to 29423877; 32435055
Phenotypes for gene: NHLRC2 were set to Fibrosis, neurodegeneration, and cerebral angiomatosis (FINCA) syndrome MIM#618278
Review for gene: NHLRC2 was set to GREEN
gene: NHLRC2 was marked as current diagnostic
Added comment: 3 families with compound het variants in total, all share one missense variant (p.Asp148Tyr)

PMID 29423877: 3 patients from 2 Finnish families compound het for the same missense variant (122 hets 0 homs) and the same frameshift variant (12 hets 0 homs), main clinical features included progressive cerebropulmonary symptoms, malabsorption, progressive growth failure, recurrent infections, chronic haemolytic anaemia and transient liver dysfunction. Expression studies in patient-derived fibroblasts supported the frameshift variant leading to NMD. Zebrafish knockdown affected the integrity of cells in the midbrain region.

PMID 32435055: patient with the same phenotype from a Ukrainian family chet for two missense variants, one shared with the Finnish families and one novel.
Sources: Literature
Dystonia and Chorea v0.152 ALK Dean Phelan gene: ALK was added
gene: ALK was added to Dystonia - complex. Sources: Literature
Mode of inheritance for gene: ALK was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ALK were set to PMID: 32989326
Phenotypes for gene: ALK were set to Spastic-dystonic diplegia
Review for gene: ALK was set to AMBER
Added comment: PMID: 32989326 - Large cohort study of cerebral palsy cases identified two de novo variants in two patients with spastic diplegia with mild tremor, scattered subcortical hyperintensities and an atrial septal defect; and spastic-dystonic diplegia, white matter abnormalities and epilepsy, respectively, with no evidence of neuroblastoma in either patient
Sources: Literature
Pulmonary Fibrosis_Interstitial Lung Disease v0.15 NHLRC2 Paul De Fazio gene: NHLRC2 was added
gene: NHLRC2 was added to Pulmonary Fibrosis_Interstitial Lung Disease. Sources: Literature
Mode of inheritance for gene: NHLRC2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NHLRC2 were set to 29423877; 32435055
Phenotypes for gene: NHLRC2 were set to Fibrosis, neurodegeneration, and cerebral angiomatosis (FINCA) syndrome MIM#618278
Review for gene: NHLRC2 was set to GREEN
gene: NHLRC2 was marked as current diagnostic
Added comment: 3 families with compound het variants in total, all share one missense variant (p.Asp148Ty)

PMID 29423877: 3 patients from 2 Finnish families compound het for the same missense variant (122 hets 0 homs) and the same frameshift variant (12 hets 0 homs), main clinical features included progressive cerebropulmonary symptoms, malabsorption, progressive growth failure, recurrent infections, chronic haemolytic anaemia and transient liver dysfunction. Expression studies in patient-derived fibroblasts supported the frameshift variant leading to NMD. Zebrafish knockdown affected the integrity of cells in the midbrain region.

PMID 32435055: patient with the same phenotype from a Ukrainian family chet for two missense variants, one shared with the Finnish families and one novel.
Sources: Literature
Mendeliome v0.5254 NHLRC2 Zornitza Stark Marked gene: NHLRC2 as ready
Mendeliome v0.5254 NHLRC2 Zornitza Stark Gene: nhlrc2 has been classified as Green List (High Evidence).
Mendeliome v0.5254 NHLRC2 Zornitza Stark Phenotypes for gene: NHLRC2 were changed from to Fibrosis, neurodegeneration, and cerebral angiomatosis (FINCA) syndrome MIM#618278
Mendeliome v0.5253 FBXO31 Kristin Rigbye reviewed gene: FBXO31: Rating: AMBER; Mode of pathogenicity: Other; Publications: PMID: 32989326; Phenotypes: Cerebral palsy; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.5253 NHLRC2 Zornitza Stark Publications for gene: NHLRC2 were set to
Cerebral Palsy v0.50 DHX32 Dean Phelan gene: DHX32 was added
gene: DHX32 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: DHX32 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DHX32 were set to PMID: 32989326
Phenotypes for gene: DHX32 were set to Intellectual disability, spastic diplegia, dystonia, brain abnormalities
Review for gene: DHX32 was set to AMBER
Added comment: PMID: 32989326 - Large cohort study of cerebral palsy cases identified two de novo variants in two unrelated patients with intellectual disability, one with spastic diplegia, and the other characterised as generalised dystonia. Brain abnormalities were identified also.
Sources: Literature
Mendeliome v0.5252 NHLRC2 Zornitza Stark Mode of inheritance for gene: NHLRC2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5251 RHOB Crystle Lee gene: RHOB was added
gene: RHOB was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: RHOB was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: RHOB were set to 32989326
Phenotypes for gene: RHOB were set to Cerebral Palsy (PMID:32989326)
Mode of pathogenicity for gene: RHOB was set to Other
Review for gene: RHOB was set to AMBER
Added comment: Candidate disease-causing gene for CP. Recurrent de novo missense variant reported in 2 unrelated families with supporting functional studies.
Sources: Expert list
Skeletal dysplasia v0.58 BCAP31 Sue White Classified gene: BCAP31 as Green List (high evidence)
Skeletal dysplasia v0.58 BCAP31 Sue White Gene: bcap31 has been classified as Green List (High Evidence).
Skeletal dysplasia v0.57 BCAP31 Sue White gene: BCAP31 was added
gene: BCAP31 was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: BCAP31 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: BCAP31 were set to 32681719
Phenotypes for gene: BCAP31 were set to XL-Schimke; deafness, dystonia and hypomyelination phenotype
Added comment: Deafness, dystonia and hypomyelination phenotype with short stature and features of XL-Schimke syndrome (MIM 300475)
Sources: Literature
Cerebral Palsy v0.50 RHOB Seb Lunke Marked gene: RHOB as ready
Cerebral Palsy v0.50 RHOB Seb Lunke Gene: rhob has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v0.50 RHOB Seb Lunke Classified gene: RHOB as Amber List (moderate evidence)
Cerebral Palsy v0.50 RHOB Seb Lunke Gene: rhob has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v0.49 FBXO31 Seb Lunke Marked gene: FBXO31 as ready
Cerebral Palsy v0.49 FBXO31 Seb Lunke Gene: fbxo31 has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v0.49 FBXO31 Seb Lunke Classified gene: FBXO31 as Amber List (moderate evidence)
Cerebral Palsy v0.49 FBXO31 Seb Lunke Gene: fbxo31 has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v0.48 ALK Zornitza Stark Marked gene: ALK as ready
Cerebral Palsy v0.48 ALK Zornitza Stark Gene: alk has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v0.48 ALK Zornitza Stark Classified gene: ALK as Amber List (moderate evidence)
Cerebral Palsy v0.48 ALK Zornitza Stark Gene: alk has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5251 CTLA4 Zornitza Stark Marked gene: CTLA4 as ready
Mendeliome v0.5251 CTLA4 Zornitza Stark Gene: ctla4 has been classified as Green List (High Evidence).
Mendeliome v0.5251 CTLA4 Zornitza Stark Phenotypes for gene: CTLA4 were changed from to Autoimmune lymphoproliferative syndrome, type V (MIM#616100), AD
Cerebral Palsy v0.47 TUBA1A Seb Lunke Marked gene: TUBA1A as ready
Cerebral Palsy v0.47 TUBA1A Seb Lunke Gene: tuba1a has been classified as Green List (High Evidence).
Cerebral Palsy v0.47 TUBA1A Seb Lunke Phenotypes for gene: TUBA1A were changed from to Cerebral Palsy (PMID:32989326)
Mendeliome v0.5250 CTLA4 Zornitza Stark Mode of inheritance for gene: CTLA4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v0.46 TUBA1A Seb Lunke Publications for gene: TUBA1A were set to 32989326; 25666757
Mendeliome v0.5249 VIM Zornitza Stark Marked gene: VIM as ready
Mendeliome v0.5249 VIM Zornitza Stark Gene: vim has been classified as Green List (High Evidence).
Cerebral Palsy v0.45 TUBA1A Seb Lunke Publications for gene: TUBA1A were set to
Mendeliome v0.5249 VIM Zornitza Stark Phenotypes for gene: VIM were changed from to Cataract 30, pulverulent 116300; frontonasal dysostosis and premature aging
Mendeliome v0.5248 NHLRC2 Paul De Fazio changed review comment from: 3 families with compound het variants in total, all share one missense variant (p.Asp148Ty)

PMID 29423877: 3 patients from 2 Finnish families compound het for the same missense variant (122 hets 0 homs) and the same frameshift variant (12 hets 0 homs), main clinical features included progressive cerebropulmonary symptoms, malabsorption, progressive growth failure, recurrent infections, chronic haemolytic anaemia and transient liver dysfunction. Expression studies in patient-derived fibroblasts supported the frameshift variant leading to NMD. Zebrafish knockdown affected the integrity of cells in the midbrain region.

PMID 32435055: patient with the same phenotype from a Ukrainian family chet for two missense variants, one shared with the Finnish families and one novel.; to: 3 families with compound het variants in total, all share one missense variant (p.Asp148Ty)

PMID 29423877: 3 patients from 2 Finnish families compound het for the same missense variant (122 hets 0 homs) and the same frameshift variant (12 hets 0 homs), main clinical features included progressive cerebropulmonary symptoms, malabsorption, progressive growth failure, recurrent infections, chronic haemolytic anaemia and transient liver dysfunction. Expression studies in patient-derived fibroblasts supported the frameshift variant leading to NMD. Zebrafish knockdown affected the integrity of cells in the midbrain region.

PMID 32435055: patient with the same phenotype from a Ukrainian family chet for two missense variants, one shared with the Finnish families and one novel.
Mendeliome v0.5248 NHLRC2 Paul De Fazio changed review comment from: 3 families with compound het variants in total, all share one missense variant (p.Asp148Ty)

PMID 29423877: 3 patients from 2 Finnish families compound het for the same missense variant (122 hets 0 homs) and the same frameshift variant (12 hets 0 homs), main clinical features included progressive cerebropulmonary symptoms, malabsorption, progressive growth failure, recurrent infections, chronic haemolytic anaemia and transient liver dysfunction. Zebrafish knockdown affected the integrity of cells in the midbrain region.

PMID 32435055: patient with the same phenotype from a Ukrainian family chet for two missense variants, one shared with the Finnish families and one novel.; to: 3 families with compound het variants in total, all share one missense variant (p.Asp148Ty)

PMID 29423877: 3 patients from 2 Finnish families compound het for the same missense variant (122 hets 0 homs) and the same frameshift variant (12 hets 0 homs), main clinical features included progressive cerebropulmonary symptoms, malabsorption, progressive growth failure, recurrent infections, chronic haemolytic anaemia and transient liver dysfunction. Expression studies in patient-derived fibroblasts supported the frameshift variant leading to NMD. Zebrafish knockdown affected the integrity of cells in the midbrain region.

PMID 32435055: patient with the same phenotype from a Ukrainian family chet for two missense variants, one shared with the Finnish families and one novel.
Cerebral Palsy v0.44 ATL1 Kristin Rigbye gene: ATL1 was added
gene: ATL1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: ATL1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ATL1 were set to PMID: 32989326
Phenotypes for gene: ATL1 were set to Cerebral palsy
Review for gene: ATL1 was set to AMBER
Added comment: Two CP cohort patients with de novo ATL1 missense variants (p.Ala350Val and p.Lys406Gln) located in the GBP domain. Patients exhibited spasticity and dystonia with brain findings of T2 hyperintensities and bihemispheric periventricular leukomalacia. No functional studies.
Sources: Literature
Mendeliome v0.5248 VIM Zornitza Stark Publications for gene: VIM were set to
Cerebral Palsy v0.44 TUBA1A Seb Lunke Mode of inheritance for gene: TUBA1A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.5247 VIM Zornitza Stark Mode of inheritance for gene: VIM was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5246 VIM Zornitza Stark reviewed gene: VIM: Rating: GREEN; Mode of pathogenicity: None; Publications: 19126778, 26694549, 28450710; Phenotypes: Cataract 30, pulverulent 116300; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Achromatopsia v1.2 STN1 Sue White Classified gene: STN1 as Green List (high evidence)
Achromatopsia v1.2 STN1 Sue White Gene: stn1 has been classified as Green List (High Evidence).
Achromatopsia v1.1 STN1 Sue White Marked gene: STN1 as ready
Achromatopsia v1.1 STN1 Sue White Gene: stn1 has been classified as Red List (Low Evidence).
Achromatopsia v1.1 STN1 Sue White gene: STN1 was added
gene: STN1 was added to Achromatopsia. Sources: Literature
Mode of inheritance for gene: STN1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: STN1 were set to 27432940; 32627942
Phenotypes for gene: STN1 were set to bone marrow failure; dystonia; premature ageing; leukodystrophy; retinal telangiactasis
Penetrance for gene: STN1 were set to Complete
Cerebral Palsy v0.43 TUBA1A Crystle Lee changed review comment from: >3 de novo CP families reported; to: 3 de novo CP families reported
Intellectual disability syndromic and non-syndromic v0.3132 STN1 Sue White Classified gene: STN1 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.3132 STN1 Sue White Gene: stn1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5246 NHLRC2 Paul De Fazio reviewed gene: NHLRC2: Rating: GREEN; Mode of pathogenicity: None; Publications: 29423877, 32435055; Phenotypes: Fibrosis, neurodegeneration, and cerebral angiomatosis (FINCA) syndrome MIM#618278; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.3131 STN1 Sue White gene: STN1 was added
gene: STN1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: STN1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: STN1 were set to 32627942; 27432940
Phenotypes for gene: STN1 were set to cerebral calcification; premature ageing; bone marrow failure; retinal telangiactasia; hepatic fibrosis
Penetrance for gene: STN1 were set to Complete
Added comment: 3 unrelated patients reported with Coats-plus syndrome. Developmental delay noted in two.
Sources: Literature
Syndromic Retinopathy v0.153 STN1 Zornitza Stark Marked gene: STN1 as ready
Syndromic Retinopathy v0.153 STN1 Zornitza Stark Gene: stn1 has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.153 STN1 Zornitza Stark Classified gene: STN1 as Green List (high evidence)
Syndromic Retinopathy v0.153 STN1 Zornitza Stark Gene: stn1 has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.152 STN1 Zornitza Stark gene: STN1 was added
gene: STN1 was added to Syndromic Retinopathy. Sources: Literature
Mode of inheritance for gene: STN1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: STN1 were set to 27432940; 32627942
Phenotypes for gene: STN1 were set to Cerebroretinal microangiopathy with calcification and cysts 2, MIM#617341
Review for gene: STN1 was set to GREEN
Added comment: Three unrelated families described with a multisystem disorder characterized by premature aging, pancytopaenia, hypocellular bone marrow, osteopenia, liver fibrosis, and vascular telangiectasia resulting in gastrointestinal bleeding, as well as intracranial calcifications and leukodystrophy, resulting in spasticity, ataxia, or dystonia.

Retinal telangiectasia.
Sources: Literature
Mendeliome v0.5246 STN1 Zornitza Stark Publications for gene: STN1 were set to 27432940
Mendeliome v0.5245 STN1 Zornitza Stark Classified gene: STN1 as Green List (high evidence)
Mendeliome v0.5245 STN1 Zornitza Stark Gene: stn1 has been classified as Green List (High Evidence).
Cerebral Palsy v0.43 FBXO31 Kristin Rigbye gene: FBXO31 was added
gene: FBXO31 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: FBXO31 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FBXO31 were set to PMID: 32989326
Phenotypes for gene: FBXO31 were set to Cerebral palsy
Penetrance for gene: FBXO31 were set to unknown
Mode of pathogenicity for gene: FBXO31 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: FBXO31 was set to AMBER
Added comment: 2 unrelated probands with CP harbouring the same de novo missense variant (p.Asp334Asn). The variant affects the cyclin D interaction site, leading to an apparent gain of function of cyclin D degradation, supported by Western blots from patient fibroblasts which showed decreased cyclin D expression.
Sources: Literature
Mendeliome v0.5244 STN1 Zornitza Stark edited their review of gene: STN1: Added comment: Third unrelated family reported, promote to Green.; Changed rating: GREEN; Changed publications: 27432940, 32627942
Liver Failure_Paediatric v0.77 STN1 Zornitza Stark Marked gene: STN1 as ready
Liver Failure_Paediatric v0.77 STN1 Zornitza Stark Gene: stn1 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.77 STN1 Zornitza Stark Classified gene: STN1 as Green List (high evidence)
Liver Failure_Paediatric v0.77 STN1 Zornitza Stark Gene: stn1 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.76 STN1 Zornitza Stark gene: STN1 was added
gene: STN1 was added to Liver Failure_Paediatric. Sources: Literature
Mode of inheritance for gene: STN1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: STN1 were set to 27432940; 32627942
Phenotypes for gene: STN1 were set to Cerebroretinal microangiopathy with calcification and cysts 2, MIM#617341
Review for gene: STN1 was set to GREEN
Added comment: Three unrelated families described with a multisystem disorder characterized by premature aging, pancytopaenia, hypocellular bone marrow, osteopenia, liver fibrosis, and vascular telangiectasia resulting in gastrointestinal bleeding, as well as intracranial calcifications and leukodystrophy, resulting in spasticity, ataxia, or dystonia.
Sources: Literature
Cerebral Palsy v0.43 ALK Dean Phelan gene: ALK was added
gene: ALK was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: ALK was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ALK were set to PMID: 32989326
Phenotypes for gene: ALK were set to Spastic-dystonic diplegia
Review for gene: ALK was set to AMBER
Added comment: PMID: 32989326 - Large cohort study of cerebral palsy cases identified two de novo variants in two patients with spastic diplegia with mild tremor, scattered subcortical hyperintensities and an atrial septal defect; and spastic-dystonic diplegia, white matter abnormalities and epilepsy, respectively, with no evidence of neuroblastoma in either patient.
Sources: Literature
Brain Calcification v0.46 STN1 Zornitza Stark Publications for gene: STN1 were set to 27432940
Bone Marrow Failure v0.169 STN1 Zornitza Stark Publications for gene: STN1 were set to 27432940
Brain Calcification v0.45 STN1 Zornitza Stark Classified gene: STN1 as Green List (high evidence)
Brain Calcification v0.45 STN1 Zornitza Stark Gene: stn1 has been classified as Green List (High Evidence).
Cerebral Palsy v0.43 RHOB Crystle Lee gene: RHOB was added
gene: RHOB was added to Cerebral Palsy. Sources: Expert Review
Mode of inheritance for gene: RHOB was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: RHOB were set to 32989326
Phenotypes for gene: RHOB were set to Cerebral Palsy (PMID:32989326)
Mode of pathogenicity for gene: RHOB was set to Other
Review for gene: RHOB was set to AMBER
Added comment: Candidate disease-causing gene for CP. Recurrent de novo missense variant reported in 2 unrelated families with supporting functional studies.
Sources: Expert Review
Brain Calcification v0.44 STN1 Zornitza Stark edited their review of gene: STN1: Added comment: Third unrelated family reported, promoted to Green.; Changed rating: GREEN; Changed publications: 27432940, 32627942; Changed phenotypes: Cerebroretinal microangiopathy with calcifications and cysts 2, MIM# 617341
Mendeliome v0.5244 CTLA4 Teresa Zhao reviewed gene: CTLA4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Autoimmune lymphoproliferative syndrome, type V (MIM#616100), AD; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Bone Marrow Failure v0.168 STN1 Zornitza Stark Marked gene: STN1 as ready
Bone Marrow Failure v0.168 STN1 Zornitza Stark Added comment: Comment when marking as ready: Promoted to Green, highly specific constellation of features.
Bone Marrow Failure v0.168 STN1 Zornitza Stark Gene: stn1 has been classified as Green List (High Evidence).
Bone Marrow Failure v0.168 STN1 Zornitza Stark Classified gene: STN1 as Green List (high evidence)
Bone Marrow Failure v0.168 STN1 Zornitza Stark Gene: stn1 has been classified as Green List (High Evidence).
Cerebral Palsy v0.43 TUBA1A Crystle Lee reviewed gene: TUBA1A: Rating: GREEN; Mode of pathogenicity: None; Publications: 32989326, 25666757; Phenotypes: Cerebral Palsy (PMID:32989326); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.5244 ITPR3 Zornitza Stark Marked gene: ITPR3 as ready
Mendeliome v0.5244 ITPR3 Zornitza Stark Gene: itpr3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5244 VIM Ee Ming Wong reviewed gene: VIM: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 32066935; Phenotypes: frontonasal dysostosis, premature aging; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Bone Marrow Failure v0.167 STN1 Sue White reviewed gene: STN1: Rating: GREEN; Mode of pathogenicity: None; Publications: 32627942; Phenotypes: Coats-plus syndrome, intracranial calcification, retinal telangiactasia, bone marrow failure; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5244 ITPR3 Zornitza Stark Classified gene: ITPR3 as Amber List (moderate evidence)
Mendeliome v0.5244 ITPR3 Zornitza Stark Gene: itpr3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5243 ITPR3 Zornitza Stark gene: ITPR3 was added
gene: ITPR3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ITPR3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ITPR3 were set to 32949214
Phenotypes for gene: ITPR3 were set to Charcot-Marie-Tooth disease
Review for gene: ITPR3 was set to AMBER
Added comment: Two unrelated families reported: variant segregated in four affected individuals in one family and was de novo in the second family where there was a single affected person. Some evidence for dominant-negative effect.
Sources: Literature
Mendeliome v0.5242 SOCS1 Zornitza Stark Phenotypes for gene: SOCS1 were changed from Common variable immunodeficiency to Common variable immunodeficiency; Early-onset autoimmunity
Mendeliome v0.5241 SOCS1 Zornitza Stark Publications for gene: SOCS1 were set to 32499645; 10490099; 10490100
Mendeliome v0.5240 SOCS1 Zornitza Stark reviewed gene: SOCS1: Rating: GREEN; Mode of pathogenicity: None; Publications: 33087723; Phenotypes: Early-onset autoimmunity; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Disorders of immune dysregulation v0.72 SOCS1 Zornitza Stark Marked gene: SOCS1 as ready
Disorders of immune dysregulation v0.72 SOCS1 Zornitza Stark Gene: socs1 has been classified as Green List (High Evidence).
Disorders of immune dysregulation v0.72 SOCS1 Zornitza Stark Classified gene: SOCS1 as Green List (high evidence)
Disorders of immune dysregulation v0.72 SOCS1 Zornitza Stark Gene: socs1 has been classified as Green List (High Evidence).
Disorders of immune dysregulation v0.71 SOCS1 Zornitza Stark gene: SOCS1 was added
gene: SOCS1 was added to Disorders of immune dysregulation. Sources: Literature
Mode of inheritance for gene: SOCS1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SOCS1 were set to 33087723
Phenotypes for gene: SOCS1 were set to Early-onset autoimmunity
Review for gene: SOCS1 was set to GREEN
Added comment: Ten individuals from 5 unrelated families with LOF variants in this gene and early-onset autoimmunity. Functional data indicates cytokine hypersensitivity of immune cells.
Sources: Literature
Mendeliome v0.5240 AMOTL1 Zornitza Stark Marked gene: AMOTL1 as ready
Mendeliome v0.5240 AMOTL1 Zornitza Stark Gene: amotl1 has been classified as Red List (Low Evidence).
Mendeliome v0.5240 AMOTL1 Zornitza Stark gene: AMOTL1 was added
gene: AMOTL1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: AMOTL1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: AMOTL1 were set to 33026150
Phenotypes for gene: AMOTL1 were set to Cleft lip and palate; imperforate anus; dysmorphism
Review for gene: AMOTL1 was set to RED
Added comment: Two unrelated families reported. In one, the variant was identified in parent and child who had orofacial cleft and cardiac abnormalities. Second report in PMID 33026150, de novo missense variant and cleft lip/palate, imperforate anus and dysmorphism. Mouse model does not recapitulate phenotype.
Sources: Literature
Cancer Predisposition_Paediatric v0.93 PAX5 Zornitza Stark Marked gene: PAX5 as ready
Cancer Predisposition_Paediatric v0.93 PAX5 Zornitza Stark Gene: pax5 has been classified as Green List (High Evidence).
Cancer Predisposition_Paediatric v0.93 PAX5 Zornitza Stark Phenotypes for gene: PAX5 were changed from to {Leukemia, acute lymphoblastic, susceptibility to, 3}, MIM# 615545
Cancer Predisposition_Paediatric v0.92 PAX5 Zornitza Stark Publications for gene: PAX5 were set to
Cancer Predisposition_Paediatric v0.91 PAX5 Zornitza Stark Mode of inheritance for gene: PAX5 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cancer Predisposition_Paediatric v0.90 PAX5 Zornitza Stark reviewed gene: PAX5: Rating: GREEN; Mode of pathogenicity: None; Publications: 24013638, 30643249, 33036026; Phenotypes: {Leukemia, acute lymphoblastic, susceptibility to, 3}, MIM# 615545; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5239 KIRREL1 Zornitza Stark Marked gene: KIRREL1 as ready
Mendeliome v0.5239 KIRREL1 Zornitza Stark Gene: kirrel1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5239 KIRREL1 Zornitza Stark Classified gene: KIRREL1 as Amber List (moderate evidence)
Mendeliome v0.5239 KIRREL1 Zornitza Stark Gene: kirrel1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5238 KIRREL1 Zornitza Stark gene: KIRREL1 was added
gene: KIRREL1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: KIRREL1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIRREL1 were set to 31472902
Phenotypes for gene: KIRREL1 were set to Steroid-resistant nephrotic syndrome
Review for gene: KIRREL1 was set to AMBER
Added comment: Two unrelated families reported with bi-allelic variants and limited functional data.
Sources: Literature
Proteinuria v0.142 KIRREL1 Zornitza Stark Marked gene: KIRREL1 as ready
Proteinuria v0.142 KIRREL1 Zornitza Stark Gene: kirrel1 has been classified as Amber List (Moderate Evidence).
Proteinuria v0.142 KIRREL1 Zornitza Stark Classified gene: KIRREL1 as Amber List (moderate evidence)
Proteinuria v0.142 KIRREL1 Zornitza Stark Gene: kirrel1 has been classified as Amber List (Moderate Evidence).
Proteinuria v0.141 KIRREL1 Zornitza Stark gene: KIRREL1 was added
gene: KIRREL1 was added to Proteinuria. Sources: Literature
Mode of inheritance for gene: KIRREL1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIRREL1 were set to 31472902
Phenotypes for gene: KIRREL1 were set to Steroid-resistant nephrotic syndrome
Review for gene: KIRREL1 was set to AMBER
Added comment: Two unrelated families reported with bi-allelic variants and limited functional data.
Sources: Literature
Mendeliome v0.5237 GFRA1 Zornitza Stark Marked gene: GFRA1 as ready
Mendeliome v0.5237 GFRA1 Zornitza Stark Gene: gfra1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5237 GFRA1 Zornitza Stark Classified gene: GFRA1 as Amber List (moderate evidence)
Mendeliome v0.5237 GFRA1 Zornitza Stark Gene: gfra1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5236 GFRA1 Zornitza Stark gene: GFRA1 was added
gene: GFRA1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GFRA1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GFRA1 were set to 33020172
Phenotypes for gene: GFRA1 were set to Renal agenesis
Review for gene: GFRA1 was set to AMBER
Added comment: Two unrelated families reported with bi-allelic LOF variants identified in individuals with bilateral renal agenesis. GFRA1 gene encodes a receptor on the Wolffian duct that regulates ureteric bud outgrowth in the development of a functional renal system.
Sources: Literature
Mendeliome v0.5235 GNB2 Bryony Thompson reviewed gene: GNB2: Rating: AMBER; Mode of pathogenicity: None; Publications: 33057194; Phenotypes: Developmental disorder, sinus node dysfunction and atrioventricular block; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5235 GIGYF1 Bryony Thompson Marked gene: GIGYF1 as ready
Mendeliome v0.5235 GIGYF1 Bryony Thompson Gene: gigyf1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5235 GIGYF1 Bryony Thompson Classified gene: GIGYF1 as Amber List (moderate evidence)
Mendeliome v0.5235 GIGYF1 Bryony Thompson Gene: gigyf1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5234 GIGYF1 Bryony Thompson gene: GIGYF1 was added
gene: GIGYF1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GIGYF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GIGYF1 were set to 33057194
Phenotypes for gene: GIGYF1 were set to Developmental disorder
Review for gene: GIGYF1 was set to AMBER
Added comment: PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 14 de novo variants (4 frameshift, 5 missense, 1 splice donor, 3 stopgain, 1 synonymous) identified in ~10,000 cases with developmental disorders (no other phenotype info provided).
Sources: Literature
Mendeliome v0.5233 FBXW7 Bryony Thompson Marked gene: FBXW7 as ready
Mendeliome v0.5233 FBXW7 Bryony Thompson Gene: fbxw7 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5233 FBXW7 Bryony Thompson Classified gene: FBXW7 as Amber List (moderate evidence)
Mendeliome v0.5233 FBXW7 Bryony Thompson Gene: fbxw7 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5232 FBXW7 Bryony Thompson gene: FBXW7 was added
gene: FBXW7 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: FBXW7 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FBXW7 were set to 33057194
Phenotypes for gene: FBXW7 were set to Developmental disorder
Review for gene: FBXW7 was set to AMBER
Added comment: PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio developmental disorder study. 12 de novo missense and 1 de novo synonymous variant identified in ~10,000 cases with developmental disorders (no other phenotype info provided)
Sources: Literature
Liver Failure_Paediatric v0.75 BCS1L Zornitza Stark Marked gene: BCS1L as ready
Liver Failure_Paediatric v0.75 BCS1L Zornitza Stark Gene: bcs1l has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.75 BCS1L Zornitza Stark Classified gene: BCS1L as Green List (high evidence)
Liver Failure_Paediatric v0.75 BCS1L Zornitza Stark Gene: bcs1l has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.74 BCS1L Zornitza Stark gene: BCS1L was added
gene: BCS1L was added to Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: BCS1L was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BCS1L were set to 12910490; 12215968; 21274865
Phenotypes for gene: BCS1L were set to GRACILE syndrome, MIM# 603358; Mitochondrial complex III deficiency, nuclear type 1 , MIM#124000
Review for gene: BCS1L was set to GREEN
Added comment: The two phenotypes pertinent to this panel are a Leigh-like syndrome; and growth retardation, aminoaciduria, cholestasis, iron overload, lactic acidosis and early death (GRACILE syndrome). Mitochondrial hepatopathy.
Sources: Expert list
Liver Failure_Paediatric v0.73 POLG2 Zornitza Stark Marked gene: POLG2 as ready
Liver Failure_Paediatric v0.73 POLG2 Zornitza Stark Gene: polg2 has been classified as Amber List (Moderate Evidence).
Liver Failure_Paediatric v0.73 POLG2 Zornitza Stark Classified gene: POLG2 as Amber List (moderate evidence)
Liver Failure_Paediatric v0.73 POLG2 Zornitza Stark Gene: polg2 has been classified as Amber List (Moderate Evidence).
Liver Failure_Paediatric v0.72 POLG2 Zornitza Stark gene: POLG2 was added
gene: POLG2 was added to Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: POLG2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: POLG2 were set to 27592148; 30157269; 21555342
Phenotypes for gene: POLG2 were set to Mitochondrial DNA depletion syndrome 16 (hepatic type), MIM# 618528; Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant, MIM# 4 610131
Review for gene: POLG2 was set to AMBER
Added comment: Single family reported with bi-allelic variants in POLG2 and severe neonatal hepatic failure, some functional data to support variant pathogenicity. Note mono-allelic variants in this gene are associated with PEO phenotype, but onset and severity are highly variable including reports of childhood manifestations with liver dysfunction.
Sources: Expert list
Liver Failure_Paediatric v0.71 SH2D1A Zornitza Stark Marked gene: SH2D1A as ready
Liver Failure_Paediatric v0.71 SH2D1A Zornitza Stark Gene: sh2d1a has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.71 SH2D1A Zornitza Stark Classified gene: SH2D1A as Green List (high evidence)
Liver Failure_Paediatric v0.71 SH2D1A Zornitza Stark Gene: sh2d1a has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.70 SH2D1A Zornitza Stark gene: SH2D1A was added
gene: SH2D1A was added to Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: SH2D1A was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: SH2D1A were set to 6306053; 9771704
Phenotypes for gene: SH2D1A were set to Lymphoproliferative syndrome, X-linked, 1, MIM# 308240
Review for gene: SH2D1A was set to GREEN
Added comment: A primary immunodeficiency characterized by severe immune dysregulation often after viral infection, typically with Epstein-Barr virus (EBV). It is a complex phenotype manifest as severe or fatal mononucleosis, acquired hypogammaglobulinema, hemophagocytic lymphohistiocytosis (HLH), and/or malignant lymphoma. Other features may include aplastic anemia, red cell aplasia, and lymphomatoid granulomatosis. Liver dysfunction, hepatic necrosis and liver failure reported.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.3130 TKFC Zornitza Stark Phenotypes for gene: TKFC were changed from Developmental delay; cataracts; liver dysfunction to Triokinase and FMN cyclase deficiency syndrome, MIM#618805; Developmental delay; cataracts; liver dysfunction
Intellectual disability syndromic and non-syndromic v0.3129 TKFC Zornitza Stark edited their review of gene: TKFC: Changed phenotypes: Triokinase and FMN cyclase deficiency syndrome, MIM#618805, Developmental delay, cataracts, liver dysfunction
Mendeliome v0.5231 TKFC Zornitza Stark Phenotypes for gene: TKFC were changed from Developmental delay; cataracts; liver dysfunction to Triokinase and FMN cyclase deficiency syndrome, MIM#618805; Developmental delay; cataracts; liver dysfunction
Mendeliome v0.5230 TKFC Zornitza Stark edited their review of gene: TKFC: Changed phenotypes: Triokinase and FMN cyclase deficiency syndrome, MIM#618805, Developmental delay, cataracts, liver dysfunction
Cataract v0.239 TKFC Zornitza Stark edited their review of gene: TKFC: Changed phenotypes: Triokinase and FMN cyclase deficiency syndrome, MIM#618805, Developmental delay, cataracts, liver dysfunction
Cataract v0.239 TKFC Zornitza Stark Phenotypes for gene: TKFC were changed from Developmental delay; cataracts; liver dysfunction to Triokinase and FMN cyclase deficiency syndrome, MIM#618805; Developmental delay; cataracts; liver dysfunction
Liver Failure_Paediatric v0.69 TKFC Zornitza Stark Marked gene: TKFC as ready
Liver Failure_Paediatric v0.69 TKFC Zornitza Stark Gene: tkfc has been classified as Amber List (Moderate Evidence).
Liver Failure_Paediatric v0.69 TKFC Zornitza Stark Classified gene: TKFC as Amber List (moderate evidence)
Liver Failure_Paediatric v0.69 TKFC Zornitza Stark Gene: tkfc has been classified as Amber List (Moderate Evidence).
Liver Failure_Paediatric v0.68 TKFC Zornitza Stark gene: TKFC was added
gene: TKFC was added to Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: TKFC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TKFC were set to 32004446
Phenotypes for gene: TKFC were set to Triokinase and FMN cyclase deficiency syndrome, MIM#618805; Developmental delay; cataracts; liver dysfunction
Review for gene: TKFC was set to AMBER
Added comment: Two unrelated families reported. Liver dysfunction, including liver failure in one.
Sources: Expert list
Liver Failure_Paediatric v0.67 ATP6AP1 Zornitza Stark Marked gene: ATP6AP1 as ready
Liver Failure_Paediatric v0.67 ATP6AP1 Zornitza Stark Gene: atp6ap1 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.67 ATP6AP1 Zornitza Stark Classified gene: ATP6AP1 as Green List (high evidence)
Liver Failure_Paediatric v0.67 ATP6AP1 Zornitza Stark Gene: atp6ap1 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.66 ATP6AP1 Zornitza Stark gene: ATP6AP1 was added
gene: ATP6AP1 was added to Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: ATP6AP1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: ATP6AP1 were set to 27231034; 32216104; 32058063; 29192153
Phenotypes for gene: ATP6AP1 were set to Immunodeficiency 47, MIM# 300972
Review for gene: ATP6AP1 was set to GREEN
Added comment: X-linked recessive complex syndrome characterized by liver dysfunction, recurrent bacterial infections, hypogammaglobulinemia, and defective glycosylation of serum proteins. Liver failure reported.
Sources: Expert list
Liver Failure_Paediatric v0.65 IL18BP Zornitza Stark Marked gene: IL18BP as ready
Liver Failure_Paediatric v0.65 IL18BP Zornitza Stark Gene: il18bp has been classified as Red List (Low Evidence).
Liver Failure_Paediatric v0.65 IL18BP Zornitza Stark gene: IL18BP was added
gene: IL18BP was added to Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: IL18BP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IL18BP were set to 31213488
Phenotypes for gene: IL18BP were set to {?Hepatitis, fulminant viral, susceptibility to} 618549
Review for gene: IL18BP was set to RED
Added comment: Single individual reported with homozygous 40bp deletion in this gene and fulminant Hep A hepatitis.
Sources: Expert list
Mendeliome v0.5230 PRKAR1B Zornitza Stark Marked gene: PRKAR1B as ready
Mendeliome v0.5230 PRKAR1B Zornitza Stark Gene: prkar1b has been classified as Green List (High Evidence).
Mendeliome v0.5230 PRKAR1B Zornitza Stark Classified gene: PRKAR1B as Green List (high evidence)
Mendeliome v0.5230 PRKAR1B Zornitza Stark Gene: prkar1b has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3129 PRKAR1B Zornitza Stark Marked gene: PRKAR1B as ready
Intellectual disability syndromic and non-syndromic v0.3129 PRKAR1B Zornitza Stark Gene: prkar1b has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3129 PRKAR1B Zornitza Stark Classified gene: PRKAR1B as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.3129 PRKAR1B Zornitza Stark Gene: prkar1b has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.64 TFAM Zornitza Stark Marked gene: TFAM as ready
Liver Failure_Paediatric v0.64 TFAM Zornitza Stark Gene: tfam has been classified as Amber List (Moderate Evidence).
Liver Failure_Paediatric v0.64 TFAM Zornitza Stark Classified gene: TFAM as Amber List (moderate evidence)
Liver Failure_Paediatric v0.64 TFAM Zornitza Stark Gene: tfam has been classified as Amber List (Moderate Evidence).
Liver Failure_Paediatric v0.63 TFAM Zornitza Stark gene: TFAM was added
gene: TFAM was added to Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: TFAM was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TFAM were set to 27448789; 29021295; 9500544
Phenotypes for gene: TFAM were set to Mitochondrial DNA depletion syndrome 15 (hepatocerebral type) MIM#617156
Review for gene: TFAM was set to AMBER
Added comment: Two sibs from one consanguineous family presenting with severe progressive liver disease and segregating a homozygous variant. Tfam knockout mouse has a mitochondrial cardiomyopathy phenotype and severe mtDNA depletion with abolished oxidative phosphorylation.
Sources: Expert list
Liver Failure_Paediatric v0.62 COQ2 Zornitza Stark Marked gene: COQ2 as ready
Liver Failure_Paediatric v0.62 COQ2 Zornitza Stark Gene: coq2 has been classified as Red List (Low Evidence).
Liver Failure_Paediatric v0.62 COQ2 Zornitza Stark gene: COQ2 was added
gene: COQ2 was added to Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: COQ2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COQ2 were set to 17332895
Phenotypes for gene: COQ2 were set to Coenzyme Q10 deficiency, primary, 1, MIM#607426
Review for gene: COQ2 was set to RED
Added comment: Manifestations of this disorder are principally encephalomyopathic and renal, however at least one report of liver failure.
Sources: Expert list
Liver Failure_Paediatric v0.61 SERAC1 Zornitza Stark Marked gene: SERAC1 as ready
Liver Failure_Paediatric v0.61 SERAC1 Zornitza Stark Gene: serac1 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.61 SERAC1 Zornitza Stark Classified gene: SERAC1 as Green List (high evidence)
Liver Failure_Paediatric v0.61 SERAC1 Zornitza Stark Gene: serac1 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.60 SERAC1 Zornitza Stark gene: SERAC1 was added
gene: SERAC1 was added to Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: SERAC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SERAC1 were set to 29205472
Phenotypes for gene: SERAC1 were set to 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome, MIM# 614739
Review for gene: SERAC1 was set to GREEN
Added comment: Autosomal recessive disorder characterized by childhood onset of delayed psychomotor development or psychomotor regression, sensorineural deafness, spasticity or dystonia, and increased excretion of 3-methylglutaconic acid. About 50% develop severe, but transient, liver dysfunction and/or signs of liver failure, in the neonatal period or during the first year of life.

