PanelApp

Activity

Date Panel Item Activity
3000 actions
Fetal anomalies v2.79 MMP21 Zornitza Stark Publications for gene: MMP21 were set to 26429889; 26437028; 26437029
Fetal anomalies v2.78 MMP21 Zornitza Stark Mode of inheritance for gene: MMP21 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v2.77 MMP21 Zornitza Stark edited their review of gene: MMP21: Added comment: Monoallelic association: PMID 36123719 reports three de novo heterozygous missense MMP21 variants; variant‑specific zebrafish rescue data presented for two of the variants.

AMBER for this association.; Changed publications: 42630107, 40679208, 40467998, 39858609, 39513328, 36123719, 33240936, 33131162, 30622330, 29263817, 26437029, 26437028, 26429889; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Heterotaxy v2.5 MMP21 Zornitza Stark Publications for gene: MMP21 were set to 26429889; 26437028; 26437029
Heterotaxy v2.4 MMP21 Zornitza Stark Mode of inheritance for gene: MMP21 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Heterotaxy v2.3 MMP21 Zornitza Stark edited their review of gene: MMP21: Added comment: Monoallelic association: PMID 36123719 reports three de novo heterozygous missense MMP21 variants; variant‑specific zebrafish rescue data presented for two of the variants.

AMBER for this association.; Changed publications: 42630107, 40679208, 40467998, 39858609, 39513328, 36123719, 33240936, 33131162, 30622330, 29263817, 26437029, 26437028, 26429889; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Heterotaxy v2.3 Zornitza Stark Added reviews for gene MMP21 from panel Mendeliome
Fetal anomalies v2.77 Zornitza Stark Added reviews for gene MMP21 from panel Mendeliome
Mendeliome v2.548 MMP21 Zornitza Stark Publications for gene: MMP21 were set to 26429889; 26437028; 26437029
Mendeliome v2.547 MMP21 Zornitza Stark Mode of inheritance for gene: MMP21 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v2.546 MMP21 Zornitza Stark edited their review of gene: MMP21: Added comment: Monoallelic association: PMID 36123719 reports three de novo heterozygous missense MMP21 variants; variant‑specific zebrafish rescue data presented for two of the variants.

AMBER for this association.; Changed publications: 42630107, 40679208, 40467998, 39858609, 39513328, 36123719, 33240936, 33131162, 30622330, 29263817, 26437029, 26437028, 26429889; Changed phenotypes: heterotaxy, visceral, 7, autosomal, MONDO:0014762; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Infertility and Recurrent Pregnancy Loss v2.46 FTO Zornitza Stark Marked gene: FTO as ready
Infertility and Recurrent Pregnancy Loss v2.46 FTO Zornitza Stark Gene: fto has been classified as Amber List (Moderate Evidence).
Infertility and Recurrent Pregnancy Loss v2.46 FTO Zornitza Stark Phenotypes for gene: FTO were changed from Growth retardation, developmental delay, facial dysmorphism MIM#612938 to Infertility disorder, MONDO:0005047, FTO-related
Infertility and Recurrent Pregnancy Loss v2.45 FTO Zornitza Stark Publications for gene: FTO were set to 19234441; 19559399; 26378117; 26697951; 26378117; 26740239
Infertility and Recurrent Pregnancy Loss v2.44 FTO Zornitza Stark Mode of inheritance for gene: FTO was changed from BIALLELIC, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Infertility and Recurrent Pregnancy Loss v2.43 FTO Zornitza Stark Classified gene: FTO as Amber List (moderate evidence)
Infertility and Recurrent Pregnancy Loss v2.43 FTO Zornitza Stark Gene: fto has been classified as Amber List (Moderate Evidence).
Infertility and Recurrent Pregnancy Loss v2.42 FTO Zornitza Stark edited their review of gene: FTO: Changed rating: AMBER; Changed publications: 42576609, 37146971; Changed phenotypes: Infertility disorder, MONDO:0005047, FTO-related; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Infertility and Recurrent Pregnancy Loss v2.42 Zornitza Stark Copied gene FTO from panel Mendeliome
Infertility and Recurrent Pregnancy Loss v2.42 FTO Zornitza Stark gene: FTO was added
gene: FTO was added to Infertility and Recurrent Pregnancy Loss. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: FTO was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FTO were set to 19234441; 19559399; 26378117; 26697951; 26378117; 26740239
Phenotypes for gene: FTO were set to Growth retardation, developmental delay, facial dysmorphism MIM#612938
Mendeliome v2.546 FTO Zornitza Stark reviewed gene: FTO: Rating: GREEN; Mode of pathogenicity: None; Publications: 42576609, 37529081, 37146971, 30926952, 29161441, 27241786, 26740239, 26697951, 26378117, 19559399; Phenotypes: Infertility disorder, MONDO:0005047, FTO-related, lethal polymalformative syndrome, Boissel type, MONDO:0013050; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v2.546 KIRREL3 Sarah Milton reviewed gene: KIRREL3: Rating: RED; Mode of pathogenicity: None; Publications: 42590949; Phenotypes: complex neurodevelopmental disorder, MONDO:0100038, KIRREL3-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v2.546 CHD9 Sarah Milton Marked gene: CHD9 as ready
Mendeliome v2.546 CHD9 Sarah Milton Gene: chd9 has been classified as Red List (Low Evidence).
Mendeliome v2.546 CHD9 Sarah Milton gene: CHD9 was added
gene: CHD9 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CHD9 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CHD9 were set to 42640505; 35183220
Phenotypes for gene: CHD9 were set to Neurodevelopmental disorder, MONDO:0700092, CHD9-related
Review for gene: CHD9 was set to RED
Added comment: 2 papers assert CHD9 as a candidate gene for Chiari I malformation and a neurodevelopmental disorder respectively. Plausible biologically given other CHD proteins are disease associated but requires further literature to be considered in a diagnostic setting.
Sources: Literature
Nucleotide metabolism disorders v1.1 Richard Lin Copied gene PAICS from panel Mendeliome
Nucleotide metabolism disorders v1.1 PAICS Richard Lin gene: PAICS was added
gene: PAICS was added to Nucleotide metabolism disorders. Sources: Expert Review Red,Literature
Mode of inheritance for gene: PAICS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PAICS were set to 31600779
Phenotypes for gene: PAICS were set to PAICS deficiency MONDO:0859003
Mendeliome v2.545 PAICS Richard Lin edited their review of gene: PAICS: Changed phenotypes: PAICS deficiency, MONDO:0859003, Phosphoribosylaminoimidazole carboxylase deficiency, MIM:619859, Disorders of purine metabolism
Mendeliome v2.545 PAICS Richard Lin reviewed gene: PAICS: Rating: AMBER; Mode of pathogenicity: None; Publications: 42569864, 39726239, 39604553, 31600779; Phenotypes: PAICS deficiency, MONDO:0859003, Phosphoribosylaminoimidazole carboxylase deficiency, MIM:619859; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Renal Tubulopathies and related disorders v2.8 Lucy Spencer Copied gene BICC1 from panel Mendeliome
Renal Tubulopathies and related disorders v2.8 BICC1 Lucy Spencer gene: BICC1 was added
gene: BICC1 was added to Renal Tubulopathies and related disorders. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: BICC1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: BICC1 were set to 21922595, 35005812, 39253489, 39655693, 41278337
Phenotypes for gene: BICC1 were set to Kidney disorder MONDO:0005240, BICC1-related
Renal Tubulointerstitial Disease v2.1 Lucy Spencer Copied gene BICC1 from panel Mendeliome
Renal Tubulointerstitial Disease v2.1 BICC1 Lucy Spencer gene: BICC1 was added
gene: BICC1 was added to Renal Tubulointerstitial Disease. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: BICC1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: BICC1 were set to 21922595, 35005812, 39253489, 39655693, 41278337
Phenotypes for gene: BICC1 were set to Kidney disorder MONDO:0005240, BICC1-related
Mendeliome v2.545 BICC1 Lucy Spencer Phenotypes for gene: BICC1 were changed from Multicystic dysplastic kidney, MONDO:0015988; polycystic kidney disease, MONDO:0020642 to Kidney disorder MONDO:0005240, BICC1-related
Mendeliome v2.544 BICC1 Lucy Spencer Classified gene: BICC1 as Green List (high evidence)
Mendeliome v2.544 BICC1 Lucy Spencer Gene: bicc1 has been classified as Green List (High Evidence).
Mendeliome v2.543 BICC1 Lucy Spencer reviewed gene: BICC1: Rating: GREEN; Mode of pathogenicity: None; Publications: doi.org/10.64898/2026.08.20.26360556; Phenotypes: Kidney disorder MONDO:0005240, BICC1-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Ataxia v2.154 NEU1 Bryony Thompson Classified gene: NEU1 as Green List (high evidence)
Ataxia v2.154 NEU1 Bryony Thompson Gene: neu1 has been classified as Green List (High Evidence).
Ataxia v2.153 NEU1 Bryony Thompson gene: NEU1 was added
gene: NEU1 was added to Ataxia. Sources: Literature
Mode of inheritance for gene: NEU1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NEU1 were set to 39482827; 38600684; 33516873; 32753397; 32472645
Phenotypes for gene: NEU1 were set to sialidosis type 1, MONDO:0019346
Review for gene: NEU1 was set to GREEN
Added comment: NEU1 encodes the lysosomal sialidase Neu1. Biallelic loss‑of‑function variants in NEU1 cause sialidosis type 1, an autosomal recessive lysosomal storage disorder characterised by progressive myoclonic ataxia, myoclonus, seizures and visual impairment. Functional assays in patient‑derived iPSC neurons and HEK293T cells demonstrate reduced Neu1 protein and enzymatic activity, supporting loss‑of‑function as the disease mechanism.
Sources: Literature
Ataxia v2.152 NAXE Bryony Thompson Marked gene: NAXE as ready
Ataxia v2.152 NAXE Bryony Thompson Gene: naxe has been classified as Green List (High Evidence).
Ataxia v2.152 NAXE Bryony Thompson Classified gene: NAXE as Green List (high evidence)
Ataxia v2.152 NAXE Bryony Thompson Gene: naxe has been classified as Green List (High Evidence).
Ataxia v2.151 NAXE Bryony Thompson gene: NAXE was added
gene: NAXE was added to Ataxia. Sources: Literature
Mode of inheritance for gene: NAXE was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NAXE were set to 38419707; 37274027; 36773198; 35637064; 34678889; 34120322; 31745726; 30022751; 27616477
Phenotypes for gene: NAXE were set to encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, 1, MONDO:0020781
Review for gene: NAXE was set to GREEN
Added comment: At least 8 families with biallelic loss‑of‑function NAXE variants cause early‑onset progressive encephalopathy with brain edema/leukoencephalopathy and cerebellar ataxia. Functional fibroblast studies show loss of NAXE protein but no rescue experiments; no cis‑regulatory variants are reported. The autosomal recessive inheritance and prominent ataxia make NAXE deficiency (PEBEL1) relevant for the Ataxia gene panel.
Sources: Literature
Epidermolysis bullosa v2.1 CSTB Rylee Peters Classified gene: CSTB as Red List (low evidence)
Epidermolysis bullosa v2.1 CSTB Rylee Peters Gene: cstb has been classified as Red List (Low Evidence).
Mendeliome v2.543 CSTB Rylee Peters Phenotypes for gene: CSTB were changed from Epilepsy, progressive myoclonic 1A (Unverricht and Lundborg) MIM# 254800; Keratolytic winter erythema (MIM#148370) to Epilepsy, progressive myoclonic 1A (Unverricht and Lundborg) MIM# 254800
Mendeliome v2.542 CSTB Rylee Peters Mode of inheritance for gene: CSTB was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Severe Combined Immunodeficiency v2.6 Krithika Murali Added reviews for Region ISCA-37446-Loss from panel Common deletion and duplication syndromes
Disorders of immune dysregulation v2.11 Krithika Murali Copied Region ISCA-37446-Loss from panel Common deletion and duplication syndromes
Disorders of immune dysregulation v2.11 ISCA-37446-Loss Krithika Murali Region: ISCA-37446-Loss was added
Region: ISCA-37446-Loss was added to Disorders of immune dysregulation. Sources: ClinGen,Expert Review Green
SV/CNV tags were added to Region: ISCA-37446-Loss.
Mode of inheritance for Region: ISCA-37446-Loss was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for Region: ISCA-37446-Loss were set to 18179902; 23765049; 21671380
Phenotypes for Region: ISCA-37446-Loss were set to Chromosome 22q11.2 deletion syndrome, distal MIM#611867; intellectual disability; autism; multiple congenital anomalies
Fetal anomalies v2.76 RRAGC Zornitza Stark Marked gene: RRAGC as ready
Fetal anomalies v2.76 RRAGC Zornitza Stark Gene: rragc has been classified as Green List (High Evidence).
Fetal anomalies v2.76 Zornitza Stark Copied gene RRAGC from panel Mendeliome
Fetal anomalies v2.76 RRAGC Zornitza Stark gene: RRAGC was added
gene: RRAGC was added to Fetal anomalies. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: RRAGC was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RRAGC were set to 37057673; 27234373; 33057194
Phenotypes for gene: RRAGC were set to Long-Olsen syndrome, MIM# 620609
Inflammatory bowel disease v1.3 AIRE Tiarni Templeton gene: AIRE was added
gene: AIRE was added to Inflammatory bowel disease. Sources: Literature,Expert Review
Mode of inheritance for gene: AIRE was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AIRE were set to 37067225; 23314667
Phenotypes for gene: AIRE were set to Autoimmune polyendocrinopathy syndrome , type I, with or without reversible metaphyseal dysplasia
Penetrance for gene: AIRE were set to Complete
Review for gene: AIRE was set to GREEN
Added comment: Is currently in the congenital diarrhoea panel but not in IBD panel which we use for our VEO-IBD patients or treatment refractory patients; recommend including in IBD panel.
Sources: Literature, Expert Review
Ataxia v2.150 NARS1 Bryony Thompson Marked gene: NARS1 as ready
Ataxia v2.150 NARS1 Bryony Thompson Gene: nars1 has been classified as Green List (High Evidence).
Ataxia v2.150 NARS1 Bryony Thompson Classified gene: NARS1 as Green List (high evidence)
Ataxia v2.150 NARS1 Bryony Thompson Gene: nars1 has been classified as Green List (High Evidence).
Ataxia v2.149 NARS1 Bryony Thompson gene: NARS1 was added
gene: NARS1 was added to Ataxia. Sources: Literature
Mode of inheritance for gene: NARS1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: NARS1 were set to 38495304; 32738225
Phenotypes for gene: NARS1 were set to Neurodevelopmental disorder, MONDO:0700092; neurodevelopmental disorder with microcephaly, impaired language, and gait abnormalities, MONDO:0100348; neurodevelopmental disorder with microcephaly, impaired language, epilepsy, and gait abnormalities, MONDO:0030837
Review for gene: NARS1 was set to GREEN
Added comment: Both dominant and recessive NARS1‑related neurodevelopmental disorders feature ataxia, aligning them with the Ataxia panel's scope.
Manole2020 reports eight unrelated families with de novo heterozygous NARS1 variants causing a dominant neurodevelopmental disorder with microcephaly, seizures and gait ataxia (toxic gain‑of‑function).
Beijer2024 describes a de novo in‑frame deletion in a single family causing a dominant neurodevelopmental disorder characterised by cerebellar ataxia, pyramidal signs, developmental delay, intellectual disability and peripheral neuropathy.
Manole2020 also identifies thirteen unrelated families with biallelic NARS1 variants resulting in a recessive neurodevelopmental disorder with microcephaly, impaired language and gait ataxia (partial loss‑of‑function).
Sources: Literature
Ataxia v2.148 TELO2 Sangavi Sivagnanasundram gene: TELO2 was added
gene: TELO2 was added to Ataxia. Sources: Literature
Mode of inheritance for gene: TELO2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TELO2 were set to 36797513
Phenotypes for gene: TELO2 were set to TELO2-related intellectual disability-neurodevelopmental disorder, MONDO:0014848
Review for gene: TELO2 was set to GREEN
Added comment: PMID 36797513 reports 13 individuals from 17 families with biallelic TELO2 variants presenting with developmental delay, intellectual disability, microcephaly and ataxia.
Ataxia is a prominent feature of this condition.
Sources: Literature
Ataxia v2.147 TARS2 Sangavi Sivagnanasundram gene: TARS2 was added
gene: TARS2 was added to Ataxia. Sources: Literature
Mode of inheritance for gene: TARS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TARS2 were set to 37454282
Phenotypes for gene: TARS2 were set to combined oxidative phosphorylation defect type 21, MONDO:0014398
Review for gene: TARS2 was set to GREEN
Added comment: PMID 37454282 reports at least 5 unrelated families with biallelic TARS2 variants presenting with combined oxidative phosphorylation deficiency type 21, a mitochondrial disorder characterised by developmental delay, intellectual disability, progressive cerebellar ataxia, hypotonia, seizures and elevated lactate. Some of the affected individuals presented with an ataxic gait as well.
Sources: Literature
Ataxia v2.146 SRPK3 Sangavi Sivagnanasundram gene: SRPK3 was added
gene: SRPK3 was added to Ataxia. Sources: Literature
Mode of inheritance for gene: SRPK3 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: SRPK3 were set to 39073169
Phenotypes for gene: SRPK3 were set to intellectual developmental disorder, X-linked 114, MONDO:0975828
Review for gene: SRPK3 was set to AMBER
Added comment: PMID 39073169 reports two individuals presenting with intellectual disability, agenesis of the corpus callosum, cerebellar atrophy, abnormal eye movements and progressive ataxia and X-linked variants in SRPK3.
One of the variants c.1585G>A:p.Glu529Lys has a FAF of 0.006% in gnomAD v4.1 (96 hets and 32 hemizygotes globally).
Supportive knockout zebrafish models recapitulated the ocular and motor phenotype, including evidence of ataxia.
Sources: Literature
Ataxia v2.145 PIEZO2 Sangavi Sivagnanasundram gene: PIEZO2 was added
gene: PIEZO2 was added to Ataxia. Sources: Literature
Mode of inheritance for gene: PIEZO2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PIEZO2 were set to 27974811; 27653382
Phenotypes for gene: PIEZO2 were set to arthrogryposis, distal, with impaired proprioception and touch, MONDO:0014941
Review for gene: PIEZO2 was set to GREEN
Added comment: Distal arthrogryposis with impaired proprioception and touch characterised by reduced proprioceptive and tactile sensation, resulting in ataxia, impaired walking, dysmetria, muscle weakness and atrophy, and progressive joint contractures.