More than 50 unrelated families reported.
Sources: Expert list
Liver Failure_Paediatric v0.59 ABCD3 Zornitza Stark Marked gene: ABCD3 as ready
Liver Failure_Paediatric v0.59 ABCD3 Zornitza Stark Gene: abcd3 has been classified as Amber List (Moderate Evidence).
Liver Failure_Paediatric v0.59 ABCD3 Zornitza Stark Classified gene: ABCD3 as Amber List (moderate evidence)
Liver Failure_Paediatric v0.59 ABCD3 Zornitza Stark Gene: abcd3 has been classified as Amber List (Moderate Evidence).
Liver Failure_Paediatric v0.58 ABCD3 Zornitza Stark gene: ABCD3 was added
gene: ABCD3 was added to Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: ABCD3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ABCD3 were set to 25168382
Phenotypes for gene: ABCD3 were set to Bile acid synthesis defect, congenital, 5 (MIM#616278)
Review for gene: ABCD3 was set to AMBER
Added comment: Single individual reported in 2015. Evidence of a bile acid biosynthesis defect in both the affected individual and knock out mice.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.3128 PRKAR1B Konstantinos Varvagiannis edited their review of gene: PRKAR1B: Changed publications: https://doi.org/10.1101/2020.09.10.20190314, 25414040
Mendeliome v0.5229 PRKAR1B Konstantinos Varvagiannis gene: PRKAR1B was added
gene: PRKAR1B was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PRKAR1B was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PRKAR1B were set to https://doi.org/10.1101/2020.09.10.20190314; 25414040
Phenotypes for gene: PRKAR1B were set to Global developmental delay; Intellectual disability; Autism; Attention deficit hyperactivity disorder; Aggressive behavior; Abnormality of movement; Upslanted palpebral fissure
Penetrance for gene: PRKAR1B were set to unknown
Review for gene: PRKAR1B was set to AMBER
Added comment: Please consider inclusion of this gene with amber rating pending publication of the preprint and/or additional evidence.

Marbach et al. (2020 - medRxiv : https://doi.org/10.1101/2020.09.10.20190314 - last author : C. Schaaf) report 6 unrelated individuals with heterozygous missense PRKAR1B variants.

All presented formal ASD diagnosis (6/6), global developmental delay (6/6) and intellectual disability (all - formal evaluations were lacking though). Additional features included neurologic anomalies (movement disorders : dyspraxia, apraxia, clumsiness in all, with tremor/dystonia or involuntary movements as single occurrences). Three displayed high pain tolerance. Regression in speech was a feature in two. Additional behavior anomalies included ADHD (4-5/6) or aggression (3/6). There was no consistent pattern of malformations, physical anomalies or facial features (with the exception of uplsanted palpebral fissures reported in 4).

3 different missense variants were identified (NM_00116470:c.1003C>T - p.Arg335Trp, c.586G>A - p.Glu196Lys, c.500_501delAAinsTT - p.Gln167Leu) with Arg355Trp being a recurrent one within this cohort (4/6 subjects). A possible splicing effect may apply for the MNV. All variants are absent from gnomAD and the SNVs had CADD scores > 24.

In all cases were parental samples were available (5/6), the variant had occurred as a de novo event.

Protein kinase A (PKA) is a tetrameric holoenzyme formed by the association of 2 catalytic (C) subunits with a regulatory (R) subunit dimer. Activation of PKA is achieved through binding of 2 cAMP molecules to each R-subunit, and unleashing(/dissociation) of C-subunits to engage substrates. PRKACA/B genes encode the Cα- and Cβ-subunits while the 4 functionally non-redundant regulatory subunits are encoded by PRKAR1A/1B/2A/2B genes. As the authors comment, the RIβ subunit is primarily expressed in brain with higher expression in cortex and hypothalamus.

The functional consequences of the variants at cellular level were not studied.

Previous studies have demonstrated that downregulation of RIβ in murine hippocampal cultures, reduced phosphorylation of CREB, a transcription factor involved in long-term memory formation. The authors speculate that a similar effect on cAMP/PKA/CREB cascade may mediate the cognitive effects in humans. RIβ deficient mice also display diminished nociceptive pain, similar to the human phenotype. [Several refs provided].

The authors cite the study by Kaplanis et al (2020 - PMID: 33057194), where in a large sample of 31,058 trio exomes of children with developmental disorders, PRKAR1B was among the genes with significant enrichment for de novo missense variants. [The gene has a pLI score of 0.18 in gnomAD / o/e = 0.26 - so pLoF variants may not be deleterious].

Please note that a specific PRKAR1B variant (NM_002735.2:c.149T>G - p.Leu50Arg) has been previous reported to segregate with a late-onset neurodegenerative disorder characterized by dementia and/or parkinsonism within a large pedigree with 12 affected individuals [Wong et al 2014 - PMID: 25414040].
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3128 PRKAR1B Konstantinos Varvagiannis gene: PRKAR1B was added
gene: PRKAR1B was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: PRKAR1B was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PRKAR1B were set to https://doi.org/10.1101/2020.09.10.20190314; 33057194
Phenotypes for gene: PRKAR1B were set to Global developmental delay; Intellectual disability; Autism; Attention deficit hyperactivity disorder; Aggressive behavior; Abnormality of movement; Upslanted palpebral fissure
Penetrance for gene: PRKAR1B were set to unknown
Review for gene: PRKAR1B was set to AMBER
Added comment: Please consider inclusion of this gene with amber rating pending publication of the preprint and/or additional evidence.

Marbach et al. (2020 - medRxiv : https://doi.org/10.1101/2020.09.10.20190314 - last author : C. Schaaf) report 6 unrelated individuals with heterozygous missense PRKAR1B variants.

All presented formal ASD diagnosis (6/6), global developmental delay (6/6) and intellectual disability (all - formal evaluations were lacking though). Additional features included neurologic anomalies (movement disorders : dyspraxia, apraxia, clumsiness in all, with tremor/dystonia or involuntary movements as single occurrences). Three displayed high pain tolerance. Regression in speech was a feature in two. Additional behavior anomalies included ADHD (4-5/6) or aggression (3/6). There was no consistent pattern of malformations, physical anomalies or facial features (with the exception of uplsanted palpebral fissures reported in 4).

3 different missense variants were identified (NM_00116470:c.1003C>T - p.Arg335Trp, c.586G>A - p.Glu196Lys, c.500_501delAAinsTT - p.Gln167Leu) with Arg355Trp being a recurrent one within this cohort (4/6 subjects). A possible splicing effect may apply for the MNV. All variants are absent from gnomAD and the SNVs had CADD scores > 24.

In all cases were parental samples were available (5/6), the variant had occurred as a de novo event.

Protein kinase A (PKA) is a tetrameric holoenzyme formed by the association of 2 catalytic (C) subunits with a regulatory (R) subunit dimer. Activation of PKA is achieved through binding of 2 cAMP molecules to each R-subunit, and unleashing(/dissociation) of C-subunits to engage substrates. PRKACA/B genes encode the Cα- and Cβ-subunits while the 4 functionally non-redundant regulatory subunits are encoded by PRKAR1A/1B/2A/2B genes. As the authors comment, the RIβ subunit is primarily expressed in brain with higher expression in cortex and hypothalamus.

The functional consequences of the variants at cellular level were not studied.

Previous studies have demonstrated that downregulation of RIβ in murine hippocampal cultures, reduced phosphorylation of CREB, a transcription factor involved in long-term memory formation. The authors speculate that a similar effect on cAMP/PKA/CREB cascade may mediate the cognitive effects in humans. RIβ deficient mice also display diminished nociceptive pain, similar to the human phenotype. [Several refs provided].

The authors cite the study by Kaplanis et al (2020 - PMID: 33057194), where in a large sample of 31,058 trio exomes of children with developmental disorders, PRKAR1B was among the genes with significant enrichment for de novo missense variants. [The gene has a pLI score of 0.18 in gnomAD / o/e = 0.26 - so pLoF variants may not be deleterious].

Please note that a specific PRKAR1B variant (NM_002735.2:c.149T>G - p.Leu50Arg) has been previous reported to segregate with a late-onset neurodegenerative disorder characterized by dementia and/or parkinsonism within a large pedigree with 12 affected individuals [Wong et al 2014 - PMID: 25414040].
Sources: Literature
Liver Failure_Paediatric v0.57 GFM1 Zornitza Stark Marked gene: GFM1 as ready
Liver Failure_Paediatric v0.57 GFM1 Zornitza Stark Gene: gfm1 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.57 GFM1 Zornitza Stark Classified gene: GFM1 as Green List (high evidence)
Liver Failure_Paediatric v0.57 GFM1 Zornitza Stark Gene: gfm1 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.56 GFM1 Zornitza Stark gene: GFM1 was added
gene: GFM1 was added to Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: GFM1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GFM1 were set to 31680380; 23430926
Phenotypes for gene: GFM1 were set to Combined oxidative phosphorylation deficiency 1, MIM# 609060
Review for gene: GFM1 was set to GREEN
Added comment: Multi-system mitochondrial disorder, predominantly neurological features with or without hepatic involvement. Liver failure reported.
Sources: Expert list
Mendeliome v0.5229 NR1H4 Zornitza Stark Marked gene: NR1H4 as ready
Mendeliome v0.5229 NR1H4 Zornitza Stark Gene: nr1h4 has been classified as Green List (High Evidence).
Mendeliome v0.5229 NR1H4 Zornitza Stark Phenotypes for gene: NR1H4 were changed from to Cholestasis, progressive familial intrahepatic, 5, MIM# 617049
Mendeliome v0.5228 NR1H4 Zornitza Stark Publications for gene: NR1H4 were set to
Mendeliome v0.5227 NR1H4 Zornitza Stark Mode of inheritance for gene: NR1H4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5226 NR1H4 Zornitza Stark reviewed gene: NR1H4: Rating: GREEN; Mode of pathogenicity: None; Publications: 26888176, 32443034; Phenotypes: Cholestasis, progressive familial intrahepatic, 5, MIM# 617049; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cholestasis v0.186 NR1H4 Zornitza Stark Marked gene: NR1H4 as ready
Cholestasis v0.186 NR1H4 Zornitza Stark Gene: nr1h4 has been classified as Green List (High Evidence).
Cholestasis v0.186 NR1H4 Zornitza Stark Phenotypes for gene: NR1H4 were changed from to Cholestasis, progressive familial intrahepatic, 5, MIM# 617049
Cholestasis v0.185 NR1H4 Zornitza Stark Publications for gene: NR1H4 were set to
Cholestasis v0.184 NR1H4 Zornitza Stark Mode of inheritance for gene: NR1H4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Cholestasis v0.183 NR1H4 Zornitza Stark reviewed gene: NR1H4: Rating: GREEN; Mode of pathogenicity: None; Publications: 26888176, 32443034; Phenotypes: Cholestasis, progressive familial intrahepatic, 5, MIM# 617049; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Liver Failure_Paediatric v0.55 NR1H4 Zornitza Stark Marked gene: NR1H4 as ready
Liver Failure_Paediatric v0.55 NR1H4 Zornitza Stark Gene: nr1h4 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.55 NR1H4 Zornitza Stark Classified gene: NR1H4 as Green List (high evidence)
Liver Failure_Paediatric v0.55 NR1H4 Zornitza Stark Gene: nr1h4 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.54 NR1H4 Zornitza Stark gene: NR1H4 was added
gene: NR1H4 was added to Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: NR1H4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NR1H4 were set to 26888176; 32443034
Phenotypes for gene: NR1H4 were set to Cholestasis, progressive familial intrahepatic, 5, MIM# 617049
Review for gene: NR1H4 was set to GREEN
Added comment: Autosomal recessive severe liver disorder characterized by onset of intralobular cholestasis in the neonatal period. The disease is rapidly progressive, leading to liver failure and death if liver transplant is not performed. Other features include abnormal liver enzymes, low to normal gamma-glutamyl transferase (GGT) activity, increased alpha-fetoprotein, and a vitamin K-independent coagulopathy.

At least 5 unrelated families reported.
Sources: Expert list
Liver Failure_Paediatric v0.53 JAG1 Zornitza Stark Marked gene: JAG1 as ready
Liver Failure_Paediatric v0.53 JAG1 Zornitza Stark Gene: jag1 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.53 JAG1 Zornitza Stark Classified gene: JAG1 as Green List (high evidence)
Liver Failure_Paediatric v0.53 JAG1 Zornitza Stark Gene: jag1 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.52 JAG1 Zornitza Stark gene: JAG1 was added
gene: JAG1 was added to Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: JAG1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: JAG1 were set to Alagille syndrome, MIM# 118450
Review for gene: JAG1 was set to GREEN
Added comment: Well established gene disease association. Severity of liver disease is variable but includes progressive liver failure.
Sources: Expert list
Mendeliome v0.5226 PTF1A Zornitza Stark Marked gene: PTF1A as ready
Mendeliome v0.5226 PTF1A Zornitza Stark Gene: ptf1a has been classified as Green List (High Evidence).
Mendeliome v0.5226 PTF1A Zornitza Stark Phenotypes for gene: PTF1A were changed from to Pancreatic agenesis 2, MIM# 615935; Pancreatic and cerebellar agenesis, MIM# 609069
Mendeliome v0.5225 PTF1A Zornitza Stark Publications for gene: PTF1A were set to
Mendeliome v0.5224 PTF1A Zornitza Stark Mode of inheritance for gene: PTF1A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5223 PTF1A Zornitza Stark reviewed gene: PTF1A: Rating: GREEN; Mode of pathogenicity: None; Publications: 24212882, 21749365, 10507728, 15543146, 19650412; Phenotypes: Pancreatic agenesis 2, MIM# 615935, Pancreatic and cerebellar agenesis, MIM# 609069; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Liver Failure_Paediatric v0.51 PTF1A Zornitza Stark Marked gene: PTF1A as ready
Liver Failure_Paediatric v0.51 PTF1A Zornitza Stark Gene: ptf1a has been classified as Red List (Low Evidence).
Liver Failure_Paediatric v0.51 PTF1A Zornitza Stark gene: PTF1A was added
gene: PTF1A was added to Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: PTF1A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PTF1A were set to 24212882
Phenotypes for gene: PTF1A were set to Pancreatic agenesis 2, MIM# 615935
Review for gene: PTF1A was set to RED
Added comment: 14 affected individuals from 10 families with isolated pancreatic hypoplasia or agenesis reported. Patients were typically diagnosed with insulin-dependent diabetes mellitus at birth or in infancy, although 2 individuals were diagnosed at ages 8 and 10 years, respectively, and 1 at 22 years of age. All patients also had pancreatic exocrine insufficiency, with low or undetectable stool elastase in all who were tested. Pancreatic hypoplasia or agenesis was documented by ultrasound, CT, or MRI in the 9 patients studied. No neurologic features were reported, except for 1 patient who exhibited mild developmental delay, and no other abnormalities were reported, except for 1 patient who had fatal cholestatic liver failure
Sources: Expert list
Liver Failure_Paediatric v0.50 FH Zornitza Stark Marked gene: FH as ready
Liver Failure_Paediatric v0.50 FH Zornitza Stark Gene: fh has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.50 FH Zornitza Stark Phenotypes for gene: FH were changed from to Fumarase deficiency, MIM#606812
Liver Failure_Paediatric v0.49 FH Zornitza Stark Classified gene: FH as Green List (high evidence)
Liver Failure_Paediatric v0.49 FH Zornitza Stark Gene: fh has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.48 FH Zornitza Stark edited their review of gene: FH: Changed phenotypes: Fumarase deficiency, MIM#606812
Liver Failure_Paediatric v0.48 FH Zornitza Stark gene: FH was added
gene: FH was added to Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: FH was set to BIALLELIC, autosomal or pseudoautosomal
Review for gene: FH was set to GREEN
Added comment: Autosomal recessive metabolic disorder characterized by early-onset hypotonia, profound psychomotor retardation, and brain abnormalities, such as agenesis of the corpus callosum, gyral defects, and ventriculomegaly. Many patients show neonatal distress, metabolic acidosis, and/or encephalopathy. Cholestasis, liver fibrosis and failure reported.
Sources: Expert list
Mendeliome v0.5223 MPP5 Zornitza Stark Marked gene: MPP5 as ready
Mendeliome v0.5223 MPP5 Zornitza Stark Gene: mpp5 has been classified as Green List (High Evidence).
Mendeliome v0.5223 MPP5 Zornitza Stark Classified gene: MPP5 as Green List (high evidence)
Mendeliome v0.5223 MPP5 Zornitza Stark Gene: mpp5 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3128 MPP5 Zornitza Stark Marked gene: MPP5 as ready
Intellectual disability syndromic and non-syndromic v0.3128 MPP5 Zornitza Stark Gene: mpp5 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3128 MPP5 Zornitza Stark Classified gene: MPP5 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.3128 MPP5 Zornitza Stark Gene: mpp5 has been classified as Green List (High Evidence).
Mendeliome v0.5222 MPP5 Konstantinos Varvagiannis gene: MPP5 was added
gene: MPP5 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MPP5 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: MPP5 were set to 33073849
Phenotypes for gene: MPP5 were set to Global developmental delay; Intellectual disability; Delayed speech and language development; Developmental regression; Behavioral abnormality
Penetrance for gene: MPP5 were set to unknown
Review for gene: MPP5 was set to GREEN
Added comment: Sterling et al (2020 - PMID: 33073849) provide information on the phenotype of 3 individuals with de novo MPP5 variants.

Common features included global developmental delay, intellectual disability (3/3 - severe in 2/3), speech delay/regression (the latter in at least 2) and behavioral abnormalities. Variable other features were reported, among others microcephaly (1/3), abnormal vision (1/3 : CVI, retinal dystrophy, nystagmus), brain MRI abnormalities (2/3), late-onset seizures (1/3). These subjects displayed variable and non-specific dysmorphic features.

All were investigated by exome sequencing (previous investigations not mentioned).

One subject was found to harbor a de novo mosaic (5/25 reads) stopgain variant, further confirmed by Sanger sequencing [NM_022474.4:c.1555C>T - p.(Arg519Ter). The specific variant is reported once in gnomAD (1/251338). Two de novo missense variants were identified in the remaining individuals [c.1289A>G - p.Glu430Gly / c.974A>C - p.His325Pro). All variants had in silico predictions in favor of a deleterious effect (CADD score >24).

The authors comment that MPP5 encodes an apical complex protein with asymmetric localization to the apical side of polarized cells. It is expressed in brain, peripheral nervous system and other tissues. MPP5 is a member of the membrane-associated guanylate kinase family of proteins (MAGUK p55 subfamily), determining cell polarity at tight junctions.

Previous animal models suggest that complete Mpp5(Pals1) KO in mice leads to near absence of cerebral cortical neurons. Htz KO display reduction in size of cerebral cortex and hippocampus. The gene is expressed in proliferating cell populations of cerebellum and important for establishment cerebellar architecture. Conditional KO of Mpp5(Pals1) in retinal progenitor cells mimics the retinal pathology observed in LCA. [Several refs. provided]

The authors studied a heterozygous CNS-specific Mpp5 KO mouse model. These mice presented microcephaly, decreased cerebellar volume and cortical thickness, decreased ependymal cells and Mpp5 at the apical surface of cortical vertrical zone. The proportion of cortical cells undergoing apoptotic cell death was increased. Mice displayed behavioral abnormalities (hyperactivity) and visual deficits, with ERG traces further suggesting retinal blindness.

Overall the mouse model was thought to recapitulate the behavioral abnormalities observed in affected subjects as well as individual rare features such as microcephaly and abnormal vision.

Haploinsufficiency (rather than a dominant negative effect) is favored as the underlying disease mechanism. This is also in line with a dose dependent effect observed in mice.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3127 MPP5 Konstantinos Varvagiannis gene: MPP5 was added
gene: MPP5 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: MPP5 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: MPP5 were set to 33073849
Phenotypes for gene: MPP5 were set to Global developmental delay; Intellectual disability; Delayed speech and language development; Developmental regression; Behavioral abnormality
Penetrance for gene: MPP5 were set to unknown
Review for gene: MPP5 was set to GREEN
Added comment: Sterling et al (2020 - PMID: 33073849) provide information on the phenotype of 3 individuals with de novo MPP5 variants.

Common features included global developmental delay, intellectual disability (3/3 - severe in 2/3), speech delay/regression (the latter in at least 2) and behavioral abnormalities. Variable other features were reported, among others microcephaly (1/3), abnormal vision (1/3 : CVI, retinal dystrophy, nystagmus), brain MRI abnormalities (2/3), late-onset seizures (1/3). These subjects displayed variable and non-specific dysmorphic features.

All were investigated by exome sequencing (previous investigations not mentioned).

One subject was found to harbor a de novo mosaic (5/25 reads) stopgain variant, further confirmed by Sanger sequencing [NM_022474.4:c.1555C>T - p.(Arg519Ter). The specific variant is reported once in gnomAD (1/251338). Two de novo missense variants were identified in the remaining individuals [c.1289A>G - p.Glu430Gly / c.974A>C - p.His325Pro). All variants had in silico predictions in favor of a deleterious effect (CADD score >24).

The authors comment that MPP5 encodes an apical complex protein with asymmetric localization to the apical side of polarized cells. It is expressed in brain, peripheral nervous system and other tissues. MPP5 is a member of the membrane-associated guanylate kinase family of proteins (MAGUK p55 subfamily), determining cell polarity at tight junctions.

Previous animal models suggest that complete Mpp5(Pals1) KO in mice leads to near absence of cerebral cortical neurons. Htz KO display reduction in size of cerebral cortex and hippocampus. The gene is expressed in proliferating cell populations of cerebellum and important for establishment cerebellar architecture. Conditional KO of Mpp5(Pals1) in retinal progenitor cells mimics the retinal pathology observed in LCA. [Several refs. provided]

The authors studied a heterozygous CNS-specific Mpp5 KO mouse model. These mice presented microcephaly, decreased cerebellar volume and cortical thickness, decreased ependymal cells and Mpp5 at the apical surface of cortical vertrical zone. The proportion of cortical cells undergoing apoptotic cell death was increased. Mice displayed behavioral abnormalities (hyperactivity) and visual deficits, with ERG traces further suggesting retinal blindness.

Overall the mouse model was thought to recapitulate the behavioral abnormalities observed in affected subjects as well as individual rare features such as microcephaly and abnormal vision.

Haploinsufficiency (rather than a dominant negative effect) is favored as the underlying disease mechanism. This is also in line with a dose dependent effect observed in mice.
Sources: Literature
Liver Failure_Paediatric v0.47 TALDO1 Zornitza Stark Marked gene: TALDO1 as ready
Liver Failure_Paediatric v0.47 TALDO1 Zornitza Stark Gene: taldo1 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.47 TALDO1 Zornitza Stark Classified gene: TALDO1 as Green List (high evidence)
Liver Failure_Paediatric v0.47 TALDO1 Zornitza Stark Gene: taldo1 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.46 TALDO1 Zornitza Stark gene: TALDO1 was added
gene: TALDO1 was added to Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: TALDO1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TALDO1 were set to 29923087; 23315216; 26238251; 18331807
Phenotypes for gene: TALDO1 were set to Transaldolase deficiency, MIM#606003
Review for gene: TALDO1 was set to GREEN
Added comment: Typical features include intrauterine growth restriction, triangular face, loose wrinkly skin at birth, and development of progressive liver failure. More than 5 unrelated families reported.
Sources: Expert list
Cholestasis v0.183 AKR1D1 Zornitza Stark Marked gene: AKR1D1 as ready
Cholestasis v0.183 AKR1D1 Zornitza Stark Gene: akr1d1 has been classified as Green List (High Evidence).
Cholestasis v0.183 AKR1D1 Zornitza Stark Phenotypes for gene: AKR1D1 were changed from to Bile acid synthesis defect, congenital, 2, MIM# 235555
Cholestasis v0.182 AKR1D1 Zornitza Stark Publications for gene: AKR1D1 were set to
Cholestasis v0.181 AKR1D1 Zornitza Stark Mode of inheritance for gene: AKR1D1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Cholestasis v0.180 AKR1D1 Zornitza Stark reviewed gene: AKR1D1: Rating: GREEN; Mode of pathogenicity: None; Publications: 12970144, 20522910; Phenotypes: Bile acid synthesis defect, congenital, 2, MIM# 235555; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5222 AKR1D1 Zornitza Stark Marked gene: AKR1D1 as ready
Mendeliome v0.5222 AKR1D1 Zornitza Stark Gene: akr1d1 has been classified as Green List (High Evidence).
Mendeliome v0.5222 AKR1D1 Zornitza Stark Phenotypes for gene: AKR1D1 were changed from to Bile acid synthesis defect, congenital, 2, MIM# 235555
Mendeliome v0.5221 AKR1D1 Zornitza Stark Publications for gene: AKR1D1 were set to
Mendeliome v0.5220 AKR1D1 Zornitza Stark Mode of inheritance for gene: AKR1D1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5219 AKR1D1 Zornitza Stark reviewed gene: AKR1D1: Rating: GREEN; Mode of pathogenicity: None; Publications: 12970144, 20522910; Phenotypes: Bile acid synthesis defect, congenital, 2, MIM# 235555; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Liver Failure_Paediatric v0.45 AKR1D1 Zornitza Stark Publications for gene: AKR1D1 were set to 12970144
Liver Failure_Paediatric v0.44 AKR1D1 Zornitza Stark edited their review of gene: AKR1D1: Changed publications: 12970144, 20522910; Changed phenotypes: Bile acid synthesis defect, congenital, 2, MIM# 235555
Liver Failure_Paediatric v0.44 AKR1D1 Zornitza Stark Marked gene: AKR1D1 as ready
Liver Failure_Paediatric v0.44 AKR1D1 Zornitza Stark Gene: akr1d1 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.44 AKR1D1 Zornitza Stark Classified gene: AKR1D1 as Green List (high evidence)
Liver Failure_Paediatric v0.44 AKR1D1 Zornitza Stark Gene: akr1d1 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.43 AKR1D1 Zornitza Stark gene: AKR1D1 was added
gene: AKR1D1 was added to Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: AKR1D1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AKR1D1 were set to 12970144
Phenotypes for gene: AKR1D1 were set to Bile acid synthesis defect, congenital, 2, MIM# 235555
Review for gene: AKR1D1 was set to GREEN
Added comment: Severe intrahepatic cholestasis progressing to liver failure. More than 3 unrelated families reported.
Sources: Expert list
Liver Failure_Paediatric v0.42 SLC25A13 Zornitza Stark Marked gene: SLC25A13 as ready
Liver Failure_Paediatric v0.42 SLC25A13 Zornitza Stark Gene: slc25a13 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.42 SLC25A13 Zornitza Stark Classified gene: SLC25A13 as Green List (high evidence)
Liver Failure_Paediatric v0.42 SLC25A13 Zornitza Stark Gene: slc25a13 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.41 SLC25A13 Zornitza Stark gene: SLC25A13 was added
gene: SLC25A13 was added to Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: SLC25A13 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC25A13 were set to 21424115; 11343052
Phenotypes for gene: SLC25A13 were set to Citrullinemia, type II, neonatal-onset, MIM# 605814
Review for gene: SLC25A13 was set to GREEN
Added comment: Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) is an autosomal recessive metabolic disorder characterized by poor growth, intrahepatic cholestasis, and increased serum citrulline. Most individuals show spontaneous improvement by 1 year of age. However, some individuals may have a progressive course with continued failure to thrive and dyslipidemia caused by citrin deficiency (FTTDCD), and some may develop chronic or fatal liver disease.