PMID 27974811 reports 1 individual from a consanguineous family (2nd-degree cousins) with a biallelic stop PIEZO2 variant causing distal arthrogryposis with sensory ataxia, proprioceptive loss, scoliosis and distal muscle weakness

PMID 27653382 reports 2 families with compound heterozygous truncating variants (and one missense variant) causing sensory ataxia with proprioceptive loss, progressive scoliosis and congenital joint contractures.
Sources: Literature
Ataxia v2.144 DYRK1A Sangavi Sivagnanasundram gene: DYRK1A was added
gene: DYRK1A was added to Ataxia. Sources: Literature
Mode of inheritance for gene: DYRK1A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DYRK1A were set to 40206408; 25944381
Phenotypes for gene: DYRK1A were set to DYRK1A-related intellectual disability syndrome, MONDO:0013578
Review for gene: DYRK1A was set to GREEN
Added comment: DYRK1A syndrome is associated with intellectual disability, speech impairment, autism spectrum disorder, and microcephaly. Affected individuals often share characteristic facial features and may experience feeding difficulties, seizures, hypertonia, walking abnormalities, and foot anomalies.

>5 unrelated individuals with monoallelic loss-of-function variants presented with ataxia/ataxic gait abnormalities.
Sources: Literature
Ataxia v2.143 NALCN Bryony Thompson gene: NALCN was added
gene: NALCN was added to Ataxia. Sources: Literature
Mode of inheritance for gene: NALCN was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NALCN were set to 41153398; 37469362; 27633718; 25864427
Phenotypes for gene: NALCN were set to congenital contractures of the limbs and face, hypotonia, and developmental delay, MONDO:0014556
Review for gene: NALCN was set to GREEN
Added comment: PMID 25864427, PMID 27633718 and PMID 41153398 report 3 individuals from 3 families with heterozygous de novo missense variants in NALCN causing congenital contractures of the limbs and face, hypotonia, developmental delay and cerebellar ataxia. PMID 37469362 reports 1 proband with mild cerebellar atrophy but no ataxia at the time of assessment. Ataxia can be a feature of the condition.
Sources: Literature
Ataxia v2.142 MT-TL1 Bryony Thompson Marked gene: MT-TL1 as ready
Ataxia v2.142 MT-TL1 Bryony Thompson Gene: mt-tl1 has been classified as Green List (High Evidence).
Ataxia v2.142 MT-TL1 Bryony Thompson Classified gene: MT-TL1 as Green List (high evidence)
Ataxia v2.142 MT-TL1 Bryony Thompson Gene: mt-tl1 has been classified as Green List (High Evidence).
Ataxia v2.141 MT-TL1 Bryony Thompson gene: MT-TL1 was added
gene: MT-TL1 was added to Ataxia. Sources: Literature
Mode of inheritance for gene gene: MT-TL1 was set to MITOCHONDRIAL
Publications for gene: MT-TL1 were set to 40787093; 40707189; 37311680; 36684660; 35869996; 32821290; 32357846; 32357846; 29430542; 28458318
Phenotypes for gene: MT-TL1 were set to MERRF syndrome, MONDO:0010790; Mitochondrial disease, MONDO:0044970
Review for gene: MT-TL1 was set to GREEN
Added comment: MELAS syndrome with cerebellar ataxia, stroke‑like episodes and lactic acidosis—Bogdan2022 reports 1 family, PMID 32357846 reports 1 family, PMID 40707189 reports 1 family and PMID 28458318 reports 1 family (total 4 families, 4 independent).
MELAS/Kearns–Sayre overlap syndrome with progressive cerebellar ataxia, myoclonus epilepsy and ophthalmoplegia—Yu2018 reports 1 family (1 independent).
Adult‑onset cerebellar ataxia with diabetes mellitus and sensorineural hearing loss—Liao2023 reports 2 families (1 independent) carrying the recurrent m.3243A>G variant.
Wernicke‑Korsakoff syndrome with gait ataxia, memory loss and thalamic/mammillary lesions—Jimoh2020 reports 1 family (1 independent).
MERRF syndrome with myoclonic epilepsy, ataxia, proximal limb weakness, cerebellar atrophy and ragged‑red fibres—Huang2023 reports 1 family (1 independent).
Mitochondrial disease with cerebellar ataxia, progressive myopathy, seizures and nephrotic syndrome—Gillespie2025 reports 1 family (1 independent).

These mitochondrial disease phenotypes frequently include cerebellar ataxia, aligning with the Ataxia panel's focus on disorders where ataxia is a prominent feature; therefore MT‑TL1 is appropriate for inclusion as a diagnostic‑grade gene on this panel.
Sources: Literature
Ataxia v2.140 MT-TK Bryony Thompson Marked gene: MT-TK as ready
Ataxia v2.140 MT-TK Bryony Thompson Gene: mt-tk has been classified as Green List (High Evidence).
Ataxia v2.140 MT-TK Bryony Thompson Classified gene: MT-TK as Green List (high evidence)
Ataxia v2.140 MT-TK Bryony Thompson Gene: mt-tk has been classified as Green List (High Evidence).
Ataxia v2.139 MT-TK Bryony Thompson gene: MT-TK was added
gene: MT-TK was added to Ataxia. Sources: Literature
Mode of inheritance for gene gene: MT-TK was set to MITOCHONDRIAL
Publications for gene: MT-TK were set to 34025555; 32538863; 29756269; 26995359; 25559684
Phenotypes for gene: MT-TK were set to MERRF syndrome, MONDO:0010790; Mitochondrial disease, MONDO:0044970
Review for gene: MT-TK was set to GREEN
Added comment: Variants in MT‑TK cause mitochondrial disease, most prominently MERRF syndrome, in which cerebellar ataxia is a frequent manifestation, and have also been reported in a rare MELAS/LS overlap presentation.