Well established gene-disease association.
Sources: Expert list
Mendeliome v0.5219 SCYL1 Zornitza Stark Marked gene: SCYL1 as ready
Mendeliome v0.5219 SCYL1 Zornitza Stark Gene: scyl1 has been classified as Green List (High Evidence).
Mendeliome v0.5219 SCYL1 Zornitza Stark Phenotypes for gene: SCYL1 were changed from to Spinocerebellar ataxia, autosomal recessive 21, MIM# 616719
Mendeliome v0.5218 SCYL1 Zornitza Stark Publications for gene: SCYL1 were set to
Mendeliome v0.5217 SCYL1 Zornitza Stark Mode of inheritance for gene: SCYL1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5216 SCYL1 Zornitza Stark Deleted their comment
Mendeliome v0.5216 SCYL1 Zornitza Stark commented on gene: SCYL1: Autosomal recessive spinocerebellar ataxia-21 is a neurologic disorder characterized by onset of cerebellar ataxia associated with cerebellar atrophy in early childhood. Affected individuals also have recurrent episodes of liver failure in the first decade, resulting in chronic liver fibrosis, as well as later onset of a peripheral neuropathy. Mild learning disabilities may also occur. More than 5 unrelated families reported.
Liver Failure_Paediatric v0.40 SCYL1 Zornitza Stark Marked gene: SCYL1 as ready
Liver Failure_Paediatric v0.40 SCYL1 Zornitza Stark Gene: scyl1 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.40 SCYL1 Zornitza Stark Classified gene: SCYL1 as Green List (high evidence)
Liver Failure_Paediatric v0.40 SCYL1 Zornitza Stark Gene: scyl1 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.39 SCYL1 Zornitza Stark gene: SCYL1 was added
gene: SCYL1 was added to Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: SCYL1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SCYL1 were set to 26581903; 29419818; 30531813
Phenotypes for gene: SCYL1 were set to Spinocerebellar ataxia, autosomal recessive 21, MIM#616719
Review for gene: SCYL1 was set to GREEN
Added comment: Autosomal recessive spinocerebellar ataxia-21 is a neurologic disorder characterized by onset of cerebellar ataxia associated with cerebellar atrophy in early childhood. Affected individuals also have recurrent episodes of liver failure in the first decade, resulting in chronic liver fibrosis, as well as later onset of a peripheral neuropathy. Mild learning disabilities may also occur.

More than 5 unrelated families reported.
Sources: Expert list
Pulmonary Fibrosis_Interstitial Lung Disease v0.15 MARS Zornitza Stark Marked gene: MARS as ready
Pulmonary Fibrosis_Interstitial Lung Disease v0.15 MARS Zornitza Stark Gene: mars has been classified as Green List (High Evidence).
Pulmonary Fibrosis_Interstitial Lung Disease v0.15 MARS Zornitza Stark Classified gene: MARS as Green List (high evidence)
Pulmonary Fibrosis_Interstitial Lung Disease v0.15 MARS Zornitza Stark Gene: mars has been classified as Green List (High Evidence).
Pulmonary Fibrosis_Interstitial Lung Disease v0.14 MARS Zornitza Stark gene: MARS was added
gene: MARS was added to Pulmonary Fibrosis_Interstitial Lung Disease. Sources: Expert list
Mode of inheritance for gene: MARS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MARS were set to 24103465; 25913036
Phenotypes for gene: MARS were set to Interstitial lung and liver disease, MIM#615486
Review for gene: MARS was set to GREEN
Added comment: Autosomal recessive disorder characterized by onset of respiratory insufficiency and progressive liver disease in infancy or early childhood. More than 5 unrelated families reported. Founder variants in Reunion Island, p.Ser567Leu and p.Ala393Thr, in cis.

Pathologic examination of lung lavage is consistent with pulmonary alveolar proteinosis.
Sources: Expert list
Liver Failure_Paediatric v0.38 MARS Zornitza Stark Marked gene: MARS as ready
Liver Failure_Paediatric v0.38 MARS Zornitza Stark Gene: mars has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.38 MARS Zornitza Stark Classified gene: MARS as Green List (high evidence)
Liver Failure_Paediatric v0.38 MARS Zornitza Stark Gene: mars has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.37 MARS Zornitza Stark gene: MARS was added
gene: MARS was added to Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: MARS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MARS were set to 24103465; 25913036
Phenotypes for gene: MARS were set to Interstitial lung and liver disease, MIM#615486
Review for gene: MARS was set to GREEN
Added comment: Autosomal recessive disorder characterized by onset of respiratory insufficiency and progressive liver disease in infancy or early childhood.

More than 5 unrelated families reported. Founder variants in Reunion Island, p.Ser567Leu and p.Ala393Thr, in cis.
Sources: Expert list
Liver Failure_Paediatric v0.36 ATP7B Zornitza Stark Marked gene: ATP7B as ready
Liver Failure_Paediatric v0.36 ATP7B Zornitza Stark Gene: atp7b has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.36 ATP7B Zornitza Stark Classified gene: ATP7B as Green List (high evidence)
Liver Failure_Paediatric v0.36 ATP7B Zornitza Stark Gene: atp7b has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.35 ATP7B Zornitza Stark gene: ATP7B was added
gene: ATP7B was added to Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: ATP7B was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ATP7B were set to Wilson disease, MIM#277900
Review for gene: ATP7B was set to GREEN
Added comment: Well established gene-disease association. Can present with liver failure in childhood.
Sources: Expert list
Regression v0.205 SLC30A10 Zornitza Stark Marked gene: SLC30A10 as ready
Regression v0.205 SLC30A10 Zornitza Stark Gene: slc30a10 has been classified as Green List (High Evidence).
Regression v0.205 SLC30A10 Zornitza Stark Phenotypes for gene: SLC30A10 were changed from to Hypermanganesemia with dystonia 1, MIM# 613280
Regression v0.204 SLC30A10 Zornitza Stark Publications for gene: SLC30A10 were set to
Regression v0.203 SLC30A10 Zornitza Stark Mode of inheritance for gene: SLC30A10 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Regression v0.202 SLC30A10 Zornitza Stark reviewed gene: SLC30A10: Rating: GREEN; Mode of pathogenicity: None; Publications: 22341972, 22341971, 29193034; Phenotypes: Hypermanganesemia with dystonia 1, MIM# 613280; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5216 SLC30A10 Zornitza Stark Marked gene: SLC30A10 as ready
Mendeliome v0.5216 SLC30A10 Zornitza Stark Gene: slc30a10 has been classified as Green List (High Evidence).
Mendeliome v0.5216 SLC30A10 Zornitza Stark Phenotypes for gene: SLC30A10 were changed from to Hypermanganesemia with dystonia 1, MIM# 613280
Mendeliome v0.5215 SLC30A10 Zornitza Stark Publications for gene: SLC30A10 were set to
Mendeliome v0.5214 SLC30A10 Zornitza Stark Mode of inheritance for gene: SLC30A10 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5213 SLC30A10 Zornitza Stark reviewed gene: SLC30A10: Rating: GREEN; Mode of pathogenicity: None; Publications: 22341972, 22341971, 29193034; Phenotypes: Hypermanganesemia with dystonia 1, MIM# 613280; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Liver Failure_Paediatric v0.34 SLC30A10 Zornitza Stark Marked gene: SLC30A10 as ready
Liver Failure_Paediatric v0.34 SLC30A10 Zornitza Stark Gene: slc30a10 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.34 SLC30A10 Zornitza Stark Classified gene: SLC30A10 as Green List (high evidence)
Liver Failure_Paediatric v0.34 SLC30A10 Zornitza Stark Gene: slc30a10 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.33 SLC30A10 Zornitza Stark changed review comment from: autosomal recessive metabolic disorder characterized by increased serum manganese, motor neurodegeneration with extrapyramidal features, polycythemia, and hepatic dysfunction, which leads to cirrhosis in some cases. Intellectual function is preserved.

More than 10 unrelated families reported.
Sources: Expert list; to: Autosomal recessive metabolic disorder characterized by increased serum manganese, motor neurodegeneration with extrapyramidal features, polycythemia, and hepatic dysfunction, which leads to cirrhosis in some cases. Intellectual function is preserved.

More than 10 unrelated families reported.
Sources: Expert list
Liver Failure_Paediatric v0.33 SLC30A10 Zornitza Stark gene: SLC30A10 was added
gene: SLC30A10 was added to Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: SLC30A10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC30A10 were set to 22341972; 22341971; 29193034
Phenotypes for gene: SLC30A10 were set to Hypermanganesemia with dystonia 1, MIM# 613280
Review for gene: SLC30A10 was set to GREEN
Added comment: autosomal recessive metabolic disorder characterized by increased serum manganese, motor neurodegeneration with extrapyramidal features, polycythemia, and hepatic dysfunction, which leads to cirrhosis in some cases. Intellectual function is preserved.

More than 10 unrelated families reported.
Sources: Expert list
Liver Failure_Paediatric v0.32 Zornitza Stark Panel name changed from Acute Liver Failure_Paediatric to Liver Failure_Paediatric
Cholestasis v0.180 SLC27A5 Zornitza Stark Phenotypes for gene: SLC27A5 were changed from to Disorder of bile acid metabolism
Cholestasis v0.179 SLC27A5 Zornitza Stark edited their review of gene: SLC27A5: Changed phenotypes: Disorder of bile acid metabolism
Liver Failure_Paediatric v0.31 MPI Zornitza Stark Marked gene: MPI as ready
Liver Failure_Paediatric v0.31 MPI Zornitza Stark Gene: mpi has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.31 MPI Zornitza Stark Classified gene: MPI as Green List (high evidence)
Liver Failure_Paediatric v0.31 MPI Zornitza Stark Gene: mpi has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.30 MPI Zornitza Stark gene: MPI was added
gene: MPI was added to Acute Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: MPI was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MPI were set to 25902754
Phenotypes for gene: MPI were set to Congenital disorder of glycosylation, type Ib, MIM# 602579
Review for gene: MPI was set to GREEN
Added comment: Hepatic involvement is prominent and liver failure reported.
Sources: Expert list
Liver Failure_Paediatric v0.29 LIPA Zornitza Stark Marked gene: LIPA as ready
Liver Failure_Paediatric v0.29 LIPA Zornitza Stark Gene: lipa has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.29 LIPA Zornitza Stark Classified gene: LIPA as Green List (high evidence)
Liver Failure_Paediatric v0.29 LIPA Zornitza Stark Gene: lipa has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.28 LIPA Zornitza Stark gene: LIPA was added
gene: LIPA was added to Acute Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: LIPA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LIPA were set to 8617513; 21963785
Phenotypes for gene: LIPA were set to Cholesteryl ester storage disease, MIM# 278000; Wolman disease, MIM# 278000
Review for gene: LIPA was set to GREEN
Added comment: Liver failure can be of early onset and rapidly progressive or more chronic.
Sources: Expert list
Liver Failure_Paediatric v0.27 NPC1 Zornitza Stark Marked gene: NPC1 as ready
Liver Failure_Paediatric v0.27 NPC1 Zornitza Stark Gene: npc1 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.27 NPC1 Zornitza Stark Classified gene: NPC1 as Green List (high evidence)
Liver Failure_Paediatric v0.27 NPC1 Zornitza Stark Gene: npc1 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.26 NPC1 Zornitza Stark gene: NPC1 was added
gene: NPC1 was added to Acute Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: NPC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NPC1 were set to 25902754
Phenotypes for gene: NPC1 were set to Niemann-Pick disease, MIM# 257220
Review for gene: NPC1 was set to GREEN
Added comment: Rare presentations with liver failure reported.
Sources: Expert list
Liver Failure_Paediatric v0.25 TRMU Zornitza Stark Marked gene: TRMU as ready
Liver Failure_Paediatric v0.25 TRMU Zornitza Stark Gene: trmu has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.25 TRMU Zornitza Stark Classified gene: TRMU as Green List (high evidence)
Liver Failure_Paediatric v0.25 TRMU Zornitza Stark Gene: trmu has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.24 TRMU Zornitza Stark gene: TRMU was added
gene: TRMU was added to Acute Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: TRMU was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRMU were set to 19732863
Phenotypes for gene: TRMU were set to Liver failure, transient infantile, MIM# 613070
Review for gene: TRMU was set to GREEN
Added comment: Acute infantile liver failure resulting from variants in TRMU is a transient disorder of hepatic function. In addition to elevated liver enzymes, jaundice, vomiting, coagulopathy, and hyperbilirubinemia, the presence of increased serum lactate is consistent with a defect in mitochondrial respiratory function. With supportive care, patients who survive the initial acute episode can recover and show normal development.

Thirteen individuals reported, including 7 of Yemenite Jewish origin with same recurrent founder variant, p.Tyr77His.
Sources: Expert list
Liver Failure_Paediatric v0.23 RINT1 Zornitza Stark Marked gene: RINT1 as ready
Liver Failure_Paediatric v0.23 RINT1 Zornitza Stark Gene: rint1 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.23 RINT1 Zornitza Stark Classified gene: RINT1 as Green List (high evidence)
Liver Failure_Paediatric v0.23 RINT1 Zornitza Stark Gene: rint1 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.22 RINT1 Zornitza Stark gene: RINT1 was added
gene: RINT1 was added to Acute Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: RINT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RINT1 were set to 31204009
Phenotypes for gene: RINT1 were set to Infantile liver failure syndrome 3, MIM# 618641
Review for gene: RINT1 was set to GREEN
Added comment: Recurrent episodes of acute liver failure during intercurrent febrile illness. Patients first present in infancy or early childhood, and there usually is complete recovery between episodes with conservative treatment. Affected individuals also have skeletal anomalies of the vertebral bodies and femoral heads.

Three unrelated families reported.
Sources: Expert list
Liver Failure_Paediatric v0.21 LARS Zornitza Stark Marked gene: LARS as ready
Liver Failure_Paediatric v0.21 LARS Zornitza Stark Gene: lars has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.21 LARS Zornitza Stark Classified gene: LARS as Green List (high evidence)
Liver Failure_Paediatric v0.21 LARS Zornitza Stark Gene: lars has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.20 LARS Zornitza Stark gene: LARS was added
gene: LARS was added to Acute Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: LARS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LARS were set to 30349989
Phenotypes for gene: LARS were set to Infantile liver failure syndrome 1, MIM# 615438
Review for gene: LARS was set to GREEN
Added comment: Six unrelated families reported in the literature, reviewed in PMID: 30349989.
Sources: Expert list
Liver Failure_Paediatric v0.19 NBAS Zornitza Stark Marked gene: NBAS as ready
Liver Failure_Paediatric v0.19 NBAS Zornitza Stark Gene: nbas has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.19 NBAS Zornitza Stark Classified gene: NBAS as Green List (high evidence)
Liver Failure_Paediatric v0.19 NBAS Zornitza Stark Gene: nbas has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.18 NBAS Zornitza Stark gene: NBAS was added
gene: NBAS was added to Acute Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: NBAS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NBAS were set to 26073778
Phenotypes for gene: NBAS were set to Infantile liver failure syndrome 2, MIM# 616483
Review for gene: NBAS was set to GREEN
Added comment: Recurrent episodes of acute liver failure during intercurrent febrile illness. More than 10 unrelated families reported.
Sources: Expert list
Liver Failure_Paediatric v0.17 OTC Zornitza Stark Marked gene: OTC as ready
Liver Failure_Paediatric v0.17 OTC Zornitza Stark Gene: otc has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.17 OTC Zornitza Stark Classified gene: OTC as Green List (high evidence)
Liver Failure_Paediatric v0.17 OTC Zornitza Stark Gene: otc has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.16 OTC Zornitza Stark gene: OTC was added
gene: OTC was added to Acute Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: OTC 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: OTC were set to 28887792; 25902754
Phenotypes for gene: OTC were set to Ornithine transcarbamylase deficiency, MIM# 311250
Review for gene: OTC was set to GREEN
Added comment: Well established gene disease association.

Reports of presentations with liver failure.
Sources: Expert list
Liver Failure_Paediatric v0.15 MPV17 Zornitza Stark Marked gene: MPV17 as ready
Liver Failure_Paediatric v0.15 MPV17 Zornitza Stark Gene: mpv17 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.15 MPV17 Zornitza Stark Classified gene: MPV17 as Green List (high evidence)
Liver Failure_Paediatric v0.15 MPV17 Zornitza Stark Gene: mpv17 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.14 MPV17 Zornitza Stark gene: MPV17 was added
gene: MPV17 was added to Acute Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: MPV17 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MPV17 were set to 18695062
Phenotypes for gene: MPV17 were set to Mitochondrial DNA depletion syndrome 6 (hepatocerebral type), MIM# 256810
Review for gene: MPV17 was set to GREEN
Added comment: Well established gene-disease association.

Mitochondrial DNA depletion syndrome-6 is an autosomal recessive disorder characterized by infantile onset of progressive liver failure, often leading to death in the first year of life. Those that survive develop progressive neurologic involvement, including ataxia, hypotonia, dystonia, and psychomotor regression.
Sources: Expert list
Liver Failure_Paediatric v0.13 DGUOK Zornitza Stark Marked gene: DGUOK as ready
Liver Failure_Paediatric v0.13 DGUOK Zornitza Stark Gene: dguok has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.13 DGUOK Zornitza Stark Classified gene: DGUOK as Green List (high evidence)
Liver Failure_Paediatric v0.13 DGUOK Zornitza Stark Gene: dguok has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.12 DGUOK Zornitza Stark Classified gene: DGUOK as Green List (high evidence)
Liver Failure_Paediatric v0.12 DGUOK Zornitza Stark Gene: dguok has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.11 DGUOK Zornitza Stark gene: DGUOK was added
gene: DGUOK was added to Acute Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: DGUOK was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: DGUOK were set to Mitochondrial DNA depletion syndrome 3 (hepatocerebral type), MIM#251880
Review for gene: DGUOK was set to GREEN
Added comment: Well established gene-disease association.

Mitochondrial DNA depletion syndrome-3 is a severe autosomal recessive disorder characterized by onset in infancy of progressive liver failure and neurologic abnormalities, hypoglycemia, and increased lactate in body fluids. Affected tissues show both decreased activity of the mtDNA-encoded respiratory chain complexes (I, III, IV, and V) and mtDNA depletion.
Sources: Expert list
Liver Failure_Paediatric v0.10 POLG Zornitza Stark Marked gene: POLG as ready
Liver Failure_Paediatric v0.10 POLG Zornitza Stark Gene: polg has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.10 POLG Zornitza Stark Classified gene: POLG as Green List (high evidence)
Liver Failure_Paediatric v0.10 POLG Zornitza Stark Gene: polg has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.9 POLG Zornitza Stark gene: POLG was added
gene: POLG was added to Acute Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: POLG was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POLG were set to 20220442
Phenotypes for gene: POLG were set to Mitochondrial DNA depletion syndrome 4A (Alpers type), MIM# 203700
Review for gene: POLG was set to GREEN
Added comment: Well established gene-disease association.

Alpers syndrome is an autosomal recessive disorder characterized by a clinical triad of psychomotor retardation, intractable epilepsy, and liver failure in infants and young children. Pathologic findings include neuronal loss in the cerebral gray matter with reactive astrocytosis and liver cirrhosis. The disorder is progressive and often leads to death from hepatic failure or status epilepticus before age 3 years.
Sources: Expert list
Liver Failure_Paediatric v0.8 ACADM Zornitza Stark Marked gene: ACADM as ready
Liver Failure_Paediatric v0.8 ACADM Zornitza Stark Gene: acadm has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.8 ACADM Zornitza Stark Classified gene: ACADM as Green List (high evidence)
Liver Failure_Paediatric v0.8 ACADM Zornitza Stark Gene: acadm has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.7 ACADM Zornitza Stark gene: ACADM was added
gene: ACADM was added to Acute Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: ACADM was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ACADM were set to Acyl-CoA dehydrogenase, medium chain, deficiency of, MIM# 201450
Review for gene: ACADM was set to GREEN
Added comment: Inherited deficiency of medium-chain acyl-CoA dehydrogenase is characterized by intolerance to prolonged fasting, recurrent episodes of hypoglycemic coma with medium-chain dicarboxylic aciduria, impaired ketogenesis, and low plasma and tissue carnitine levels. Can progress to liver failure.
Sources: Expert list
Liver Failure_Paediatric v0.6 ALDOB Zornitza Stark Marked gene: ALDOB as ready
Liver Failure_Paediatric v0.6 ALDOB Zornitza Stark Gene: aldob has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.6 ALDOB Zornitza Stark Classified gene: ALDOB as Green List (high evidence)
Liver Failure_Paediatric v0.6 ALDOB Zornitza Stark Gene: aldob has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.5 ALDOB Zornitza Stark gene: ALDOB was added
gene: ALDOB was added to Acute Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: ALDOB was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ALDOB were set to Fructose intolerance, hereditary, MIM# 229600
Review for gene: ALDOB was set to GREEN
Added comment: Well established gene-disease association.

Hereditary fructose intolerance (HFI) becomes apparent in infancy at the time of weaning, when fructose or sucrose is added to the diet. Clinical features include recurrent vomiting, abdominal pain, and hypoglycemia that may be fatal. Long-term exposure to fructose can result in liver failure, renal tubulopathy, and growth retardation.
Sources: Expert list
Liver Failure_Paediatric v0.4 FAH Zornitza Stark Marked gene: FAH as ready
Liver Failure_Paediatric v0.4 FAH Zornitza Stark Gene: fah has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.4 FAH Zornitza Stark Classified gene: FAH as Green List (high evidence)
Liver Failure_Paediatric v0.4 FAH Zornitza Stark Gene: fah has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.3 FAH Zornitza Stark gene: FAH was added
gene: FAH was added to Acute Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: FAH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FAH were set to 15759101
Phenotypes for gene: FAH were set to Tyrosinemia, type I, MIM#276700
Review for gene: FAH was set to GREEN
Added comment: Well established gene-disease association.

The disorder is characterized by progressive liver disease and a secondary renal tubular dysfunction leading to hypophosphatemic rickets. Onset varies from infancy to adolescence. In the most acute form patients present with severe liver failure within weeks after birth, whereas rickets may be the major symptom in chronic tyrosinemia. Untreated, death ensues from cirrhosis or hepatocellular carcinoma at a young age.
Sources: Expert list
Liver Failure_Paediatric v0.2 GALT Zornitza Stark Marked gene: GALT as ready
Liver Failure_Paediatric v0.2 GALT Zornitza Stark Gene: galt has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.2 GALT Zornitza Stark Classified gene: GALT as Green List (high evidence)
Liver Failure_Paediatric v0.2 GALT Zornitza Stark Gene: galt has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.1 GALT Zornitza Stark gene: GALT was added
gene: GALT was added to Acute Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: GALT was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: GALT were set to Galactosaemia, MIM#230400
Review for gene: GALT was set to GREEN
Added comment: Well established gene-disease association. Most individuals present in the neonatal period, after ingestion of galactose, with jaundice, hepatosplenomegaly, hepatocellular insufficiency, food intolerance, hypoglycemia, renal tubular dysfunction, muscle hypotonia, sepsis, and cataract. Long-term complications include intellectual disability, verbal dyspraxia, motor abnormalities, and hypergonadotropic hypogonadism.

Commonly part of newborn screening program but currently not in Victoria.
Sources: Expert list
Liver Failure_Paediatric v0.0 Zornitza Stark Added Panel Acute Liver Failure_Paediatric
Set panel types to: Victorian Clinical Genetics Services; Rare Disease
Mendeliome v0.5213 DDX23 Bryony Thompson Classified gene: DDX23 as Amber List (moderate evidence)
Mendeliome v0.5213 DDX23 Bryony Thompson Gene: ddx23 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5212 DDX23 Bryony Thompson gene: DDX23 was added
gene: DDX23 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: DDX23 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DDX23 were set to 33057194
Phenotypes for gene: DDX23 were set to Developmental disorder
Review for gene: DDX23 was set to AMBER
Added comment: PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio developmental disorder study. 6 de novo missense identified in ~10,000 cases with developmental disorders (no other phenotype info provided)
Sources: Literature
Mendeliome v0.5211 ATP6V0A1 Bryony Thompson Classified gene: ATP6V0A1 as Amber List (moderate evidence)
Mendeliome v0.5211 ATP6V0A1 Bryony Thompson Gene: atp6v0a1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5210 ATP6V0A1 Bryony Thompson gene: ATP6V0A1 was added
gene: ATP6V0A1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ATP6V0A1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ATP6V0A1 were set to 30842224; 33057194
Phenotypes for gene: ATP6V0A1 were set to Developmental disorder; Rett syndrome-like
Review for gene: ATP6V0A1 was set to AMBER
Added comment: PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio developmental disorder study. 11 de novo missense identified in ~10,000 cases with developmental disorders (no other phenotype info provided).
PMID: 30842224 - identified a de novo missense variant in a single individual with atypical Rett syndrome phenotype
Sources: Literature
Mendeliome v0.5209 ARHGAP35 Bryony Thompson Marked gene: ARHGAP35 as ready
Mendeliome v0.5209 ARHGAP35 Bryony Thompson Gene: arhgap35 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5209 ARHGAP35 Bryony Thompson Classified gene: ARHGAP35 as Amber List (moderate evidence)
Mendeliome v0.5209 ARHGAP35 Bryony Thompson Gene: arhgap35 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5208 ARHGAP35 Bryony Thompson gene: ARHGAP35 was added
gene: ARHGAP35 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ARHGAP35 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ARHGAP35 were set to 33057194
Phenotypes for gene: ARHGAP35 were set to Developmental disorder
Review for gene: ARHGAP35 was set to AMBER
Added comment: Has been identified as a gene with significant de novo enrichment in a large trio developmental disorder study. 16 de novo variants (3 frameshift, 2 in-frame, 10 missense, 1 stopgain) identified in ~10,000 cases with developmental disorders (no other phenotype info provided).
Sources: Literature
Mendeliome v0.5207 AP2S1 Bryony Thompson Added comment: Comment on phenotypes: Established hypercalcaemia gene.
PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio developmental disorder study. 5 de novo missense identified in ~10,000 cases with developmental disorders (no other phenotype info provided)
Mendeliome v0.5207 AP2S1 Bryony Thompson Phenotypes for gene: AP2S1 were changed from Hypocalciuric hypercalcemia, type III MIM#600740 to Hypocalciuric hypercalcemia, type III MIM#600740
Mendeliome v0.5206 AP2S1 Bryony Thompson Mode of inheritance for gene: AP2S1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5205 AP2S1 Bryony Thompson Phenotypes for gene: AP2S1 were changed from to Hypocalciuric hypercalcemia, type III MIM#600740
Central Hypoventilation v0.27 RET Zornitza Stark Marked gene: RET as ready
Central Hypoventilation v0.27 RET Zornitza Stark Gene: ret has been classified as Red List (Low Evidence).
Central Hypoventilation v0.27 RET Zornitza Stark Phenotypes for gene: RET were changed from to Central hypoventilation syndrome, congenital, MIM#209880
Central Hypoventilation v0.26 RET Zornitza Stark Publications for gene: RET were set to
Central Hypoventilation v0.25 RET Zornitza Stark Mode of inheritance for gene: RET was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Central Hypoventilation v0.24 RET Zornitza Stark Classified gene: RET as Red List (low evidence)
Central Hypoventilation v0.24 RET Zornitza Stark Gene: ret has been classified as Red List (Low Evidence).
Central Hypoventilation v0.23 RET Zornitza Stark reviewed gene: RET: Rating: RED; Mode of pathogenicity: None; Publications: 18438890, 16443855, 12566528, 12086152; Phenotypes: Central hypoventilation syndrome, congenital, MIM#209880; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Central Hypoventilation v0.23 GDNF Zornitza Stark Marked gene: GDNF as ready
Central Hypoventilation v0.23 GDNF Zornitza Stark Gene: gdnf has been classified as Red List (Low Evidence).
Central Hypoventilation v0.23 GDNF Zornitza Stark Phenotypes for gene: GDNF were changed from to Central hypoventilation syndrome, MIM# 209880
Central Hypoventilation v0.22 GDNF Zornitza Stark Mode of inheritance for gene: GDNF was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Central Hypoventilation v0.21 GDNF Zornitza Stark Classified gene: GDNF as Red List (low evidence)
Central Hypoventilation v0.21 GDNF Zornitza Stark Gene: gdnf has been classified as Red List (Low Evidence).
Central Hypoventilation v0.20 GDNF Zornitza Stark reviewed gene: GDNF: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Central hypoventilation syndrome, MIM# 209880; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Central Hypoventilation v0.20 PHOX2B Zornitza Stark Marked gene: PHOX2B as ready
Central Hypoventilation v0.20 PHOX2B Zornitza Stark Gene: phox2b has been classified as Green List (High Evidence).
Central Hypoventilation v0.20 PHOX2B Zornitza Stark Phenotypes for gene: PHOX2B were changed from to Central hypoventilation syndrome, congenital, with or without Hirschsprung disease, MIM# 209880
Central Hypoventilation v0.19 PHOX2B Zornitza Stark Publications for gene: PHOX2B were set to
Central Hypoventilation v0.18 PHOX2B Zornitza Stark Mode of inheritance for gene: PHOX2B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Central Hypoventilation v0.17 PHOX2B Zornitza Stark reviewed gene: PHOX2B: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301600; Phenotypes: Central hypoventilation syndrome, congenital, with or without Hirschsprung disease, MIM# 209880; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Central Hypoventilation v0.17 BDNF Zornitza Stark Phenotypes for gene: BDNF were changed from to Central hypoventilation syndrome, congenital, MIM#209880
Central Hypoventilation v0.16 BDNF Zornitza Stark Mode of inheritance for gene: BDNF was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Central Hypoventilation v0.15 BDNF Zornitza Stark Tag refuted tag was added to gene: BDNF.
Central Hypoventilation v0.14 EDN3 Zornitza Stark Marked gene: EDN3 as ready
Central Hypoventilation v0.14 EDN3 Zornitza Stark Gene: edn3 has been classified as Red List (Low Evidence).
Central Hypoventilation v0.14 EDN3 Zornitza Stark Phenotypes for gene: EDN3 were changed from to Central hypoventilation syndrome, congenital, MIM# 209880
Central Hypoventilation v0.13 EDN3 Zornitza Stark Publications for gene: EDN3 were set to
Central Hypoventilation v0.12 EDN3 Zornitza Stark Mode of inheritance for gene: EDN3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Central Hypoventilation v0.11 EDN3 Zornitza Stark Classified gene: EDN3 as Red List (low evidence)
Central Hypoventilation v0.11 EDN3 Zornitza Stark Gene: edn3 has been classified as Red List (Low Evidence).
Central Hypoventilation v0.10 EDN3 Zornitza Stark Tag disputed tag was added to gene: EDN3.
Central Hypoventilation v0.10 EDN3 Zornitza Stark reviewed gene: EDN3: Rating: RED; Mode of pathogenicity: None; Publications: 8696331; Phenotypes: Central hypoventilation syndrome, congenital, MIM# 209880; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5204 ASCL1 Zornitza Stark Marked gene: ASCL1 as ready
Mendeliome v0.5204 ASCL1 Zornitza Stark Gene: ascl1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5204 ASCL1 Zornitza Stark Phenotypes for gene: ASCL1 were changed from to Central hypoventilation syndrome, congenital, MIM# 209880
Mendeliome v0.5203 ASCL1 Zornitza Stark Publications for gene: ASCL1 were set to
Mendeliome v0.5202 ASCL1 Zornitza Stark Mode of inheritance for gene: ASCL1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5201 ASCL1 Zornitza Stark Classified gene: ASCL1 as Amber List (moderate evidence)
Mendeliome v0.5201 ASCL1 Zornitza Stark Gene: ascl1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5200 ASCL1 Zornitza Stark reviewed gene: ASCL1: Rating: AMBER; Mode of pathogenicity: None; Publications: 14532329; Phenotypes: Central hypoventilation syndrome, congenital, MIM# 209880; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Central Hypoventilation v0.10 ASCL1 Zornitza Stark Marked gene: ASCL1 as ready
Central Hypoventilation v0.10 ASCL1 Zornitza Stark Gene: ascl1 has been classified as Amber List (Moderate Evidence).
Central Hypoventilation v0.10 ASCL1 Zornitza Stark Phenotypes for gene: ASCL1 were changed from to Central hypoventilation syndrome, congenital, MIM# 209880
Central Hypoventilation v0.9 ASCL1 Zornitza Stark Publications for gene: ASCL1 were set to
Central Hypoventilation v0.8 ASCL1 Zornitza Stark Mode of inheritance for gene: ASCL1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Central Hypoventilation v0.7 ASCL1 Zornitza Stark Classified gene: ASCL1 as Amber List (moderate evidence)
Central Hypoventilation v0.7 ASCL1 Zornitza Stark Gene: ascl1 has been classified as Amber List (Moderate Evidence).
Central Hypoventilation v0.6 ASCL1 Zornitza Stark reviewed gene: ASCL1: Rating: AMBER; Mode of pathogenicity: None; Publications: 14532329; Phenotypes: Central hypoventilation syndrome, congenital, MIM# 209880; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Chronic granulomatous disease v0.12 Zornitza Stark Panel types changed to Victorian Clinical Genetics Services; Royal Melbourne Hospital; Rare Disease
Mendeliome v0.5200 ODC1 Zornitza Stark Phenotypes for gene: ODC1 were changed from Intellectual disability; macrocephaly; dysmorphism to Neurodevelopmental disorder with alopecia and brain imaging abnormalities (NEDABIA), MIM#619075
Mendeliome v0.5199 ODC1 Zornitza Stark Publications for gene: ODC1 were set to 30475435
Intellectual disability syndromic and non-syndromic v0.3127 ODC1 Zornitza Stark Publications for gene: ODC1 were set to 30475435
Intellectual disability syndromic and non-syndromic v0.3126 ODC1 Zornitza Stark edited their review of gene: ODC1: Added comment: Fifth individual reported in PMID 30239107: de novo nonsense variant identified, molecular modeling suggested that due to lack of a C terminus in the mutant protein, antizyme binding does not induce ODC degradation, leading to accumulation of active protein.; Changed publications: 30475435, 30239107
Mendeliome v0.5198 ODC1 Zornitza Stark commented on gene: ODC1: Fifth individual reported in PMID 30239107: de novo nonsense variant identified, molecular modeling suggested that due to lack of a C terminus in the mutant protein, antizyme binding does not induce ODC degradation, leading to accumulation of active protein.
Mendeliome v0.5198 ODC1 Zornitza Stark changed review comment from: Four individuals with de novo GoF variants in this gene reported.
Sources: Literature; to: Four individuals with de novo GoF variants in this gene reported.
Sources: Literature
Mendeliome v0.5198 ODC1 Zornitza Stark edited their review of gene: ODC1: Changed publications: 30475435, 30239107
Mendeliome v0.5198 ODC1 Zornitza Stark edited their review of gene: ODC1: Changed phenotypes: Neurodevelopmental disorder with alopecia and brain imaging abnormalities (NEDABIA), MIM#619075
Intellectual disability syndromic and non-syndromic v0.3126 ODC1 Zornitza Stark Phenotypes for gene: ODC1 were changed from Intellectual disability; macrocephaly; dysmorphism to Neurodevelopmental disorder with alopecia and brain imaging abnormalities (NEDABIA), MIM#619075
Intellectual disability syndromic and non-syndromic v0.3125 ODC1 Zornitza Stark edited their review of gene: ODC1: Changed phenotypes: Neurodevelopmental disorder with alopecia and brain imaging abnormalities (NEDABIA), MIM#619075
Intellectual disability syndromic and non-syndromic v0.3125 ODC1 Zornitza Stark edited their review of gene: ODC1: Changed phenotypes: neurodevelopmental disorder with alopecia and brain imaging abnormalities (NEDABIA), MIM#619075
Mendeliome v0.5198 KDELR2 Zornitza Stark Marked gene: KDELR2 as ready
Mendeliome v0.5198 KDELR2 Zornitza Stark Gene: kdelr2 has been classified as Green List (High Evidence).
Mendeliome v0.5198 KDELR2 Zornitza Stark Classified gene: KDELR2 as Green List (high evidence)
Mendeliome v0.5198 KDELR2 Zornitza Stark Gene: kdelr2 has been classified as Green List (High Evidence).
Mendeliome v0.5197 KDELR2 Zornitza Stark gene: KDELR2 was added
gene: KDELR2 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: KDELR2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KDELR2 were set to 33053334
Phenotypes for gene: KDELR2 were set to Increased susceptibility to fractures; joint hypermobility; Scoliosis; Bowing of the legs; Bowing of the arms
Review for gene: KDELR2 was set to GREEN
Added comment: 4 families with osteogenesis imperfecta reported with functional studies.
Sources: Expert list
Osteogenesis Imperfecta and Osteoporosis v0.48 KDELR2 Zornitza Stark Marked gene: KDELR2 as ready
Osteogenesis Imperfecta and Osteoporosis v0.48 KDELR2 Zornitza Stark Gene: kdelr2 has been classified as Green List (High Evidence).
Osteogenesis Imperfecta and Osteoporosis v0.48 KDELR2 Zornitza Stark Classified gene: KDELR2 as Green List (high evidence)
Osteogenesis Imperfecta and Osteoporosis v0.48 KDELR2 Zornitza Stark Gene: kdelr2 has been classified as Green List (High Evidence).
Osteogenesis Imperfecta and Osteoporosis v0.47 KDELR2 Zornitza Stark gene: KDELR2 was added
gene: KDELR2 was added to Osteogenesis Imperfecta. Sources: Expert Review
Mode of inheritance for gene: KDELR2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KDELR2 were set to 33053334
Phenotypes for gene: KDELR2 were set to Increased susceptibility to fractures; joint hypermobility; Scoliosis; Bowing of the legs; Bowing of the arms
Review for gene: KDELR2 was set to GREEN
Added comment: 4 families with osteogenesis imperfecta reported with functional studies.
Sources: Expert Review
Mendeliome v0.5196 SCN8A Zornitza Stark Marked gene: SCN8A as ready
Mendeliome v0.5196 SCN8A Zornitza Stark Gene: scn8a has been classified as Green List (High Evidence).
Mendeliome v0.5196 SCN8A Zornitza Stark Phenotypes for gene: SCN8A were changed from to Developmental and epileptic encephalopathy 13, MIM#614558, dominant and recessive; Myoclonus, familial, 2, MIM# 618364; paroxysmal kinesigenic dyskinesias; Cognitive impairment with or without cerebellar ataxia, MIM# 614306
Mendeliome v0.5195 SCN8A Zornitza Stark Publications for gene: SCN8A were set to
Mendeliome v0.5194 SCN8A Zornitza Stark Mode of pathogenicity for gene: SCN8A was changed from to Other
Mendeliome v0.5193 SCN8A Zornitza Stark Mode of inheritance for gene: SCN8A was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.5192 SCN8A Zornitza Stark reviewed gene: SCN8A: Rating: GREEN; Mode of pathogenicity: Other; Publications: 31625145, 29726066, 27098556, 28702509, 16236810, 31904124, 31887642, 31675620; Phenotypes: Developmental and epileptic encephalopathy 13, MIM#614558, dominant and recessive, Myoclonus, familial, 2, MIM# 618364, paroxysmal kinesigenic dyskinesias, Cognitive impairment with or without cerebellar ataxia, MIM# 614306; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Differences of Sex Development v0.179 GATA4 Zornitza Stark Marked gene: GATA4 as ready
Differences of Sex Development v0.179 GATA4 Zornitza Stark Gene: gata4 has been classified as Amber List (Moderate Evidence).
Differences of Sex Development v0.179 GATA4 Zornitza Stark Phenotypes for gene: GATA4 were changed from to Testicular anomalies with or without congenital heart disease, MIM# 615542
Differences of Sex Development v0.178 GATA4 Zornitza Stark Publications for gene: GATA4 were set to
Differences of Sex Development v0.177 GATA4 Zornitza Stark Mode of inheritance for gene: GATA4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Differences of Sex Development v0.176 GATA4 Zornitza Stark Classified gene: GATA4 as Amber List (moderate evidence)
Differences of Sex Development v0.176 GATA4 Zornitza Stark Gene: gata4 has been classified as Amber List (Moderate Evidence).
Incidentalome v0.48 RAD51D Zornitza Stark Marked gene: RAD51D as ready
Incidentalome v0.48 RAD51D Zornitza Stark Gene: rad51d has been classified as Green List (High Evidence).
Incidentalome v0.48 RAD51D Zornitza Stark Classified gene: RAD51D as Green List (high evidence)
Incidentalome v0.48 RAD51D Zornitza Stark Gene: rad51d has been classified as Green List (High Evidence).
Incidentalome v0.47 RAD51D Elena Savva gene: RAD51D was added
gene: RAD51D was added to Incidentalome. Sources: Literature
Mode of inheritance for gene: RAD51D was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: RAD51D were set to PMID: 28646019; 31937788; 26057125
Phenotypes for gene: RAD51D were set to {Breast-ovarian cancer, familial, susceptibility to, 4} 614291
Review for gene: RAD51D was set to GREEN
Added comment: Pure cancer susceptibility gene, no relationship found with germline mutations and other mendelian disease.
Sources: Literature
Differences of Sex Development v0.175 GATA4 Michelle Torres reviewed gene: GATA4: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 21220346, 30455927, 29735817, 27899157, 26490186, 29670578, 32992319; Phenotypes: ?Testicular anomalies with or without congenital heart disease 615542 AD, Atrial septal defect 2 607941 AD, Atrioventricular septal defect 4 614430 AD, Tetralogy of Fallot 187500 AD, Ventricular septal defect 1 614429 AD; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Syndromic Retinopathy v0.151 LRRC32 Zornitza Stark Marked gene: LRRC32 as ready
Syndromic Retinopathy v0.151 LRRC32 Zornitza Stark Gene: lrrc32 has been classified as Amber List (Moderate Evidence).
Syndromic Retinopathy v0.151 LRRC32 Zornitza Stark Classified gene: LRRC32 as Amber List (moderate evidence)
Syndromic Retinopathy v0.151 LRRC32 Zornitza Stark Gene: lrrc32 has been classified as Amber List (Moderate Evidence).
Syndromic Retinopathy v0.150 LRRC32 Zornitza Stark gene: LRRC32 was added
gene: LRRC32 was added to Syndromic Retinopathy. Sources: Literature
Mode of inheritance for gene: LRRC32 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LRRC32 were set to 30976112
Phenotypes for gene: LRRC32 were set to Cleft palate, proliferative retinopathy, and developmental delay (CPPRDD) syndrome, MIM# 619074
Review for gene: LRRC32 was set to AMBER
Added comment: Three individuals from two consanguineous families segregated the same homozygous bi-allelic variant, c.1630C>T; p.(Arg544Ter), shared haplotype indicative of founder effect. Mouse model has cleft palate and neonatal death.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3125 LRRC32 Zornitza Stark Phenotypes for gene: LRRC32 were changed from Intellectual disability; cleft palate; proliferative retinopathy to Cleft palate, proliferative retinopathy, and developmental delay (CPPRDD) syndrome, MIM# 619074
Intellectual disability syndromic and non-syndromic v0.3124 LRRC32 Zornitza Stark edited their review of gene: LRRC32: Changed phenotypes: Cleft palate, proliferative retinopathy, and developmental delay (CPPRDD) syndrome, MIM# 619074
Mendeliome v0.5192 LRRC32 Zornitza Stark Phenotypes for gene: LRRC32 were changed from Intellectual disability; cleft palate; proliferative retinopathy to Cleft palate, proliferative retinopathy, and developmental delay (CPPRDD) syndrome, MIM# 619074
Mendeliome v0.5191 LRRC32 Zornitza Stark edited their review of gene: LRRC32: Changed phenotypes: Cleft palate, proliferative retinopathy, and developmental delay (CPPRDD) syndrome, MIM# 619074
Syndromic Retinopathy v0.149 ALPK1 Zornitza Stark Marked gene: ALPK1 as ready
Syndromic Retinopathy v0.149 ALPK1 Zornitza Stark Gene: alpk1 has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.149 ALPK1 Zornitza Stark Phenotypes for gene: ALPK1 were changed from ROSAH syndrome; retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache to Retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache (ROSAH) syndrome, MIM#614979
Syndromic Retinopathy v0.148 ALPK1 Zornitza Stark edited their review of gene: ALPK1: Changed phenotypes: Retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache (ROSAH) syndrome, MIM#614979
Mendeliome v0.5191 ALPK1 Zornitza Stark edited their review of gene: ALPK1: Changed phenotypes: Periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome, Retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache (ROSAH) syndrome, MIM#614979
Mendeliome v0.5191 ALPK1 Zornitza Stark Publications for gene: ALPK1 were set to 31053777
Mendeliome v0.5190 ALPK1 Zornitza Stark Phenotypes for gene: ALPK1 were changed from Periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome; Retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache syndrome ROSAH syndrome, MIM#614979 to Periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome; Retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache (ROSAH) syndrome, MIM#614979
Mendeliome v0.5189 ALPK1 Zornitza Stark Phenotypes for gene: ALPK1 were changed from Periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome; ROSAH syndrome; retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache to Periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome; Retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache syndrome ROSAH syndrome, MIM#614979
Mendeliome v0.5188 ALPK1 Zornitza Stark edited their review of gene: ALPK1: Changed phenotypes: Periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome, Retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache syndromeROSAH syndrome, MIM#614979
Genetic Epilepsy v0.895 NUS1 Zornitza Stark Phenotypes for gene: NUS1 were changed from Epilepsy; intellectual disability to Mental retardation, autosomal dominant 55, with seizures, MIM# 617831
Genetic Epilepsy v0.894 NUS1 Zornitza Stark edited their review of gene: NUS1: Changed phenotypes: Mental retardation, autosomal dominant 55, with seizures, MIM# 617831
Intellectual disability syndromic and non-syndromic v0.3124 NUS1 Zornitza Stark Phenotypes for gene: NUS1 were changed from Epilepsy; intellectual disability to Mental retardation, autosomal dominant 55, with seizures, MIM# 617831
Intellectual disability syndromic and non-syndromic v0.3123 NUS1 Zornitza Stark edited their review of gene: NUS1: Changed phenotypes: Mental retardation, autosomal dominant 55, with seizures, MIM# 617831
Mendeliome v0.5188 NUS1 Zornitza Stark Phenotypes for gene: NUS1 were changed from Epilepsy; intellectual disability to Congenital disorder of glycosylation, type 1aa 617082; Mental retardation, autosomal dominant 55, with seizures 617831
Mendeliome v0.5187 NUS1 Zornitza Stark Publications for gene: NUS1 were set to 31656175; 29100083
Mendeliome v0.5186 NUS1 Zornitza Stark Mode of inheritance for gene: NUS1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3123 COG8 Zornitza Stark Marked gene: COG8 as ready
Intellectual disability syndromic and non-syndromic v0.3123 COG8 Zornitza Stark Gene: cog8 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3123 COG8 Zornitza Stark Phenotypes for gene: COG8 were changed from to Congenital disorder of glycosylation, type IIh, MIM# 611182
Intellectual disability syndromic and non-syndromic v0.3122 COG8 Zornitza Stark Publications for gene: COG8 were set to
Intellectual disability syndromic and non-syndromic v0.3121 COG8 Zornitza Stark Mode of inheritance for gene: COG8 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3120 COG8 Zornitza Stark changed review comment from: Four unrelated families reported with bi-allelic LOF variants and a broad range of predominantly neurological features (ID, seizures, arthrogryposis, brain malformations).