MERRF syndrome (mitochondrial disease with myoclonus, epilepsy, myopathy, cardiac involvement and ataxia) is associated with the heteroplasmic m.8344A>G mt‑tRNA Lys mutation in 26 independent families (56 patients) across Italian, German, Chinese and other cohorts; the phenotype includes cerebellar ataxia in a majority of cases.
Sources: Literature
Hereditary Neuropathy v2.101 FICD Zornitza Stark Marked gene: FICD as ready
Hereditary Neuropathy v2.101 FICD Zornitza Stark Gene: ficd has been classified as Green List (High Evidence).
Hereditary Neuropathy v2.101 FGD4 Zornitza Stark Marked gene: FGD4 as ready
Hereditary Neuropathy v2.101 FGD4 Zornitza Stark Gene: fgd4 has been classified as Green List (High Evidence).
Hereditary Neuropathy v2.101 FGD4 Zornitza Stark Phenotypes for gene: FGD4 were changed from Charcot Marie Tooth disease, type 4H, 609311; MONDO:0012250; HMSN to Charcot Marie Tooth disease, type 4H, 609311; MONDO:0012250
Hereditary Neuropathy v2.100 FBLN5 Zornitza Stark Marked gene: FBLN5 as ready
Hereditary Neuropathy v2.100 FBLN5 Zornitza Stark Gene: fbln5 has been classified as Green List (High Evidence).
Hereditary Neuropathy v2.100 FBLN5 Zornitza Stark Phenotypes for gene: FBLN5 were changed from HMSN; Neuropathy, hereditary, with or without age-related macular degeneration, MIM#608895 to Neuropathy, hereditary, with or without age-related macular degeneration, MIM#608895
Hereditary Neuropathy v2.99 ELP1 Zornitza Stark Marked gene: ELP1 as ready
Hereditary Neuropathy v2.99 ELP1 Zornitza Stark Gene: elp1 has been classified as Green List (High Evidence).
Hereditary Neuropathy v2.99 ELP1 Zornitza Stark Phenotypes for gene: ELP1 were changed from Dysautonomia, familial, 223900; Riley-Day syndrome MONDO:0009131; Hereditary sensory and autonomic neuropathy 3; HSAN/SFN to Dysautonomia, familial, MIM# 223900; Riley-Day syndrome MONDO:0009131
Hereditary Neuropathy v2.98 EGR2 Zornitza Stark Marked gene: EGR2 as ready
Hereditary Neuropathy v2.98 EGR2 Zornitza Stark Gene: egr2 has been classified as Green List (High Evidence).
Hereditary Neuropathy v2.98 DYNC1H1 Zornitza Stark Marked gene: DYNC1H1 as ready
Hereditary Neuropathy v2.98 DYNC1H1 Zornitza Stark Gene: dync1h1 has been classified as Green List (High Evidence).
Hereditary Neuropathy v2.98 DYNC1H1 Zornitza Stark Publications for gene: DYNC1H1 were set to 21820100; 32788638; 27549087
Hereditary Neuropathy v2.97 DST Zornitza Stark Marked gene: DST as ready
Hereditary Neuropathy v2.97 DST Zornitza Stark Gene: dst has been classified as Green List (High Evidence).
Hereditary Neuropathy v2.97 DST Zornitza Stark Phenotypes for gene: DST were changed from Neuropathy, hereditary sensory and autonomic, type VI, MIM# 614653; MONDO:0013839; HSAN/SFN to Neuropathy, hereditary sensory and autonomic, type VI, MIM# 614653; MONDO:0013839
Mendeliome v2.541 DRP2 Zornitza Stark edited their review of gene: DRP2: Changed phenotypes: Peripheral neuropathy, MONDO:0005244, DRP2-related
Mendeliome v2.541 DRP2 Zornitza Stark Phenotypes for gene: DRP2 were changed from Charcot Marie Tooth, intermediate X-linked; HMSN to Peripheral neuropathy, MONDO:0005244, DRP2-related
Hereditary Neuropathy v2.96 DRP2 Zornitza Stark Marked gene: DRP2 as ready
Hereditary Neuropathy v2.96 DRP2 Zornitza Stark Gene: drp2 has been classified as Green List (High Evidence).
Hereditary Neuropathy v2.96 DRP2 Zornitza Stark Phenotypes for gene: DRP2 were changed from Charcot Marie Tooth, intermediate X-linked; HMSN to Peripheral neuropathy, MONDO:0005244, DRP2-related
Hereditary Neuropathy v2.95 DRP2 Zornitza Stark edited their review of gene: DRP2: Changed phenotypes: Peripheral neuropathy, MONDO:0005244, DRP2-related
Hereditary Neuropathy v2.95 DNMT1 Zornitza Stark Marked gene: DNMT1 as ready
Hereditary Neuropathy v2.95 DNMT1 Zornitza Stark Gene: dnmt1 has been classified as Green List (High Evidence).
Hereditary Neuropathy v2.95 DNMT1 Zornitza Stark Publications for gene: DNMT1 were set to 22328086, 23904686, 24727570, 25678562, 23521649, 23365052, 21532572, 27602171, 25033457, 31984424
Hereditary Neuropathy v2.94 DNM2 Zornitza Stark Marked gene: DNM2 as ready
Hereditary Neuropathy v2.94 DNM2 Zornitza Stark Gene: dnm2 has been classified as Green List (High Evidence).
Hereditary Neuropathy v2.94 DNAJB2 Zornitza Stark Marked gene: DNAJB2 as ready
Hereditary Neuropathy v2.94 DNAJB2 Zornitza Stark Gene: dnajb2 has been classified as Green List (High Evidence).
Hereditary Neuropathy v2.94 DHX9 Zornitza Stark Marked gene: DHX9 as ready
Hereditary Neuropathy v2.94 DHX9 Zornitza Stark Gene: dhx9 has been classified as Green List (High Evidence).
Hereditary Neuropathy v2.94 DCTN1 Zornitza Stark Marked gene: DCTN1 as ready
Hereditary Neuropathy v2.94 DCTN1 Zornitza Stark Gene: dctn1 has been classified as Green List (High Evidence).
Hereditary Neuropathy v2.94 CYP7B1 Zornitza Stark reviewed gene: CYP7B1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Spastic paraplegia 5A, autosomal recessive, MIM# 270800; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Neuropathy v2.94 CYP27A1 Zornitza Stark Marked gene: CYP27A1 as ready
Hereditary Neuropathy v2.94 CYP27A1 Zornitza Stark Gene: cyp27a1 has been classified as Green List (High Evidence).
Hereditary Neuropathy v2.94 CYP27A1 Zornitza Stark Phenotypes for gene: CYP27A1 were changed from HMSN; Cholestanol storage disease to Cerebrotendinous xanthomatosis MIM#213700
Hereditary Neuropathy v2.93 CYP27A1 Zornitza Stark Publications for gene: CYP27A1 were set to
Hereditary Neuropathy v2.92 CYP27A1 Zornitza Stark reviewed gene: CYP27A1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cerebrotendinous xanthomatosis MIM#213700; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Neuropathy v2.92 COX6A1 Zornitza Stark Marked gene: COX6A1 as ready
Hereditary Neuropathy v2.92 COX6A1 Zornitza Stark Gene: cox6a1 has been classified as Green List (High Evidence).
Hereditary Neuropathy v2.92 COX6A1 Zornitza Stark Phenotypes for gene: COX6A1 were changed from Charcot Marie Tooth disease, recessive intermediate D, 616039; MONDO:0014467; HMSN to Charcot Marie Tooth disease, recessive intermediate D, MIM#616039; MONDO:0014467
Hereditary Neuropathy v2.91 COX20 Zornitza Stark edited their review of gene: COX20: Changed phenotypes: Mitochondrial complex IV deficiency, nuclear type 11, MIM#619054
Hereditary Neuropathy v2.91 COX20 Zornitza Stark Marked gene: COX20 as ready
Hereditary Neuropathy v2.91 COX20 Zornitza Stark Gene: cox20 has been classified as Green List (High Evidence).
Hereditary Neuropathy v2.91 COX20 Zornitza Stark Phenotypes for gene: COX20 were changed from sensory neuronopathy; sensory neuron disease; ganglionopathy to Mitochondrial complex IV deficiency, nuclear type 11, MIM#619054
Hereditary Neuropathy v2.90 COA7 Zornitza Stark Marked gene: COA7 as ready
Hereditary Neuropathy v2.90 COA7 Zornitza Stark Gene: coa7 has been classified as Green List (High Evidence).
Hereditary Neuropathy v2.90 COA7 Zornitza Stark Phenotypes for gene: COA7 were changed from Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 3, 618387; Cerebellar atrophy, leukoencephalopathy and spinal cord atrophy in some patients. Axonal sensory and motor neuropathy to Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 3, MIM#618387
Hereditary Neuropathy v2.89 COA7 Zornitza Stark Publications for gene: COA7 were set to
Hereditary Neuropathy v2.88 CNBP_DM2_CCTG Zornitza Stark Marked STR: CNBP_DM2_CCTG as ready
Hereditary Neuropathy v2.88 CNBP_DM2_CCTG Zornitza Stark Str: cnbp_dm2_cctg has been classified as Green List (High Evidence).
Hereditary Neuropathy v2.88 CNBP_DM2_CCTG Zornitza Stark Publications for STR: CNBP_DM2_CCTG were set to 20301639; 11486088
Hereditary Neuropathy v2.87 CLP1 Zornitza Stark Marked gene: CLP1 as ready
Hereditary Neuropathy v2.87 CLP1 Zornitza Stark Gene: clp1 has been classified as Green List (High Evidence).
Hereditary Neuropathy v2.87 CLP1 Zornitza Stark Phenotypes for gene: CLP1 were changed from Pontocerebellar hypoplasia, type 10; dHMN/dSMA to Pontocerebellar hypoplasia, type 10 (MIM#615803)
Hereditary Neuropathy v2.86 CLP1 Zornitza Stark Publications for gene: CLP1 were set to
Hereditary Neuropathy v2.85 CHCHD10 Zornitza Stark Marked gene: CHCHD10 as ready
Hereditary Neuropathy v2.85 CHCHD10 Zornitza Stark Gene: chchd10 has been classified as Green List (High Evidence).
Hereditary Neuropathy v2.85 CHCHD10 Zornitza Stark Phenotypes for gene: CHCHD10 were changed from Spinal muscular atrophy, Jokela type: 615048; CMT2; dHMN/dSMA to Spinal muscular atrophy, Jokela type, MIM# 615048
Hereditary Neuropathy v2.84 CHCHD10 Zornitza Stark Publications for gene: CHCHD10 were set to 22535186; 27066538
Hereditary Neuropathy v2.83 CADM3 Zornitza Stark Marked gene: CADM3 as ready
Hereditary Neuropathy v2.83 CADM3 Zornitza Stark Gene: cadm3 has been classified as Green List (High Evidence).
Hereditary Neuropathy v2.83 C19orf12 Zornitza Stark Marked gene: C19orf12 as ready
Hereditary Neuropathy v2.83 C19orf12 Zornitza Stark Gene: c19orf12 has been classified as Green List (High Evidence).
Hereditary Neuropathy v2.83 C19orf12 Zornitza Stark Phenotypes for gene: C19orf12 were changed from Childhood-onset spastic paraplegia and sensory-motor axonal neuropathy, NBIA with optic atrophy, extrapyramidal signs to Neurodegeneration with brain iron accumulation 4 (NBIA) (MONDO:0013674)
Hereditary Neuropathy v2.82 C19orf12 Zornitza Stark Publications for gene: C19orf12 were set to
Hereditary Neuropathy v2.81 C19orf12 Zornitza Stark Mode of inheritance for gene: C19orf12 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hereditary Neuropathy v2.80 BSCL2 Zornitza Stark Marked gene: BSCL2 as ready
Hereditary Neuropathy v2.80 BSCL2 Zornitza Stark Gene: bscl2 has been classified as Green List (High Evidence).
Hereditary Neuropathy v2.80 BSCL2 Zornitza Stark Publications for gene: BSCL2 were set to 14981520; 15732094
Hereditary Neuropathy v2.79 BICD2 Zornitza Stark Marked gene: BICD2 as ready
Hereditary Neuropathy v2.79 BICD2 Zornitza Stark Gene: bicd2 has been classified as Green List (High Evidence).
Hereditary Neuropathy v2.79 BICD2 Zornitza Stark Phenotypes for gene: BICD2 were changed from Spinal muscular atrophy, lower extremity-predominant, 2A, autosomal dominant, MIM# 615290; MONDO:0014121; Spinal muscular atrophy, lower extremity-predominant, 2B, autosomal dominant, MIM# 618291; dHMN/dSMA to Spinal muscular atrophy, lower extremity-predominant, 2A, autosomal dominant, MIM# 615290; MONDO:0014121; Spinal muscular atrophy, lower extremity-predominant, 2B, autosomal dominant, MIM# 618291
Hereditary Neuropathy v2.78 ATP7A Zornitza Stark Marked gene: ATP7A as ready
Hereditary Neuropathy v2.78 ATP7A Zornitza Stark Gene: atp7a has been classified as Green List (High Evidence).
Hereditary Neuropathy v2.78 ATP7A Zornitza Stark Phenotypes for gene: ATP7A were changed from Spinal muscular atrophy, distal, X-linked 3, MIM# 300489; dHMN/dSMA to X-linked distal spinal muscular atrophy type 3 (MONDO:0010338)
Hereditary Neuropathy v2.77 ATP7A Zornitza Stark Publications for gene: ATP7A were set to 20170900; 33137485; 31969342; 31558336
Hereditary Neuropathy v2.76 ATP1A1 Zornitza Stark Marked gene: ATP1A1 as ready
Hereditary Neuropathy v2.76 ATP1A1 Zornitza Stark Gene: atp1a1 has been classified as Green List (High Evidence).
Hereditary Neuropathy v2.76 ATL3 Zornitza Stark Marked gene: ATL3 as ready
Hereditary Neuropathy v2.76 ATL3 Zornitza Stark Gene: atl3 has been classified as Green List (High Evidence).
Hereditary Neuropathy v2.76 ATL3 Zornitza Stark Phenotypes for gene: ATL3 were changed from Hereditary sensory neuropathy type IF; HSAN/SFN to neuropathy, hereditary sensory, type 1F (MONDO:0014286)
Hereditary Neuropathy v2.75 ATL3 Zornitza Stark Tag founder tag was added to gene: ATL3.
Hereditary Neuropathy v2.75 ATL1 Zornitza Stark Marked gene: ATL1 as ready
Hereditary Neuropathy v2.75 ATL1 Zornitza Stark Gene: atl1 has been classified as Green List (High Evidence).
Hereditary Neuropathy v2.75 ATL1 Zornitza Stark Phenotypes for gene: ATL1 were changed from HSAN/SFN; Neuropathy, hereditary sensory, type ID , MIM#613708; MONDO:0013381 to Neuropathy, hereditary sensory, type ID , MIM#613708; MONDO:0013381
Hereditary Neuropathy v2.74 ATAD3A Zornitza Stark Marked gene: ATAD3A as ready
Hereditary Neuropathy v2.74 ATAD3A Zornitza Stark Gene: atad3a has been classified as Green List (High Evidence).
Hereditary Neuropathy v2.74 ATAD3A Zornitza Stark Phenotypes for gene: ATAD3A were changed from Global developmental delay, optic atrophy, axonal neuropathy, hypertrophic cardiomyopathy to Harel-Yoon Syndrome (MIM#6173183)
Hereditary Neuropathy v2.73 ATAD3A Zornitza Stark Publications for gene: ATAD3A were set to
Hereditary Neuropathy v2.72 ATAD3A Zornitza Stark Mode of pathogenicity for gene: ATAD3A was changed from to Other
Hereditary Neuropathy v2.71 ASAH1 Zornitza Stark Marked gene: ASAH1 as ready
Hereditary Neuropathy v2.71 ASAH1 Zornitza Stark Gene: asah1 has been classified as Green List (High Evidence).
Hereditary Neuropathy v2.71 ASAH1 Zornitza Stark Phenotypes for gene: ASAH1 were changed from Spinal muscular atrophy with progressive myoclonic epilepsy; dHMN/dSMA to Spinal muscular atrophy with progressive myoclonic epilepsy (MIM#159950)
Hereditary Neuropathy v2.70 ASAH1 Zornitza Stark Publications for gene: ASAH1 were set to
Hereditary Neuropathy v2.69 ARHGAP19 Zornitza Stark Marked gene: ARHGAP19 as ready
Hereditary Neuropathy v2.69 ARHGAP19 Zornitza Stark Gene: arhgap19 has been classified as Green List (High Evidence).
Hereditary Neuropathy v2.69 AR_SBMA_CAG Zornitza Stark Marked STR: AR_SBMA_CAG as ready
Hereditary Neuropathy v2.69 AR_SBMA_CAG Zornitza Stark Str: ar_sbma_cag has been classified as Green List (High Evidence).
Hereditary Neuropathy v2.69 ALDH18A1 Zornitza Stark Marked gene: ALDH18A1 as ready
Hereditary Neuropathy v2.69 ALDH18A1 Zornitza Stark Gene: aldh18a1 has been classified as Green List (High Evidence).
Hereditary Neuropathy v2.69 ALDH18A1 Zornitza Stark Phenotypes for gene: ALDH18A1 were changed from Adolescent-onset and adult-onset spastic paraplegia, dysarthria and motor neuronopathy, cataracts, skeletal abnormalities to Spastic paraplegia 9A, autosomal dominant MIM#601162
Hereditary Neuropathy v2.68 ALDH18A1 Zornitza Stark Publications for gene: ALDH18A1 were set to
Hereditary Neuropathy v2.67 ALDH18A1 Zornitza Stark Mode of inheritance for gene: ALDH18A1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary Neuropathy v2.66 ALDH18A1 Zornitza Stark reviewed gene: ALDH18A1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Spastic paraplegia 9A, autosomal dominant MIM#601162; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary Neuropathy v2.66 ABHD12 Zornitza Stark Marked gene: ABHD12 as ready
Hereditary Neuropathy v2.66 ABHD12 Zornitza Stark Gene: abhd12 has been classified as Green List (High Evidence).
Hereditary Neuropathy v2.66 ABHD12 Zornitza Stark Phenotypes for gene: ABHD12 were changed from Onset 2nd decade, neuropathy with SNCV, sensory neuronal hearing loss, retinitis pigmentosa, spastic paraplegia, ataxia; Neurodegeneration, childhood-onset, with cerebellar atrophy,612674; HMSN to Polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataract MIM#612674
Hereditary Neuropathy v2.65 ABHD12 Zornitza Stark Publications for gene: ABHD12 were set to
Hereditary Neuropathy v2.64 AARS1 Zornitza Stark Marked gene: AARS1 as ready
Hereditary Neuropathy v2.64 AARS1 Zornitza Stark Gene: aars1 has been classified as Green List (High Evidence).
Hereditary Neuropathy v2.64 AARS1 Zornitza Stark Phenotypes for gene: AARS1 were changed from Charcot Marie Tooth disease, axonal, type 2N, 613287; HMSN, dHMN/dSMA to Charcot-Marie-Tooth disease, axonal, type 2N, MIM# 613287
Hereditary Neuropathy v2.63 DNM1L Zornitza Stark Marked gene: DNM1L as ready
Hereditary Neuropathy v2.63 DNM1L Zornitza Stark Gene: dnm1l has been classified as Green List (High Evidence).
Hereditary Neuropathy v2.63 GLDN Zornitza Stark Marked gene: GLDN as ready
Hereditary Neuropathy v2.63 GLDN Zornitza Stark Gene: gldn has been classified as Green List (High Evidence).
Hereditary Neuropathy v2.63 MMACHC Zornitza Stark Marked gene: MMACHC as ready
Hereditary Neuropathy v2.63 MMACHC Zornitza Stark Gene: mmachc has been classified as Green List (High Evidence).
Hereditary Neuropathy v2.63 MTHFR Zornitza Stark Marked gene: MTHFR as ready
Hereditary Neuropathy v2.63 MTHFR Zornitza Stark Gene: mthfr has been classified as Green List (High Evidence).
Ataxia v2.138 RFC4 Sangavi Sivagnanasundram Classified gene: RFC4 as Green List (high evidence)
Ataxia v2.138 RFC4 Sangavi Sivagnanasundram Gene: rfc4 has been classified as Green List (High Evidence).
Ataxia v2.137 RFC4 Sangavi Sivagnanasundram gene: RFC4 was added
gene: RFC4 was added to Ataxia. Sources: Literature
Mode of inheritance for gene: RFC4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RFC4 were set to 39106866
Phenotypes for gene: RFC4 were set to Morimoto-Ryu-Malicdan neuromuscular syndrome, MONDO:0975848
Review for gene: RFC4 was set to GREEN
Added comment: PMID 39106866 reports four individuals from four unrelated families with biallelic RFC4 variants presenting with a multisystemic disorder that includes cerebellar ataxia, incoordination, muscle weakness, hearing impairment and reduced body weight. Two of the affected individuals also presented with gait ataxia.
Note: one of the reported variants has a high FAF in gnomAD v4.1 for an AR gene (c.996+2dup - FAF 0.0581%).
Sources: Literature
Hydrops fetalis v1.5 NPHS1 Krithika Murali Marked gene: NPHS1 as ready
Hydrops fetalis v1.5 NPHS1 Krithika Murali Gene: nphs1 has been classified as Green List (High Evidence).
Hydrops fetalis v1.5 Krithika Murali Added reviews for gene SGPL1 from panel Proteinuria
Hydrops fetalis v1.4 Krithika Murali Copied gene NPHS1 from panel Fetal anomalies
Hydrops fetalis v1.4 NPHS1 Krithika Murali gene: NPHS1 was added
gene: NPHS1 was added to Hydrops fetalis. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: NPHS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NPHS1 were set to 10577936; 17413422
Phenotypes for gene: NPHS1 were set to Nephrotic syndrome, type 1 (MIM#256300)
Ataxia v2.136 NOTCH2NLC_NIID_GGC Bryony Thompson Marked STR: NOTCH2NLC_NIID_GGC as ready
Ataxia v2.136 NOTCH2NLC_NIID_GGC Bryony Thompson Str: notch2nlc_niid_ggc has been classified as Green List (High Evidence).
Ataxia v2.136 NOTCH2NLC_NIID_GGC Bryony Thompson changed review comment from: NM_001364012.2:c.-164GGC[X]
Expanded repeat in NOTCH2NLC sequence is (GGC)9(GGA)2(GGC)2.
Large number of families and sporadic cases reported with expansions, with a range of neurodegenerative phenotypes, including: dementia, Parkinsonism/tremor, peripheral neuropathy, leukoencephalopathy, myopathy, motor neurone disease.
Normal repeat range: 4-40, 1 control had 61 repeats and may have been a presymptomatic carrier.
Intermediate range: 41-60 identified in Parkinson's disease
Pathogenic repeat range: >=60-520
Mechanism of disease is translation of repeat expansion into a toxic polyglycine protein, identified in both mouse models and tissue samples from affected individuals.
Sources: Expert list; to: NM_001364012.2:c.-164GGC[X]
Expanded repeat in NOTCH2NLC sequence is (GGC)9(GGA)2(GGC)2.
Large number of families and sporadic cases reported with expansions, with a range of neurodegenerative phenotypes, including: dementia, Parkinsonism/tremor, peripheral neuropathy, leukoencephalopathy, myopathy, motor neurone disease, ataxia.
Normal repeat range: 4-40, 1 control had 61 repeats and may have been a presymptomatic carrier.
Intermediate range: 41-60 identified in Parkinson's disease
Pathogenic repeat range: >=60-520
Mechanism of disease is translation of repeat expansion into a toxic polyglycine protein, identified in both mouse models and tissue samples from affected individuals.
Sources: Expert list
Ataxia v2.136 Bryony Thompson Copied STR NOTCH2NLC_NIID_GGC from panel Repeat Disorders
Ataxia v2.136 NOTCH2NLC_NIID_GGC Bryony Thompson STR: NOTCH2NLC_NIID_GGC was added
STR: NOTCH2NLC_NIID_GGC was added to Ataxia. Sources: Expert Review Green,Expert list
adult-onset tags were added to STR: NOTCH2NLC_NIID_GGC.
Mode of inheritance for STR: NOTCH2NLC_NIID_GGC was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: NOTCH2NLC_NIID_GGC were set to 31178126; 31332381; 31819945; 33887199; 33943039; 32250060; 31332380; 32852534; 32989102; 34333668
Phenotypes for STR: NOTCH2NLC_NIID_GGC were set to Neuronal intranuclear inclusion disease MIM#603472; Oculopharyngodistal myopathy 3 MIM#619473; Tremor, hereditary essential, 6 MIM#618866
Intellectual disability syndromic and non-syndromic v2.135 ZNF536 Zornitza Stark Marked gene: ZNF536 as ready
Intellectual disability syndromic and non-syndromic v2.135 ZNF536 Zornitza Stark Gene: znf536 has been classified as Green List (High Evidence).
Genetic Epilepsy v2.40 ZNF536 Zornitza Stark Marked gene: ZNF536 as ready
Genetic Epilepsy v2.40 ZNF536 Zornitza Stark Gene: znf536 has been classified as Green List (High Evidence).
Autism v1.19 ZNF536 Zornitza Stark Marked gene: ZNF536 as ready
Autism v1.19 ZNF536 Zornitza Stark Gene: znf536 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v2.135 Zornitza Stark Copied gene ZNF536 from panel Mendeliome
Intellectual disability syndromic and non-syndromic v2.135 ZNF536 Zornitza Stark gene: ZNF536 was added
gene: ZNF536 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Green,Literature
Mode of inheritance for gene: ZNF536 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ZNF536 were set to 42697193
Phenotypes for gene: ZNF536 were set to Neurodevelopmental disorder, MONDO:0700092, ZNF536-related
Genetic Epilepsy v2.40 Zornitza Stark Copied gene ZNF536 from panel Mendeliome
Genetic Epilepsy v2.40 ZNF536 Zornitza Stark gene: ZNF536 was added
gene: ZNF536 was added to Genetic Epilepsy. Sources: Expert Review Green,Literature
Mode of inheritance for gene: ZNF536 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ZNF536 were set to 42697193
Phenotypes for gene: ZNF536 were set to Neurodevelopmental disorder, MONDO:0700092, ZNF536-related
Autism v1.19 Zornitza Stark Copied gene ZNF536 from panel Mendeliome
Autism v1.19 ZNF536 Zornitza Stark gene: ZNF536 was added
gene: ZNF536 was added to Autism. Sources: Expert Review Green,Literature
Mode of inheritance for gene: ZNF536 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ZNF536 were set to 42697193
Phenotypes for gene: ZNF536 were set to Neurodevelopmental disorder, MONDO:0700092, ZNF536-related
Mendeliome v2.540 ZNF536 Zornitza Stark Marked gene: ZNF536 as ready
Mendeliome v2.540 ZNF536 Zornitza Stark Gene: znf536 has been classified as Green List (High Evidence).
Mendeliome v2.540 ZNF536 Zornitza Stark Classified gene: ZNF536 as Green List (high evidence)
Mendeliome v2.540 ZNF536 Zornitza Stark Gene: znf536 has been classified as Green List (High Evidence).
Mendeliome v2.539 ZNF536 Zornitza Stark gene: ZNF536 was added
gene: ZNF536 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ZNF536 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ZNF536 were set to 42697193
Phenotypes for gene: ZNF536 were set to Neurodevelopmental disorder, MONDO:0700092, ZNF536-related
Review for gene: ZNF536 was set to GREEN
Added comment: PMID 42697193 reports 21 affected individuals with 18 unique, rare, heterozygous, protein-altering ZNF536 variants. Most variants (15/18) were predicted loss-of-function (LoF) alleles, with the remainder being missense variants. Among families with available inheritance data (17/20), most variants arose de novo (12/17), while others were inherited from mosaic or mildly affected parents (5/17).