ID present in 3/4, presentation in the 4th family was antenatal but with severe neurological phenotype that would have been expected to result in ID.; to: Four unrelated families reported with bi-allelic LOF variants and a broad range of predominantly neurological features (ID, seizures, arthrogryposis, brain malformations).

ID reported in 3/4, presentation in the 4th family was antenatal but with severe neurological phenotype that would have been expected to result in ID.
Intellectual disability syndromic and non-syndromic v0.3120 COG8 Zornitza Stark reviewed gene: COG8: Rating: GREEN; Mode of pathogenicity: None; Publications: 17220172, 28619360, 30690882, 17331980; Phenotypes: Congenital disorder of glycosylation, type IIh, MIM# 611182; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Disorders of Glycosylation v0.180 COG8 Zornitza Stark Marked gene: COG8 as ready
Congenital Disorders of Glycosylation v0.180 COG8 Zornitza Stark Gene: cog8 has been classified as Green List (High Evidence).
Congenital Disorders of Glycosylation v0.180 COG8 Zornitza Stark Phenotypes for gene: COG8 were changed from to Congenital disorder of glycosylation, type IIh, MIM# 611182
Congenital Disorders of Glycosylation v0.179 COG8 Zornitza Stark Publications for gene: COG8 were set to
Congenital Disorders of Glycosylation v0.178 COG8 Zornitza Stark Mode of inheritance for gene: COG8 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Congenital Disorders of Glycosylation v0.177 COG8 Zornitza Stark reviewed gene: COG8: Rating: GREEN; Mode of pathogenicity: None; Publications: 17220172, 28619360, 30690882, 17331980; Phenotypes: Congenital disorder of glycosylation, type IIh, MIM# 611182; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5185 COG8 Zornitza Stark Marked gene: COG8 as ready
Mendeliome v0.5185 COG8 Zornitza Stark Gene: cog8 has been classified as Green List (High Evidence).
Mendeliome v0.5185 COG8 Zornitza Stark Phenotypes for gene: COG8 were changed from to Congenital disorder of glycosylation, type IIh, MIM# 611182
Mendeliome v0.5184 COG8 Zornitza Stark Publications for gene: COG8 were set to
Mendeliome v0.5183 COG8 Zornitza Stark reviewed gene: COG8: Rating: GREEN; Mode of pathogenicity: None; Publications: 17220172, 28619360; Phenotypes: Congenital disorder of glycosylation, type IIh, MIM# 611182; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5183 COG8 Zornitza Stark Mode of inheritance for gene: COG8 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5182 HBB Zornitza Stark Marked gene: HBB as ready
Mendeliome v0.5182 HBB Zornitza Stark Gene: hbb has been classified as Green List (High Evidence).
Mendeliome v0.5182 HBB Zornitza Stark Phenotypes for gene: HBB were changed from to Delta-beta thalassemia 141749; Erythrocytosis 6 617980; Heinz body anemia 140700; Hereditary persistence of fetal hemoglobin 141749; Methemoglobinemia, beta type 617971; Sickle cell anemia 603903; Thalassemia-beta, dominant inclusion-body 603902; Thalassemia, beta 613985
Mendeliome v0.5181 HBB Zornitza Stark Publications for gene: HBB were set to
Mendeliome v0.5180 SCN8A Elena Savva reviewed gene: SCN8A: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID 30615093, 31904124; Phenotypes: ?Myoclonus, familial, 2 618364, Cognitive impairment with or without cerebellar ataxia 614306, Epileptic encephalopathy, early infantile, 13 614558, Seizures, benign familial infantile, 5 617080; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.5180 HBB Zornitza Stark Mode of inheritance for gene: HBB was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Muscular dystrophy and myopathy_Paediatric v0.76 ISPD Zornitza Stark Tag SV/CNV tag was added to gene: ISPD.
Muscular dystrophy and myopathy_Paediatric v0.76 ISPD Zornitza Stark edited their review of gene: ISPD: Added comment: - No distinct genotype-phenotype correlation. - Congenital MD is more commonly reported and has been reported in patients with hom PTCs, missense and chet (missense/PTCs) (OMIM). - Limb girdle MD has also been reported for chet patients (PMID: 28688748; PMID: 30060766). Patient fibroblasts showed impaired O-mannosylation, and transfection with wildtype protein have restored function (rescue) (PMID: 22522420). Intragenic CNVs are commonly reported for this gene (OMIM).; Changed publications: 22522421, 23217329, 23390185, 30060766, 28688748, 26404900, 30060766
Mendeliome v0.5179 ISPD Zornitza Stark Tag SV/CNV tag was added to gene: ISPD.
Mendeliome v0.5179 ISPD Zornitza Stark Publications for gene: ISPD were set to 22522421; 23217329; 23390185; 30060766; 28688748; 26404900
Mendeliome v0.5178 RAD51D Zornitza Stark Marked gene: RAD51D as ready
Mendeliome v0.5178 RAD51D Zornitza Stark Gene: rad51d has been classified as Red List (Low Evidence).
Mendeliome v0.5178 RAD51D Zornitza Stark Phenotypes for gene: RAD51D were changed from to {Breast-ovarian cancer, familial, susceptibility to, 4} 614291
Mendeliome v0.5177 RAD51D Zornitza Stark Publications for gene: RAD51D were set to
Mendeliome v0.5176 RAD51D Zornitza Stark Mode of inheritance for gene: RAD51D was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5175 RAD51D Zornitza Stark Classified gene: RAD51D as Red List (low evidence)
Mendeliome v0.5175 RAD51D Zornitza Stark Gene: rad51d has been classified as Red List (Low Evidence).
Mendeliome v0.5174 NUS1 Elena Savva reviewed gene: NUS1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 25066056, 29100083, 31656175, 32485575; Phenotypes: ?Congenital disorder of glycosylation, type 1aa 617082, Mental retardation, autosomal dominant 55, with seizures 617831; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.5174 COG8 Elena Savva reviewed gene: COG8: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 30690882, 17331980; Phenotypes: Congenital disorder of glycosylation, type IIh 611182; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5174 HBB Elena Savva reviewed gene: HBB: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31788855, 20301599, 29700171; Phenotypes: {Malaria, resistance to} 611162, Delta-beta thalassemia 141749, Erythrocytosis 6 617980, Heinz body anemia 140700, Hereditary persistence of fetal hemoglobin 141749, Methemoglobinemia, beta type 617971, Sickle cell anemia 603903, Thalassemia-beta, dominant inclusion-body 603902, Thalassemia, beta 613985; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.5174 ISPD Elena Savva reviewed gene: ISPD: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 28688748, 30060766, 22522420; Phenotypes: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7 614643, Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 7 616052; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5174 TPO Zornitza Stark Marked gene: TPO as ready
Mendeliome v0.5174 TPO Zornitza Stark Gene: tpo has been classified as Green List (High Evidence).
Mendeliome v0.5174 TPO Zornitza Stark Phenotypes for gene: TPO were changed from to Thyroid dyshormonogenesis 2A, MIM# 274500
Mendeliome v0.5173 TPO Zornitza Stark Publications for gene: TPO were set to
Mendeliome v0.5172 TPO Zornitza Stark Mode of inheritance for gene: TPO was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5171 TPO Zornitza Stark reviewed gene: TPO: Rating: GREEN; Mode of pathogenicity: None; Publications: 8027236, 10084596; Phenotypes: Thyroid dyshormonogenesis 2A, MIM# 274500; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5171 RAD51D Elena Savva reviewed gene: RAD51D: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 28646019, 31937788, 26057125; Phenotypes: {Breast-ovarian cancer, familial, susceptibility to, 4} 614291; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Congenital Disorders of Glycosylation v0.177 SLC37A4 Zornitza Stark Marked gene: SLC37A4 as ready
Congenital Disorders of Glycosylation v0.177 SLC37A4 Zornitza Stark Gene: slc37a4 has been classified as Red List (Low Evidence).
Congenital Disorders of Glycosylation v0.177 SLC37A4 Zornitza Stark gene: SLC37A4 was added
gene: SLC37A4 was added to Congenital Disorders of Glycosylation. Sources: Literature
Mode of inheritance for gene: SLC37A4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SLC37A4 were set to 32884905
Phenotypes for gene: SLC37A4 were set to Congenital disorder of glycosylation
Review for gene: SLC37A4 was set to RED
Added comment: Bi-allelic LOF variants in this gene cause glycogen storage disorder.

Single individual reported with heterozygous de novo variant in this gene. Clinical features included dysmorphic features (low set ears, a broad nose, mandibular micrognathia and facial asymmetry) and hepatopathy. The variant abolishes the ER retention signal of the transporter and generates a weak Golgi retention signal. Intracellular mislocalization of the transporter is postulated to lead to a congenital disorder of glycosylation instead of glycogen storage disease.
Sources: Literature
Mendeliome v0.5171 SLC35A3 Zornitza Stark Phenotypes for gene: SLC35A3 were changed from Arthrogryposis, mental retardation, and seizures; OMIM #615553 to Arthrogryposis, mental retardation, and seizures OMIM #615553; Skeletal dysplasia; Congenital disorder of glycosylation
Mendeliome v0.5170 SLC35A3 Zornitza Stark Publications for gene: SLC35A3 were set to 28328131; 24031089
Mendeliome v0.5169 SLC35A3 Zornitza Stark Classified gene: SLC35A3 as Green List (high evidence)
Mendeliome v0.5169 SLC35A3 Zornitza Stark Gene: slc35a3 has been classified as Green List (High Evidence).
Mendeliome v0.5168 SLC35A3 Zornitza Stark edited their review of gene: SLC35A3: Added comment: Third unrelated family reported in PMID 28777481 with prenatally diagnosed anomalous vertebrae, including butterfly, and hemivertebrae throughout the spine, as well as cleft palate, micrognathia, patent foramen ovale, patent ductus arteriosus, posterior embryotoxon, short limbs, camptodactyly, talipes valgus, rocker bottom feet, and facial dysmorphism including proptosis, nevus flammeus, and a cupped left ear. Unclear if this is a distinct phenotype (note Holstein cows with variants in this gene have a skeletal phenotype) or part of a spectrum for a CDG. However, abnormal protein glycosylation, consistent with a defective Golgi UDP-GlcNAc transporter demonstrated, so overall, promoted to Green for CDG.; Changed rating: GREEN; Changed publications: 28777481, 28328131, 24031089; Changed phenotypes: Arthrogryposis, mental retardation, and seizures OMIM #615553, Skeletal dysplasia, Congenital disorder of glycosylation; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Disorders of Glycosylation v0.176 SLC35A3 Zornitza Stark Publications for gene: SLC35A3 were set to 28328131; 24031089; 28777481
Congenital Disorders of Glycosylation v0.175 SLC35A3 Zornitza Stark Phenotypes for gene: SLC35A3 were changed from Arthrogryposis, mental retardation, and seizures; OMIM #615553 to Arthrogryposis, mental retardation, and seizures OMIM #615553; Skeletal dysplasia; Congenital disorder of glycosylation
Congenital Disorders of Glycosylation v0.175 SLC35A3 Zornitza Stark Publications for gene: SLC35A3 were set to 28328131; 24031089
Congenital Disorders of Glycosylation v0.174 SLC35A3 Zornitza Stark Classified gene: SLC35A3 as Green List (high evidence)
Congenital Disorders of Glycosylation v0.174 SLC35A3 Zornitza Stark Gene: slc35a3 has been classified as Green List (High Evidence).
Congenital Disorders of Glycosylation v0.173 SLC35A3 Zornitza Stark edited their review of gene: SLC35A3: Added comment: Third unrelated family reported in PMID 28777481 with prenatally diagnosed anomalous vertebrae, including butterfly, and hemivertebrae throughout the spine, as well as cleft palate, micrognathia, patent foramen ovale, patent ductus arteriosus, posterior embryotoxon, short limbs, camptodactyly, talipes valgus, rocker bottom feet, and facial dysmorphism including proptosis, nevus flammeus, and a cupped left ear. Unclear if this is a distinct phenotype (note Holstein cows with variants in this gene have a skeletal phenotype) or part of a spectrum for a CDG. However, abnormal protein glycosylation, consistent with a defective Golgi UDP-GlcNAc transporter demonstrated, so overall, promoted to Green for CDG.; Changed rating: GREEN; Changed publications: 28777481, 28328131, 24031089; Changed phenotypes: Arthrogryposis, mental retardation, and seizures OMIM #615553, Skeletal dysplasia, Congenital disorder of glycosylation; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3120 SLC35A3 Zornitza Stark Phenotypes for gene: SLC35A3 were changed from ?Arthrogryposis, mental retardation, and seizures; OMIM #615553 to Arthrogryposis, mental retardation, and seizures OMIM #615553; Skeletal dysplasia
Intellectual disability syndromic and non-syndromic v0.3119 SLC35A3 Zornitza Stark Publications for gene: SLC35A3 were set to PMID: 28328131; 24031089
Intellectual disability syndromic and non-syndromic v0.3118 SLC35A3 Zornitza Stark reviewed gene: SLC35A3: Rating: AMBER; Mode of pathogenicity: None; Publications: 28777481; Phenotypes: Skeletal dysplasia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mackenzie's Mission_Reproductive Carrier Screening v0.44 EMG1 Sarah Righetti reviewed gene: EMG1: Rating: GREEN; Mode of pathogenicity: None; Publications: 19463982; Phenotypes: Bowen-Conradi syndrome MIM #2111180; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mackenzie's Mission_Reproductive Carrier Screening v0.44 SLC35A3 Sarah Righetti reviewed gene: SLC35A3: Rating: GREEN; Mode of pathogenicity: None; Publications: 24031089, 28777481, 28328131; Phenotypes: Arthrogryposis, mental retardation, and seizures; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Regression v0.202 VAC14 Zornitza Stark Marked gene: VAC14 as ready
Regression v0.202 VAC14 Zornitza Stark Gene: vac14 has been classified as Green List (High Evidence).
Regression v0.202 VAC14 Zornitza Stark Phenotypes for gene: VAC14 were changed from to Striatonigral degeneration, childhood-onset, MIM#617054
Regression v0.201 VAC14 Zornitza Stark Publications for gene: VAC14 were set to
Regression v0.200 VAC14 Zornitza Stark Mode of inheritance for gene: VAC14 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5168 VAC14 Zornitza Stark Marked gene: VAC14 as ready
Mendeliome v0.5168 VAC14 Zornitza Stark Gene: vac14 has been classified as Green List (High Evidence).
Regression v0.199 VAC14 Zornitza Stark reviewed gene: VAC14: Rating: GREEN; Mode of pathogenicity: None; Publications: 27292112, 31392254, 31591492, 31387860, 31876398; Phenotypes: Striatonigral degeneration, childhood-onset, MIM#617054; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5168 VAC14 Zornitza Stark Phenotypes for gene: VAC14 were changed from to Striatonigral degeneration, childhood-onset, MIM#617054
Mendeliome v0.5167 VAC14 Zornitza Stark Publications for gene: VAC14 were set to
Mendeliome v0.5166 VAC14 Zornitza Stark Mode of inheritance for gene: VAC14 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5165 VAC14 Zornitza Stark reviewed gene: VAC14: Rating: GREEN; Mode of pathogenicity: None; Publications: 27292112, 31392254, 31591492, 31387860, 31876398; Phenotypes: Striatonigral degeneration, childhood-onset, MIM#617054; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mackenzie's Mission_Reproductive Carrier Screening v0.44 ERBB3 Sarah Righetti changed review comment from: PMID 17701904: Lod score >9 in large Israeli family, also a second unrelated isolated case. Both families: hom 8bp insertion. Phenotype similar to that of null mice.

PMID 31752936: Compound het variants identified in 24mo Chinese female patient with a novel multisystem syndrome disorder without congenital contracture

PMID 28454995: Hom missense in Saudi Arabian individual with lethal congenital contractural syndrome, additional features: dysmorphic features, knee dislocation, bilaterial hip dislocation; to: PMID 17701904: Lod score >9 in large Israeli family, also a second unrelated isolated case. Both families: hom splice variant in intron 10 (IVS10-8A→G) causing fs & premature protein truncation. Fnal studies confirm aberrant splicing. Phenotype similar to that of null mice.

PMID 31752936: Compound het variants identified in 24mo Chinese female patient with a novel multisystem syndrome disorder without congenital contracture

PMID 28454995: Hom missense in Saudi Arabian individual with lethal congenital contractural syndrome, additional features: dysmorphic features, knee dislocation, bilaterial hip dislocation
Mackenzie's Mission_Reproductive Carrier Screening v0.44 IL10RB Seb Lunke Marked gene: IL10RB as ready
Mackenzie's Mission_Reproductive Carrier Screening v0.44 IL10RB Seb Lunke Gene: il10rb has been classified as Green List (High Evidence).
Mackenzie's Mission_Reproductive Carrier Screening v0.44 IL10RB Seb Lunke Classified gene: IL10RB as Green List (high evidence)
Mackenzie's Mission_Reproductive Carrier Screening v0.44 IL10RB Seb Lunke Gene: il10rb has been classified as Green List (High Evidence).
Mackenzie's Mission_Reproductive Carrier Screening v0.43 PRKRA Seb Lunke Marked gene: PRKRA as ready
Mackenzie's Mission_Reproductive Carrier Screening v0.43 PRKRA Seb Lunke Gene: prkra has been classified as Green List (High Evidence).
Mackenzie's Mission_Reproductive Carrier Screening v0.43 PRKRA Seb Lunke Classified gene: PRKRA as Green List (high evidence)
Mackenzie's Mission_Reproductive Carrier Screening v0.43 PRKRA Seb Lunke Gene: prkra has been classified as Green List (High Evidence).
Mackenzie's Mission_Reproductive Carrier Screening v0.42 MSTO1 Seb Lunke Marked gene: MSTO1 as ready
Mackenzie's Mission_Reproductive Carrier Screening v0.42 MSTO1 Seb Lunke Gene: msto1 has been classified as Green List (High Evidence).
Mackenzie's Mission_Reproductive Carrier Screening v0.42 MSTO1 Seb Lunke Classified gene: MSTO1 as Green List (high evidence)
Mackenzie's Mission_Reproductive Carrier Screening v0.42 MSTO1 Seb Lunke Gene: msto1 has been classified as Green List (High Evidence).
Mackenzie's Mission_Reproductive Carrier Screening v0.41 XPNPEP3 Seb Lunke Marked gene: XPNPEP3 as ready
Mackenzie's Mission_Reproductive Carrier Screening v0.41 XPNPEP3 Seb Lunke Gene: xpnpep3 has been classified as Amber List (Moderate Evidence).
Mackenzie's Mission_Reproductive Carrier Screening v0.41 XPNPEP3 Seb Lunke Classified gene: XPNPEP3 as Amber List (moderate evidence)
Mackenzie's Mission_Reproductive Carrier Screening v0.41 XPNPEP3 Seb Lunke Gene: xpnpep3 has been classified as Amber List (Moderate Evidence).
Mackenzie's Mission_Reproductive Carrier Screening v0.40 UQCRC2 Seb Lunke Marked gene: UQCRC2 as ready
Mackenzie's Mission_Reproductive Carrier Screening v0.40 UQCRC2 Seb Lunke Gene: uqcrc2 has been classified as Red List (Low Evidence).
Mackenzie's Mission_Reproductive Carrier Screening v0.40 UQCRC2 Seb Lunke Classified gene: UQCRC2 as Red List (low evidence)
Mackenzie's Mission_Reproductive Carrier Screening v0.40 UQCRC2 Seb Lunke Added comment: Comment on list classification: Single variant only, borderline amber for dx, red for screening.
Mackenzie's Mission_Reproductive Carrier Screening v0.40 UQCRC2 Seb Lunke Gene: uqcrc2 has been classified as Red List (Low Evidence).
Mackenzie's Mission_Reproductive Carrier Screening v0.39 PPIB Seb Lunke Marked gene: PPIB as ready
Mackenzie's Mission_Reproductive Carrier Screening v0.39 PPIB Seb Lunke Gene: ppib has been classified as Green List (High Evidence).
Mackenzie's Mission_Reproductive Carrier Screening v0.39 PPIB Seb Lunke Classified gene: PPIB as Green List (high evidence)
Mackenzie's Mission_Reproductive Carrier Screening v0.39 PPIB Seb Lunke Gene: ppib has been classified as Green List (High Evidence).
Mackenzie's Mission_Reproductive Carrier Screening v0.38 GALT Seb Lunke Classified gene: GALT as Green List (high evidence)
Mackenzie's Mission_Reproductive Carrier Screening v0.38 GALT Seb Lunke Gene: galt has been classified as Green List (High Evidence).
Mackenzie's Mission_Reproductive Carrier Screening v0.37 TUBA8 Seb Lunke Marked gene: TUBA8 as ready
Mackenzie's Mission_Reproductive Carrier Screening v0.37 TUBA8 Seb Lunke Gene: tuba8 has been classified as Red List (Low Evidence).
Mackenzie's Mission_Reproductive Carrier Screening v0.37 TUBA8 Seb Lunke Classified gene: TUBA8 as Red List (low evidence)
Mackenzie's Mission_Reproductive Carrier Screening v0.37 TUBA8 Seb Lunke Gene: tuba8 has been classified as Red List (Low Evidence).
Mackenzie's Mission_Reproductive Carrier Screening v0.36 SPEG Seb Lunke Classified gene: SPEG as Green List (high evidence)
Mackenzie's Mission_Reproductive Carrier Screening v0.36 SPEG Seb Lunke Added comment: Comment on list classification: Agreed green gene, update gene selection committee at next meeting.
Mackenzie's Mission_Reproductive Carrier Screening v0.36 SPEG Seb Lunke Gene: speg has been classified as Green List (High Evidence).
Mackenzie's Mission_Reproductive Carrier Screening v0.35 TSPYL1 Seb Lunke Marked gene: TSPYL1 as ready
Mackenzie's Mission_Reproductive Carrier Screening v0.35 TSPYL1 Seb Lunke Gene: tspyl1 has been classified as Red List (Low Evidence).
Mackenzie's Mission_Reproductive Carrier Screening v0.35 TSPYL1 Seb Lunke Classified gene: TSPYL1 as Red List (low evidence)
Mackenzie's Mission_Reproductive Carrier Screening v0.35 TSPYL1 Seb Lunke Added comment: Comment on list classification: Agreed amber in diagnostic, but for screening test would need a fair bit of extra evidence.
Mackenzie's Mission_Reproductive Carrier Screening v0.35 TSPYL1 Seb Lunke Gene: tspyl1 has been classified as Red List (Low Evidence).
Mackenzie's Mission_Reproductive Carrier Screening v0.34 PIP5K1C Seb Lunke Marked gene: PIP5K1C as ready
Mackenzie's Mission_Reproductive Carrier Screening v0.34 PIP5K1C Seb Lunke Gene: pip5k1c has been classified as Red List (Low Evidence).
Mackenzie's Mission_Reproductive Carrier Screening v0.34 PIP5K1C Seb Lunke Classified gene: PIP5K1C as Red List (low evidence)
Mackenzie's Mission_Reproductive Carrier Screening v0.34 PIP5K1C Seb Lunke Added comment: Comment on list classification: Agreed amber in diagnostic, but for screening test would need a fair bit of extra evidence.
Mackenzie's Mission_Reproductive Carrier Screening v0.34 PIP5K1C Seb Lunke Gene: pip5k1c has been classified as Red List (Low Evidence).
Mackenzie's Mission_Reproductive Carrier Screening v0.33 VAC14 Sarah Righetti gene: VAC14 was added
gene: VAC14 was added to Mackenzie's Mission_Reproductive Carrier Screening. Sources: Expert Review
Mode of inheritance for gene: VAC14 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: VAC14 were set to 27292112; 31392254; 31591492; 31387860; 31876398
Phenotypes for gene: VAC14 were set to Striatonigral degeneration, childhood-onset, MIM#617054
Review for gene: VAC14 was set to GREEN
Added comment: Multiple reports in unrelated patients
Sources: Expert Review
Mackenzie's Mission_Reproductive Carrier Screening v0.33 AFF2 Seb Lunke Marked gene: AFF2 as ready
Mackenzie's Mission_Reproductive Carrier Screening v0.33 AFF2 Seb Lunke Gene: aff2 has been classified as Red List (Low Evidence).
Mackenzie's Mission_Reproductive Carrier Screening v0.33 AFF2 Seb Lunke Classified gene: AFF2 as Red List (low evidence)
Mackenzie's Mission_Reproductive Carrier Screening v0.33 AFF2 Seb Lunke Gene: aff2 has been classified as Red List (Low Evidence).
Myopathy Superpanel v1.3 Zornitza Stark Panel types changed to Victorian Clinical Genetics Services; Royal Melbourne Hospital; Rare Disease
Mackenzie's Mission_Reproductive Carrier Screening v0.32 PRKRA Sarah Righetti gene: PRKRA was added
gene: PRKRA was added to Mackenzie's Mission_Reproductive Carrier Screening. Sources: Expert Review
Mode of inheritance for gene: PRKRA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PRKRA were set to 29279192; 25142429
Phenotypes for gene: PRKRA were set to Dystonia 16, MIM#612067
Review for gene: PRKRA was set to GREEN
Added comment: Sufficient reports - most common variant is c.665C>T p.Pro222Leu, rs121434410

PMID 29279192 (2017)- 7 patients in Brazilian cohort - most homozygous for P222L
PMID 2514249: (2014) - 2 Polish sibs - hom for P222L
Sources: Expert Review
Mackenzie's Mission_Reproductive Carrier Screening v0.32 MSTO1 Sarah Righetti gene: MSTO1 was added
gene: MSTO1 was added to Mackenzie's Mission_Reproductive Carrier Screening. Sources: Expert Review
Mode of inheritance for gene: MSTO1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MSTO1 were set to 31463572; 30684668
Phenotypes for gene: MSTO1 were set to Myopathy, mitochondrial, and ataxia, MIM#617675
Review for gene: MSTO1 was set to GREEN
Added comment: PMID 31463572: 12 patients
PMID 30684668: 2 sibs - compound het fs and missense.
Sources: Expert Review
Mackenzie's Mission_Reproductive Carrier Screening v0.32 IL10RB Sarah Righetti changed review comment from: Sufficient patients reported (note protein encoded by IL10RB is IL10R2)

19890111: 2 affected sibs with hom stop-gain.
22549091: 8 patients - although a couple where the pathogenicity is in doubt, sufficient overall evidence. Note patient 1 and patient 2 (siblings sharing the same homozygous mutation) had different disease severity) - likely to be other factors which contribute to phenotype.