Affected individuals presented with developmental delay, autism spectrum disorder, intellectual disability, hyperactivity, aggressive behavior, anxiety, and hyperphagia; epilepsy and sleep disturbances were also frequently observed.

Homozygous mice with a Zfp536p.Gln169Ter knock-in were non-viable, while heterozygotes survived but displayed autism-like behaviours, increased anxiety, and impaired recognition memory. Embryonic brain analysis revealed reduced cortical size, cortical thickness, and decreased deep-layer neuronal density.
Sources: Literature
Ataxia v2.135 PYCR2 Sangavi Sivagnanasundram gene: PYCR2 was added
gene: PYCR2 was added to Ataxia. Sources: Literature
Mode of inheritance for gene: PYCR2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PYCR2 were set to 27860360; 27130255
Phenotypes for gene: PYCR2 were set to hypomyelinating leukodystrophy 10, MONDO:0014632
Review for gene: PYCR2 was set to GREEN
Added comment: PMID 27860360 reports only one individual with homozygous c.577G>A p.Val193Met variants presenting with progressive microcephaly, severe global developmental delay, failure to thrive, hypomyelinating leukodystrophy and an ataxic gait.

PMID: 27130255 reports 11 families (10 consanguineous families) with homozygous PYCR2 variants presenting with a range of neurodevelopmental phenotypes including ataxia, failure to thrive, microcephaly, craniofacial dysmorphism, progressive psychomotor disability, hyperkinetic movements, and axial hypotonia with variable appendicular spasticity.
Sources: Literature
Ataxia v2.134 PTPMT1 Sangavi Sivagnanasundram gene: PTPMT1 was added
gene: PTPMT1 was added to Ataxia. Sources: Literature
Mode of inheritance for gene: PTPMT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PTPMT1 were set to 39279645
Phenotypes for gene: PTPMT1 were set to Neurodevelopmental disorder with ataxia and brain abnormalities MONDO:0978300
Review for gene: PTPMT1 was set to GREEN
Added comment: Neurodevelopmental disorder with ataxia and brain abnormalities (NEDAXBA) is characterised by developmental delay, microcephaly, facial dysmorphism, epilepsy, spasticity, cerebellar ataxia and nystagmus, sensorineural hearing loss, optic atrophy, and bulbar dysfunction with neonatal/infantile onset.

PMID 39279645 reports five individuals from two consanguineous families with biallelic loss-of-function PTPMT1 variants presenting with infantile-onset cerebellar ataxia, developmental delay, microcephaly, epilepsy, sensorineural hearing loss and optic atrophy. Patient fibroblast rescue of mitochondrial fragmentation and a zebrafish ptpmt1 knockout recapitulating mitochondrial dysfunction support pathogenicity.
Sources: Literature
Genomic newborn screening: BabyScreen+ v2.7 SDHA TRAIL SCHN gene: SDHA was added
gene: SDHA was added to Genomic newborn screening: BabyScreen+. Sources: Expert Review
Mode of inheritance for gene: SDHA was set to BIALLELIC, autosomal or pseudoautosomal
Review for gene: SDHA was set to AMBER
Added comment: Please tag as "TRAIL Study"

Rationale: Clinician supported inclusion
Sources: Expert Review
Ataxia v2.133 POLR2A Sangavi Sivagnanasundram gene: POLR2A was added
gene: POLR2A was added to Ataxia. Sources: Literature
Mode of inheritance for gene: POLR2A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: POLR2A were set to 33665635
Phenotypes for gene: POLR2A were set to neurodevelopmental disorder with hypotonia and variable intellectual and behavioral abnormalities, MONDO:0032829
Review for gene: POLR2A was set to GREEN
Added comment: Ataxia isn't a prominent feature in all POLR2A-affected individuals; however, it can be a presenting feature in most individuals.
PMID 33665635 reports 7/12 individuals with heterozygous POLR2A variants presenting with a neurodevelopmental disorder featuring ataxia, developmental delay, seizures, hypotonia, joint hypermobility and short stature.
Sources: Literature
Ataxia v2.132 PIGK Sangavi Sivagnanasundram gene: PIGK was added
gene: PIGK was added to Ataxia. Sources: Literature
Mode of inheritance for gene: PIGK was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PIGK were set to 32220290
Phenotypes for gene: PIGK were set to neurodevelopmental disorder with hypotonia and cerebellar atrophy, with or without seizures, MONDO:0030037
Review for gene: PIGK was set to GREEN
Added comment: PMID 32220290 reports 5 of 8 individuals (four independent families) with biallelic PIGK variants presenting with developmental delay/intellectual disability, hypotonia, cerebellar atrophy, cerebellar ataxia, epilepsy and dysmorphic features.
Ataxia is a prominent feature of this condition.
Sources: Literature
Ataxia v2.131 PAK1 Sangavi Sivagnanasundram gene: PAK1 was added
gene: PAK1 was added to Ataxia. Sources: Literature
Mode of inheritance for gene: PAK1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PAK1 were set to 30290153
Phenotypes for gene: PAK1 were set to intellectual developmental disorder with macrocephaly, seizures, and speech delay, MONDO:0032568
Mode of pathogenicity for gene: PAK1 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: PAK1 was set to GREEN
Added comment: PMID 30290153 reports 2 individuals from 2 families with de novo heterozygous PAK1 missense variants presenting with developmental delay, macrocephaly, seizures and ataxic gait. Patient fibroblast assays show gain‑of‑function effects (increased JNK/AKT phosphorylation, reduced dimerisation, enhanced filopodia) that are rescued by the PAK1 inhibitor FRAX486.
Ataxia is a prominent feature of this condition.
Sources: Literature
Fetal anomalies v2.75 CDK5RAP3 Zornitza Stark Marked gene: CDK5RAP3 as ready
Fetal anomalies v2.75 CDK5RAP3 Zornitza Stark Gene: cdk5rap3 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v2.75 CDK5RAP3 Zornitza Stark Tag founder tag was added to gene: CDK5RAP3.
Multiple pterygium syndrome_Fetal akinesia sequence v2.1 CDK5RAP3 Zornitza Stark Marked gene: CDK5RAP3 as ready
Multiple pterygium syndrome_Fetal akinesia sequence v2.1 CDK5RAP3 Zornitza Stark Gene: cdk5rap3 has been classified as Amber List (Moderate Evidence).
Multiple pterygium syndrome_Fetal akinesia sequence v2.1 CDK5RAP3 Zornitza Stark Tag founder tag was added to gene: CDK5RAP3.
Ataxia v2.130 OGDHL Sangavi Sivagnanasundram Classified gene: OGDHL as Green List (high evidence)
Ataxia v2.130 OGDHL Sangavi Sivagnanasundram Gene: ogdhl has been classified as Green List (High Evidence).
Ataxia v2.129 OGDHL Sangavi Sivagnanasundram gene: OGDHL was added
gene: OGDHL was added to Ataxia. Sources: Literature
Mode of inheritance for gene: OGDHL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: OGDHL were set to 34800363
Phenotypes for gene: OGDHL were set to Yoon-Bellen neurodevelopmental syndrome, MONDO:0859221
Review for gene: OGDHL was set to GREEN
Added comment: Affected individuals with biallelic mutations in OGDHL present with gait ataxia, epilepsy, hearing loss, visual impairment, and developmental delay. 4 of 8 families reported ataxia as a presenting phenotype.
Functional studies in Drosophila and human neuronal cells demonstrate loss of OGDHL function.
Sources: Literature
Cerebellar and Pontocerebellar Hypoplasia v2.6 CDK5RAP3 Zornitza Stark Marked gene: CDK5RAP3 as ready
Cerebellar and Pontocerebellar Hypoplasia v2.6 CDK5RAP3 Zornitza Stark Gene: cdk5rap3 has been classified as Amber List (Moderate Evidence).
Cerebellar and Pontocerebellar Hypoplasia v2.6 CDK5RAP3 Zornitza Stark Tag founder tag was added to gene: CDK5RAP3.
Arthrogryposis v2.4 CDK5RAP3 Zornitza Stark Marked gene: CDK5RAP3 as ready
Arthrogryposis v2.4 CDK5RAP3 Zornitza Stark Gene: cdk5rap3 has been classified as Amber List (Moderate Evidence).
Arthrogryposis v2.4 CDK5RAP3 Zornitza Stark Tag founder tag was added to gene: CDK5RAP3.
Mendeliome v2.538 CDK5RAP3 Zornitza Stark Tag founder tag was added to gene: CDK5RAP3.
Multiple pterygium syndrome_Fetal akinesia sequence v2.1 Zornitza Stark Copied gene CDK5RAP3 from panel Mendeliome
Multiple pterygium syndrome_Fetal akinesia sequence v2.1 CDK5RAP3 Zornitza Stark gene: CDK5RAP3 was added
gene: CDK5RAP3 was added to Multiple pterygium syndrome_Fetal akinesia sequence. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: CDK5RAP3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CDK5RAP3 were set to 42045457
Phenotypes for gene: CDK5RAP3 were set to Neurodevelopmental disorder, MONDO:0700092, CDK5RAP3-related
Fetal anomalies v2.75 Zornitza Stark Copied gene CDK5RAP3 from panel Mendeliome
Fetal anomalies v2.75 CDK5RAP3 Zornitza Stark gene: CDK5RAP3 was added
gene: CDK5RAP3 was added to Fetal anomalies. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: CDK5RAP3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CDK5RAP3 were set to 42045457
Phenotypes for gene: CDK5RAP3 were set to Neurodevelopmental disorder, MONDO:0700092, CDK5RAP3-related
Cerebellar and Pontocerebellar Hypoplasia v2.6 Zornitza Stark Copied gene CDK5RAP3 from panel Mendeliome
Cerebellar and Pontocerebellar Hypoplasia v2.6 CDK5RAP3 Zornitza Stark gene: CDK5RAP3 was added
gene: CDK5RAP3 was added to Cerebellar and Pontocerebellar Hypoplasia. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: CDK5RAP3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CDK5RAP3 were set to 42045457
Phenotypes for gene: CDK5RAP3 were set to Neurodevelopmental disorder, MONDO:0700092, CDK5RAP3-related
Arthrogryposis v2.4 Zornitza Stark Copied gene CDK5RAP3 from panel Mendeliome
Arthrogryposis v2.4 CDK5RAP3 Zornitza Stark gene: CDK5RAP3 was added
gene: CDK5RAP3 was added to Arthrogryposis. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: CDK5RAP3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CDK5RAP3 were set to 42045457
Phenotypes for gene: CDK5RAP3 were set to Neurodevelopmental disorder, MONDO:0700092, CDK5RAP3-related
Mendeliome v2.538 CDK5RAP3 Zornitza Stark Marked gene: CDK5RAP3 as ready
Mendeliome v2.538 CDK5RAP3 Zornitza Stark Gene: cdk5rap3 has been classified as Amber List (Moderate Evidence).
Ataxia v2.128 NDUFA13 Sangavi Sivagnanasundram Classified gene: NDUFA13 as Green List (high evidence)
Ataxia v2.128 NDUFA13 Sangavi Sivagnanasundram Gene: ndufa13 has been classified as Green List (High Evidence).
Mendeliome v2.538 CDK5RAP3 Zornitza Stark Phenotypes for gene: CDK5RAP3 were changed from Neurodevelopmental disorder, MONDO:0700092 to Neurodevelopmental disorder, MONDO:0700092, CDK5RAP3-related
Ataxia v2.127 NDUFA13 Sangavi Sivagnanasundram changed review comment from: PMID 39963288 reports >5 unrelated individuals with biallelic NDUFA13 variants presenting with infantile‑onset neurodevelopmental disorder characterised by cerebellar ataxia, spasticity, hypotonia and epilepsy.
Note: One of the reported variants has a higher FAF in gnomAD v4.1 for an AR gene - c.187G>A (Glu63Lys).
Sources: Literature; to: PMID 39963288 reports >5 unrelated individuals with biallelic NDUFA13 variants presenting with infantile‑onset neurodevelopmental disorder characterised by cerebellar ataxia, spasticity, hypotonia and epilepsy.
Note: One of the reported variants has a higher FAF in gnomAD v4.1 for an AR gene - c.187G>A (Glu63Lys) FAF
0.06%.
Sources: Literature
Mendeliome v2.537 CDK5RAP3 Zornitza Stark Classified gene: CDK5RAP3 as Amber List (moderate evidence)
Mendeliome v2.537 CDK5RAP3 Zornitza Stark Gene: cdk5rap3 has been classified as Amber List (Moderate Evidence).
Mendeliome v2.536 CDK5RAP3 Zornitza Stark reviewed gene: CDK5RAP3: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, CDK5RAP3-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia v2.127 NDUFA13 Sangavi Sivagnanasundram gene: NDUFA13 was added
gene: NDUFA13 was added to Ataxia. Sources: Literature
Mode of inheritance for gene: NDUFA13 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NDUFA13 were set to 39963288
Phenotypes for gene: NDUFA13 were set to mitochondrial complex I deficiency, nuclear type 28, MONDO:0032632
Review for gene: NDUFA13 was set to GREEN
Added comment: PMID 39963288 reports >5 unrelated individuals with biallelic NDUFA13 variants presenting with infantile‑onset neurodevelopmental disorder characterised by cerebellar ataxia, spasticity, hypotonia and epilepsy.
Note: One of the reported variants has a higher FAF in gnomAD v4.1 for an AR gene - c.187G>A (Glu63Lys).
Sources: Literature
Ataxia v2.126 MYORG Sangavi Sivagnanasundram gene: MYORG was added
gene: MYORG was added to Ataxia. Sources: Literature
Mode of inheritance for gene: MYORG was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MYORG were set to 39180105; 32451491
Phenotypes for gene: MYORG were set to basal ganglia calcification, idiopathic, 7, autosomal recessive, MONDO:0032673
Review for gene: MYORG was set to GREEN
Added comment: PMID 32451491 and 39180105 report 5 families with biallelic MYORG variants causing primary familial brain calcification with cerebellar ataxia, pyramidal signs and dysarthria.
Ataxia is a prominent feature of this condition.
Sources: Literature
Hereditary Pigmentary Disorders v2.0 TERC Zornitza Stark Tag non-coding gene tag was added to gene: TERC.
Additional findings_Paediatric v1.1 TERC Zornitza Stark Tag non-coding gene tag was added to gene: TERC.
Haematological malignancies v0.148 TERC Zornitza Stark Tag non-coding gene tag was added to gene: TERC.
Mackenzie's Mission_Reproductive Carrier Screening v1.0 RNU4ATAC Zornitza Stark Tag non-coding gene tag was added to gene: RNU4ATAC.
Fetal anomalies v2.74 RNU4-2 Zornitza Stark Tag non-coding gene tag was added to gene: RNU4-2.
Prepair 500+ v3.0 RMRP Zornitza Stark Tag non-coding gene tag was added to gene: RMRP.
Additional findings_Paediatric v1.1 RMRP Zornitza Stark Tag non-coding gene tag was added to gene: RMRP.
Mackenzie's Mission_Reproductive Carrier Screening v1.0 RMRP Zornitza Stark Tag non-coding gene tag was added to gene: RMRP.
Haematological malignancies v0.148 RMRP Zornitza Stark Tag non-coding gene tag was added to gene: RMRP.
Genomic newborn screening: BabyScreen+ v2.7 MIR96 Zornitza Stark Tag non-coding gene tag was added to gene: MIR96.
Additional findings_Paediatric v1.1 MIR96 Zornitza Stark Tag non-coding gene tag was added to gene: MIR96.
Corneal Dystrophy v2.4 MIR184 Zornitza Stark Tag non-coding gene tag was added to gene: MIR184.
Ataxia v2.125 MTO1 Sangavi Sivagnanasundram gene: MTO1 was added
gene: MTO1 was added to Ataxia. Sources: Literature
Mode of inheritance for gene: MTO1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MTO1 were set to 29331171
Phenotypes for gene: MTO1 were set to Mitochondrial disease, MONDO:0044970
Review for gene: MTO1 was set to GREEN
Added comment: PMID 29331171 reports 7 individuals from 7 families with biallelic MTO1 variants presenting with ataxia, lactic acidosis, developmental delay/intellectual disability, cardiomyopathy and combined oxidative phosphorylation deficiency. The condition is a mitochondrial disorder, and ataxia is a core neurological manifestation.
Sources: Literature
Ataxia v2.124 EIF2AK2 Sangavi Sivagnanasundram gene: EIF2AK2 was added
gene: EIF2AK2 was added to Ataxia. Sources: Literature
Mode of inheritance for gene: EIF2AK2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: EIF2AK2 were set to 37284702; 32197074
Phenotypes for gene: EIF2AK2 were set to leukoencephalopathy, developmental delay, and episodic neurologic regression syndrome, MONDO:0030035
Review for gene: EIF2AK2 was set to GREEN
Added comment: PMID 32197074 reports six individuals with heterozygous missense EIF2AK2 variants presenting with developmental delay, leukoencephalopathy and progressive ataxia (gait or truncal ataxia.
PMID 37284702 reports another individual with a de novo heterozygous variant and nystagmus, hypotonia, global developmental delay, ataxia and spasticity. Brain MRI at the age of two revealed diffuse hypomyelination.
All the reported missense variants are rare or absent in gnomAD v4.
Sources: Literature
Ataxia v2.123 CYP7B1 Sangavi Sivagnanasundram gene: CYP7B1 was added
gene: CYP7B1 was added to Ataxia. Sources: Literature
Mode of inheritance for gene: CYP7B1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CYP7B1 were set to 40782215; 29126212
Phenotypes for gene: CYP7B1 were set to hereditary spastic paraplegia 5A, MONDO:0010047
Review for gene: CYP7B1 was set to GREEN
Added comment: PMID 29126212 and 40782215 report multiple individuals with autosomal recessive hereditary spastic paraplegia type 5 (SPG5) characterised by progressive spastic gait and gait ataxia.
Sources: Literature
Ataxia v2.122 CTNNB1 Sangavi Sivagnanasundram gene: CTNNB1 was added
gene: CTNNB1 was added to Ataxia. Sources: Literature
Mode of inheritance for gene: CTNNB1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CTNNB1 were set to 39935833; 35880249
Phenotypes for gene: CTNNB1 were set to CTNNB1-related neurodevelopmental disorder and/or vitreoretinopathy, MONDO:0100571
Review for gene: CTNNB1 was set to GREEN
Added comment: Ataxia is a presenting feature of this GDA.