Severe phenotype.; to: Sufficient patients reported (note protein encoded by IL10RB is IL10R2)

19890111: 2 affected sibs with hom stop-gain.
22549091: 8 patients - although a couple where the pathogenicity is in doubt, sufficient overall evidence. Note patient 1 and patient 2 (siblings sharing the same homozygous mutation) had different disease severity - likely to be other factors which contribute to phenotype.

Severe phenotype.
Mackenzie's Mission_Reproductive Carrier Screening v0.32 IL10RB Sarah Righetti Deleted their comment
Mackenzie's Mission_Reproductive Carrier Screening v0.32 IL10RB Sarah Righetti commented on gene: IL10RB: Sufficient patients reported (note protein encoded by IL10RB is IL10R2)

19890111: 2 affected sibs with hom stop-gain.
22549091: 8 patients - although a couple where the pathogenicity is in doubt, sufficient overall evidence. Note patient 1 and patient 2 (siblings sharing the same homozygous mutation) had different disease severity) - likely to be other factors which contribute to phenotype.

Severe phenotype.
Mackenzie's Mission_Reproductive Carrier Screening v0.32 IL10RB Sarah Righetti reviewed gene: IL10RB: Rating: GREEN; Mode of pathogenicity: None; Publications: 19890111, 22549091; Phenotypes: Inflammatory bowel disease 25, early onset, autosomal recessive, MIM#612567; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mackenzie's Mission_Reproductive Carrier Screening v0.32 IL10RB Sarah Righetti Deleted their review
Mackenzie's Mission_Reproductive Carrier Screening v0.32 IL10RB Sarah Righetti gene: IL10RB was added
gene: IL10RB was added to Mackenzie's Mission_Reproductive Carrier Screening. Sources: Expert Review
Mode of inheritance for gene: IL10RB was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IL10RB were set to 22549091
Phenotypes for gene: IL10RB were set to Inflammatory bowel disease 25, early onset, #MIM612657
Review for gene: IL10RB was set to GREEN
Added comment: Sources: Expert Review
Mackenzie's Mission_Reproductive Carrier Screening v0.32 XPNPEP3 Sarah Righetti reviewed gene: XPNPEP3: Rating: AMBER; Mode of pathogenicity: None; Publications: 20179356, 32660933; Phenotypes: Nephronophthisis-like nephropathy 1, MIM# 613159; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mackenzie's Mission_Reproductive Carrier Screening v0.32 UQCRC2 Sarah Righetti reviewed gene: UQCRC2: Rating: AMBER; Mode of pathogenicity: None; Publications: 28275242, 23281071; Phenotypes: Mitochondrial complex III deficiency, nuclear type 5, MIM# 615160; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mackenzie's Mission_Reproductive Carrier Screening v0.32 PPIB Sarah Righetti changed review comment from: Sources: Expert Review; to: >10 cases across multiple reports, severe phenotype
Mackenzie's Mission_Reproductive Carrier Screening v0.32 PPIB Sarah Righetti gene: PPIB was added
gene: PPIB was added to Mackenzie's Mission_Reproductive Carrier Screening. Sources: Expert Review
Mode of inheritance for gene: PPIB was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PPIB were set to Osteogenesis imperfecta, type IX, #259440
Review for gene: PPIB was set to GREEN
Added comment: Sources: Expert Review
Mendeliome v0.5165 PHOX2A Zornitza Stark Publications for gene: PHOX2A were set to 11600883; 18323871
Mendeliome v0.5164 PHOX2A Zornitza Stark reviewed gene: PHOX2A: Rating: GREEN; Mode of pathogenicity: None; Publications: 16815872; Phenotypes: Fibrosis of extraocular muscles, congenital, 2 602078; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5164 PHOX2A Zornitza Stark Classified gene: PHOX2A as Green List (high evidence)
Mendeliome v0.5164 PHOX2A Zornitza Stark Gene: phox2a has been classified as Green List (High Evidence).
Mendeliome v0.5163 COL25A1 Zornitza Stark Marked gene: COL25A1 as ready
Mendeliome v0.5163 COL25A1 Zornitza Stark Gene: col25a1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5163 COL25A1 Zornitza Stark Phenotypes for gene: COL25A1 were changed from to Fibrosis of extraocular muscles, congenital, 5, MIM# 616219
Mendeliome v0.5162 COL25A1 Zornitza Stark Publications for gene: COL25A1 were set to
Mendeliome v0.5161 COL25A1 Zornitza Stark Mode of inheritance for gene: COL25A1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5160 COL25A1 Zornitza Stark Classified gene: COL25A1 as Amber List (moderate evidence)
Mendeliome v0.5160 COL25A1 Zornitza Stark Gene: col25a1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5159 COL25A1 Zornitza Stark reviewed gene: COL25A1: Rating: AMBER; Mode of pathogenicity: None; Publications: 25500261, 26486031; Phenotypes: Fibrosis of extraocular muscles, congenital, 5, MIM# 616219; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital ophthalmoplegia v0.8 COL25A1 Zornitza Stark Marked gene: COL25A1 as ready
Congenital ophthalmoplegia v0.8 COL25A1 Zornitza Stark Gene: col25a1 has been classified as Amber List (Moderate Evidence).
Congenital ophthalmoplegia v0.8 COL25A1 Zornitza Stark Phenotypes for gene: COL25A1 were changed from Fibrosis of extraocular muscles, congenital, 5; Fibrosis of extraocular muscles, congenital, 5 616219 to Fibrosis of extraocular muscles, congenital, 5, MIM# 616219
Congenital ophthalmoplegia v0.7 COL25A1 Zornitza Stark Publications for gene: COL25A1 were set to 25500261
Mendeliome v0.5159 KIF21A Zornitza Stark Marked gene: KIF21A as ready
Mendeliome v0.5159 KIF21A Zornitza Stark Gene: kif21a has been classified as Green List (High Evidence).
Mendeliome v0.5159 KIF21A Zornitza Stark Phenotypes for gene: KIF21A were changed from to Fibrosis of extraocular muscles, congenital, 1/3B, MIM# 135700
Mendeliome v0.5158 KIF21A Zornitza Stark Publications for gene: KIF21A were set to
Mendeliome v0.5157 KIF21A Zornitza Stark Mode of inheritance for gene: KIF21A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5156 KIF21A Zornitza Stark reviewed gene: KIF21A: Rating: GREEN; Mode of pathogenicity: None; Publications: 15621876, 15223798, 15621877, 18332320, 28930843, 27513105, 26190014, 24656932; Phenotypes: Fibrosis of extraocular muscles, congenital, 1/3B, MIM# 135700; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital ophthalmoplegia v0.6 KIF21A Zornitza Stark Marked gene: KIF21A as ready
Congenital ophthalmoplegia v0.6 KIF21A Zornitza Stark Gene: kif21a has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.6 KIF21A Zornitza Stark Phenotypes for gene: KIF21A were changed from Fibrosis of extraocular muscles, congenital, 1, MIM# 135700 to Fibrosis of extraocular muscles, congenital, 1/3B, MIM# 135700
Congenital ophthalmoplegia v0.5 KIF21A Zornitza Stark Phenotypes for gene: KIF21A were changed from Fibrosis of extraocular muscles, congenital, 1 135700; Congenital fibrosis of the extraocular muscles; Fibrosis of extraocular muscles, congenital, 3B 135700 to Fibrosis of extraocular muscles, congenital, 1, MIM# 135700
Congenital ophthalmoplegia v0.4 KIF21A Zornitza Stark Publications for gene: KIF21A were set to 15621876; 15223798; 15621877; 18332320
Congenital ophthalmoplegia v0.3 PHOX2A Zornitza Stark Marked gene: PHOX2A as ready
Congenital ophthalmoplegia v0.3 PHOX2A Zornitza Stark Gene: phox2a has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.3 PHOX2A Zornitza Stark Phenotypes for gene: PHOX2A were changed from Fibrosis of extraocular muscles, congenital, 2 602078; Fibrosis of extraocular muscles, congenital, 2 to Fibrosis of extraocular muscles, congenital, 2, MIM# 602078
Congenital ophthalmoplegia v0.2 PHOX2A Zornitza Stark Publications for gene: PHOX2A were set to 14597037; 22311481; 11600883
Congenital ophthalmoplegia v0.1 TUBB3 Zornitza Stark Marked gene: TUBB3 as ready
Congenital ophthalmoplegia v0.1 TUBB3 Zornitza Stark Gene: tubb3 has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.1 TUBB3 Zornitza Stark Publications for gene: TUBB3 were set to 27428177; 20074521
Congenital ophthalmoplegia v0.0 TUBB3 Zornitza Stark reviewed gene: TUBB3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Fibrosis of extraocular muscles, congenital, 3A, MIM# 600638; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital ophthalmoplegia v0.0 COL25A1 Shannon LeBlanc reviewed gene: COL25A1: Rating: AMBER; Mode of pathogenicity: None; Publications: OMID: 25500261, 26486031; Phenotypes: Fibrosis of extraocular muscles, congenital, 5, 610004; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital ophthalmoplegia v0.0 PHOX2A Shannon LeBlanc reviewed gene: PHOX2A: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 11600883, 14597037, 16815872; Phenotypes: Fibrosis of extraocular muscles, congenital, 2, 602078; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital ophthalmoplegia v0.0 KIF21A Shannon LeBlanc reviewed gene: KIF21A: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 14595441, 28930843, 27513105, 26190014, 24656932; Phenotypes: Fibrosis of extraocular muscles, congenital, 1, 135700, Fibrosis of extraocular muscles, congenital, 3B, 135700; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital ophthalmoplegia v0.0 TUBB3 Shannon LeBlanc reviewed gene: TUBB3: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID:27428177, 20074521, 26639658; Phenotypes: Fibrosis of extraocular muscles, congenital, 3A 600638, Cortical dysplasia, complex, with other brain malformations 1, 602661; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Disorders of immune dysregulation v0.70 GATA3 Zornitza Stark Mode of pathogenicity for gene: GATA3 was changed from None to Other
Disorders of immune dysregulation v0.69 GATA3 Zornitza Stark Marked gene: GATA3 as ready
Disorders of immune dysregulation v0.69 GATA3 Zornitza Stark Added comment: Comment when marking as ready: Dominant negative effect proposed.
Disorders of immune dysregulation v0.69 GATA3 Zornitza Stark Gene: gata3 has been classified as Amber List (Moderate Evidence).
Disorders of immune dysregulation v0.69 GATA3 Zornitza Stark Marked gene: GATA3 as ready
Disorders of immune dysregulation v0.69 GATA3 Zornitza Stark Gene: gata3 has been classified as Amber List (Moderate Evidence).
Disorders of immune dysregulation v0.69 GATA3 Zornitza Stark Phenotypes for gene: GATA3 were changed from Hypoparathyroidism, sensorineural deafness, and renal dysplasia MIM#146255 to Immune dysregulation; Hypoparathyroidism, sensorineural deafness, and renal dysplasia MIM#146255
Disorders of immune dysregulation v0.68 GATA3 Zornitza Stark Classified gene: GATA3 as Amber List (moderate evidence)
Disorders of immune dysregulation v0.68 GATA3 Zornitza Stark Gene: gata3 has been classified as Amber List (Moderate Evidence).
Mitochondrial disease v0.550 NDUFAF6 Zornitza Stark Marked gene: NDUFAF6 as ready
Mitochondrial disease v0.550 NDUFAF6 Zornitza Stark Gene: ndufaf6 has been classified as Green List (High Evidence).
Mitochondrial disease v0.550 NDUFAF6 Zornitza Stark Phenotypes for gene: NDUFAF6 were changed from to Mitochondrial complex I deficiency, nuclear type 17 (MIM#618239)
Mitochondrial disease v0.549 NDUFAF6 Zornitza Stark Publications for gene: NDUFAF6 were set to
Mitochondrial disease v0.548 NDUFAF6 Zornitza Stark Mode of inheritance for gene: NDUFAF6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5156 NDUFAF6 Zornitza Stark Marked gene: NDUFAF6 as ready
Mendeliome v0.5156 NDUFAF6 Zornitza Stark Gene: ndufaf6 has been classified as Green List (High Evidence).
Mendeliome v0.5156 NDUFAF6 Zornitza Stark Phenotypes for gene: NDUFAF6 were changed from to Mitochondrial complex I deficiency, nuclear type 17 (MIM#618239)
Mendeliome v0.5155 NDUFAF6 Zornitza Stark Publications for gene: NDUFAF6 were set to
Mendeliome v0.5154 NDUFAF6 Zornitza Stark Mode of inheritance for gene: NDUFAF6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v1.13 USH1C Zornitza Stark Phenotypes for gene: USH1C were changed from Usher syndrome, type 1C, MIM# 276904; Deafness, autosomal recessive 18A, MIM# 602092 to Usher syndrome, type 1C, MIM# 276904; Deafness, autosomal recessive 18A, MIM# 602092; Deafness, autosomal dominant
Deafness_IsolatedAndComplex v1.12 USH1C Zornitza Stark Publications for gene: USH1C were set to 10973247; 10973248; 11239869; 21203349; 12107438
Deafness_IsolatedAndComplex v1.11 USH1C Zornitza Stark Mode of inheritance for gene: USH1C was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mitochondrial disease v0.547 NDUFAF6 Ain Roesley reviewed gene: NDUFAF6: Rating: GREEN; Mode of pathogenicity: None; Publications: 30642748; Phenotypes: Mitochondrial complex I deficiency, nuclear type 17 (MIM#618239); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5153 NDUFAF6 Ain Roesley reviewed gene: NDUFAF6: Rating: GREEN; Mode of pathogenicity: None; Publications: 30642748; Phenotypes: Mitochondrial complex I deficiency, nuclear type 17 (MIM#618239); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v1.10 USH1C Elena Savva reviewed gene: USH1C: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31858762, 10973247, 10973248, 11239869, 21203349, 12107438; Phenotypes: Usher syndrome, type 1C, MIM# 276904, Deafness, autosomal recessive 18A, MIM# 602092, ?Non-syndromic hearing loss; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.5153 WNT5A Zornitza Stark Marked gene: WNT5A as ready
Mendeliome v0.5153 WNT5A Zornitza Stark Gene: wnt5a has been classified as Green List (High Evidence).
Mendeliome v0.5153 WNT5A Zornitza Stark Phenotypes for gene: WNT5A were changed from to Robinow syndrome, autosomal dominant 1, MIM#180700
Mendeliome v0.5152 WNT5A Zornitza Stark Publications for gene: WNT5A were set to
Mendeliome v0.5151 WNT5A Zornitza Stark Mode of inheritance for gene: WNT5A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5150 WNT5A Zornitza Stark reviewed gene: WNT5A: Rating: GREEN; Mode of pathogenicity: None; Publications: 19918918, 24716670, 27092434, 29276006, 31032853, 16602827, 12839624, 10021340; Phenotypes: Robinow syndrome, autosomal dominant 1, MIM#180700; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5150 CYP3A4 Zornitza Stark Marked gene: CYP3A4 as ready
Mendeliome v0.5150 CYP3A4 Zornitza Stark Gene: cyp3a4 has been classified as Green List (High Evidence).
Mendeliome v0.5150 CYP3A4 Zornitza Stark Phenotypes for gene: CYP3A4 were changed from to Vitamin D-dependent rickets-3, MIM#619073
Mendeliome v0.5149 CYP3A4 Zornitza Stark Publications for gene: CYP3A4 were set to
Mendeliome v0.5148 CYP3A4 Zornitza Stark Mode of pathogenicity for gene: CYP3A4 was changed from to Other
Mendeliome v0.5147 CYP3A4 Zornitza Stark Mode of inheritance for gene: CYP3A4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5146 CYP3A4 Zornitza Stark reviewed gene: CYP3A4: Rating: GREEN; Mode of pathogenicity: Other; Publications: 29461981; Phenotypes: Vitamin D-dependent rickets-3, MIM#619073; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Disorders of immune dysregulation v0.67 GATA3 Elena Savva gene: GATA3 was added
gene: GATA3 was added to Disorders of immune dysregulation. Sources: Literature
Mode of inheritance for gene: GATA3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: GATA3 were set to PMID: 31238969
Phenotypes for gene: GATA3 were set to Hypoparathyroidism, sensorineural deafness, and renal dysplasia MIM#146255
Review for gene: GATA3 was set to AMBER
gene: GATA3 was marked as current diagnostic
Added comment: PMID: 31238969: patient with protein elongation variant p.(M401Vfs*106) has an additional phenotype of juvenile idiopathic arthritis. Functional studies on the variant support pathogenicity, and analysis of patient cells indicate defective T helper cell differentiation and cytokine production.
Sources: Literature
Mendeliome v0.5146 KCTD17 Zornitza Stark Marked gene: KCTD17 as ready
Mendeliome v0.5146 KCTD17 Zornitza Stark Gene: kctd17 has been classified as Green List (High Evidence).
Mendeliome v0.5146 KCTD17 Zornitza Stark Phenotypes for gene: KCTD17 were changed from to Dystonia 26, myoclonic MIM#616398
Mendeliome v0.5145 KCTD17 Zornitza Stark Publications for gene: KCTD17 were set to
Mendeliome v0.5144 KCTD17 Zornitza Stark Mode of inheritance for gene: KCTD17 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5143 KCTD17 Zornitza Stark reviewed gene: KCTD17: Rating: GREEN; Mode of pathogenicity: None; Publications: 25983243, 30642807, 30579817; Phenotypes: Dystonia 26, myoclonic MIM#616398; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5143 TAF1 Zornitza Stark Tag deep intronic tag was added to gene: TAF1.
Tag founder tag was added to gene: TAF1.
Mendeliome v0.5143 TAF1 Zornitza Stark Marked gene: TAF1 as ready
Mendeliome v0.5143 TAF1 Zornitza Stark Gene: taf1 has been classified as Green List (High Evidence).
Mendeliome v0.5143 TAF1 Zornitza Stark Phenotypes for gene: TAF1 were changed from to Dystonia-Parkinsonism, X-linked, MIM# 314250; Mental retardation, X-linked, syndromic 33, MIM# 300966
Mendeliome v0.5142 TAF1 Zornitza Stark Publications for gene: TAF1 were set to
Mendeliome v0.5141 TAF1 Zornitza Stark Mode of inheritance for gene: TAF1 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.5140 TAF1 Zornitza Stark reviewed gene: TAF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 17273961, 31646703; Phenotypes: Dystonia-Parkinsonism, X-linked, MIM# 314250, Mental retardation, X-linked, syndromic 33, MIM# 300966; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.5140 CTNNA3 Bryony Thompson Marked gene: CTNNA3 as ready
Mendeliome v0.5140 CTNNA3 Bryony Thompson Gene: ctnna3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5140 CTNNA3 Bryony Thompson Classified gene: CTNNA3 as Amber List (moderate evidence)
Mendeliome v0.5140 CTNNA3 Bryony Thompson Gene: ctnna3 has been classified as Amber List (Moderate Evidence).
Arrhythmogenic Cardiomyopathy v0.47 CTNNA3 Bryony Thompson changed review comment from: Gene is classified as Limited by the ClinGen ARVC GCEP (Classification - 08/06/2019).
PMID: 23136403 - an assumed de novo missense (V94D) was identified in an Italian proband with arrhythmogenic right ventricular dysplasia. An inframe deletion (Leu765del) was identified in a proband with arrhythmogenic right ventricular dysplasia, and was also present in the proband's asymptomatic father and paternal aunt, who had mild right ventricular dilation on echocardiography and increased trabeculations in the right ventricular apex on MRI, respectively, as well as in the aunt's asymptomatic son. There was supporting in vitro functional assay evidence for both variants. PMID: 21254927 - a missense variant was found in one of 55 Danish ARVD patients, but was found 37 times in 276,338 (1 homozygous) reference alleles in gnomAD making it less likely as a causal variant. PMID: 22421363 - null mice exhibit progressive dilated cardiomyopathy, gap junction remodelling, and increased sensitivity to ventricular arrhythmia following acute ischaemia, but not spontaneous ARVC.
PMID: 30415094 - a VUS identified in a sudden unexpected death case with slight LV hypertrophy. PMID: 31539150 - 2 VUS and a nonsense variant identified in 3 probands with atrial fibrillation, with the nonsense variant segregating in an affected first-degree relative.
Sources: Other; to: Gene is classified as Limited by the ClinGen ARVC GCEP (Classification - 08/06/2019).
PMID: 23136403 - an assumed de novo missense (V94D) was identified in an Italian proband with arrhythmogenic right ventricular dysplasia. An inframe deletion (Leu765del) was identified in a proband with arrhythmogenic right ventricular dysplasia, and was also present in the proband's asymptomatic father and paternal aunt, who had mild right ventricular dilation on echocardiography and increased trabeculations in the right ventricular apex on MRI, respectively, as well as in the aunt's asymptomatic son. There was supporting in vitro functional assay evidence for both variants. PMID: 21254927 - a missense variant was found in one of 55 Danish ARVD patients, but was found 37 times in 276,338 (1 homozygous) reference alleles in gnomAD making it less likely as a causal variant. PMID: 22421363 - null mice exhibit progressive dilated cardiomyopathy, gap junction remodelling, and increased sensitivity to ventricular arrhythmia following acute ischaemia, but not spontaneous ARVC.
Additional publications identified - PMID: 30415094 - a VUS identified in a sudden unexpected death case with slight LV hypertrophy. PMID: 31539150 - 2 VUS and a nonsense variant identified in 3 probands with atrial fibrillation, with the nonsense variant segregating in an affected first-degree relative.
Sources: Other
Mendeliome v0.5139 CTNNA3 Bryony Thompson gene: CTNNA3 was added
gene: CTNNA3 was added to Mendeliome. Sources: ClinGen
Mode of inheritance for gene: CTNNA3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CTNNA3 were set to 23136403; 21254927; 22421363; 30415094; 31539150
Phenotypes for gene: CTNNA3 were set to Arrhythmogenic right ventricular cardiomyopathy; Arrhythmogenic right ventricular dysplasia, familial, 13 MIM#615616
Review for gene: CTNNA3 was set to AMBER
Added comment: Gene is classified as Limited by the ClinGen ARVC GCEP (Classification - 08/06/2019). PMID: 23136403 - an assumed de novo missense (V94D) was identified in an Italian proband with arrhythmogenic right ventricular dysplasia. An inframe deletion (Leu765del) was identified in a proband with arrhythmogenic right ventricular dysplasia, and was also present in the proband's asymptomatic father and paternal aunt, who had mild right ventricular dilation on echocardiography and increased trabeculations in the right ventricular apex on MRI, respectively, as well as in the aunt's asymptomatic son. There was supporting in vitro functional assay evidence for both variants. PMID: 21254927 - a missense variant was found in one of 55 Danish ARVD patients, but was found 37 times in 276,338 (1 homozygous) reference alleles in gnomAD making it less likely as a causal variant. PMID: 22421363 - null mice exhibit progressive dilated cardiomyopathy, gap junction remodelling, and increased sensitivity to ventricular arrhythmia following acute ischaemia, but not spontaneous ARVC. Additional publications identified - PMID: 30415094 - a VUS identified in a sudden unexpected death case with slight LV hypertrophy. PMID: 31539150 - 2 VUS and a nonsense variant identified in 3 probands with atrial fibrillation, with the nonsense variant segregating in an affected first-degree relative.
Sources: ClinGen
Arrhythmogenic Cardiomyopathy v0.47 CTNNA3 Bryony Thompson Classified gene: CTNNA3 as Amber List (moderate evidence)
Arrhythmogenic Cardiomyopathy v0.47 CTNNA3 Bryony Thompson Gene: ctnna3 has been classified as Amber List (Moderate Evidence).
Arrhythmogenic Cardiomyopathy v0.46 CTNNA3 Bryony Thompson gene: CTNNA3 was added
gene: CTNNA3 was added to Arrhythmogenic Cardiomyopathy. Sources: Other
Mode of inheritance for gene: CTNNA3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CTNNA3 were set to 23136403; 21254927; 22421363; 30415094; 31539150
Phenotypes for gene: CTNNA3 were set to Arrhythmogenic right ventricular cardiomyopathy; Arrhythmogenic right ventricular dysplasia, familial, 13 MIM#615616
Review for gene: CTNNA3 was set to AMBER
Added comment: Gene is classified as Limited by the ClinGen ARVC GCEP (Classification - 08/06/2019).
PMID: 23136403 - an assumed de novo missense (V94D) was identified in an Italian proband with arrhythmogenic right ventricular dysplasia. An inframe deletion (Leu765del) was identified in a proband with arrhythmogenic right ventricular dysplasia, and was also present in the proband's asymptomatic father and paternal aunt, who had mild right ventricular dilation on echocardiography and increased trabeculations in the right ventricular apex on MRI, respectively, as well as in the aunt's asymptomatic son. There was supporting in vitro functional assay evidence for both variants. PMID: 21254927 - a missense variant was found in one of 55 Danish ARVD patients, but was found 37 times in 276,338 (1 homozygous) reference alleles in gnomAD making it less likely as a causal variant. PMID: 22421363 - null mice exhibit progressive dilated cardiomyopathy, gap junction remodelling, and increased sensitivity to ventricular arrhythmia following acute ischaemia, but not spontaneous ARVC.
PMID: 30415094 - a VUS identified in a sudden unexpected death case with slight LV hypertrophy. PMID: 31539150 - 2 VUS and a nonsense variant identified in 3 probands with atrial fibrillation, with the nonsense variant segregating in an affected first-degree relative.
Sources: Other
Ataxia v0.265 NUS1 Zornitza Stark Marked gene: NUS1 as ready
Ataxia v0.265 NUS1 Zornitza Stark Gene: nus1 has been classified as Green List (High Evidence).
Ataxia v0.265 NUS1 Zornitza Stark Phenotypes for gene: NUS1 were changed from Epilepsy, myoclonus, ataxia and scoliosis; ?Congenital disorder of glycosylation, type 1aa, 617082; Mental retardation, autosomal dominant 55, with seizures, 617831 to Epilepsy, myoclonus, ataxia and scoliosis; Mental retardation, autosomal dominant 55, with seizures, 617831
Ataxia v0.264 NUS1 Zornitza Stark Classified gene: NUS1 as Green List (high evidence)
Ataxia v0.264 NUS1 Zornitza Stark Gene: nus1 has been classified as Green List (High Evidence).
Ataxia v0.263 NUS1 Elena Savva gene: NUS1 was added
gene: NUS1 was added to Ataxia - paediatric. Sources: Literature
Mode of inheritance for gene: NUS1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: NUS1 were set to PMID: 31656175; 29100083
Phenotypes for gene: NUS1 were set to Epilepsy, myoclonus, ataxia and scoliosis; ?Congenital disorder of glycosylation, type 1aa, 617082; Mental retardation, autosomal dominant 55, with seizures, 617831
Review for gene: NUS1 was set to GREEN
Added comment: PMID: 31656175 - 2 unrelated patients with the same de novo splice variant and ataxia. Splice variant undergoes partial NMD.

PMID: 29100083 - 3 unrelated patients w/ 2 PTCs and an inframe exon 2 deletion. Only 1/3 was reported to have ataxia
Sources: Literature
Brain Channelopathies v0.32 ADCY5 Zornitza Stark Marked gene: ADCY5 as ready
Brain Channelopathies v0.32 ADCY5 Zornitza Stark Gene: adcy5 has been classified as Green List (High Evidence).
Brain Channelopathies v0.32 ADCY5 Zornitza Stark Phenotypes for gene: ADCY5 were changed from to Dyskinesia, familial, with facial myokymia, MIM# 606703
Brain Channelopathies v0.31 ADCY5 Zornitza Stark Publications for gene: ADCY5 were set to
Brain Channelopathies v0.30 ADCY5 Zornitza Stark Mode of inheritance for gene: ADCY5 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Brain Channelopathies v0.29 ADCY5 Zornitza Stark reviewed gene: ADCY5: Rating: GREEN; Mode of pathogenicity: None; Publications: 24700542, 22782511, 16537460; Phenotypes: Dyskinesia, familial, with facial myokymia, MIM# 606703; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital Myasthenia v1.0 Zornitza Stark promoted panel to version 1.0
Holoprosencephaly and septo-optic dysplasia v0.48 SHH Zornitza Stark Marked gene: SHH as ready
Holoprosencephaly and septo-optic dysplasia v0.48 SHH Zornitza Stark Gene: shh has been classified as Green List (High Evidence).
Holoprosencephaly and septo-optic dysplasia v0.48 SHH Zornitza Stark Phenotypes for gene: SHH were changed from to Holoprosencephaly 3 (MIM#142945)
Holoprosencephaly and septo-optic dysplasia v0.47 SHH Zornitza Stark Publications for gene: SHH were set to
Holoprosencephaly and septo-optic dysplasia v0.46 SHH Zornitza Stark Mode of inheritance for gene: SHH was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hydrocephalus_Ventriculomegaly v0.70 COG8 Zornitza Stark Marked gene: COG8 as ready
Hydrocephalus_Ventriculomegaly v0.70 COG8 Zornitza Stark Gene: cog8 has been classified as Red List (Low Evidence).
Hydrocephalus_Ventriculomegaly v0.70 COG8 Zornitza Stark Classified gene: COG8 as Red List (low evidence)
Hydrocephalus_Ventriculomegaly v0.70 COG8 Zornitza Stark Gene: cog8 has been classified as Red List (Low Evidence).
Arthrogryposis v0.239 COG8 Zornitza Stark Marked gene: COG8 as ready
Arthrogryposis v0.239 COG8 Zornitza Stark Gene: cog8 has been classified as Red List (Low Evidence).
Arthrogryposis v0.239 COG8 Zornitza Stark Classified gene: COG8 as Red List (low evidence)
Arthrogryposis v0.239 COG8 Zornitza Stark Gene: cog8 has been classified as Red List (Low Evidence).
Holoprosencephaly and septo-optic dysplasia v0.45 SHH Teresa Zhao reviewed gene: SHH: Rating: GREEN; Mode of pathogenicity: None; Publications: 22791840, 19057928; Phenotypes: 1. Holoprosencephaly 3 (MIM#142945), AD, 2. Microphthalmia with coloboma 5 (MIM#611638), AD, 3. Schizencephaly (MIM#269160), 4. Single median maxillary central incisor (MIM#147250) AD; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hydrocephalus_Ventriculomegaly v0.69 COG8 Elena Savva gene: COG8 was added
gene: COG8 was added to Hydrocephalus_Ventriculomegaly. Sources: Literature
Mode of inheritance for gene: COG8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COG8 were set to PMID: 30690882
Phenotypes for gene: COG8 were set to Congenital disorder of glycosylation, type IIh 611182
Review for gene: COG8 was set to RED
Added comment: PMID: 30690882: single patient with a homozygous splice COG8 variant, sibling was similarly affected but no DNA available. Patient displayed antenatal phenotype arthrogryposis multiplex congenita, Dandy Walker malformation and ventriculomegaly.
Sources: Literature
Arthrogryposis v0.238 COG8 Elena Savva gene: COG8 was added
gene: COG8 was added to Arthrogryposis. Sources: Literature
Mode of inheritance for gene: COG8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COG8 were set to PMID: 30690882
Phenotypes for gene: COG8 were set to Congenital disorder of glycosylation, type IIh 611182
Review for gene: COG8 was set to RED
Added comment: PMID: 30690882: single patient with a homozygous splice COG8 variant, sibling was similarly affected but no DNA available. Patient displayed antenatal phenotype arthrogryposis multiplex congenita, Dandy Walker malformation and ventriculomegaly.
Sources: Literature
Genetic Epilepsy v0.894 STXBP1 Zornitza Stark Phenotypes for gene: STXBP1 were changed from Epileptic encephalopathy, early infantile, 4, MIM#612164 to Developmental and epileptic encephalopathy 4, MIM# 612164
Genetic Epilepsy v0.893 STXBP1 Zornitza Stark edited their review of gene: STXBP1: Changed phenotypes: Developmental and epileptic encephalopathy 4, MIM# 612164
Mendeliome v0.5138 STXBP1 Zornitza Stark Phenotypes for gene: STXBP1 were changed from Epileptic encephalopathy, early infantile, 4 612164; Rett syndrome; Rett-like phenotypes to Developmental and epileptic encephalopathy 4, MIM# 612164; Rett syndrome; Rett-like phenotypes
Mendeliome v0.5137 STXBP1 Zornitza Stark reviewed gene: STXBP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Developmental and epileptic encephalopathy 4, MIM# 612164; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Angelman Rett like syndromes v0.24 STXBP1 Zornitza Stark Marked gene: STXBP1 as ready
Angelman Rett like syndromes v0.24 STXBP1 Zornitza Stark Gene: stxbp1 has been classified as Green List (High Evidence).
Angelman Rett like syndromes v0.24 STXBP1 Zornitza Stark Phenotypes for gene: STXBP1 were changed from to Developmental and epileptic encephalopathy 4, MIM# 612164
Angelman Rett like syndromes v0.23 STXBP1 Zornitza Stark Publications for gene: STXBP1 were set to
Angelman Rett like syndromes v0.22 STXBP1 Zornitza Stark Mode of inheritance for gene: STXBP1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Angelman Rett like syndromes v0.21 STXBP1 Zornitza Stark reviewed gene: STXBP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 31344879; Phenotypes: Developmental and epileptic encephalopathy 4, MIM# 612164; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5137 UBE3A Zornitza Stark Tag SV/CNV tag was added to gene: UBE3A.
Mendeliome v0.5137 UBE3A Zornitza Stark Phenotypes for gene: UBE3A were changed from to Angelman syndrome, MIM#105830
Mendeliome v0.5136 UBE3A Zornitza Stark Mode of inheritance for gene: UBE3A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
Mendeliome v0.5135 UBE3A Zornitza Stark reviewed gene: UBE3A: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Angelman syndrome, MIM#105830; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
Angelman Rett like syndromes v0.21 UBE3A Zornitza Stark Tag SV/CNV tag was added to gene: UBE3A.
Microcephaly v0.495 UBE3A Zornitza Stark Mode of inheritance for gene: UBE3A was changed from MONOALLELIC, autosomal or pseudoautosomal, maternally imprinted (paternal allele expressed) to MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
Microcephaly v0.494 UBE3A Zornitza Stark Tag SV/CNV tag was added to gene: UBE3A.
Microcephaly v0.494 UBE3A Zornitza Stark edited their review of gene: UBE3A: Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
Angelman Rett like syndromes v0.21 UBE3A Zornitza Stark Phenotypes for gene: UBE3A were changed from Angelman syndrome, MIM#105830 to Angelman syndrome, MIM#105830
Angelman Rett like syndromes v0.21 UBE3A Zornitza Stark Phenotypes for gene: UBE3A were changed from to Angelman syndrome, MIM#105830
Angelman Rett like syndromes v0.20 UBE3A Zornitza Stark Mode of inheritance for gene: UBE3A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
Angelman Rett like syndromes v0.19 UBE3A Zornitza Stark reviewed gene: UBE3A: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Angelman syndrome, MIM#105830; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
Mendeliome v0.5135 CHRNE Zornitza Stark Marked gene: CHRNE as ready
Mendeliome v0.5135 CHRNE Zornitza Stark Gene: chrne has been classified as Green List (High Evidence).
Mendeliome v0.5135 CHRNE Zornitza Stark Phenotypes for gene: CHRNE were changed from to Myasthenic syndrome, congenital, 4B, fast-channel, 616324; Myasthenic syndrome, congenital, 4C, associated with acetylcholine receptor deficiency, 608931; Myasthenic syndrome, slow-channel congenital, 601462; Myasthenic syndrome, congenital, 4A, slow-channel, 605809
Mendeliome v0.5134 CHRNE Zornitza Stark Publications for gene: CHRNE were set to
Mendeliome v0.5133 CHRNE Zornitza Stark Mode of inheritance for gene: CHRNE was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.5132 CHRNE Zornitza Stark reviewed gene: CHRNE: Rating: GREEN; Mode of pathogenicity: None; Publications: 8755487, 8957026, 11030414, 12417530, 32727330, 32070632, 31773638; Phenotypes: Myasthenic syndrome, congenital, 4B, fast-channel, 616324, Myasthenic syndrome, congenital, 4C, associated with acetylcholine receptor deficiency, 608931, Myasthenic syndrome, slow-channel congenital, 601462, Myasthenic syndrome, congenital, 4A, slow-channel, 605809; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Congenital Myasthenia v0.50 CHRNE Zornitza Stark Marked gene: CHRNE as ready
Congenital Myasthenia v0.50 CHRNE Zornitza Stark Gene: chrne has been classified as Green List (High Evidence).
Congenital Myasthenia v0.50 CHRNE Zornitza Stark Publications for gene: CHRNE were set to
Congenital Myasthenia v0.49 CHRNE Zornitza Stark edited their review of gene: CHRNE: Changed phenotypes: Myasthenic syndrome, congenital, 4B, fast-channel, 616324, Myasthenic syndrome, congenital, 4C, associated with acetylcholine receptor deficiency, 608931, Myasthenic syndrome, slow-channel congenital, 601462, Myasthenic syndrome, congenital, 4A, slow-channel, 605809
Congenital Myasthenia v0.49 CHRNE Zornitza Stark reviewed gene: CHRNE: Rating: GREEN; Mode of pathogenicity: None; Publications: 8755487, 8957026, 11030414, 12417530, 32727330, 32070632, 31773638; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Congenital Myasthenia v0.49 CHRND Zornitza Stark Marked gene: CHRND as ready
Congenital Myasthenia v0.49 CHRND Zornitza Stark Gene: chrnd has been classified as Green List (High Evidence).
Congenital Myasthenia v0.49 CHRND Zornitza Stark Phenotypes for gene: CHRND were changed from Myasthenic syndrome, congenital, 3B, fast-channel, 616322; Myasthenic syndrome, slow-channel congenital, 601462; ?Myasthenic syndrome, congenital, 3A, slow-channel, 616321; ?Myasthenic syndrome, congenital, 3C, associated with acetylcholine receptor deficiency, 616323 to Myasthenic syndrome, congenital, 3B, fast-channel, MIM#616322; Myasthenic syndrome, congenital, 3C, associated with acetylcholine receptor deficiency, MIM#616323; Myasthenic syndrome, congenital, 3A, slow-channel, MIM#616321
Congenital Myasthenia v0.48 CHRND Zornitza Stark Publications for gene: CHRND were set to
Congenital Myasthenia v0.47 CHRND Zornitza Stark edited their review of gene: CHRND: Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Congenital Myasthenia v0.47 CHRND Zornitza Stark reviewed gene: CHRND: Rating: GREEN; Mode of pathogenicity: None; Publications: 16916845, 11435464, 12499478, 18398509, 11782989; Phenotypes: Myasthenic syndrome, congenital, 3B, fast-channel, MIM#616322, Myasthenic syndrome, congenital, 3C, associated with acetylcholine receptor deficiency, MIM#616323, Myasthenic syndrome, congenital, 3A, slow-channel, MIM#616321; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5132 COLQ Zornitza Stark Marked gene: COLQ as ready
Mendeliome v0.5132 COLQ Zornitza Stark Gene: colq has been classified as Green List (High Evidence).
Mendeliome v0.5132 COLQ Zornitza Stark Phenotypes for gene: COLQ were changed from to Myasthenic syndrome, congenital, 5, MIM# 603034
Mendeliome v0.5131 COLQ Zornitza Stark Publications for gene: COLQ were set to
Mendeliome v0.5130 COLQ Zornitza Stark Mode of inheritance for gene: COLQ was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5129 COLQ Zornitza Stark reviewed gene: COLQ: Rating: GREEN; Mode of pathogenicity: None; Publications: 9689136, 9758617, 11865139, 32978031, 31831253; Phenotypes: Myasthenic syndrome, congenital, 5, MIM# 603034; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Myasthenia v0.47 COLQ Zornitza Stark Marked gene: COLQ as ready
Congenital Myasthenia v0.47 COLQ Zornitza Stark Gene: colq has been classified as Green List (High Evidence).
Congenital Myasthenia v0.47 COLQ Zornitza Stark Phenotypes for gene: COLQ were changed from Myasthenic syndrome, congenital, 5, 603034; Congenital myasthenic syndrome with endplate acetylcholinesterase deficiency to Myasthenic syndrome, congenital, 5, MIM# 603034; Congenital myasthenic syndrome with endplate acetylcholinesterase deficiency
Congenital Myasthenia v0.46 COLQ Zornitza Stark Publications for gene: COLQ were set to
Congenital Myasthenia v0.45 COLQ Zornitza Stark reviewed gene: COLQ: Rating: GREEN; Mode of pathogenicity: None; Publications: 9689136, 9758617, 11865139, 32978031, 31831253; Phenotypes: Myasthenic syndrome, congenital, 5, MIM# 603034; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Myasthenia v0.45 CHRNG Zornitza Stark Marked gene: CHRNG as ready
Congenital Myasthenia v0.45 CHRNG Zornitza Stark Gene: chrng has been classified as Green List (High Evidence).
Congenital Myasthenia v0.45 CHRNG Zornitza Stark Phenotypes for gene: CHRNG were changed from fetal akinesia deformation sequence syndrome/FADS; multiple pterygium syndrome/MPS; Neonatal congenital myasthenia; escobar syndrome; Myasthenia gravis, neonatal transient to Multiple pterygium syndrome, lethal type, MIM# 253290; fetal akinesia deformation sequence syndrome/FADS; multiple pterygium syndrome/MPS; Neonatal congenital myasthenia; escobar syndrome; Myasthenia gravis, neonatal transient
Congenital Myasthenia v0.44 CHRNG Zornitza Stark Publications for gene: CHRNG were set to
Congenital Myasthenia v0.43 CHRNG Zornitza Stark reviewed gene: CHRNG: Rating: GREEN; Mode of pathogenicity: None; Publications: 22167768; Phenotypes: Multiple pterygium syndrome, lethal type, MIM# 253290; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v0.38 NDUFA4 Zornitza Stark Marked gene: NDUFA4 as ready
Cardiomyopathy_Paediatric v0.38 NDUFA4 Zornitza Stark Gene: ndufa4 has been classified as Red List (Low Evidence).
Cardiomyopathy_Paediatric v0.38 NDUFA4 Zornitza Stark Phenotypes for gene: NDUFA4 were changed from No OMIM phenotype to Mitochondrial complex IV deficiency, nuclear type 21, MIM#619065
Cardiomyopathy_Paediatric v0.37 NDUFA4 Zornitza Stark Publications for gene: NDUFA4 were set to 23746447, 29636225
Cardiomyopathy_Paediatric v0.36 NDUFA4 Zornitza Stark Classified gene: NDUFA4 as Red List (low evidence)
Cardiomyopathy_Paediatric v0.36 NDUFA4 Zornitza Stark Gene: ndufa4 has been classified as Red List (Low Evidence).
Cardiomyopathy_Paediatric v0.35 NDUFA4 Zornitza Stark reviewed gene: NDUFA4: Rating: RED; Mode of pathogenicity: None; Publications: 30361421, 28988874, 23746447; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 21, MIM#619065; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Regression v0.199 NDUFA4 Zornitza Stark Phenotypes for gene: NDUFA4 were changed from Leigh syndrome; Complex IV deficiency to Mitochondrial complex IV deficiency, nuclear type 21, MIM#619065; Leigh syndrome; Complex IV deficiency
Regression v0.199 NDUFA4 Zornitza Stark Mode of inheritance for gene: NDUFA4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Regression v0.198 NDUFA4 Zornitza Stark edited their review of gene: NDUFA4: Changed phenotypes: Mitochondrial complex IV deficiency, nuclear type 21, MIM#619065, Leigh syndrome, Complex IV deficiency
Mendeliome v0.5129 NDUFA4 Zornitza Stark Phenotypes for gene: NDUFA4 were changed from Leigh syndrome; Complex IV deficiency to Mitochondrial complex IV deficiency, nuclear type 21, MIM#619065; Leigh syndrome; Complex IV deficiency
Mendeliome v0.5128 NDUFA4 Zornitza Stark edited their review of gene: NDUFA4: Changed phenotypes: Mitochondrial complex IV deficiency, nuclear type 21, MIM#619065, Leigh syndrome, Complex IV deficiency
Mitochondrial disease v0.547 NDUFA4 Zornitza Stark edited their review of gene: NDUFA4: Changed phenotypes: Mitochondrial complex IV deficiency, nuclear type 21, MIM#619065, Leigh syndrome, Complex IV deficiency
Mendeliome v0.5128 COX5A Zornitza Stark Phenotypes for gene: COX5A were changed from pulmonary arterial hypertension; lactic acidemia; failure to thrive; isolated complex IV deficiency to Mitochondrial complex IV deficiency, nuclear type 20, MIM#619064; pulmonary arterial hypertension; lactic acidemia; failure to thrive; isolated complex IV deficiency
Mendeliome v0.5127 COX5A Zornitza Stark edited their review of gene: COX5A: Changed phenotypes: Mitochondrial complex IV deficiency, nuclear type 20, MIM#619064, pulmonary arterial hypertension, lactic acidemia, failure to thrive, isolated complex IV deficiency
Mitochondrial disease v0.547 COX5A Zornitza Stark Phenotypes for gene: COX5A were changed from pulmonary arterial hypertension; lactic acidemia; failure to thrive; isolated complex IV deficiency to Mitochondrial complex IV deficiency, nuclear type 20, MIM#619064; pulmonary arterial hypertension; lactic acidemia; failure to thrive; isolated complex IV deficiency
Mitochondrial disease v0.546 COX5A Zornitza Stark reviewed gene: COX5A: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 20, MIM#619064; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5127 PET117 Zornitza Stark Phenotypes for gene: PET117 were changed from Developmental delay; Regression; Complex IV deficiency to Mitochondrial complex IV deficiency, nuclear type 19, MIM#619063; Developmental delay; Regression; Complex IV deficiency
Mendeliome v0.5126 PET117 Zornitza Stark edited their review of gene: PET117: Changed phenotypes: Mitochondrial complex IV deficiency, nuclear type 19, MIM#619063, Developmental delay, Regression, Complex IV deficiency
Mitochondrial disease v0.546 PET117 Zornitza Stark Phenotypes for gene: PET117 were changed from Developmental delay to Mitochondrial complex IV deficiency, nuclear type 19, MIM#619063; Developmental delay
Mitochondrial disease v0.545 PET117 Zornitza Stark reviewed gene: PET117: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 19, MIM#619063; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5126 COX6A2 Zornitza Stark Phenotypes for gene: COX6A2 were changed from Mitochondrial complex IV deficiency, MIM# 220110 to Mitochondrial complex IV deficiency, nuclear type 18, MIM#619062
Mendeliome v0.5125 COX6A2 Zornitza Stark edited their review of gene: COX6A2: Changed phenotypes: Mitochondrial complex IV deficiency, nuclear type 18, MIM#619062
Mitochondrial disease v0.545 COX6A2 Zornitza Stark Phenotypes for gene: COX6A2 were changed from Mitochondrial complex IV deficiency, MIM# 220110 to Mitochondrial complex IV deficiency, nuclear type 18, MIM#619062
Mitochondrial disease v0.544 COX6A2 Zornitza Stark edited their review of gene: COX6A2: Changed phenotypes: Mitochondrial complex IV deficiency, nuclear type 18, MIM#619062
Intellectual disability syndromic and non-syndromic v0.3118 APOPT1 Zornitza Stark Marked gene: APOPT1 as ready
Intellectual disability syndromic and non-syndromic v0.3118 APOPT1 Zornitza Stark Gene: apopt1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3118 APOPT1 Zornitza Stark Phenotypes for gene: APOPT1 were changed from Mitochondrial complex IV deficiency, nuclear type 17, MIM#619061 to Mitochondrial complex IV deficiency, nuclear type 17, MIM#619061
Regression v0.198 APOPT1 Zornitza Stark Marked gene: APOPT1 as ready
Regression v0.198 APOPT1 Zornitza Stark Gene: apopt1 has been classified as Green List (High Evidence).
Regression v0.198 APOPT1 Zornitza Stark Classified gene: APOPT1 as Green List (high evidence)
Regression v0.198 APOPT1 Zornitza Stark Gene: apopt1 has been classified as Green List (High Evidence).
Regression v0.198 APOPT1 Zornitza Stark Classified gene: APOPT1 as Green List (high evidence)
Regression v0.198 APOPT1 Zornitza Stark Gene: apopt1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3117 APOPT1 Zornitza Stark Phenotypes for gene: APOPT1 were changed from to Mitochondrial complex IV deficiency, nuclear type 17, MIM#619061
Regression v0.197 APOPT1 Zornitza Stark gene: APOPT1 was added
gene: APOPT1 was added to Regression. Sources: Expert list
Mode of inheritance for gene: APOPT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: APOPT1 were set to 25175347
Phenotypes for gene: APOPT1 were set to Mitochondrial complex IV deficiency, nuclear type 17, MIM#619061
Review for gene: APOPT1 was set to GREEN
Added comment: 6 individuals from 5 unrelated families reported, presenting in late infancy or early childhood with evidence of complex IV deficiency. Phenotype varied widely. Five individuals had episodes of neurologic regression manifest as gait difficulties and spastic tetraparesis, sensorimotor polyneuropathy, and dysarthria that in some cases improved over time. The sixth individual never developed neurologic signs. Three had normal cognition and 3 had impaired cognition. Brain imaging showed a cavitating leukodystrophy, predominantly affecting the posterior cerebral white matter and corpus callosum, that stabilized or even improved over time.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.3116 APOPT1 Zornitza Stark Publications for gene: APOPT1 were set to
Intellectual disability syndromic and non-syndromic v0.3115 APOPT1 Zornitza Stark Mode of inheritance for gene: APOPT1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3114 APOPT1 Zornitza Stark reviewed gene: APOPT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 25175347; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 17, MIM#619061; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disease v0.544 APOPT1 Zornitza Stark Marked gene: APOPT1 as ready
Mitochondrial disease v0.544 APOPT1 Zornitza Stark Gene: apopt1 has been classified as Green List (High Evidence).
Mendeliome v0.5125 APOPT1 Zornitza Stark Marked gene: APOPT1 as ready
Mendeliome v0.5125 APOPT1 Zornitza Stark Gene: apopt1 has been classified as Green List (High Evidence).
Mitochondrial disease v0.544 APOPT1 Zornitza Stark Phenotypes for gene: APOPT1 were changed from to Mitochondrial complex IV deficiency, nuclear type 17, MIM#619061
Mendeliome v0.5125 APOPT1 Zornitza Stark Phenotypes for gene: APOPT1 were changed from to Mitochondrial complex IV deficiency, nuclear type 17, MIM#619061
Mendeliome v0.5124 APOPT1 Zornitza Stark Publications for gene: APOPT1 were set to
Mitochondrial disease v0.543 APOPT1 Zornitza Stark Publications for gene: APOPT1 were set to 25175347
Mitochondrial disease v0.542 APOPT1 Zornitza Stark Publications for gene: APOPT1 were set to 25175347]
Mendeliome v0.5123 APOPT1 Zornitza Stark Mode of inheritance for gene: APOPT1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disease v0.542 APOPT1 Zornitza Stark Publications for gene: APOPT1 were set to 25175347]
Mendeliome v0.5122 APOPT1 Zornitza Stark reviewed gene: APOPT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 25175347]; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 17, MIM#619061; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disease v0.541 APOPT1 Zornitza Stark Publications for gene: APOPT1 were set to
Mitochondrial disease v0.540 APOPT1 Zornitza Stark Mode of inheritance for gene: APOPT1 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disease v0.540 APOPT1 Zornitza Stark Mode of inheritance for gene: APOPT1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disease v0.539 APOPT1 Zornitza Stark reviewed gene: APOPT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 25175347]; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 17, MIM#619061; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Regression v0.196 COX4I1 Zornitza Stark Marked gene: COX4I1 as ready
Regression v0.196 COX4I1 Zornitza Stark Gene: cox4i1 has been classified as Amber List (Moderate Evidence).
Regression v0.196 COX4I1 Zornitza Stark Classified gene: COX4I1 as Amber List (moderate evidence)
Regression v0.196 COX4I1 Zornitza Stark Gene: cox4i1 has been classified as Amber List (Moderate Evidence).
Regression v0.195 COX4I1 Zornitza Stark gene: COX4I1 was added
gene: COX4I1 was added to Regression. Sources: Expert list
Mode of inheritance for gene: COX4I1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COX4I1 were set to 28766551; 22592081; 31290619
Phenotypes for gene: COX4I1 were set to Mitochondrial complex IV deficiency, nuclear type 16, MIM#619060
Review for gene: COX4I1 was set to AMBER
Added comment: Two unrelated families reported, regression was a feature in both.
Sources: Expert list
Mendeliome v0.5122 COX4I1 Zornitza Stark Marked gene: COX4I1 as ready
Mendeliome v0.5122 COX4I1 Zornitza Stark Gene: cox4i1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5122 COX4I1 Zornitza Stark Classified gene: COX4I1 as Amber List (moderate evidence)
Mendeliome v0.5122 COX4I1 Zornitza Stark Gene: cox4i1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5121 COX4I1 Zornitza Stark gene: COX4I1 was added
gene: COX4I1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: COX4I1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COX4I1 were set to 28766551; 22592081; 31290619
Phenotypes for gene: COX4I1 were set to Mitochondrial complex IV deficiency, nuclear type 16, MIM#619060
Review for gene: COX4I1 was set to AMBER
Added comment: Two unrelated families reported.

Two more variants reported in PMID: 22592081: one is non-coding and the other rare missense, appear to have been identified in separate individuals, i.e. heterozygous in each individual.
Sources: Expert list
Mitochondrial disease v0.539 COX4I1 Zornitza Stark Phenotypes for gene: COX4I1 were changed from short stature; mild dysmorphic features; Fanconi anemia to Mitochondrial complex IV deficiency, nuclear type 16, MIM#619060; regression; seizures; short stature; mild dysmorphic features; Fanconi anemia
Mitochondrial disease v0.538 COX4I1 Zornitza Stark Publications for gene: COX4I1 were set to 28766551; 22592081
Mitochondrial disease v0.537 COX4I1 Zornitza Stark Classified gene: COX4I1 as Amber List (moderate evidence)
Mitochondrial disease v0.537 COX4I1 Zornitza Stark Gene: cox4i1 has been classified as Amber List (Moderate Evidence).
Mitochondrial disease v0.536 COX4I1 Zornitza Stark edited their review of gene: COX4I1: Added comment: Further family with two affected sibs reported in PMID 31290619, upgrade to Amber.; Changed rating: AMBER; Changed publications: 28766551, 22592081, 31290619; Changed phenotypes: Mitochondrial complex IV deficiency, nuclear type 16, MIM#619060
Mendeliome v0.5120 COX8A Zornitza Stark Phenotypes for gene: COX8A were changed from Mitochondrial complex IV deficiency, MIM# 220110 to Mitochondrial complex IV deficiency, nuclear type 15, MIM#619059
Mendeliome v0.5119 COX8A Zornitza Stark edited their review of gene: COX8A: Changed phenotypes: Mitochondrial complex IV deficiency, nuclear type 15, MIM#619059
Mitochondrial disease v0.536 COX8A Zornitza Stark Phenotypes for gene: COX8A were changed from Mitochondrial complex IV deficiency, MIM# 220110 to Mitochondrial complex IV deficiency, nuclear type 15, MIM#619059
Mitochondrial disease v0.535 COX8A Zornitza Stark edited their review of gene: COX8A: Changed phenotypes: Mitochondrial complex IV deficiency, nuclear type 15, MIM#619059
Intellectual disability syndromic and non-syndromic v0.3114 COA3 Zornitza Stark Phenotypes for gene: COA3 were changed from Mitochondrial complex IV deficiency to Mitochondrial complex IV deficiency, nuclear type 14, MIM# 619058
Intellectual disability syndromic and non-syndromic v0.3113 COA3 Zornitza Stark edited their review of gene: COA3: Changed phenotypes: Mitochondrial complex IV deficiency, nuclear type 14, MIM# 619058
Mendeliome v0.5119 COA3 Zornitza Stark Phenotypes for gene: COA3 were changed from Mitochondrial complex IV deficiency to Mitochondrial complex IV deficiency, nuclear type 14, MIM# 619058
Mendeliome v0.5118 COA3 Zornitza Stark edited their review of gene: COA3: Changed phenotypes: Mitochondrial complex IV deficiency, nuclear type 14, MIM# 619058
Mitochondrial disease v0.535 COA3 Zornitza Stark Phenotypes for gene: COA3 were changed from Mitochondrial complex IV deficiency to Mitochondrial complex IV deficiency, nuclear type 14, MIM#619058
Mitochondrial disease v0.534 COA3 Zornitza Stark edited their review of gene: COA3: Changed phenotypes: Mitochondrial complex IV deficiency, nuclear type 14, MIM# 619058
Regression v0.194 PET100 Zornitza Stark Marked gene: PET100 as ready
Regression v0.194 PET100 Zornitza Stark Gene: pet100 has been classified as Red List (Low Evidence).
Regression v0.194 PET100 Zornitza Stark Phenotypes for gene: PET100 were changed from to Mitochondrial complex IV deficiency, nuclear type 12, MIM# 619055
Regression v0.193 PET100 Zornitza Stark Publications for gene: PET100 were set to 24462369; 25293719; 31406627
Regression v0.193 PET100 Zornitza Stark Publications for gene: PET100 were set to
Regression v0.192 PET100 Zornitza Stark Mode of inheritance for gene: PET100 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Regression v0.191 PET100 Zornitza Stark Classified gene: PET100 as Red List (low evidence)
Regression v0.191 PET100 Zornitza Stark Gene: pet100 has been classified as Red List (Low Evidence).
Regression v0.190 PET100 Zornitza Stark reviewed gene: PET100: Rating: RED; Mode of pathogenicity: None; Publications: 24462369, 25293719, 31406627; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 12, MIM# 619055; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.893 PET100 Zornitza Stark Marked gene: PET100 as ready
Genetic Epilepsy v0.893 PET100 Zornitza Stark Gene: pet100 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.893 PET100 Zornitza Stark Phenotypes for gene: PET100 were changed from to Mitochondrial complex IV deficiency, nuclear type 12, MIM# 619055
Genetic Epilepsy v0.892 PET100 Zornitza Stark Publications for gene: PET100 were set to
Genetic Epilepsy v0.891 PET100 Zornitza Stark Mode of inheritance for gene: PET100 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.890 PET100 Zornitza Stark Tag founder tag was added to gene: PET100.
Genetic Epilepsy v0.890 PET100 Zornitza Stark reviewed gene: PET100: Rating: GREEN; Mode of pathogenicity: None; Publications: 24462369, 25293719, 31406627; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 12, MIM# 619055; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3113 PET100 Zornitza Stark Phenotypes for gene: PET100 were changed from Mitochondrial complex IV deficiency, MIM# 220110 to Mitochondrial complex IV deficiency, nuclear type 12, MIM# 619055
Intellectual disability syndromic and non-syndromic v0.3112 PET100 Zornitza Stark Tag founder tag was added to gene: PET100.
Intellectual disability syndromic and non-syndromic v0.3112 PET100 Zornitza Stark edited their review of gene: PET100: Changed phenotypes: Mitochondrial complex IV deficiency, nuclear type 12, MIM# 619055
Mendeliome v0.5118 PET100 Zornitza Stark Marked gene: PET100 as ready
Mendeliome v0.5118 PET100 Zornitza Stark Gene: pet100 has been classified as Green List (High Evidence).
Mendeliome v0.5118 PET100 Zornitza Stark Phenotypes for gene: PET100 were changed from to Mitochondrial complex IV deficiency, nuclear type 12, MIM# 619055
Mendeliome v0.5117 PET100 Zornitza Stark Publications for gene: PET100 were set to
Mendeliome v0.5116 PET100 Zornitza Stark Mode of inheritance for gene: PET100 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5115 PET100 Zornitza Stark Tag founder tag was added to gene: PET100.
Mendeliome v0.5115 PET100 Zornitza Stark reviewed gene: PET100: Rating: GREEN; Mode of pathogenicity: None; Publications: 24462369, 25293719, 31406627; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 12, MIM# 619055; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disease v0.534 PET100 Zornitza Stark Marked gene: PET100 as ready
Mitochondrial disease v0.534 PET100 Zornitza Stark Gene: pet100 has been classified as Green List (High Evidence).
Mitochondrial disease v0.534 PET100 Zornitza Stark Phenotypes for gene: PET100 were changed from to Mitochondrial complex IV deficiency, nuclear type 12, MIM# 619055
Mitochondrial disease v0.533 PET100 Zornitza Stark Publications for gene: PET100 were set to
Mitochondrial disease v0.532 PET100 Zornitza Stark Mode of inheritance for gene: PET100 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disease v0.531 PET100 Zornitza Stark Tag founder tag was added to gene: PET100.
Mitochondrial disease v0.531 PET100 Zornitza Stark reviewed gene: PET100: Rating: GREEN; Mode of pathogenicity: None; Publications: 24462369, 25293719, 31406627; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 12, MIM# 619055; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5115 COX20 Zornitza Stark Marked gene: COX20 as ready
Mendeliome v0.5115 COX20 Zornitza Stark Gene: cox20 has been classified as Green List (High Evidence).
Mendeliome v0.5115 COX20 Zornitza Stark Phenotypes for gene: COX20 were changed from to Mitochondrial complex IV deficiency, nuclear type 11, MIM#619054
Mendeliome v0.5114 COX20 Zornitza Stark Publications for gene: COX20 were set to
Mendeliome v0.5113 COX20 Zornitza Stark Mode of inheritance for gene: COX20 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5112 COX20 Zornitza Stark reviewed gene: COX20: Rating: GREEN; Mode of pathogenicity: None; Publications: 24202787, 31079202, 30656193, 23125284, 32606554; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 11, MIM#619054; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disease v0.531 COX20 Zornitza Stark Marked gene: COX20 as ready
Mitochondrial disease v0.531 COX20 Zornitza Stark Gene: cox20 has been classified as Green List (High Evidence).
Mitochondrial disease v0.531 COX20 Zornitza Stark Phenotypes for gene: COX20 were changed from to Mitochondrial complex IV deficiency, nuclear type 11, MIM#619054
Mitochondrial disease v0.530 COX20 Zornitza Stark Publications for gene: COX20 were set to
Mitochondrial disease v0.529 COX20 Zornitza Stark Mode of inheritance for gene: COX20 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disease v0.528 COX20 Zornitza Stark reviewed gene: COX20: Rating: GREEN; Mode of pathogenicity: None; Publications: 24202787, 31079202, 30656193, 23125284, 32606554; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 11, MIM#619054; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v0.35 COX14 Zornitza Stark Marked gene: COX14 as ready
Cardiomyopathy_Paediatric v0.35 COX14 Zornitza Stark Gene: cox14 has been classified as Amber List (Moderate Evidence).
Cardiomyopathy_Paediatric v0.35 COX14 Zornitza Stark Phenotypes for gene: COX14 were changed from ?Mitochondrial complex IV deficiency, 220110 to Mitochondrial complex IV deficiency, nuclear type 10, MIM# 619053
Cardiomyopathy_Paediatric v0.34 COX14 Zornitza Stark Publications for gene: COX14 were set to
Cardiomyopathy_Paediatric v0.33 COX14 Zornitza Stark Classified gene: COX14 as Amber List (moderate evidence)
Cardiomyopathy_Paediatric v0.33 COX14 Zornitza Stark Gene: cox14 has been classified as Amber List (Moderate Evidence).
Cardiomyopathy_Paediatric v0.32 COX14 Zornitza Stark reviewed gene: COX14: Rating: AMBER; Mode of pathogenicity: None; Publications: 22243966; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 10, MIM# 619053; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3112 COX14 Zornitza Stark Phenotypes for gene: COX14 were changed from Mitochondrial complex IV deficiency, MIM#220110 to Mitochondrial complex IV deficiency, nuclear type 10, MIM#619053
Intellectual disability syndromic and non-syndromic v0.3111 COX14 Zornitza Stark edited their review of gene: COX14: Changed phenotypes: Mitochondrial complex IV deficiency, nuclear type 10, MIM#619053
Regression v0.190 COX14 Zornitza Stark Phenotypes for gene: COX14 were changed from Mitochondrial complex IV deficiency, MIM#220110 to Mitochondrial complex IV deficiency, nuclear type 10, MIM#619053
Regression v0.189 COX14 Zornitza Stark edited their review of gene: COX14: Changed phenotypes: Mitochondrial complex IV deficiency, nuclear type 10, MIM#619053
Mendeliome v0.5112 COX14 Zornitza Stark Phenotypes for gene: COX14 were changed from Mitochondrial complex IV deficiency, MIM#220110 to Mitochondrial complex IV deficiency, nuclear type 10, MIM#619053
Mendeliome v0.5111 COX14 Zornitza Stark edited their review of gene: COX14: Changed phenotypes: Mitochondrial complex IV deficiency, nuclear type 10, MIM#619053
Mitochondrial disease v0.528 COX14 Zornitza Stark Phenotypes for gene: COX14 were changed from Mitochondrial complex IV deficiency, MIM#220110 to Mitochondrial complex IV deficiency, nuclear type 10, MIM# 619053
Mitochondrial disease v0.527 COX14 Zornitza Stark edited their review of gene: COX14: Changed phenotypes: Mitochondrial complex IV deficiency, nuclear type 10, MIM# 619053
Regression v0.189 TACO1 Zornitza Stark Marked gene: TACO1 as ready
Regression v0.189 TACO1 Zornitza Stark Gene: taco1 has been classified as Amber List (Moderate Evidence).
Regression v0.189 TACO1 Zornitza Stark Phenotypes for gene: TACO1 were changed from to Mitochondrial complex IV deficiency, nuclear type 8, MIM# 619052
Regression v0.188 TACO1 Zornitza Stark Publications for gene: TACO1 were set to
Regression v0.187 TACO1 Zornitza Stark Mode of inheritance for gene: TACO1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Regression v0.186 TACO1 Zornitza Stark Classified gene: TACO1 as Amber List (moderate evidence)
Regression v0.186 TACO1 Zornitza Stark Gene: taco1 has been classified as Amber List (Moderate Evidence).
Regression v0.185 TACO1 Zornitza Stark reviewed gene: TACO1: Rating: AMBER; Mode of pathogenicity: None; Publications: 19503089, 20727754, 25044680, 27319982; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 8, MIM# 619052; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5111 TACO1 Zornitza Stark Marked gene: TACO1 as ready
Mendeliome v0.5111 TACO1 Zornitza Stark Gene: taco1 has been classified as Green List (High Evidence).
Mendeliome v0.5111 TACO1 Zornitza Stark Phenotypes for gene: TACO1 were changed from to Mitochondrial complex IV deficiency, nuclear type 8, MIM# 619052
Mendeliome v0.5110 TACO1 Zornitza Stark Publications for gene: TACO1 were set to
Mendeliome v0.5109 TACO1 Zornitza Stark Mode of inheritance for gene: TACO1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5108 TACO1 Zornitza Stark reviewed gene: TACO1: Rating: GREEN; Mode of pathogenicity: None; Publications: 19503089, 20727754, 25044680, 27319982; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 8, MIM# 619052; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disease v0.527 TACO1 Zornitza Stark Phenotypes for gene: TACO1 were changed from Mitochondrial complex IV deficiency; OMIM #220110 to Mitochondrial complex IV deficiency, nuclear type 8, MIM# 619052
Mitochondrial disease v0.526 TACO1 Zornitza Stark edited their review of gene: TACO1: Changed phenotypes: Mitochondrial complex IV deficiency, nuclear type 8, MIM# 619052
Ciliopathies v0.217 PRKACA Zornitza Stark Marked gene: PRKACA as ready
Ciliopathies v0.217 PRKACA Zornitza Stark Gene: prkaca has been classified as Green List (High Evidence).
Ciliopathies v0.217 PRKACA Zornitza Stark Classified gene: PRKACA as Green List (high evidence)
Ciliopathies v0.217 PRKACA Zornitza Stark Gene: prkaca has been classified as Green List (High Evidence).
Ciliopathies v0.216 PRKACA Zornitza Stark gene: PRKACA was added
gene: PRKACA was added to Ciliopathies. Sources: Literature
Mode of inheritance for gene: PRKACA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PRKACA were set to 33058759; 31130284
Phenotypes for gene: PRKACA were set to Postaxial hand polydactyly; Postaxial foot polydactyly; Common atrium; Atrioventricular canal defect; Narrow chest; Abnormality of the teeth; Intellectual disability
Mode of pathogenicity for gene: PRKACA 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: PRKACA was set to GREEN
Added comment: Palencia-Campos et al (2020 - PMID: 33058759) report on the phenotype of 3 individuals heterozygous for PRKACA and 4 individuals heterozygous for PRKACB pathogenic variants.