PMID 35880249 reports 1 individual from 1 family and PMID 39935833 reports 2 individuals from 2 families, all with de novo heterozygous CTNNB1 variants presenting with neurodevelopmental disorder with spastic diplegia, visual defects, microcephaly, severe developmental delay and ataxic gait.
Sources: Literature
Ataxia v2.121 MT-ND5 Bryony Thompson Marked gene: MT-ND5 as ready
Ataxia v2.121 MT-ND5 Bryony Thompson Gene: mt-nd5 has been classified as Green List (High Evidence).
Ataxia v2.121 MT-ND5 Bryony Thompson Classified gene: MT-ND5 as Green List (high evidence)
Ataxia v2.121 MT-ND5 Bryony Thompson Gene: mt-nd5 has been classified as Green List (High Evidence).
Ataxia v2.120 MT-ND5 Bryony Thompson gene: MT-ND5 was added
gene: MT-ND5 was added to Ataxia. Sources: Literature
Mode of inheritance for gene gene: MT-ND5 was set to MITOCHONDRIAL
Publications for gene: MT-ND5 were set to 35719398; 34025555; 29506874
Phenotypes for gene: MT-ND5 were set to Leber hereditary optic neuropathy, MONDO:0010788; MELAS syndrome, MONDO:0010789; Mitochondrial disease, MONDO:0044970
Review for gene: MT-ND5 was set to GREEN
Added comment: MT-ND5 encodes a subunit of mitochondrial Complex I and pathogenic variants are linked to a spectrum of mitochondrial disorders that can feature cerebellar ataxia, a core phenotype for the Ataxia panel.

Ng2018 reports six individuals from five families with a maternally inherited m.13094T>C (p.Val253Ala) variant presenting with progressive cerebellar ataxia; the cohort provides five independent families.

Barone2022 describes a single case with the heteroplasmic m.13513G>A (p.D393N) variant causing Leber hereditary optic neuropathy together with adult‑onset nephropathy, sensorineural deafness and cerebellar atrophy.

Wei2021 aggregates six individuals from six families harbouring the recurrent m.13513G>A variant with MELAS/Leigh overlap syndrome, where ataxia is a prominent feature of the Leigh component.
Sources: Literature
Ataxia v2.119 MPZ Bryony Thompson Marked gene: MPZ as ready
Ataxia v2.119 MPZ Bryony Thompson Gene: mpz has been classified as Green List (High Evidence).
Ataxia v2.119 MPZ Bryony Thompson Classified gene: MPZ as Green List (high evidence)
Ataxia v2.119 MPZ Bryony Thompson Gene: mpz has been classified as Green List (High Evidence).
Ataxia v2.118 MPZ Bryony Thompson gene: MPZ was added
gene: MPZ was added to Ataxia. Sources: Literature
Mode of inheritance for gene: MPZ was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MPZ were set to 33960567
Phenotypes for gene: MPZ were set to Charcot-Marie-Tooth disease type 1B, MONDO:0007307
Review for gene: MPZ was set to GREEN
Added comment: PMID 33960567 reports 6 individuals from 6 families with heterozygous truncating MPZ variants presenting with adult-onset sensory ataxia, mild weakness and demyelinating neuropathy (CMT1B); four variants arose de novo and the recurrent p.Asp104fs variant was observed in multiple families. MPZ is relevant to the Ataxia panel because sensory ataxia is a core feature of the disorder.
Sources: Literature
Ataxia v2.117 MLC1 Bryony Thompson Marked gene: MLC1 as ready
Ataxia v2.117 MLC1 Bryony Thompson Gene: mlc1 has been classified as Green List (High Evidence).
Ataxia v2.117 MLC1 Bryony Thompson Classified gene: MLC1 as Green List (high evidence)
Ataxia v2.117 MLC1 Bryony Thompson Gene: mlc1 has been classified as Green List (High Evidence).
Ataxia v2.116 MLC1 Bryony Thompson gene: MLC1 was added
gene: MLC1 was added to Ataxia. Sources: Literature
Mode of inheritance for gene: MLC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MLC1 were set to 41483250; 35468122; 34918859; 31942423
Phenotypes for gene: MLC1 were set to megalencephalic leukoencephalopathy with subcortical cysts 1, MONDO:0024555
Review for gene: MLC1 was set to GREEN
Added comment: Four studies together describe 35 individuals from three independent consanguineous families carrying biallelic loss‑of‑function MLC1 variants (homozygous missense p.Ser93Leu, splice‑site c.768+2T>C, and missense p.Cys85Trp). Segregation is confirmed in the families reported by PMID 34918859 and PMID 31942423; the PMID 35468122 variant is recurrent in a distinct South‑American cohort, satisfying the qualifying‑variant gate. The multicentre Italian cohort (PMID 41483250) adds 27 further patients, confirming the classic macrocephaly, developmental delay, cerebellar ataxia, spasticity and subcortical cysts phenotype.
Sources: Literature
Ataxia v2.115 MINPP1 Bryony Thompson Marked gene: MINPP1 as ready
Ataxia v2.115 MINPP1 Bryony Thompson Gene: minpp1 has been classified as Green List (High Evidence).
Ataxia v2.115 MINPP1 Bryony Thompson Classified gene: MINPP1 as Green List (high evidence)
Ataxia v2.115 MINPP1 Bryony Thompson Gene: minpp1 has been classified as Green List (High Evidence).
Ataxia v2.114 MINPP1 Bryony Thompson gene: MINPP1 was added
gene: MINPP1 was added to Ataxia. Sources: Literature
Mode of inheritance for gene: MINPP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MINPP1 were set to 40508022; 33257696; 33168985
Phenotypes for gene: MINPP1 were set to pontocerebellar hypoplasia, MONDO:0020135
Review for gene: MINPP1 was set to GREEN
Added comment: PMID 33168985, PMID 33257696, and PMID 40508022 report a total of 18 individuals from 12 families with biallelic loss-of-function MINPP1 variants causing pontocerebellar hypoplasia, a severe neurodevelopmental disorder characterised by cerebellar and pontine hypoplasia, ataxia and profound developmental delay.
Sources: Literature
Ataxia v2.113 MICU1 Bryony Thompson Marked gene: MICU1 as ready
Ataxia v2.113 MICU1 Bryony Thompson Gene: micu1 has been classified as Green List (High Evidence).
Ataxia v2.113 MICU1 Bryony Thompson Classified gene: MICU1 as Green List (high evidence)
Ataxia v2.113 MICU1 Bryony Thompson Gene: micu1 has been classified as Green List (High Evidence).
Ataxia v2.112 MICU1 Bryony Thompson gene: MICU1 was added
gene: MICU1 was added to Ataxia. Sources: Literature
Mode of inheritance for gene: MICU1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MICU1 were set to 40434710; 38380193; 33969448; 33428302
Phenotypes for gene: MICU1 were set to proximal myopathy with extrapyramidal signs, MONDO:0014300
Review for gene: MICU1 was set to GREEN
Added comment: Four families with biallelic loss-of-function MICU1 variants are reported across four studies. Affected individuals present with childhood‑onset proximal muscle weakness, markedly elevated CK, developmental delay and extrapyramidal manifestations including ataxia, matching the phenotype of proximal myopathy with extrapyramidal signs.
Sources: Literature
Ataxia v2.111 MFSD8 Bryony Thompson Marked gene: MFSD8 as ready
Ataxia v2.111 MFSD8 Bryony Thompson Gene: mfsd8 has been classified as Green List (High Evidence).
Ataxia v2.111 MFSD8 Bryony Thompson Classified gene: MFSD8 as Green List (high evidence)
Ataxia v2.111 MFSD8 Bryony Thompson Gene: mfsd8 has been classified as Green List (High Evidence).
Ataxia v2.110 MFSD8 Bryony Thompson gene: MFSD8 was added
gene: MFSD8 was added to Ataxia. Sources: Literature
Mode of inheritance for gene: MFSD8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MFSD8 were set to 41045016; 39108195; 38153683; 37090936; 35216386; 30144815; 27146152
Phenotypes for gene: MFSD8 were set to neuronal ceroid lipofuscinosis 7, MONDO:0012588
Review for gene: MFSD8 was set to GREEN
Added comment: PMID 41045016 reports five male patients from four families (one independent founder origin) with adult‑onset isolated cerebellar ataxia due to homozygous MFSD8 p.Ile312Thr; PMID 39108195 adds three unrelated families (including two with the same variant and one compound‑heterozygous) presenting with cerebellar ataxia and macular dystrophy; PMID 38153683 describes two siblings from a consanguineous Egyptian family harbouring a homozygous missense c.638C>A variant and a classic CLN7 phenotype of neurodevelopmental regression, seizures and gait ataxia; PMID 30144815 reports a single Russian patient with a homozygous nonsense c.525T>A variant and early‑onset CLN7 features; PMID 27146152 identifies a homozygous nonsense c.1213C>T variant in a child with early‑onset ataxic gait and cerebellar atrophy; PMID 37090936 presents a case with a homozygous splice‑site c.753A>G variant and cerebellar ataxia, myoclonus and visual loss; and PMID 35216386 reports two Turkish siblings homozygous for a synonymous c.750A>G variant causing exon‑8 skipping and CLN7 with cerebellar ataxia.
Sources: Literature
Cardiomyopathy_Paediatric v1.359 Zornitza Stark removed gene:DHCR7 from the panel
Cardiomyopathy_Paediatric v1.358 CYC1 Zornitza Stark Marked gene: CYC1 as ready
Cardiomyopathy_Paediatric v1.358 CYC1 Zornitza Stark Gene: cyc1 has been classified as Red List (Low Evidence).
Cardiomyopathy_Paediatric v1.358 CYC1 Zornitza Stark Phenotypes for gene: CYC1 were changed from Mitochondrial complex III deficiency, nuclear type 6, 615453 to Mitochondrial complex III deficiency, nuclear type 6, MIM# 615453
Cardiomyopathy_Paediatric v1.357 CYC1 Zornitza Stark reviewed gene: CYC1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Mitochondrial complex III deficiency, nuclear type 6, MIM# 615453; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v2.536 CTF1 Zornitza Stark Marked gene: CTF1 as ready
Mendeliome v2.536 CTF1 Zornitza Stark Gene: ctf1 has been classified as Red List (Low Evidence).
Dilated Cardiomyopathy v2.10 CTF1 Zornitza Stark Marked gene: CTF1 as ready
Dilated Cardiomyopathy v2.10 CTF1 Zornitza Stark Gene: ctf1 has been classified as Red List (Low Evidence).
Mendeliome v2.536 Zornitza Stark Copied gene CTF1 from panel Cardiomyopathy_Paediatric
Mendeliome v2.536 CTF1 Zornitza Stark gene: CTF1 was added
gene: CTF1 was added to Mendeliome. Sources: Expert Review Red,South West GLH,NHS GMS
Mode of inheritance for gene: CTF1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CTF1 were set to 11058912; 24503780; 26084686; 7862649; 8833032; 12234945; 24366078; 21771897; 22733458
Phenotypes for gene: CTF1 were set to dilated cardiomyopathy MONDO:0005021, CTF1-related
Dilated Cardiomyopathy v2.10 Zornitza Stark Copied gene CTF1 from panel Cardiomyopathy_Paediatric
Dilated Cardiomyopathy v2.10 CTF1 Zornitza Stark gene: CTF1 was added
gene: CTF1 was added to Dilated Cardiomyopathy. Sources: Expert Review Red,South West GLH,NHS GMS
Mode of inheritance for gene: CTF1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CTF1 were set to 11058912; 24503780; 26084686; 7862649; 8833032; 12234945; 24366078; 21771897; 22733458
Phenotypes for gene: CTF1 were set to dilated cardiomyopathy MONDO:0005021, CTF1-related
Cardiomyopathy_Paediatric v1.357 CTF1 Zornitza Stark Marked gene: CTF1 as ready
Cardiomyopathy_Paediatric v1.357 CTF1 Zornitza Stark Gene: ctf1 has been classified as Red List (Low Evidence).
Cardiomyopathy_Paediatric v1.357 CTF1 Zornitza Stark Phenotypes for gene: CTF1 were changed from to dilated cardiomyopathy MONDO:0005021, CTF1-related
Cardiomyopathy_Paediatric v1.356 CTF1 Zornitza Stark Publications for gene: CTF1 were set to
Cardiomyopathy_Paediatric v1.355 CTF1 Zornitza Stark reviewed gene: CTF1: Rating: RED; Mode of pathogenicity: None; Publications: 11058912, 24503780, 26084686, 7862649, 8833032, 12234945, 24366078, 21771897, 22733458; Phenotypes: dilated cardiomyopathy MONDO:0005021, CTF1-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cardiomyopathy_Paediatric v1.355 Zornitza Stark removed gene:CPS1 from the panel
Cardiomyopathy_Paediatric v1.354 Zornitza Stark removed gene:COX6A1 from the panel
Cardiomyopathy_Paediatric v1.353 COA8 Zornitza Stark Marked gene: COA8 as ready
Cardiomyopathy_Paediatric v1.353 COA8 Zornitza Stark Gene: coa8 has been classified as Red List (Low Evidence).
Cardiomyopathy_Paediatric v1.353 COA8 Zornitza Stark Phenotypes for gene: COA8 were changed from Mitochondrial complex IV deficiency, 220110 to Mitochondrial complex IV deficiency, nuclear type 17, MIM# 619061
Cardiomyopathy_Paediatric v1.352 COA8 Zornitza Stark reviewed gene: COA8: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 17, MIM# 619061; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v1.352 Zornitza Stark removed gene:COA7 from the panel
Cardiomyopathy_Paediatric v1.351 Zornitza Stark removed gene:BTK from the panel
Cardiomyopathy_Paediatric v1.350 B3GAT3 Zornitza Stark Marked gene: B3GAT3 as ready
Cardiomyopathy_Paediatric v1.350 B3GAT3 Zornitza Stark Gene: b3gat3 has been classified as Red List (Low Evidence).
Cardiomyopathy_Paediatric v1.350 B3GAT3 Zornitza Stark Phenotypes for gene: B3GAT3 were changed from Multiple joint dislocations, short stature, craniofacial dysmorphism, with or without congenital heart defects 245600; B3GAT3-CDG (Disorders of protein O-glycosylation, O-mannosylglycan synthesis deficiencies) to Multiple joint dislocations, short stature, craniofacial dysmorphism, with or without congenital heart defects, MIM# 245600
Cardiomyopathy_Paediatric v1.349 B3GAT3 Zornitza Stark reviewed gene: B3GAT3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Multiple joint dislocations, short stature, craniofacial dysmorphism, with or without congenital heart defects, MIM# 245600; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia v2.109 MED27 Bryony Thompson Marked gene: MED27 as ready
Ataxia v2.109 MED27 Bryony Thompson Gene: med27 has been classified as Green List (High Evidence).
Ataxia v2.109 MED27 Bryony Thompson Classified gene: MED27 as Green List (high evidence)
Ataxia v2.109 MED27 Bryony Thompson Gene: med27 has been classified as Green List (High Evidence).
Ataxia v2.108 MED27 Bryony Thompson gene: MED27 was added
gene: MED27 was added to Ataxia. Sources: Literature
Mode of inheritance for gene: MED27 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MED27 were set to 41017421; 37517035
Phenotypes for gene: MED27 were set to neurodevelopmental disorder with spasticity, cataracts, and cerebellar hypoplasia, MONDO:0859137
Review for gene: MED27 was set to GREEN
Added comment: PMID 41017421 and PMID 37517035 together report a neurodevelopmental disorder with spasticity, cataracts, cerebellar hypoplasia/ataxia, intellectual disability and developmental delay caused by biallelic MED27 variants. Across the two studies 57 affected individuals from up to 60 families (38 independent origins after collapsing recurrent variants) are described, with core features of gait ataxia, cataracts, spasticity and cerebellar atrophy.
Sources: Literature
Ataxia v2.107 MED13L Bryony Thompson Marked gene: MED13L as ready
Ataxia v2.107 MED13L Bryony Thompson Gene: med13l has been classified as Green List (High Evidence).
Ataxia v2.107 MED13L Bryony Thompson Classified gene: MED13L as Green List (high evidence)
Ataxia v2.107 MED13L Bryony Thompson Gene: med13l has been classified as Green List (High Evidence).
Ataxia v2.106 MED13L Bryony Thompson gene: MED13L was added
gene: MED13L was added to Ataxia. Sources: Literature
Mode of inheritance for gene: MED13L was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MED13L were set to 29511999