Gene included in this panel due to significant overlap with ciliopathies.

The most characteristic features in all individuals with PRKACA/PRKACB mutation, included postaxial polydactyly of hands (6/7 bilateral, 1/7 unilateral) and feet (4/7 bilateral, 1/7 unilateral), brachydactyly and congenital heart defects (CHD 5/7) namely a common atrium or AVSD. Two individuals with PRKACA variant who did not have CHD had offspring with the same variant and an AVSD.

Other variably occurring features included short stature, limbs, narrow chest, abnormal teeth, oral frenula, nail dysplasia. One individual with PRKACB variant presented tumors.

Intellectual disability was reported in 2/4 individuals with PRKACB variant (1/4: mild, 1/4: severe). The 3 individuals with PRKACA variant did not present ID.

As the phenotype was overall suggestive of Ellis-van Creveld syndrome (or the allelic Weyers acrofacial dysostosis), although these diagnoses were ruled out following analysis of EVC and EVC2 genes.

WES was carried out in all.

PRKACA : A single heterozygous missense variant was identified in 3 individuals from 3 families (NM_002730.4:c.409G>A / p.Gly137Arg) with 1 of the probands harboring the variant in mosaic state (28% of reads) and having 2 similarly affected offspring. The variant was de novo in one individual and inherited in a third one having a similarly affected fetus (narrow thorax, postaxial polyd, AVSD).

PRKACB : 4 different variants were identified (NM_002731.3: p.His88Arg/Asn, p.Gly235Arg, c.161C>T - p.Ser54Leu). One of the individuals was mosaic for the latter variant, while in all other cases the variant had occurred de novo.

Protein kinase A (PKA) is a tetrameric holoenzyme formed by the association of 2 catalytic (C) subunits with a regulatory (R) subunit dimer. Activation of PKA is achieved through binding of 2 cAMP molecules to each R-subunit, and unleashing(/dissociation) of C-subunits to engage substrates. PRKACA/B genes encode the Cα- and Cβ-subunits while the 4 functionally non-redundant regulatory subunits are encoded by PRKAR1A/1B/2A/2B genes.

The authors provide evidence that the variants confer increased sensitivity of PKA holoenzymes to activation by cAMP (compared to wt).

By performing ectopic expression of wt or mt PRKACA/B (variants studied : PRKACA p.Gly137Arg / PRKACB p.Gly235Arg) in NIH 3T3 fibroblasts, the authors demonstrate that inhibition of hedgehog signaling likely underlyies the developmental defects observed in affected individuals.

As for PRKACA, the authors cite another study where a 31-month old female with EvC syndrome diagnosis was found to harbor the aforementioned variant (NM_001304349.1:c.637G>A:p.Gly213Arg corresponding to NM_002730.4:c.409G>A / p.Gly137Arg) as a de novo event. Without additional evidence at the time, the variant was considered to be a candidate for this subject's phenotype (Monies et al 2019 – PMID: 31130284).
Sources: Literature
Polydactyly v0.182 PRKACA Zornitza Stark Classified gene: PRKACA as Green List (high evidence)
Polydactyly v0.182 PRKACA Zornitza Stark Gene: prkaca has been classified as Green List (High Evidence).
Congenital Heart Defect v0.80 PRKACA Zornitza Stark Marked gene: PRKACA as ready
Congenital Heart Defect v0.80 PRKACA Zornitza Stark Gene: prkaca has been classified as Green List (High Evidence).
Congenital Heart Defect v0.80 PRKACA Zornitza Stark Classified gene: PRKACA as Green List (high evidence)
Congenital Heart Defect v0.80 PRKACA Zornitza Stark Gene: prkaca has been classified as Green List (High Evidence).
Mendeliome v0.5108 PRKACA Zornitza Stark Marked gene: PRKACA as ready
Mendeliome v0.5108 PRKACA Zornitza Stark Gene: prkaca has been classified as Green List (High Evidence).
Mendeliome v0.5108 PRKACA Zornitza Stark Classified gene: PRKACA as Green List (high evidence)
Mendeliome v0.5108 PRKACA Zornitza Stark Gene: prkaca has been classified as Green List (High Evidence).
Ciliopathies v0.215 PRKACB Zornitza Stark Marked gene: PRKACB as ready
Ciliopathies v0.215 PRKACB Zornitza Stark Gene: prkacb has been classified as Green List (High Evidence).
Ciliopathies v0.215 PRKACB Zornitza Stark Classified gene: PRKACB as Green List (high evidence)
Ciliopathies v0.215 PRKACB Zornitza Stark Gene: prkacb has been classified as Green List (High Evidence).
Ciliopathies v0.214 PRKACB Zornitza Stark gene: PRKACB was added
gene: PRKACB was added to Ciliopathies. Sources: Literature
Mode of inheritance for gene: PRKACB was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PRKACB were set to 33058759
Phenotypes for gene: PRKACB were set to Postaxial hand polydactyly; Postaxial foot polydactyly; Common atrium; Atrioventricular canal defect; Narrow chest; Abnormality of the teeth; Intellectual disability
Mode of pathogenicity for gene: PRKACB 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: PRKACB was set to GREEN
Added comment: Palencia-Campos et al (2020 - PMID: 33058759) report on the phenotype of 3 individuals heterozygous for PRKACA and 4 individuals heterozygous for PRKACB pathogenic variants.

Gene included in this panel due to significant phenotypic overlap with ciliopathies.

The most characteristic features in all individuals with PRKACA/PRKACB mutation, included postaxial polydactyly of hands (6/7 bilateral, 1/7 unilateral) and feet (4/7 bilateral, 1/7 unilateral), brachydactyly and congenital heart defects (CHD 5/7) namely a common atrium or AVSD. Two individuals with PRKACA variant who did not have CHD had offspring with the same variant and an AVSD.

Other variably occurring features included short stature, limbs, narrow chest, abnormal teeth, oral frenula, nail dysplasia. One individual with PRKACB variant presented tumors.

Intellectual disability was reported in 2/4 individuals with PRKACB variant (1/4: mild, 1/4: severe). The 3 individuals with PRKACA variant did not present ID.

As the phenotype was overall suggestive of Ellis-van Creveld syndrome (or the allelic Weyers acrofacial dysostosis), although these diagnoses were ruled out following analysis of EVC and EVC2 genes.

WES was carried out in all.

PRKACA : A single heterozygous missense variant was identified in 3 individuals from 3 families (NM_002730.4:c.409G>A / p.Gly137Arg) with 1 of the probands harboring the variant in mosaic state (28% of reads) and having 2 similarly affected offspring. The variant was de novo in one individual and inherited in a third one having a similarly affected fetus (narrow thorax, postaxial polyd, AVSD).

PRKACB : 4 different variants were identified (NM_002731.3: p.His88Arg/Asn, p.Gly235Arg, c.161C>T - p.Ser54Leu). One of the individuals was mosaic for the latter variant, while in all other cases the variant had occurred de novo.

Protein kinase A (PKA) is a tetrameric holoenzyme formed by the association of 2 catalytic (C) subunits with a regulatory (R) subunit dimer. Activation of PKA is achieved through binding of 2 cAMP molecules to each R-subunit, and unleashing(/dissociation) of C-subunits to engage substrates. PRKACA/B genes encode the Cα- and Cβ-subunits while the 4 functionally non-redundant regulatory subunits are encoded by PRKAR1A/1B/2A/2B genes.

The authors provide evidence that the variants confer increased sensitivity of PKA holoenzymes to activation by cAMP (compared to wt).

By performing ectopic expression of wt or mt PRKACA/B (variants studied : PRKACA p.Gly137Arg / PRKACB p.Gly235Arg) in NIH 3T3 fibroblasts, the authors demonstrate that inhibition of hedgehog signaling likely underlyies the developmental defects observed in affected individuals.

As for PRKACA, the authors cite another study where a 31-month old female with EvC syndrome diagnosis was found to harbor the aforementioned variant (NM_001304349.1:c.637G>A:p.Gly213Arg corresponding to NM_002730.4:c.409G>A / p.Gly137Arg) as a de novo event. Without additional evidence at the time, the variant was considered to be a candidate for this subject's phenotype (Monies et al 2019 – PMID: 31130284).
Sources: Literature
Mendeliome v0.5107 PRKACB Zornitza Stark Classified gene: PRKACB as Green List (high evidence)
Mendeliome v0.5107 PRKACB Zornitza Stark Gene: prkacb has been classified as Green List (High Evidence).
Congenital Heart Defect v0.79 PRKACB Zornitza Stark Marked gene: PRKACB as ready
Congenital Heart Defect v0.79 PRKACB Zornitza Stark Gene: prkacb has been classified as Green List (High Evidence).
Congenital Heart Defect v0.79 PRKACB Zornitza Stark Classified gene: PRKACB as Green List (high evidence)
Congenital Heart Defect v0.79 PRKACB Zornitza Stark Gene: prkacb has been classified as Green List (High Evidence).
Polydactyly v0.181 PRKACB Zornitza Stark Marked gene: PRKACB as ready
Polydactyly v0.181 PRKACB Zornitza Stark Gene: prkacb has been classified as Green List (High Evidence).
Polydactyly v0.181 PRKACB Zornitza Stark Classified gene: PRKACB as Green List (high evidence)
Polydactyly v0.181 PRKACB Zornitza Stark Gene: prkacb has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3111 PRKACB Zornitza Stark Marked gene: PRKACB as ready
Intellectual disability syndromic and non-syndromic v0.3111 PRKACB Zornitza Stark Gene: prkacb has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.3111 PRKACB Zornitza Stark Classified gene: PRKACB as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.3111 PRKACB Zornitza Stark Gene: prkacb has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5106 CNGA2 Zornitza Stark Marked gene: CNGA2 as ready
Mendeliome v0.5106 CNGA2 Zornitza Stark Gene: cnga2 has been classified as Red List (Low Evidence).
Mendeliome v0.5106 CNGA2 Zornitza Stark gene: CNGA2 was added
gene: CNGA2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CNGA2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: CNGA2 were set to 28572688
Phenotypes for gene: CNGA2 were set to Congenital anosmia
Review for gene: CNGA2 was set to RED
Added comment: Single multiplex family with high-impact variant segregating with anosmia.
Sources: Literature
Cardiomyopathy_Paediatric v0.32 COX6B1 Zornitza Stark Marked gene: COX6B1 as ready
Cardiomyopathy_Paediatric v0.32 COX6B1 Zornitza Stark Gene: cox6b1 has been classified as Amber List (Moderate Evidence).
Cardiomyopathy_Paediatric v0.32 COX6B1 Zornitza Stark Phenotypes for gene: COX6B1 were changed from Mitochondrial complex IV deficiency, 220110 to Mitochondrial complex IV deficiency, nuclear type 7, MIM# 619051
Cardiomyopathy_Paediatric v0.31 COX6B1 Zornitza Stark Publications for gene: COX6B1 were set to
Cardiomyopathy_Paediatric v0.30 COX6B1 Zornitza Stark Classified gene: COX6B1 as Amber List (moderate evidence)
Cardiomyopathy_Paediatric v0.30 COX6B1 Zornitza Stark Gene: cox6b1 has been classified as Amber List (Moderate Evidence).
Cardiomyopathy_Paediatric v0.29 COX6B1 Zornitza Stark reviewed gene: COX6B1: Rating: AMBER; Mode of pathogenicity: None; Publications: 18499082, 24781756; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 7, MIM# 619051; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3110 COX6B1 Zornitza Stark Marked gene: COX6B1 as ready
Intellectual disability syndromic and non-syndromic v0.3110 COX6B1 Zornitza Stark Gene: cox6b1 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.3110 COX6B1 Zornitza Stark Phenotypes for gene: COX6B1 were changed from to Mitochondrial complex IV deficiency, nuclear type 7, MIM# 619051
Intellectual disability syndromic and non-syndromic v0.3109 COX6B1 Zornitza Stark Publications for gene: COX6B1 were set to
Intellectual disability syndromic and non-syndromic v0.3108 COX6B1 Zornitza Stark Mode of inheritance for gene: COX6B1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3107 COX6B1 Zornitza Stark Classified gene: COX6B1 as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.3107 COX6B1 Zornitza Stark Gene: cox6b1 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.3106 COX6B1 Zornitza Stark reviewed gene: COX6B1: Rating: RED; Mode of pathogenicity: None; Publications: 18499082, 24781756; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 7, MIM# 619051; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Regression v0.185 COX6B1 Zornitza Stark Marked gene: COX6B1 as ready
Regression v0.185 COX6B1 Zornitza Stark Gene: cox6b1 has been classified as Amber List (Moderate Evidence).
Regression v0.185 COX6B1 Zornitza Stark Phenotypes for gene: COX6B1 were changed from to Mitochondrial complex IV deficiency, nuclear type 7, MIM# 619051
Regression v0.184 COX6B1 Zornitza Stark Publications for gene: COX6B1 were set to
Regression v0.183 COX6B1 Zornitza Stark Mode of inheritance for gene: COX6B1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Regression v0.182 COX6B1 Zornitza Stark Classified gene: COX6B1 as Amber List (moderate evidence)
Regression v0.182 COX6B1 Zornitza Stark Gene: cox6b1 has been classified as Amber List (Moderate Evidence).
Regression v0.181 COX6B1 Zornitza Stark reviewed gene: COX6B1: Rating: AMBER; Mode of pathogenicity: None; Publications: 18499082, 24781756; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 7, MIM# 619051; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5105 COX6B1 Zornitza Stark Marked gene: COX6B1 as ready
Mendeliome v0.5105 COX6B1 Zornitza Stark Gene: cox6b1 has been classified as Green List (High Evidence).
Mendeliome v0.5105 COX6B1 Zornitza Stark Phenotypes for gene: COX6B1 were changed from to Mitochondrial complex IV deficiency, nuclear type 7, MIM# 619051
Mendeliome v0.5104 COX6B1 Zornitza Stark Publications for gene: COX6B1 were set to
Mendeliome v0.5103 COX6B1 Zornitza Stark Mode of inheritance for gene: COX6B1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5102 COX6B1 Zornitza Stark reviewed gene: COX6B1: Rating: GREEN; Mode of pathogenicity: None; Publications: 18499082, 24781756; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 7, MIM# 619051; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disease v0.526 COX6B1 Zornitza Stark Marked gene: COX6B1 as ready
Mitochondrial disease v0.526 COX6B1 Zornitza Stark Gene: cox6b1 has been classified as Green List (High Evidence).
Mitochondrial disease v0.526 COX6B1 Zornitza Stark Phenotypes for gene: COX6B1 were changed from to Mitochondrial complex IV deficiency, nuclear type 7, MIM# 619051
Mitochondrial disease v0.525 COX6B1 Zornitza Stark Publications for gene: COX6B1 were set to
Regression v0.181 SHANK3 Zornitza Stark Marked gene: SHANK3 as ready
Regression v0.181 SHANK3 Zornitza Stark Gene: shank3 has been classified as Green List (High Evidence).
Regression v0.181 SHANK3 Zornitza Stark Classified gene: SHANK3 as Green List (high evidence)
Regression v0.181 SHANK3 Zornitza Stark Gene: shank3 has been classified as Green List (High Evidence).
Mitochondrial disease v0.524 COX6B1 Zornitza Stark Mode of inheritance for gene: COX6B1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disease v0.523 COX6B1 Zornitza Stark reviewed gene: COX6B1: Rating: GREEN; Mode of pathogenicity: None; Publications: 18499082, 24781756; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 7, MIM# 619051; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.890 SCO1 Zornitza Stark Marked gene: SCO1 as ready
Genetic Epilepsy v0.890 SCO1 Zornitza Stark Gene: sco1 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.890 SCO1 Zornitza Stark Phenotypes for gene: SCO1 were changed from to Mitochondrial complex IV deficiency, nuclear type 4, MIM# 619048
Genetic Epilepsy v0.889 SCO1 Zornitza Stark Publications for gene: SCO1 were set to
Genetic Epilepsy v0.888 SCO1 Zornitza Stark Mode of inheritance for gene: SCO1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.887 SCO1 Zornitza Stark Classified gene: SCO1 as Amber List (moderate evidence)
Genetic Epilepsy v0.887 SCO1 Zornitza Stark Gene: sco1 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.886 SCO1 Zornitza Stark reviewed gene: SCO1: Rating: AMBER; Mode of pathogenicity: None; Publications: 11013136, 19295170, 31352446, 23878101; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 4, MIM# 619048; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v0.29 SCO1 Zornitza Stark Classified gene: SCO1 as Amber List (moderate evidence)
Cardiomyopathy_Paediatric v0.29 SCO1 Zornitza Stark Gene: sco1 has been classified as Amber List (Moderate Evidence).
Cardiomyopathy_Paediatric v0.28 SCO1 Zornitza Stark Marked gene: SCO1 as ready
Cardiomyopathy_Paediatric v0.28 SCO1 Zornitza Stark Gene: sco1 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v0.28 SCO1 Zornitza Stark Phenotypes for gene: SCO1 were changed from Mitochondrial complex IV deficiency, 220110 to Mitochondrial complex IV deficiency, nuclear type 4, MIM# 619048
Cardiomyopathy_Paediatric v0.27 SCO1 Zornitza Stark Publications for gene: SCO1 were set to
Cardiomyopathy_Paediatric v0.26 SCO1 Zornitza Stark reviewed gene: SCO1: Rating: AMBER; Mode of pathogenicity: None; Publications: 11013136, 19295170, 31352446, 23878101; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 4, MIM# 619048; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3106 SCO1 Zornitza Stark Marked gene: SCO1 as ready
Intellectual disability syndromic and non-syndromic v0.3106 SCO1 Zornitza Stark Gene: sco1 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.3106 SCO1 Zornitza Stark Phenotypes for gene: SCO1 were changed from to Mitochondrial complex IV deficiency, nuclear type 4, MIM# 619048
Intellectual disability syndromic and non-syndromic v0.3105 SCO1 Zornitza Stark Publications for gene: SCO1 were set to
Intellectual disability syndromic and non-syndromic v0.3104 SCO1 Zornitza Stark Mode of inheritance for gene: SCO1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3103 SCO1 Zornitza Stark Classified gene: SCO1 as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.3103 SCO1 Zornitza Stark Gene: sco1 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.3102 SCO1 Zornitza Stark reviewed gene: SCO1: Rating: RED; Mode of pathogenicity: None; Publications: 11013136, 19295170, 31352446, 23878101; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 4, MIM# 619048; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5102 PRKACB Konstantinos Varvagiannis gene: PRKACB was added
gene: PRKACB was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PRKACB was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PRKACB were set to 33058759
Phenotypes for gene: PRKACB were set to Postaxial hand polydactyly; Postaxial foot polydactyly; Common atrium; Atrioventricular canal defect; Narrow chest; Abnormality of the teeth; Intellectual disability
Penetrance for gene: PRKACB were set to unknown
Mode of pathogenicity for gene: PRKACB 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: PRKACB was set to GREEN
Added comment: Palencia-Campos et al (2020 - PMID: 33058759) report on the phenotype of 3 individuals heterozygous for PRKACA and 4 individuals heterozygous for PRKACB pathogenic variants.

The most characteristic features in all individuals with PRKACA/PRKACB mutation, included postaxial polydactyly of hands (6/7 bilateral, 1/7 unilateral) and feet (4/7 bilateral, 1/7 unilateral), brachydactyly and congenital heart defects (CHD 5/7) namely a common atrium or AVSD. Two individuals with PRKACA variant who did not have CHD had offspring with the same variant and an AVSD.

Other variably occurring features included short stature, limbs, narrow chest, abnormal teeth, oral frenula, nail dysplasia. One individual with PRKACB variant presented tumors.

Intellectual disability was reported in 2/4 individuals with PRKACB variant (1/4: mild, 1/4: severe). The 3 individuals with PRKACA variant did not present ID.

As the phenotype was overall suggestive of Ellis-van Creveld syndrome (or the allelic Weyers acrofacial dysostosis), although these diagnoses were ruled out following analysis of EVC and EVC2 genes.

WES was carried out in all.

PRKACA : A single heterozygous missense variant was identified in 3 individuals from 3 families (NM_002730.4:c.409G>A / p.Gly137Arg) with 1 of the probands harboring the variant in mosaic state (28% of reads) and having 2 similarly affected offspring. The variant was de novo in one individual and inherited in a third one having a similarly affected fetus (narrow thorax, postaxial polyd, AVSD).

PRKACB : 4 different variants were identified (NM_002731.3: p.His88Arg/Asn, p.Gly235Arg, c.161C>T - p.Ser54Leu). One of the individuals was mosaic for the latter variant, while in all other cases the variant had occurred de novo.

Protein kinase A (PKA) is a tetrameric holoenzyme formed by the association of 2 catalytic (C) subunits with a regulatory (R) subunit dimer. Activation of PKA is achieved through binding of 2 cAMP molecules to each R-subunit, and unleashing(/dissociation) of C-subunits to engage substrates. PRKACA/B genes encode the Cα- and Cβ-subunits while the 4 functionally non-redundant regulatory subunits are encoded by PRKAR1A/1B/2A/2B genes.

The authors provide evidence that the variants confer increased sensitivity of PKA holoenzymes to activation by cAMP (compared to wt).

By performing ectopic expression of wt or mt PRKACA/B (variants studied : PRKACA p.Gly137Arg / PRKACB p.Gly235Arg) in NIH 3T3 fibroblasts, the authors demonstrate that inhibition of hedgehog signaling likely underlyies the developmental defects observed in affected individuals.

As for PRKACA, the authors cite another study where a 31-month old female with EvC syndrome diagnosis was found to harbor the aforementioned variant (NM_001304349.1:c.637G>A:p.Gly213Arg corresponding to NM_002730.4:c.409G>A / p.Gly137Arg) as a de novo event. Without additional evidence at the time, the variant was considered to be a candidate for this subject's phenotype (Monies et al 2019 – PMID: 31130284).
Sources: Literature
Mendeliome v0.5102 PRKACA Konstantinos Varvagiannis gene: PRKACA was added
gene: PRKACA was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PRKACA was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PRKACA were set to 33058759; 31130284
Phenotypes for gene: PRKACA were set to Postaxial hand polydactyly; Postaxial foot polydactyly; Common atrium; Atrioventricular canal defect; Narrow chest; Abnormality of the teeth; Intellectual disability
Penetrance for gene: PRKACA were set to unknown
Mode of pathogenicity for gene: PRKACA 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: PRKACA was set to GREEN
Added comment: Palencia-Campos et al (2020 - PMID: 33058759) report on the phenotype of 3 individuals heterozygous for PRKACA and 4 individuals heterozygous for PRKACB pathogenic variants.

The most characteristic features in all individuals with PRKACA/PRKACB mutation, included postaxial polydactyly of hands (6/7 bilateral, 1/7 unilateral) and feet (4/7 bilateral, 1/7 unilateral), brachydactyly and congenital heart defects (CHD 5/7) namely a common atrium or AVSD. Two individuals with PRKACA variant who did not have CHD had offspring with the same variant and an AVSD.

Other variably occurring features included short stature, limbs, narrow chest, abnormal teeth, oral frenula, nail dysplasia. One individual with PRKACB variant presented tumors.

Intellectual disability was reported in 2/4 individuals with PRKACB variant (1/4: mild, 1/4: severe). The 3 individuals with PRKACA variant did not present ID.

As the phenotype was overall suggestive of Ellis-van Creveld syndrome (or the allelic Weyers acrofacial dysostosis), although these diagnoses were ruled out following analysis of EVC and EVC2 genes.

WES was carried out in all.

PRKACA : A single heterozygous missense variant was identified in 3 individuals from 3 families (NM_002730.4:c.409G>A / p.Gly137Arg) with 1 of the probands harboring the variant in mosaic state (28% of reads) and having 2 similarly affected offspring. The variant was de novo in one individual and inherited in a third one having a similarly affected fetus (narrow thorax, postaxial polyd, AVSD).

PRKACB : 4 different variants were identified (NM_002731.3: p.His88Arg/Asn, p.Gly235Arg, c.161C>T - p.Ser54Leu). One of the individuals was mosaic for the latter variant, while in all other cases the variant had occurred de novo.

Protein kinase A (PKA) is a tetrameric holoenzyme formed by the association of 2 catalytic (C) subunits with a regulatory (R) subunit dimer. Activation of PKA is achieved through binding of 2 cAMP molecules to each R-subunit, and unleashing(/dissociation) of C-subunits to engage substrates. PRKACA/B genes encode the Cα- and Cβ-subunits while the 4 functionally non-redundant regulatory subunits are encoded by PRKAR1A/1B/2A/2B genes.

The authors provide evidence that the variants confer increased sensitivity of PKA holoenzymes to activation by cAMP (compared to wt).

By performing ectopic expression of wt or mt PRKACA/B (variants studied : PRKACA p.Gly137Arg / PRKACB p.Gly235Arg) in NIH 3T3 fibroblasts, the authors demonstrate that inhibition of hedgehog signaling likely underlyies the developmental defects observed in affected individuals.

As for PRKACA, the authors cite another study where a 31-month old female with EvC syndrome diagnosis was found to harbor the aforementioned variant (NM_001304349.1:c.637G>A:p.Gly213Arg corresponding to NM_002730.4:c.409G>A / p.Gly137Arg) as a de novo event. Without additional evidence at the time, the variant was considered to be a candidate for this subject's phenotype (Monies et al 2019 – PMID: 31130284).
Sources: Literature
Polydactyly v0.180 PRKACA Konstantinos Varvagiannis commented on gene: PRKACA: [ Please note that PRKACA / PRKACB may be considered in the differential diagnosis of several ciliopathies (polydactyly, narrow chest, heart defects) ]
Polydactyly v0.180 PRKACB Konstantinos Varvagiannis commented on gene: PRKACB: [ Please note that PRKACA / PRKACB may be considered in the differential diagnosis of several ciliopathies (polydactyly, narrow chest, heart defects) ]
Congenital Heart Defect v0.78 PRKACA Konstantinos Varvagiannis gene: PRKACA was added
gene: PRKACA was added to Congenital Heart Defect. Sources: Literature
Mode of inheritance for gene: PRKACA was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PRKACA were set to 33058759; 31130284
Phenotypes for gene: PRKACA were set to Postaxial hand polydactyly; Postaxial foot polydactyly; Common atrium; Atrioventricular canal defect; Narrow chest; Abnormality of the teeth; Intellectual disability
Penetrance for gene: PRKACA were set to unknown
Mode of pathogenicity for gene: PRKACA 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: PRKACA was set to GREEN
Added comment: Palencia-Campos et al (2020 - PMID: 33058759) report on the phenotype of 3 individuals heterozygous for PRKACA and 4 individuals heterozygous for PRKACB pathogenic variants.

The most characteristic features in all individuals with PRKACA/PRKACB mutation, included postaxial polydactyly of hands (6/7 bilateral, 1/7 unilateral) and feet (4/7 bilateral, 1/7 unilateral), brachydactyly and congenital heart defects (CHD 5/7) namely a common atrium or AVSD. Two individuals with PRKACA variant who did not have CHD had offspring with the same variant and an AVSD.

Other variably occurring features included short stature, limbs, narrow chest, abnormal teeth, oral frenula, nail dysplasia. One individual with PRKACB variant presented tumors.

Intellectual disability was reported in 2/4 individuals with PRKACB variant (1/4: mild, 1/4: severe). The 3 individuals with PRKACA variant did not present ID.

As the phenotype was overall suggestive of Ellis-van Creveld syndrome (or the allelic Weyers acrofacial dysostosis), although these diagnoses were ruled out following analysis of EVC and EVC2 genes.

WES was carried out in all.

PRKACA : A single heterozygous missense variant was identified in 3 individuals from 3 families (NM_002730.4:c.409G>A / p.Gly137Arg) with 1 of the probands harboring the variant in mosaic state (28% of reads) and having 2 similarly affected offspring. The variant was de novo in one individual and inherited in a third one having a similarly affected fetus (narrow thorax, postaxial polyd, AVSD).

PRKACB : 4 different variants were identified (NM_002731.3: p.His88Arg/Asn, p.Gly235Arg, c.161C>T - p.Ser54Leu). One of the individuals was mosaic for the latter variant, while in all other cases the variant had occurred de novo.

Protein kinase A (PKA) is a tetrameric holoenzyme formed by the association of 2 catalytic (C) subunits with a regulatory (R) subunit dimer. Activation of PKA is achieved through binding of 2 cAMP molecules to each R-subunit, and unleashing(/dissociation) of C-subunits to engage substrates. PRKACA/B genes encode the Cα- and Cβ-subunits while the 4 functionally non-redundant regulatory subunits are encoded by PRKAR1A/1B/2A/2B genes.

The authors provide evidence that the variants confer increased sensitivity of PKA holoenzymes to activation by cAMP (compared to wt).

By performing ectopic expression of wt or mt PRKACA/B (variants studied : PRKACA p.Gly137Arg / PRKACB p.Gly235Arg) in NIH 3T3 fibroblasts, the authors demonstrate that inhibition of hedgehog signaling likely underlyies the developmental defects observed in affected individuals.

As for PRKACA, the authors cite another study where a 31-month old female with EvC syndrome diagnosis was found to harbor the aforementioned variant (NM_001304349.1:c.637G>A:p.Gly213Arg corresponding to NM_002730.4:c.409G>A / p.Gly137Arg) as a de novo event. Without additional evidence at the time, the variant was considered to be a candidate for this subject's phenotype (Monies et al 2019 – PMID: 31130284).
Sources: Literature
Congenital Heart Defect v0.78 PRKACB Konstantinos Varvagiannis gene: PRKACB was added
gene: PRKACB was added to Congenital Heart Defect. Sources: Literature
Mode of inheritance for gene: PRKACB was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PRKACB were set to 33058759
Phenotypes for gene: PRKACB were set to Postaxial hand polydactyly; Postaxial foot polydactyly; Common atrium; Atrioventricular canal defect; Narrow chest; Abnormality of the teeth; Intellectual disability
Penetrance for gene: PRKACB were set to Complete
Mode of pathogenicity for gene: PRKACB 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: PRKACB was set to GREEN
Added comment: Palencia-Campos et al (2020 - PMID: 33058759) report on the phenotype of 3 individuals heterozygous for PRKACA and 4 individuals heterozygous for PRKACB pathogenic variants.

The most characteristic features in all individuals with PRKACA/PRKACB mutation, included postaxial polydactyly of hands (6/7 bilateral, 1/7 unilateral) and feet (4/7 bilateral, 1/7 unilateral), brachydactyly and congenital heart defects (CHD 5/7) namely a common atrium or AVSD. Two individuals with PRKACA variant who did not have CHD had offspring with the same variant and an AVSD.

Other variably occurring features included short stature, limbs, narrow chest, abnormal teeth, oral frenula, nail dysplasia. One individual with PRKACB variant presented tumors.

Intellectual disability was reported in 2/4 individuals with PRKACB variant (1/4: mild, 1/4: severe). The 3 individuals with PRKACA variant did not present ID.

As the phenotype was overall suggestive of Ellis-van Creveld syndrome (or the allelic Weyers acrofacial dysostosis), although these diagnoses were ruled out following analysis of EVC and EVC2 genes.

WES was carried out in all.

PRKACA : A single heterozygous missense variant was identified in 3 individuals from 3 families (NM_002730.4:c.409G>A / p.Gly137Arg) with 1 of the probands harboring the variant in mosaic state (28% of reads) and having 2 similarly affected offspring. The variant was de novo in one individual and inherited in a third one having a similarly affected fetus (narrow thorax, postaxial polyd, AVSD).

PRKACB : 4 different variants were identified (NM_002731.3: p.His88Arg/Asn, p.Gly235Arg, c.161C>T - p.Ser54Leu). One of the individuals was mosaic for the latter variant, while in all other cases the variant had occurred de novo.

Protein kinase A (PKA) is a tetrameric holoenzyme formed by the association of 2 catalytic (C) subunits with a regulatory (R) subunit dimer. Activation of PKA is achieved through binding of 2 cAMP molecules to each R-subunit, and unleashing(/dissociation) of C-subunits to engage substrates. PRKACA/B genes encode the Cα- and Cβ-subunits while the 4 functionally non-redundant regulatory subunits are encoded by PRKAR1A/1B/2A/2B genes.

The authors provide evidence that the variants confer increased sensitivity of PKA holoenzymes to activation by cAMP (compared to wt).

By performing ectopic expression of wt or mt PRKACA/B (variants studied : PRKACA p.Gly137Arg / PRKACB p.Gly235Arg) in NIH 3T3 fibroblasts, the authors demonstrate that inhibition of hedgehog signaling likely underlyies the developmental defects observed in affected individuals.

As for PRKACA, the authors cite another study where a 31-month old female with EvC syndrome diagnosis was found to harbor the aforementioned variant (NM_001304349.1:c.637G>A:p.Gly213Arg corresponding to NM_002730.4:c.409G>A / p.Gly137Arg) as a de novo event. Without additional evidence at the time, the variant was considered to be a candidate for this subject's phenotype (Monies et al 2019 – PMID: 31130284).
Sources: Literature
Polydactyly v0.180 PRKACB Konstantinos Varvagiannis gene: PRKACB was added
gene: PRKACB was added to Polydactyly. Sources: Literature
Mode of inheritance for gene: PRKACB was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PRKACB were set to 33058759
Phenotypes for gene: PRKACB were set to Postaxial hand polydactyly; Postaxial foot polydactyly; Common atrium; Atrioventricular canal defect; Narrow chest; Abnormality of the teeth; Intellectual disability
Penetrance for gene: PRKACB were set to Complete
Mode of pathogenicity for gene: PRKACB 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: PRKACB was set to GREEN
Added comment: Palencia-Campos et al (2020 - PMID: 33058759) report on the phenotype of 3 individuals heterozygous for PRKACA and 4 individuals heterozygous for PRKACB pathogenic variants.

The most characteristic features in all individuals with PRKACA/PRKACB mutation, included postaxial polydactyly of hands (6/7 bilateral, 1/7 unilateral) and feet (4/7 bilateral, 1/7 unilateral), brachydactyly and congenital heart defects (CHD 5/7) namely a common atrium or AVSD. Two individuals with PRKACA variant who did not have CHD had offspring with the same variant and an AVSD.

Other variably occurring features included short stature, limbs, narrow chest, abnormal teeth, oral frenula, nail dysplasia. One individual with PRKACB variant presented tumors.

Intellectual disability was reported in 2/4 individuals with PRKACB variant (1/4: mild, 1/4: severe). The 3 individuals with PRKACA variant did not present ID.

As the phenotype was overall suggestive of Ellis-van Creveld syndrome (or the allelic Weyers acrofacial dysostosis), although these diagnoses were ruled out following analysis of EVC and EVC2 genes.

WES was carried out in all.

PRKACA : A single heterozygous missense variant was identified in 3 individuals from 3 families (NM_002730.4:c.409G>A / p.Gly137Arg) with 1 of the probands harboring the variant in mosaic state (28% of reads) and having 2 similarly affected offspring. The variant was de novo in one individual and inherited in a third one having a similarly affected fetus (narrow thorax, postaxial polyd, AVSD).

PRKACB : 4 different variants were identified (NM_002731.3: p.His88Arg/Asn, p.Gly235Arg, c.161C>T - p.Ser54Leu). One of the individuals was mosaic for the latter variant, while in all other cases the variant had occurred de novo.

Protein kinase A (PKA) is a tetrameric holoenzyme formed by the association of 2 catalytic (C) subunits with a regulatory (R) subunit dimer. Activation of PKA is achieved through binding of 2 cAMP molecules to each R-subunit, and unleashing(/dissociation) of C-subunits to engage substrates. PRKACA/B genes encode the Cα- and Cβ-subunits while the 4 functionally non-redundant regulatory subunits are encoded by PRKAR1A/1B/2A/2B genes.

The authors provide evidence that the variants confer increased sensitivity of PKA holoenzymes to activation by cAMP (compared to wt).

By performing ectopic expression of wt or mt PRKACA/B (variants studied : PRKACA p.Gly137Arg / PRKACB p.Gly235Arg) in NIH 3T3 fibroblasts, the authors demonstrate that inhibition of hedgehog signaling likely underlyies the developmental defects observed in affected individuals.

As for PRKACA, the authors cite another study where a 31-month old female with EvC syndrome diagnosis was found to harbor the aforementioned variant (NM_001304349.1:c.637G>A:p.Gly213Arg corresponding to NM_002730.4:c.409G>A / p.Gly137Arg) as a de novo event. Without additional evidence at the time, the variant was considered to be a candidate for this subject's phenotype (Monies et al 2019 – PMID: 31130284).
Sources: Literature
Polydactyly v0.180 PRKACA Konstantinos Varvagiannis gene: PRKACA was added
gene: PRKACA was added to Polydactyly. Sources: Literature
Mode of inheritance for gene: PRKACA was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PRKACA were set to 33058759; 31130284
Phenotypes for gene: PRKACA were set to Postaxial hand polydactyly; Postaxial foot polydactyly; Common atrium; Atrioventricular canal defect; Narrow chest; Abnormality of the teeth; Intellectual disability
Penetrance for gene: PRKACA were set to Complete
Mode of pathogenicity for gene: PRKACA 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: PRKACA was set to GREEN
Added comment: Palencia-Campos et al (2020 - PMID: 33058759) report on the phenotype of 3 individuals heterozygous for PRKACA and 4 individuals heterozygous for PRKACB pathogenic variants.

The most characteristic features in all individuals with PRKACA/PRKACB mutation, included postaxial polydactyly of hands (6/7 bilateral, 1/7 unilateral) and feet (4/7 bilateral, 1/7 unilateral), brachydactyly and congenital heart defects (CHD 5/7) namely a common atrium or AVSD. Two individuals with PRKACA variant who did not have CHD had offspring with the same variant and an AVSD.

Other variably occurring features included short stature, limbs, narrow chest, abnormal teeth, oral frenula, nail dysplasia. One individual with PRKACB variant presented tumors.

Intellectual disability was reported in 2/4 individuals with PRKACB variant (1/4: mild, 1/4: severe). The 3 individuals with PRKACA variant did not present ID.

As the phenotype was overall suggestive of Ellis-van Creveld syndrome (or the allelic Weyers acrofacial dysostosis), although these diagnoses were ruled out following analysis of EVC and EVC2 genes.

WES was carried out in all.

PRKACA : A single heterozygous missense variant was identified in 3 individuals from 3 families (NM_002730.4:c.409G>A / p.Gly137Arg) with 1 of the probands harboring the variant in mosaic state (28% of reads) and having 2 similarly affected offspring. The variant was de novo in one individual and inherited in a third one having a similarly affected fetus (narrow thorax, postaxial polyd, AVSD).

PRKACB : 4 different variants were identified (NM_002731.3: p.His88Arg/Asn, p.Gly235Arg, c.161C>T - p.Ser54Leu). One of the individuals was mosaic for the latter variant, while in all other cases the variant had occurred de novo.

Protein kinase A (PKA) is a tetrameric holoenzyme formed by the association of 2 catalytic (C) subunits with a regulatory (R) subunit dimer. Activation of PKA is achieved through binding of 2 cAMP molecules to each R-subunit, and unleashing(/dissociation) of C-subunits to engage substrates. PRKACA/B genes encode the Cα- and Cβ-subunits while the 4 functionally non-redundant regulatory subunits are encoded by PRKAR1A/1B/2A/2B genes.

The authors provide evidence that the variants confer increased sensitivity of PKA holoenzymes to activation by cAMP (compared to wt).

By performing ectopic expression of wt or mt PRKACA/B (variants studied : PRKACA p.Gly137Arg / PRKACB p.Gly235Arg) in NIH 3T3 fibroblasts, the authors demonstrate that inhibition of hedgehog signaling likely underlyies the developmental defects observed in affected individuals.

As for PRKACA, the authors cite another study where a 31-month old female with EvC syndrome diagnosis was found to harbor the aforementioned variant (NM_001304349.1:c.637G>A:p.Gly213Arg corresponding to NM_002730.4:c.409G>A / p.Gly137Arg) as a de novo event. Without additional evidence at the time, the variant was considered to be a candidate for this subject's phenotype (Monies et al 2019 – PMID: 31130284).
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3102 PRKACB Konstantinos Varvagiannis edited their review of gene: PRKACB: Changed mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Intellectual disability syndromic and non-syndromic v0.3102 PRKACB Konstantinos Varvagiannis gene: PRKACB was added
gene: PRKACB was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: PRKACB was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PRKACB were set to 33058759
Phenotypes for gene: PRKACB were set to Postaxial hand polydactyly; Postaxial foot polydactyly; Common atrium; Atrioventricular canal defect; Narrow chest; Abnormality of the teeth; Intellectual disability
Penetrance for gene: PRKACB were set to Complete
Review for gene: PRKACB was set to AMBER
Added comment: ID was a feature in 2/4 individuals with PRKACB pathogenic variant reported to date.
------
Palencia-Campos et al (2020 - PMID: 33058759) report on the phenotype of 3 individuals heterozygous for PRKACA and 4 individuals heterozygous for PRKACB pathogenic variants.

The most characteristic features in all individuals with PRKACA/PRKACB mutation, included postaxial polydactyly of hands (6/7 bilateral, 1/7 unilateral) and feet (4/7 bilateral, 1/7 unilateral), brachydactyly and congenital heart defects (CHD 5/7) namely a common atrium or AVSD. Two individuals with PRKACA variant who did not have CHD had offspring with the same variant and an AVSD.

Other variably occurring features included short stature, limbs, narrow chest, abnormal teeth, oral frenula, nail dysplasia. One individual with PRKACB variant presented tumors.

Intellectual disability was reported in 2/4 individuals with PRKACB variant (1/4: mild, 1/4: severe). The 3 individuals with PRKACA variant did not present ID.

As the phenotype was overall suggestive of Ellis-van Creveld syndrome (or the allelic Weyers acrofacial dysostosis), although these diagnoses were ruled out following analysis of EVC and EVC2 genes.

WES was carried out in all.

PRKACA : A single heterozygous missense variant was identified in 3 individuals from 3 families (NM_002730.4:c.409G>A / p.Gly137Arg) with 1 of the probands harboring the variant in mosaic state (28% of reads) and having 2 similarly affected offspring. The variant was de novo in one individual and inherited in a third one having a similarly affected fetus (narrow thorax, postaxial polyd, AVSD).

PRKACB : 4 different variants were identified (NM_002731.3: p.His88Arg/Asn, p.Gly235Arg, c.161C>T - p.Ser54Leu). One of the individuals was mosaic for the latter variant, while in all other cases the variant had occurred de novo.

Protein kinase A (PKA) is a tetrameric holoenzyme formed by the association of 2 catalytic (C) subunits with a regulatory (R) subunit dimer. Activation of PKA is achieved through binding of 2 cAMP molecules to each R-subunit, and unleashing(/dissociation) of C-subunits to engage substrates. PRKACA/B genes encode the Cα- and Cβ-subunits while the 4 functionally non-redundant regulatory subunits are encoded by PRKAR1A/1B/2A/2B genes.

The authors provide evidence that the variants confer increased sensitivity of PKA holoenzymes to activation by cAMP (compared to wt).

By performing ectopic expression of wt or mt PRKACA/B (variants studied : PRKACA p.Gly137Arg / PRKACB p.Gly235Arg) in NIH 3T3 fibroblasts, the authors demonstrate that inhibition of hedgehog signaling likely underlyies the developmental defects observed in affected individuals.

As for PRKACA, the authors cite another study where a 31-month old female with EvC syndrome diagnosis was found to harbor the aforementioned variant (NM_001304349.1:c.637G>A:p.Gly213Arg corresponding to NM_002730.4:c.409G>A / p.Gly137Arg) as a de novo event. Without additional evidence at the time, the variant was considered to be a candidate for this subject's phenotype (Monies et al 2019 – PMID: 31130284).
Sources: Literature
Regression v0.180 SHANK3 Konstantinos Varvagiannis gene: SHANK3 was added
gene: SHANK3 was added to Regression. Sources: Literature
Mode of inheritance for gene: SHANK3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SHANK3 were set to 32050889, 29719671
Phenotypes for gene: SHANK3 were set to # 606232. PHELAN-MCDERMID SYNDROME - PHMDS
Penetrance for gene: SHANK3 were set to Complete
Review for gene: SHANK3 was set to GREEN
Added comment: Regression has been reported in several individuals with Phelan-McDermid syndrome due to SHANK3 variants or deletions encompassing this gene.
Sources: Literature
Regression v0.180 SCO1 Zornitza Stark Marked gene: SCO1 as ready
Regression v0.180 SCO1 Zornitza Stark Gene: sco1 has been classified as Red List (Low Evidence).
Regression v0.180 SCO1 Zornitza Stark Phenotypes for gene: SCO1 were changed from to Mitochondrial complex IV deficiency, nuclear type 4, MIM# 619048
Regression v0.179 SCO1 Zornitza Stark Publications for gene: SCO1 were set to
Regression v0.178 SCO1 Zornitza Stark Mode of inheritance for gene: SCO1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Regression v0.177 SCO1 Zornitza Stark Classified gene: SCO1 as Red List (low evidence)
Regression v0.177 SCO1 Zornitza Stark Gene: sco1 has been classified as Red List (Low Evidence).
Regression v0.176 SCO1 Zornitza Stark reviewed gene: SCO1: Rating: RED; Mode of pathogenicity: None; Publications: 11013136, 19295170, 31352446, 23878101; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 4, MIM# 619048; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5102 SCO1 Zornitza Stark Marked gene: SCO1 as ready
Mendeliome v0.5102 SCO1 Zornitza Stark Gene: sco1 has been classified as Green List (High Evidence).
Mendeliome v0.5102 SCO1 Zornitza Stark Phenotypes for gene: SCO1 were changed from to Mitochondrial complex IV deficiency, nuclear type 4, MIM# 619048
Mendeliome v0.5101 SCO1 Zornitza Stark Publications for gene: SCO1 were set to
Mendeliome v0.5100 SCO1 Zornitza Stark Mode of inheritance for gene: SCO1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5099 SCO1 Zornitza Stark reviewed gene: SCO1: Rating: GREEN; Mode of pathogenicity: None; Publications: 11013136, 19295170, 31352446, 23878101; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 4, MIM# 619048; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disease v0.523 SCO1 Zornitza Stark Marked gene: SCO1 as ready
Mitochondrial disease v0.523 SCO1 Zornitza Stark Gene: sco1 has been classified as Green List (High Evidence).
Mitochondrial disease v0.523 SCO1 Zornitza Stark Phenotypes for gene: SCO1 were changed from to Mitochondrial complex IV deficiency, nuclear type 4, MIM# 619048
Mitochondrial disease v0.522 SCO1 Zornitza Stark Publications for gene: SCO1 were set to
Mitochondrial disease v0.521 SCO1 Zornitza Stark Mode of inheritance for gene: SCO1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disease v0.520 SCO1 Zornitza Stark reviewed gene: SCO1: Rating: GREEN; Mode of pathogenicity: None; Publications: 11013136, 19295170, 31352446, 23878101; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 4, MIM# 619048; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3102 COX10 Zornitza Stark Marked gene: COX10 as ready
Intellectual disability syndromic and non-syndromic v0.3102 COX10 Zornitza Stark Gene: cox10 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3102 COX10 Zornitza Stark Phenotypes for gene: COX10 were changed from to Mitochondrial complex IV deficiency, nuclear type 3, MIM# 619046
Intellectual disability syndromic and non-syndromic v0.3101 COX10 Zornitza Stark Publications for gene: COX10 were set to
Intellectual disability syndromic and non-syndromic v0.3100 COX10 Zornitza Stark Mode of inheritance for gene: COX10 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3099 COX10 Zornitza Stark reviewed gene: COX10: Rating: GREEN; Mode of pathogenicity: None; Publications: 10767350, 12928484, 15455402, 27290639; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 3, MIM# 619046; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Regression v0.176 COX10 Zornitza Stark Marked gene: COX10 as ready
Regression v0.176 COX10 Zornitza Stark Gene: cox10 has been classified as Green List (High Evidence).
Regression v0.176 COX10 Zornitza Stark Phenotypes for gene: COX10 were changed from to Mitochondrial complex IV deficiency, nuclear type 3, MIM# 619046
Regression v0.175 COX10 Zornitza Stark Publications for gene: COX10 were set to
Regression v0.174 COX10 Zornitza Stark Mode of inheritance for gene: COX10 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Regression v0.173 COX10 Zornitza Stark reviewed gene: COX10: Rating: GREEN; Mode of pathogenicity: None; Publications: 10767350, 12928484, 15455402, 27290639; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 3, MIM# 619046; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5099 COX10 Zornitza Stark Marked gene: COX10 as ready
Mendeliome v0.5099 COX10 Zornitza Stark Gene: cox10 has been classified as Green List (High Evidence).
Mendeliome v0.5099 COX10 Zornitza Stark Phenotypes for gene: COX10 were changed from to Mitochondrial complex IV deficiency, nuclear type 3, MIM# 619046
Mendeliome v0.5098 COX10 Zornitza Stark Publications for gene: COX10 were set to
Mendeliome v0.5097 COX10 Zornitza Stark Mode of inheritance for gene: COX10 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5096 COX10 Zornitza Stark reviewed gene: COX10: Rating: GREEN; Mode of pathogenicity: None; Publications: 10767350, 12928484, 15455402, 27290639; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 3, MIM# 619046; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disease v0.520 COX10 Zornitza Stark Marked gene: COX10 as ready
Mitochondrial disease v0.520 COX10 Zornitza Stark Gene: cox10 has been classified as Green List (High Evidence).
Mitochondrial disease v0.520 COX10 Zornitza Stark Phenotypes for gene: COX10 were changed from to Mitochondrial complex IV deficiency, nuclear type 3, MIM# 619046
Mitochondrial disease v0.519 COX10 Zornitza Stark Publications for gene: COX10 were set to
Mitochondrial disease v0.518 COX10 Zornitza Stark Mode of inheritance for gene: COX10 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disease v0.517 COX10 Zornitza Stark reviewed gene: COX10: Rating: GREEN; Mode of pathogenicity: None; Publications: 10767350, 12928484, 15455402, 27290639; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 3, MIM# 619046; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Myasthenia v0.43 RAPSN Zornitza Stark Marked gene: RAPSN as ready
Congenital Myasthenia v0.43 RAPSN Zornitza Stark Gene: rapsn has been classified as Green List (High Evidence).
Congenital Myasthenia v0.43 RAPSN Zornitza Stark Publications for gene: RAPSN were set to
Congenital Myasthenia v0.42 RAPSN Zornitza Stark Tag SV/CNV tag was added to gene: RAPSN.
Tag founder tag was added to gene: RAPSN.
Congenital Myasthenia v0.42 RAPSN Zornitza Stark reviewed gene: RAPSN: Rating: GREEN; Mode of pathogenicity: None; Publications: 11791205, 14504330, 20930056, 25194721; Phenotypes: Myasthenic syndrome, congenital, 11, associated with acetylcholine receptor deficiency, MIM#616326; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Myasthenia v0.42 LRP4 Zornitza Stark Marked gene: LRP4 as ready
Congenital Myasthenia v0.42 LRP4 Zornitza Stark Gene: lrp4 has been classified as Green List (High Evidence).
Congenital Myasthenia v0.42 LRP4 Zornitza Stark Publications for gene: LRP4 were set to
Congenital Myasthenia v0.41 LRP4 Zornitza Stark reviewed gene: LRP4: Rating: GREEN; Mode of pathogenicity: None; Publications: 24234652, 26052878, 24200689; Phenotypes: Myasthenic syndrome, congenital, 17, MIM# 616304; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Myasthenia v0.41 LAMA5 Zornitza Stark Marked gene: LAMA5 as ready
Congenital Myasthenia v0.41 LAMA5 Zornitza Stark Gene: lama5 has been classified as Red List (Low Evidence).
Congenital Myasthenia v0.41 LAMA5 Zornitza Stark Phenotypes for gene: LAMA5 were changed from muscle weakness, myopia, and facial tics to Presynaptic congenital myasthenic syndrome
Congenital Myasthenia v0.40 LAMA5 Zornitza Stark Publications for gene: LAMA5 were set to 28544784
Congenital Myasthenia v0.39 LAMA5 Zornitza Stark reviewed gene: LAMA5: Rating: RED; Mode of pathogenicity: None; Publications: 28544784, 29377152; Phenotypes: Presynaptic congenital myasthenic syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Myasthenia v0.39 DPAGT1 Zornitza Stark Marked gene: DPAGT1 as ready
Congenital Myasthenia v0.39 DPAGT1 Zornitza Stark Gene: dpagt1 has been classified as Green List (High Evidence).
Congenital Myasthenia v0.39 DPAGT1 Zornitza Stark Publications for gene: DPAGT1 were set to
Congenital Myasthenia v0.38 DPAGT1 Zornitza Stark reviewed gene: DPAGT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 22742743, 29356258, 28712839, 28662078; Phenotypes: Myasthenic syndrome, congenital, 13, with tubular aggregates, MIM# 614750; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Disorders of Glycosylation v0.173 GFPT1 Zornitza Stark changed review comment from: 15 unrelated families reported with bi-allelic variants and a congenital myasthenic syndrome. Two families with leukoencephalopathy as well as CMS.

The GFPT1 gene encodes an isoform of glutamine:fructose-6-phosphate amidotransferase (GFAT), which catalyzes the transfer of an amino group from glutamine onto fructose-6-phosphate, yielding glucosamine 6-phosphate and glutamate. It is the first and rate-limiting enzyme of the hexosamine biosynthetic pathway. Hexosamine is the obligatory source of essential amino sugars for the synthesis of glycoproteins, glycolipids, and proteoglycans. Muscle samples from several patients showed decreased protein glycosylation.; to: 15 unrelated families reported with bi-allelic variants and a congenital myasthenic syndrome. Two families with leukoencephalopathy as well as CMS.

The GFPT1 gene encodes an isoform of glutamine:fructose-6-phosphate amidotransferase (GFAT), which catalyzes the transfer of an amino group from glutamine onto fructose-6-phosphate, yielding glucosamine 6-phosphate and glutamate. It is the first and rate-limiting enzyme of the hexosamine biosynthetic pathway. Hexosamine is the obligatory source of essential amino sugars for the synthesis of glycoproteins, glycolipids, and proteoglycans. Muscle samples from several patients showed decreased protein glycosylation, suggesting this is a disorder of glycosylation. However, there is also some data put forward in PMID 30635494 that this may be a mitochondrial condition.
Congenital Disorders of Glycosylation v0.173 GFPT1 Zornitza Stark Marked gene: GFPT1 as ready
Congenital Disorders of Glycosylation v0.173 GFPT1 Zornitza Stark Gene: gfpt1 has been classified as Green List (High Evidence).
Congenital Disorders of Glycosylation v0.173 GFPT1 Zornitza Stark Phenotypes for gene: GFPT1 were changed from to Myasthenia, congenital, 12, with tubular aggregates, 610542; Limb-girdle congenital myasthenic syndrome; Leukoencephalopathy
Congenital Disorders of Glycosylation v0.172 GFPT1 Zornitza Stark Publications for gene: GFPT1 were set to
Congenital Disorders of Glycosylation v0.171 GFPT1 Zornitza Stark Mode of inheritance for gene: GFPT1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Congenital Disorders of Glycosylation v0.170 GFPT1 Zornitza Stark reviewed gene: GFPT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 21310273, 30635494; Phenotypes: Myasthenia, congenital, 12, with tubular aggregates, 610542, Limb-girdle congenital myasthenic syndrome, Leukoencephalopathy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5096 GFPT1 Zornitza Stark Marked gene: GFPT1 as ready
Mendeliome v0.5096 GFPT1 Zornitza Stark Gene: gfpt1 has been classified as Green List (High Evidence).
Mendeliome v0.5096 GFPT1 Zornitza Stark Phenotypes for gene: GFPT1 were changed from to Myasthenia, congenital, 12, with tubular aggregates, 610542; Limb-girdle congenital myasthenic syndrome; Leukoencephalopathy
Mendeliome v0.5095 GFPT1 Zornitza Stark Publications for gene: GFPT1 were set to
Mendeliome v0.5094 GFPT1 Zornitza Stark Mode of inheritance for gene: GFPT1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5093 GFPT1 Zornitza Stark reviewed gene: GFPT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 21310273, 30635494; Phenotypes: Myasthenia, congenital, 12, with tubular aggregates, 610542, Limb-girdle congenital myasthenic syndrome, Leukoencephalopathy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Myasthenia v0.38 GFPT1 Zornitza Stark Marked gene: GFPT1 as ready
Congenital Myasthenia v0.38 GFPT1 Zornitza Stark Gene: gfpt1 has been classified as Green List (High Evidence).
Congenital Myasthenia v0.38 GFPT1 Zornitza Stark Publications for gene: GFPT1 were set to
Congenital Myasthenia v0.37 GFPT1 Zornitza Stark reviewed gene: GFPT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 21310273, 30635494]; Phenotypes: Myasthenia, congenital, 12, with tubular aggregates, MIM# 610542; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Myasthenia v0.37 GMPPB Zornitza Stark Marked gene: GMPPB as ready
Congenital Myasthenia v0.37 GMPPB Zornitza Stark Gene: gmppb has been classified as Green List (High Evidence).
Congenital Myasthenia v0.37 GMPPB Zornitza Stark Phenotypes for gene: GMPPB were changed from Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 14 with features of congenital myasthenic syndrome to Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 14 with features of congenital myasthenic syndrome
Congenital Myasthenia v0.36 GMPPB Zornitza Stark reviewed gene: GMPPB: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Congenital myasthenic syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hair disorders v0.39 Zornitza Stark Panel types changed to Victorian Clinical Genetics Services; Royal Melbourne Hospital; Rare Disease
Mendeliome v0.5093 BMP7 Zornitza Stark Marked gene: BMP7 as ready
Mendeliome v0.5093 BMP7 Zornitza Stark Gene: bmp7 has been classified as Red List (Low Evidence).
Mendeliome v0.5093 BMP7 Zornitza Stark gene: BMP7 was added
gene: BMP7 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: BMP7 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: BMP7 were set to 32266521; 24429398
Phenotypes for gene: BMP7 were set to Non-syndromic metopic craniosynostosis
Mode of pathogenicity for gene: BMP7 was set to Other
Review for gene: BMP7 was set to RED
Added comment: Non-syndromic metopic craniosynostosis: PMID 32266521 reports rs6127972 as a susceptibility SNP for non-syndromic metopic craniosynostosis

CAKUT: PMID 24429398 1 family with mouse model in large cohort of CAKUT.
Sources: Literature
Craniosynostosis v1.11 BMP7 Zornitza Stark Marked gene: BMP7 as ready
Craniosynostosis v1.11 BMP7 Zornitza Stark Gene: bmp7 has been classified as Red List (Low Evidence).
Craniosynostosis v1.11 BMP7 Zornitza Stark gene: BMP7 was added
gene: BMP7 was added to Craniosynostosis. Sources: Literature
Mode of inheritance for gene: BMP7 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: BMP7 were set to 32266521
Phenotypes for gene: BMP7 were set to Non-syndromic metopic craniosynostosis
Mode of pathogenicity for gene: BMP7 was set to Other
Review for gene: BMP7 was set to RED
Added comment: rs6127972 identified as a susceptibility SNP for non-syndromic metopic craniosynostosis.
Sources: Literature
Congenital Myasthenia v0.36 MUSK Zornitza Stark Marked gene: MUSK as ready
Congenital Myasthenia v0.36 MUSK Zornitza Stark Gene: musk has been classified as Green List (High Evidence).
Congenital Myasthenia v0.36 MUSK Zornitza Stark Publications for gene: MUSK were set to
Congenital Myasthenia v0.35 MUSK Zornitza Stark reviewed gene: MUSK: Rating: GREEN; Mode of pathogenicity: None; Publications: 15496425, 19949040, 20371544, 32253145; Phenotypes: Myasthenic syndrome, congenital, 9, associated with acetylcholine receptor deficiency, MIM# 616325; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hydrocephalus_Ventriculomegaly v0.69 MTOR Zornitza Stark Marked gene: MTOR as ready
Hydrocephalus_Ventriculomegaly v0.69 MTOR Zornitza Stark Gene: mtor has been classified as Amber List (Moderate Evidence).
Hydrocephalus_Ventriculomegaly v0.69 MTOR Zornitza Stark Classified gene: MTOR as Amber List (moderate evidence)
Hydrocephalus_Ventriculomegaly v0.69 MTOR Zornitza Stark Gene: mtor has been classified as Amber List (Moderate Evidence).
Hydrocephalus_Ventriculomegaly v0.68 MTOR Zornitza Stark gene: MTOR was added
gene: MTOR was added to Hydrocephalus_Ventriculomegaly. Sources: Literature
Mode of inheritance for gene: MTOR was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MTOR were set to 33077954
Phenotypes for gene: MTOR were set to Congenital hydrocephalus; macrocephaly
Mode of pathogenicity for gene: MTOR was set to Other
Review for gene: MTOR was set to AMBER
Added comment: Two de novo missense variants reported in this cohort, along with other variants involved in the MTOR pathway. GOF postulated.
Sources: Literature
Hydrocephalus_Ventriculomegaly v0.67 SMARCC1 Zornitza Stark Publications for gene: SMARCC1 were set to 33077954
Mendeliome v0.5092 SMARCC1 Zornitza Stark Publications for gene: SMARCC1 were set to 33077954
Mendeliome v0.5091 SMARCC1 Zornitza Stark changed review comment from: Three de novo variants, two LOF, one missense, reported in this hydrocephalus cohort.
Sources: Literature; to: Three de novo variants, two LOF, one missense, reported in this hydrocephalus cohort. Supportive mouse model.
Sources: Literature
Mendeliome v0.5091 SMARCC1 Zornitza Stark edited their review of gene: SMARCC1: Changed publications: 33077954, 24170322
Hydrocephalus_Ventriculomegaly v0.66 SMARCC1 Zornitza Stark changed review comment from: Three de novo variants, two LOF, one missense, reported in this hydrocephalus cohort.
Sources: Literature; to: Three de novo variants, two LOF, one missense, reported in this hydrocephalus cohort. Supportive mouse model.
Sources: Literature
Hydrocephalus_Ventriculomegaly v0.66 SMARCC1 Zornitza Stark edited their review of gene: SMARCC1: Changed publications: 33077954, 24170322
Hydrocephalus_Ventriculomegaly v0.66 FOXJ1 Zornitza Stark Marked gene: FOXJ1 as ready
Hydrocephalus_Ventriculomegaly v0.66 FOXJ1 Zornitza Stark Gene: foxj1 has been classified as Green List (High Evidence).
Hydrocephalus_Ventriculomegaly v0.66 FOXJ1 Zornitza Stark Classified gene: FOXJ1 as Green List (high evidence)
Hydrocephalus_Ventriculomegaly v0.66 FOXJ1 Zornitza Stark Gene: foxj1 has been classified as Green List (High Evidence).
Hydrocephalus_Ventriculomegaly v0.65 FOXJ1 Zornitza Stark changed review comment from: Two de novo LOF reported as part of this large hydrocephalus cohort.
Sources: Literature; to: 8 unrelated individuals reported with de novo variants in this gene, primary ciliary dyskinesia and significant obstructive hydrocephalus.
Sources: Literature
Hydrocephalus_Ventriculomegaly v0.65 FOXJ1 Zornitza Stark edited their review of gene: FOXJ1: Changed rating: GREEN; Changed publications: 33077954, 31630787
Hydrocephalus_Ventriculomegaly v0.65 FOXJ1 Zornitza Stark gene: FOXJ1 was added
gene: FOXJ1 was added to Hydrocephalus_Ventriculomegaly. Sources: Literature
Mode of inheritance for gene: FOXJ1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FOXJ1 were set to 33077954
Phenotypes for gene: FOXJ1 were set to Congenital hydrocephalus
Review for gene: FOXJ1 was set to AMBER
Added comment: Two de novo LOF reported as part of this large hydrocephalus cohort.
Sources: Literature
Mendeliome v0.5091 SMARCC1 Zornitza Stark Marked gene: SMARCC1 as ready
Mendeliome v0.5091 SMARCC1 Zornitza Stark Gene: smarcc1 has been classified as Green List (High Evidence).
Mendeliome v0.5091 SMARCC1 Zornitza Stark Classified gene: SMARCC1 as Green List (high evidence)
Mendeliome v0.5091 SMARCC1 Zornitza Stark Gene: smarcc1 has been classified as Green List (High Evidence).
Mendeliome v0.5090 SMARCC1 Zornitza Stark gene: SMARCC1 was added
gene: SMARCC1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SMARCC1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SMARCC1 were set to 33077954
Phenotypes for gene: SMARCC1 were set to Congenital hydrocephalus
Review for gene: SMARCC1 was set to GREEN
Added comment: Three de novo variants, two LOF, one missense, reported in this hydrocephalus cohort.
Sources: Literature
Hydrocephalus_Ventriculomegaly v0.64 SMARCC1 Zornitza Stark Marked gene: SMARCC1 as ready
Hydrocephalus_Ventriculomegaly v0.64 SMARCC1 Zornitza Stark Gene: smarcc1 has been classified as Green List (High Evidence).
Hydrocephalus_Ventriculomegaly v0.64 SMARCC1 Zornitza Stark Classified gene: SMARCC1 as Green List (high evidence)