Phenotypes for gene: MED13L were set to syndromic intellectual disability, MONDO:0000508
Review for gene: MED13L was set to GREEN
Added comment: PMID 29511999 reports 36 individuals from 35 families with heterozygous de novo loss-of-function or missense variants in MED13L, presenting with intellectual disability, severe speech impairment, hypotonia and ataxia (observed in ~34% of cases). The gene acts via haploinsufficiency (loss-of-function) with an autosomal dominant de novo inheritance pattern and no contradictory evidence.
Sources: Literature
Ataxia v2.105 MBOAT7 Bryony Thompson Marked gene: MBOAT7 as ready
Ataxia v2.105 MBOAT7 Bryony Thompson Gene: mboat7 has been classified as Green List (High Evidence).
Ataxia v2.105 MBOAT7 Bryony Thompson Classified gene: MBOAT7 as Green List (high evidence)
Ataxia v2.105 MBOAT7 Bryony Thompson Gene: mboat7 has been classified as Green List (High Evidence).
Ataxia v2.104 MBOAT7 Bryony Thompson gene: MBOAT7 was added
gene: MBOAT7 was added to Ataxia. Sources: Literature
Mode of inheritance for gene: MBOAT7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MBOAT7 were set to 30701556
Phenotypes for gene: MBOAT7 were set to complex neurodevelopmental disorder, MONDO:0100038
Review for gene: MBOAT7 was set to GREEN
Added comment: PMID 30701556 reports 12 individuals from 7 consanguineous Turkish families (5 independent) with biallelic loss‑of‑function variants in MBOAT7 presenting with global developmental delay, severe speech impairment, intellectual disability, early‑onset epilepsy and a characteristic wide‑based ataxic gait with cerebellar dysgenesis. This neurodevelopmental disorder with prominent ataxia aligns with the Ataxia panel’s scope, as ataxic gait is a core feature of the phenotype.
Sources: Literature
Ataxia v2.103 MAN2B1 Bryony Thompson Marked gene: MAN2B1 as ready
Ataxia v2.103 MAN2B1 Bryony Thompson Gene: man2b1 has been classified as Green List (High Evidence).
Ataxia v2.103 MAN2B1 Bryony Thompson Classified gene: MAN2B1 as Green List (high evidence)
Ataxia v2.103 MAN2B1 Bryony Thompson Gene: man2b1 has been classified as Green List (High Evidence).
Ataxia v2.102 MAN2B1 Bryony Thompson gene: MAN2B1 was added
gene: MAN2B1 was added to Ataxia. Sources: Literature
Mode of inheritance for gene: MAN2B1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MAN2B1 were set to 35242565; 34486965
Phenotypes for gene: MAN2B1 were set to alpha-mannosidosis, MONDO:0009561
Review for gene: MAN2B1 was set to GREEN
Added comment: PMID 35242565 reports 12 individuals from 9 families and PMID 34486965 reports 1 individual from 1 family with autosomal recessive alpha‑mannosidosis presenting with childhood‑onset progressive ataxia, hearing loss, intellectual disability and immune deficiency. In total, 13 patients from 10 families (4 independent) carry biallelic loss‑of‑function MAN2B1 variants, including three families with truncating null alleles and one family with a missense allele (c.1061C>T) with variant‑specific functional validation. The disease is a lysosomal storage disorder with a recognisable multisystem phenotype that includes ataxia, making MAN2B1 relevant to the Ataxia panel.
Sources: Literature
Ataxia v2.101 MAB21L1 Bryony Thompson Marked gene: MAB21L1 as ready
Ataxia v2.101 MAB21L1 Bryony Thompson Gene: mab21l1 has been classified as Green List (High Evidence).
Ataxia v2.101 MAB21L1 Bryony Thompson Classified gene: MAB21L1 as Green List (high evidence)
Ataxia v2.101 MAB21L1 Bryony Thompson Gene: mab21l1 has been classified as Green List (High Evidence).
Ataxia v2.100 MAB21L1 Bryony Thompson gene: MAB21L1 was added
gene: MAB21L1 was added to Ataxia. Sources: Literature
Mode of inheritance for gene: MAB21L1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MAB21L1 were set to 30487245
Phenotypes for gene: MAB21L1 were set to cerebellar, ocular, craniofacial, and genital syndrome, MONDO:0032774
Review for gene: MAB21L1 was set to GREEN
Added comment: PMID 30487245 reports 10 individuals from 5 families with biallelic loss-of-function variants in MAB21L1 presenting with Cerebello-Oculo-Facio-Genital (COFG) syndrome, characterised by cerebellar hypoplasia with ataxia, ocular anomalies, distinctive facial features and genital anomalies. This gene is relevant to the Ataxia panel because the syndrome includes cerebellar hypoplasia and ataxia, core features of the panel's scope.
Sources: Literature
Ataxia v2.99 LYST Bryony Thompson Marked gene: LYST as ready
Ataxia v2.99 LYST Bryony Thompson Gene: lyst has been classified as Green List (High Evidence).
Ataxia v2.99 LYST Bryony Thompson Classified gene: LYST as Green List (high evidence)
Ataxia v2.99 LYST Bryony Thompson Gene: lyst has been classified as Green List (High Evidence).
Ataxia v2.98 LYST Bryony Thompson gene: LYST was added
gene: LYST was added to Ataxia. Sources: Literature
Mode of inheritance for gene: LYST was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LYST were set to 34483340; 28193763; 26944273; 26307451
Phenotypes for gene: LYST were set to Chediak-Higashi syndrome, MONDO:0008963
Review for gene: LYST was set to GREEN
Added comment: Multiple studies report that biallelic loss‑of‑function variants in LYST cause Chediak‑Higashi syndrome, a Mendelian lysosomal trafficking disorder that frequently includes cerebellar ataxia. PMID 34483340 describes four families (two independent) with spastic paraplegia, cerebellar ataxia and intellectual disability; PMID 26307451 reports a single adult‑onset family of three siblings with ataxia, parkinsonism and spastic paraparesis; PMID 26944273 (and the overlapping PMID 28193763 cohort) document nine patients from seven families (six independent) with childhood‑onset cerebellar ataxia and progressive neurodegeneration. Across the literature 12 families (9 independent) harbour qualifying biallelic truncating or nonsense LYST variants.
Sources: Literature
Ataxia v2.97 LRSAM1 Bryony Thompson Marked gene: LRSAM1 as ready
Ataxia v2.97 LRSAM1 Bryony Thompson Gene: lrsam1 has been classified as Green List (High Evidence).
Ataxia v2.97 LRSAM1 Bryony Thompson Classified gene: LRSAM1 as Green List (high evidence)
Ataxia v2.97 LRSAM1 Bryony Thompson Gene: lrsam1 has been classified as Green List (High Evidence).
Ataxia v2.96 LRSAM1 Bryony Thompson gene: LRSAM1 was added
gene: LRSAM1 was added to Ataxia. Sources: Literature
Mode of inheritance for gene: LRSAM1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: LRSAM1 were set to 30996334
Phenotypes for gene: LRSAM1 were set to Charcot-Marie-Tooth disease axonal type 2P, MONDO:0013753
Review for gene: LRSAM1 was set to GREEN
Added comment: PMID 30996334 reports 72 individuals from 8 families (5 independent) with heterozygous in‑frame LRSAM1 variants presenting with adult‑onset sensory ataxia, neuropathic pain and length‑dependent sensory loss. This dominant‑negative mechanism causes Charcot‑Marie‑Tooth disease type 2P, an ataxic neuropathy that falls within the Ataxia panel’s scope of disorders featuring prominent ataxia.
Sources: Literature
Ataxia v2.95 L2HGDH Bryony Thompson Marked gene: L2HGDH as ready
Ataxia v2.95 L2HGDH Bryony Thompson Gene: l2hgdh has been classified as Green List (High Evidence).
Ataxia v2.95 L2HGDH Bryony Thompson Classified gene: L2HGDH as Green List (high evidence)
Ataxia v2.95 L2HGDH Bryony Thompson Gene: l2hgdh has been classified as Green List (High Evidence).
Ataxia v2.94 L2HGDH Bryony Thompson gene: L2HGDH was added
gene: L2HGDH was added to Ataxia. Sources: Literature
Mode of inheritance for gene: L2HGDH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: L2HGDH were set to 42205672; 40870031; 40660807; 38716347; 37275239; 36462087; 33061758
Phenotypes for gene: L2HGDH were set to L-2-hydroxyglutaric aciduria, MONDO:0009370
Review for gene: L2HGDH was set to GREEN
Added comment: PMID 36462087, PMID 37275239, PMID 33061758, PMID 40660807, PMID 38716347, PMID 40870031 and PMID 42205672 together report 52 individuals from 38 families with biallelic L2HGDH loss‑of‑function variants presenting with L‑2‑hydroxyglutaric aciduria, characterised by progressive cerebellar ataxia, developmental delay, seizures and movement disorders.
Sources: Literature
Ataxia v2.93 KIF5A Bryony Thompson Marked gene: KIF5A as ready
Ataxia v2.93 KIF5A Bryony Thompson Gene: kif5a has been classified as Green List (High Evidence).
Ataxia v2.93 KIF5A Bryony Thompson Classified gene: KIF5A as Green List (high evidence)
Ataxia v2.93 KIF5A Bryony Thompson Gene: kif5a has been classified as Green List (High Evidence).
Ataxia v2.92 KIF5A Bryony Thompson gene: KIF5A was added
gene: KIF5A was added to Ataxia. Sources: Literature
Mode of inheritance for gene: KIF5A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KIF5A were set to 40518753; 31286494; 30778698; 30480035; 29892902
Phenotypes for gene: KIF5A were set to hereditary spastic paraplegia 10, MONDO:0011408
Review for gene: KIF5A was set to GREEN
Added comment: Four papers report 12 affected individuals from 4 independent families with heterozygous KIF5A variants (missense and splice) presenting with hereditary spastic paraplegia and cerebellar ataxia; this phenotype includes prominent ataxia and aligns with the Ataxia panel’s scope of disorders where ataxia is a core feature.
Sources: Literature
Cardiomyopathy_Paediatric v1.349 ANKRD1 Zornitza Stark Marked gene: ANKRD1 as ready
Cardiomyopathy_Paediatric v1.349 ANKRD1 Zornitza Stark Gene: ankrd1 has been classified as Red List (Low Evidence).
Cardiomyopathy_Paediatric v1.349 ANKRD1 Zornitza Stark Phenotypes for gene: ANKRD1 were changed from Dilated Cardiomyopathy, Dominant to dilated cardiomyopathy MONDO:0005021; hypertrophic cardiomyopathy MONDO:0005045
Cardiomyopathy_Paediatric v1.348 ANKRD1 Zornitza Stark edited their review of gene: ANKRD1: Changed phenotypes: dilated cardiomyopathy MONDO:0005021, hypertrophic cardiomyopathy MONDO:0005045
Cardiomyopathy_Paediatric v1.348 ANKRD1 Zornitza Stark Publications for gene: ANKRD1 were set to
Cardiomyopathy_Paediatric v1.347 ANKRD1 Zornitza Stark reviewed gene: ANKRD1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Cardiomyopathy_Paediatric v1.347 UQCC2 Zornitza Stark Marked gene: UQCC2 as ready
Cardiomyopathy_Paediatric v1.347 UQCC2 Zornitza Stark Gene: uqcc2 has been classified as Red List (Low Evidence).
Cardiomyopathy_Paediatric v1.347 UQCC2 Zornitza Stark Phenotypes for gene: UQCC2 were changed from Mitochondrial complex III deficiency, nuclear type 7, 615824 to Mitochondrial complex III deficiency, nuclear type 7, MIM# 615824
Cardiomyopathy_Paediatric v1.346 UQCC2 Zornitza Stark Classified gene: UQCC2 as Red List (low evidence)
Cardiomyopathy_Paediatric v1.346 UQCC2 Zornitza Stark Gene: uqcc2 has been classified as Red List (Low Evidence).
Cardiomyopathy_Paediatric v1.345 UQCC2 Zornitza Stark reviewed gene: UQCC2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Mitochondrial complex III deficiency, nuclear type 7, MIM# 615824; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v1.345 SGSH Zornitza Stark Marked gene: SGSH as ready
Cardiomyopathy_Paediatric v1.345 SGSH Zornitza Stark Gene: sgsh has been classified as Amber List (Moderate Evidence).
Cardiomyopathy_Paediatric v1.345 PET100 Zornitza Stark Marked gene: PET100 as ready
Cardiomyopathy_Paediatric v1.345 PET100 Zornitza Stark Gene: pet100 has been classified as Red List (Low Evidence).
Cardiomyopathy_Paediatric v1.345 PET100 Zornitza Stark Phenotypes for gene: PET100 were changed from Mitochondrial complex IV deficiency, 220110 to Mitochondrial complex IV deficiency, nuclear type 12, MIM# 619055
Cardiomyopathy_Paediatric v1.344 PET100 Zornitza Stark Classified gene: PET100 as Red List (low evidence)
Cardiomyopathy_Paediatric v1.344 PET100 Zornitza Stark Gene: pet100 has been classified as Red List (Low Evidence).
Cardiomyopathy_Paediatric v1.343 PET100 Zornitza Stark reviewed gene: PET100: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 12, MIM# 619055; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v2.535 NDUFB8 Zornitza Stark Publications for gene: NDUFB8 were set to 29429571
Mendeliome v2.534 NDUFB8 Zornitza Stark reviewed gene: NDUFB8: Rating: GREEN; Mode of pathogenicity: None; Publications: 30770271; Phenotypes: Mitochondrial complex I deficiency, nuclear type 32 - MIM#618252; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disease v2.9 NDUFB8 Zornitza Stark Publications for gene: NDUFB8 were set to 29429571
Mitochondrial disease v2.8 NDUFB8 Zornitza Stark reviewed gene: NDUFB8: Rating: GREEN; Mode of pathogenicity: None; Publications: 30770271; Phenotypes: Mitochondrial complex I deficiency, nuclear type 32 - MIM#618252; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v1.343 NDUFB8 Zornitza Stark Marked gene: NDUFB8 as ready
Cardiomyopathy_Paediatric v1.343 NDUFB8 Zornitza Stark Gene: ndufb8 has been classified as Amber List (Moderate Evidence).
Cardiomyopathy_Paediatric v1.343 NDUFB8 Zornitza Stark Phenotypes for gene: NDUFB8 were changed from Mitochondrial complex I deficiency, nuclear type 32, 618252 to Mitochondrial complex I deficiency, nuclear type 32, MIM# 618252
Cardiomyopathy_Paediatric v1.342 NDUFB8 Zornitza Stark changed review comment from: Cardiomyopathy reported in one of the two original families.; to: Cardiomyopathy reported in one of the two original families.

The gene-disease relationship has been rated as MODERATE by ClinGen, with only 3 families reported -- the third family in PMID 30770271 had predominantly neurological involvement.
Cardiomyopathy_Paediatric v1.342 NDUFB8 Zornitza Stark reviewed gene: NDUFB8: Rating: AMBER; Mode of pathogenicity: None; Publications: 29429571; Phenotypes: Mitochondrial complex I deficiency, nuclear type 32, MIM# 618252; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia v2.91 KIF1A Bryony Thompson Marked gene: KIF1A as ready
Ataxia v2.91 KIF1A Bryony Thompson Gene: kif1a has been classified as Green List (High Evidence).
Ataxia v2.91 KIF1A Bryony Thompson Classified gene: KIF1A as Green List (high evidence)
Ataxia v2.91 KIF1A Bryony Thompson Gene: kif1a has been classified as Green List (High Evidence).
Ataxia v2.90 KIF1A Bryony Thompson gene: KIF1A was added
gene: KIF1A was added to Ataxia. Sources: Literature
Mode of inheritance for gene: KIF1A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KIF1A were set to 38785164; 38681507; 36305856; 36233161; 35326432; 30778698; 27146152
Phenotypes for gene: KIF1A were set to Neurodevelopmental disorder, MONDO:0700092
Review for gene: KIF1A was set to GREEN
Added comment: KIF1A is associated with a dominant neurodevelopmental disorder characterised by early‑onset progressive ataxia, cerebellar atrophy, spasticity, hypotonia, seizures, optic nerve atrophy and cognitive impairment. Across 191 reported families (190 independent qualifying families) de novo heterozygous missense variants have been documented with ataxia. A single recessive case with biallelic KIF1A variants and a similar phenotype has also been described but does not meet the family‑count threshold for Green classification. The dominant KIF1A‑associated ataxia phenotype aligns with the Ataxia panel’s scope of disorders where ataxia is a prominent feature.
Sources: Literature
Ataxia v2.89 KIAA0586 Bryony Thompson Marked gene: KIAA0586 as ready
Ataxia v2.89 KIAA0586 Bryony Thompson Gene: kiaa0586 has been classified as Green List (High Evidence).
Ataxia v2.89 KIAA0586 Bryony Thompson Classified gene: KIAA0586 as Green List (high evidence)
Ataxia v2.89 KIAA0586 Bryony Thompson Gene: kiaa0586 has been classified as Green List (High Evidence).
Ataxia v2.88 KIAA0586 Bryony Thompson gene: KIAA0586 was added
gene: KIAA0586 was added to Ataxia. Sources: Literature
Mode of inheritance for gene: KIAA0586 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIAA0586 were set to 40448720; 39898050; 37131188; 36635699; 32381069; 30120217; 26386247; 26386044; 26026149
Phenotypes for gene: KIAA0586 were set to Joubert syndrome 23, MONDO:0014664
Review for gene: KIAA0586 was set to GREEN
Added comment: Across nine studies, 33 families (32 independent) with 37 affected individuals have been reported harbouring biallelic loss‑of‑function KIAA0586 variants. All families present the core Joubert syndrome phenotype – cerebellar vermis hypoplasia, molar‑tooth sign, ataxia, developmental delay and hypotonia – with variable additional features such as chronic airway disease, thoracic dysplasia, ocular‑motor apraxia, epilepsy or SUDEP. Autosomal recessive inheritance is consistently demonstrated (e.g., PMID 26026149 box 30, PMID 26386247 box 31). Functional assays show absent KIAA0586 protein or shortened cilia in patient fibroblasts, but no rescue experiments or orthogonal animal models (e.g., PMID 26026149 box 114; PMID 26386247 box 28). A recurrent frameshift allele (c.428delG) is common (gnomAD AF ≈ 0.003) and observed homozygously in healthy individuals, yet is interpreted as a hypomorphic variant that contributes to disease when paired with a second loss‑of‑function allele. No convincing contradictory evidence has been published. The phenotype’s hallmark ataxia makes KIAA0586 a clear fit for the Ataxia panel, which prioritises genes causing disorders where ataxia is a prominent feature.
Sources: Literature
Ataxia v2.87 KCTD7 Bryony Thompson Marked gene: KCTD7 as ready
Ataxia v2.87 KCTD7 Bryony Thompson Gene: kctd7 has been classified as Green List (High Evidence).
Ataxia v2.87 KCTD7 Bryony Thompson Classified gene: KCTD7 as Green List (high evidence)
Ataxia v2.87 KCTD7 Bryony Thompson Gene: kctd7 has been classified as Green List (High Evidence).
Ataxia v2.86 KCTD7 Bryony Thompson gene: KCTD7 was added
gene: KCTD7 was added to Ataxia. Sources: Literature
Mode of inheritance for gene: KCTD7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KCTD7 were set to 38231304; 27742667
Phenotypes for gene: KCTD7 were set to progressive myoclonic epilepsy type 3, MONDO:0012721
Review for gene: KCTD7 was set to GREEN
Added comment: PMID 27742667 reports 2 individuals from 1 family with a homozygous frameshift KCTD7 variant presenting with early‑onset progressive myoclonic epilepsy, severe ataxia and neuroregression; functional assays show loss of K⁺ conductance and impaired glutamine transport. PMID 38231304 adds 42 individuals from 36 families (30 independent) with biallelic KCTD7 loss‑of‑function variants (including recurrent missense alleles) who exhibit drug‑resistant seizures, myoclonus, neuroregression and ataxia. The combined evidence of 31 independent families with ataxia. This association aligns with the Ataxia panel’s scope because ataxia is a core, frequently reported feature of KCTD7‑related progressive myoclonic epilepsy.
Sources: Literature
Ataxia v2.85 KCNMA1 Bryony Thompson Marked gene: KCNMA1 as ready
Ataxia v2.85 KCNMA1 Bryony Thompson Gene: kcnma1 has been classified as Green List (High Evidence).
Ataxia v2.85 KCNMA1 Bryony Thompson Classified gene: KCNMA1 as Green List (high evidence)
Ataxia v2.85 KCNMA1 Bryony Thompson Gene: kcnma1 has been classified as Green List (High Evidence).
Ataxia v2.84 KCNMA1 Bryony Thompson gene: KCNMA1 was added
gene: KCNMA1 was added to Ataxia. Sources: Literature
Mode of inheritance for gene: KCNMA1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KCNMA1 were set to 35730691; 35156297; 33178487; 32132200; 31152168
Phenotypes for gene: KCNMA1 were set to Liang-Wang syndrome, MONDO:0032886; Neurodevelopmental disorder, MONDO:0700092
Review for gene: KCNMA1 was set to GREEN
Added comment: Liang‑Wang syndrome (loss‑of‑function KCNMA1) is a monoallelic disorder characterised by developmental delay, cognitive impairment, progressive ataxia and movement abnormalities. Across four studies, 12 independent families with de novo LoF variants have been reported (PMID 32132200, PMID 31152168, PMID 35156297, PMID 33178487). A second, recessive loss‑of‑function neurodevelopmental disorder with ataxia has been described in a single compound‑heterozygous family (PMID 31152168); while supportive, it does not meet the family‑count threshold for a diagnostic‑grade rating.
Sources: Literature
Ataxia v2.83 KCNC1 Bryony Thompson Marked gene: KCNC1 as ready
Ataxia v2.83 KCNC1 Bryony Thompson Gene: kcnc1 has been classified as Green List (High Evidence).
Ataxia v2.83 KCNC1 Bryony Thompson Classified gene: KCNC1 as Green List (high evidence)
Ataxia v2.83 KCNC1 Bryony Thompson Gene: kcnc1 has been classified as Green List (High Evidence).
Ataxia v2.82 KCNC1 Bryony Thompson gene: KCNC1 was added
gene: KCNC1 was added to Ataxia. Sources: Literature
Mode of inheritance for gene: KCNC1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KCNC1 were set to 42347804; 40765656; 37203213; 34733949; 32972906; 31353862; 28380698; 27629860
Phenotypes for gene: KCNC1 were set to complex neurodevelopmental disorder, MONDO:0100038; progressive myoclonic epilepsy type 7, MONDO:0014521
Review for gene: KCNC1 was set to GREEN
Added comment: Both progressive myoclonic epilepsy with ataxia (MEAK/EPM7) and milder epilepsy with ataxia phenotypes are associated with KCNC1 variants. PMID 28380698, PMID 27629860, PMID 40765656, PMID 32972906 and PMID 34733949 report 31 families (39 patients) with dominant‑negative loss‑of‑function KCNC1 variants causing progressive myoclonus epilepsy, seizures and cerebellar ataxia, fulfilling diagnostic criteria. PMID 31353862, PMID 42347804 and PMID 37203213 describe 6 families (6 patients) with de novo missense KCNC1 variants leading to epilepsy, mild developmental delay and non‑progressive ataxia, also meeting diagnostic criteria. Ataxia is a core feature of both disease spectrums, making KCNC1 a suitable gene for the Ataxia panel.
Sources: Literature
Ataxia v2.81 KATNIP Bryony Thompson Marked gene: KATNIP as ready
Ataxia v2.81 KATNIP Bryony Thompson Gene: katnip has been classified as Green List (High Evidence).
Ataxia v2.81 KATNIP Bryony Thompson Classified gene: KATNIP as Green List (high evidence)
Ataxia v2.81 KATNIP Bryony Thompson Gene: katnip has been classified as Green List (High Evidence).
Ataxia v2.80 KATNIP Bryony Thompson gene: KATNIP was added
gene: KATNIP was added to Ataxia. Sources: Literature
Mode of inheritance for gene: KATNIP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KATNIP were set to 40621737; 32164589; 32164589; 30982090; 30982090; 27245168; 27245168; 26714646; 26714646
Phenotypes for gene: KATNIP were set to Joubert syndrome, MONDO:0018772
Review for gene: KATNIP was set to GREEN
Added comment: Seven families (11 affected individuals) with Joubert syndrome, a neurodevelopmental ciliopathy featuring ataxia, hypotonia, developmental delay and cerebellar vermis hypoplasia, harbour homozygous loss‑of‑function KATNIP variants (c.2674C>T (p.Q892*), c.4420del, c.222_232del, c.3756dupC, R1253Qfs*, M1474Cfs*). Zebrafish morpholino knockdown rescued by wild‑type mRNA provides functional validation, and mouse knockout phenotypes support the loss‑of‑function mechanism. Recessive inheritance is well documented across independent families. Joubert syndrome includes prominent ataxia, making KATNIP relevant to the Ataxia panel.
Sources: Literature
Ataxia v2.79 KARS1 Bryony Thompson Marked gene: KARS1 as ready
Ataxia v2.79 KARS1 Bryony Thompson Gene: kars1 has been classified as Green List (High Evidence).
Ataxia v2.79 KARS1 Bryony Thompson Classified gene: KARS1 as Green List (high evidence)
Ataxia v2.79 KARS1 Bryony Thompson Gene: kars1 has been classified as Green List (High Evidence).
Ataxia v2.78 KARS1 Bryony Thompson gene: KARS1 was added
gene: KARS1 was added to Ataxia. Sources: Literature
Mode of inheritance for gene: KARS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KARS1 were set to 34172899; 31192300; 31192300
Phenotypes for gene: KARS1 were set to leukoencephalopathy, progressive, infantile-onset, with or without deafness, MONDO:0030893
Review for gene: KARS1 was set to GREEN
Added comment: PMID 34172899 reports 22 individuals from 16 families and PMID 31192300 reports 5 individuals from 4 families with biallelic KARS1 loss-of-function variants causing early-onset leukoencephalopathy with cerebellar ataxia. Segregation is confirmed in multiple pedigrees, and functional studies—including zebrafish knockout rescue and aminoacyl‑tRNA synthetase activity assays—support a loss‑of‑function mechanism. In total 27 patients from 20 independent families with ataxia.
Sources: Literature
Ataxia v2.77 JAM2 Bryony Thompson Marked gene: JAM2 as ready
Ataxia v2.77 JAM2 Bryony Thompson Gene: jam2 has been classified as Green List (High Evidence).
Ataxia v2.77 JAM2 Bryony Thompson Classified gene: JAM2 as Green List (high evidence)
Ataxia v2.77 JAM2 Bryony Thompson Gene: jam2 has been classified as Green List (High Evidence).
Ataxia v2.76 JAM2 Bryony Thompson gene: JAM2 was added
gene: JAM2 was added to Ataxia. Sources: Literature
Mode of inheritance for gene: JAM2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: JAM2 were set to 32142645
Phenotypes for gene: JAM2 were set to basal ganglia calcification, idiopathic, 8, autosomal recessive, MONDO:0032938
Review for gene: JAM2 was set to GREEN
Added comment: PMID 32142645 reports 7 individuals from 4 families with biallelic loss-of-function JAM2 variants presenting with primary familial brain calcification and cerebellar ataxia. The cerebellar ataxia aligns JAM2 with the Ataxia panel, which captures disorders where ataxia is a prominent feature.
Sources: Literature
Ataxia v2.75 IQSEC2 Bryony Thompson Marked gene: IQSEC2 as ready
Ataxia v2.75 IQSEC2 Bryony Thompson Gene: iqsec2 has been classified as Green List (High Evidence).
Ataxia v2.75 IQSEC2 Bryony Thompson Classified gene: IQSEC2 as Green List (high evidence)
Ataxia v2.75 IQSEC2 Bryony Thompson Gene: iqsec2 has been classified as Green List (High Evidence).
Ataxia v2.74 IQSEC2 Bryony Thompson gene: IQSEC2 was added
gene: IQSEC2 was added to Ataxia. Sources: Literature
Mode of inheritance for gene: IQSEC2 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: IQSEC2 were set to 30666632
Phenotypes for gene: IQSEC2 were set to intellectual disability, X-linked 1, MONDO:0010656
Review for gene: IQSEC2 was set to GREEN
Added comment: PMID 30666632 reports 7/9 individuals with X‑linked IQSEC2 variants, including de novo loss‑of‑function frameshift and nonsense mutations, with features of gait ataxia.
Sources: Literature
Ataxia v2.73 INPP4A Bryony Thompson Marked gene: INPP4A as ready
Ataxia v2.73 INPP4A Bryony Thompson Gene: inpp4a has been classified as Green List (High Evidence).
Ataxia v2.73 INPP4A Bryony Thompson Classified gene: INPP4A as Green List (high evidence)
Ataxia v2.73 INPP4A Bryony Thompson Gene: inpp4a has been classified as Green List (High Evidence).
Ataxia v2.72 INPP4A Bryony Thompson gene: INPP4A was added
gene: INPP4A was added to Ataxia. Sources: Literature
Mode of inheritance for gene: INPP4A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: INPP4A were set to 39315527
Phenotypes for gene: INPP4A were set to Neurodevelopmental disorder, MONDO:0700092
Review for gene: INPP4A was set to GREEN
Added comment: PMID 39315527 reports 21 affected individuals from 12 families (9 independent) with biallelic loss‑of‑function INPP4A variants causing a neurodevelopmental disorder characterised by global developmental delay, severe intellectual disability, microcephaly, limb weakness, cerebellar signs and prominent ataxia. Multiple unrelated families (≥3) harbour qualifying LoF variants, and mouse knockout models recapitulate the phenotype.
Sources: Literature
Ataxia v2.71 HSPD1 Bryony Thompson Marked gene: HSPD1 as ready
Ataxia v2.71 HSPD1 Bryony Thompson Gene: hspd1 has been classified as Green List (High Evidence).
Ataxia v2.71 HSPD1 Bryony Thompson Classified gene: HSPD1 as Green List (high evidence)
Ataxia v2.71 HSPD1 Bryony Thompson Gene: hspd1 has been classified as Green List (High Evidence).
Ataxia v2.70 HSPD1 Bryony Thompson gene: HSPD1 was added
gene: HSPD1 was added to Ataxia. Sources: Literature
Mode of inheritance for gene: HSPD1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HSPD1 were set to 39500555
Phenotypes for gene: HSPD1 were set to hypomyelinating leukodystrophy 4, MONDO:0012824
Review for gene: HSPD1 was set to GREEN
Added comment: PMID 39500555 reports 8 individuals with heterozygous de novo missense HSPD1 variants (p.Ala536Pro, p.Ala536Val) presenting with early‑onset hypomyelinating leukodystrophy characterised by nystagmus, tremor, hypotonia, spasticity, ataxia and neuroregression. The dominant‑negative mechanism impairs HSP60 oligomerisation. Ataxia is a core feature, aligning this gene with the Ataxia panel.
Sources: Literature
Cardiomyopathy_Paediatric v1.342 NAGLU Zornitza Stark Marked gene: NAGLU as ready
Cardiomyopathy_Paediatric v1.342 NAGLU Zornitza Stark Gene: naglu has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.342 NAGLU Zornitza Stark Phenotypes for gene: NAGLU were changed from Mucopolysaccharidosis Type III; MPS IIIB, Sanfilippo B disease (Mucopolysaccharidoses); Mucopolysaccharidosis, Type III; MUCOPOLYSACCHARIDOSIS TYPE 3B; Mucopolysaccharidosis type IIIB (Sanfilippo B), 252920; Mucopolysaccharidosis Type IIIB to Mucopolysaccharidosis type IIIB (Sanfilippo B), MIM# 252920
Cardiomyopathy_Paediatric v1.341 NAGLU Zornitza Stark Publications for gene: NAGLU were set to 27604308
Cardiomyopathy_Paediatric v1.340 NAGLU Zornitza Stark Classified gene: NAGLU as Green List (high evidence)
Cardiomyopathy_Paediatric v1.340 NAGLU Zornitza Stark Gene: naglu has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.339 NAGLU Zornitza Stark reviewed gene: NAGLU: Rating: GREEN; Mode of pathogenicity: None; Publications: 37239976; Phenotypes: Mucopolysaccharidosis type IIIB (Sanfilippo B), MIM# 252920; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia v2.69 HSD17B4 Bryony Thompson Marked gene: HSD17B4 as ready
Ataxia v2.69 HSD17B4 Bryony Thompson Gene: hsd17b4 has been classified as Green List (High Evidence).
Ataxia v2.69 HSD17B4 Bryony Thompson Classified gene: HSD17B4 as Green List (high evidence)
Ataxia v2.69 HSD17B4 Bryony Thompson Gene: hsd17b4 has been classified as Green List (High Evidence).
Ataxia v2.68 HSD17B4 Bryony Thompson gene: HSD17B4 was added
gene: HSD17B4 was added to Ataxia. Sources: Literature
Mode of inheritance for gene: HSD17B4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HSD17B4 were set to 42231982; 41367148; 40102401; 39379670; 38249302; 32042923; 28830375; 27790638; 27528516
Phenotypes for gene: HSD17B4 were set to Perrault syndrome 1, MONDO:0009300; d-bifunctional protein deficiency, MONDO:0009855
Review for gene: HSD17B4 was set to GREEN
Added comment: Both d‑bifunctional protein deficiency and Perrault syndrome caused by biallelic HSD17B4 variants present with cerebellar ataxia, making HSD17B4 relevant to the Ataxia panel. PMID 41367148, PMID 40102401, PMID 27790638, PMID 32042923 and PMID 42231982 together report 11 families (10 independent) with loss‑of‑function HSD17B4 variants causing d‑bifunctional protein deficiency, featuring early‑ to adult‑onset cerebellar ataxia, hearing loss and sometimes seizures or hypergonadotropic hypogonadism. Functional studies in patient fibroblasts, mouse knock‑out models and cilia‑rescue experiments support pathogenicity. Additionally, three families (PMID 27528516, PMID 38249302, PMID 28830375) report Perrault syndrome with ataxia, hearing loss and ovarian dysgenesis (or male infertility).
Sources: Literature
Ataxia v2.67 GRN Bryony Thompson Marked gene: GRN as ready
Ataxia v2.67 GRN Bryony Thompson Gene: grn has been classified as Green List (High Evidence).
Ataxia v2.67 GRN Bryony Thompson Classified gene: GRN as Green List (high evidence)
Ataxia v2.67 GRN Bryony Thompson Gene: grn has been classified as Green List (High Evidence).
Ataxia v2.66 GRN Bryony Thompson gene: GRN was added
gene: GRN was added to Ataxia. Sources: Literature
Mode of inheritance for gene: GRN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GRN were set to 39812704; 39394881; 31855245
Phenotypes for gene: GRN were set to neuronal ceroid lipofuscinosis 11, MONDO:0013866
Review for gene: GRN was set to GREEN
Added comment: PMID 39812704 reports 1 individual from 1 family with a homozygous frameshift GRN variant presenting with cerebellar ataxia, cone‑rod dystrophy, seizures and cognitive decline. PMID 39394881 describes 9 individuals from 9 unrelated families, all with biallelic loss‑of‑function GRN variants and a core cerebellar ataxia phenotype; seven families share the recurrent frameshift c.768_769dup. PMID 31855245 adds 3 individuals from 2 families carrying distinct homozygous loss‑of‑function GRN variants (c.1A>T and c.709‑3C>G) with early‑onset ataxia, seizures and retinitis pigmentosa. In total these studies comprise 13 patients from 12 families, representing five independent biallelic loss‑of‑function GRN variant origins that cause neuronal ceroid lipofuscinosis 11 (CLN11) with cerebellar ataxia.
Sources: Literature
Ataxia v2.65 GLS Bryony Thompson Marked gene: GLS as ready
Ataxia v2.65 GLS Bryony Thompson Gene: gls has been classified as Green List (High Evidence).
Ataxia v2.65 GLS Bryony Thompson Classified gene: GLS as Green List (high evidence)
Ataxia v2.65 GLS Bryony Thompson Gene: gls has been classified as Green List (High Evidence).
Ataxia v2.64 GLS Bryony Thompson gene: GLS was added
gene: GLS was added to Ataxia. Sources: Literature
Mode of inheritance for gene: GLS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GLS were set to 38877099; 38260514; 35913761; 30970188
Phenotypes for gene: GLS were set to glutaminase deficiency, MONDO:0600001
Review for gene: GLS was set to GREEN
Added comment: PMID 30970188 reports three families and PMID 35913761 reports two families (total five families, six patients) with biallelic GLS loss‑of‑function variants (5'UTR repeat expansions, frameshift, nonsense or missense coding changes) causing early‑onset developmental delay, progressive cerebellar ataxia and markedly elevated plasma glutamine. Functional studies show ~4‑fold reduced GLS mRNA in patient iPSCs, markedly decreased enzyme activity in patient fibroblasts, and zebrafish glsa knockdown recapitulating neurodevelopmental defects, though rescue experiments are lacking. These findings align with the Ataxia panel because progressive ataxia is a core feature of the panel’s scope of neurological disorders with ataxia.
Sources: Literature
Ataxia v2.63 Bryony Thompson Copied STR GLS_GDPAG_GCA from panel Repeat Disorders
Ataxia v2.63 GLS_GDPAG_GCA Bryony Thompson STR: GLS_GDPAG_GCA was added
STR: GLS_GDPAG_GCA was added to Ataxia. Sources: Expert Review Green,Literature
paediatric-onset tags were added to STR: GLS_GDPAG_GCA.
Mode of inheritance for STR: GLS_GDPAG_GCA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for STR: GLS_GDPAG_GCA were set to 30970188
Phenotypes for STR: GLS_GDPAG_GCA were set to Global developmental delay, progressive ataxia, and elevated glutamine MIM#618412
Ataxia v2.62 GBA1 Bryony Thompson Marked gene: GBA1 as ready
Ataxia v2.62 GBA1 Bryony Thompson Gene: gba1 has been classified as Green List (High Evidence).
Ataxia v2.62 GBA1 Bryony Thompson Classified gene: GBA1 as Green List (high evidence)
Ataxia v2.62 GBA1 Bryony Thompson Gene: gba1 has been classified as Green List (High Evidence).
Ataxia v2.61 GBA1 Bryony Thompson gene: GBA1 was added
gene: GBA1 was added to Ataxia. Sources: Literature
Mode of inheritance for gene: GBA1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GBA1 were set to 28736718; 28736718; 28003644; 28003644
Phenotypes for gene: GBA1 were set to Gaucher disease type III, MONDO:0009267
Review for gene: GBA1 was set to GREEN
Added comment: PMID 28736718 reports four individuals from four families with biallelic GBA1 missense variants (p.L444P or p.D409H) presenting with neuronopathic Gaucher disease type III, characterised by cerebellar ataxia, ophthalmoplegia and seizures. PMID 28003644 describes five individuals from four families homozygous for p.L444P with the same phenotype, confirming segregation in consanguineous families and excluding a shared founder haplotype. Combined, nine patients from eight independent families carry qualifying GBA1 variants, establishing GBA1‑related type III Gaucher disease as an autosomal recessive loss‑of‑function disorder with high penetrance. Cerebellar ataxia is a prominent feature, making GBA1 a relevant gene for the Ataxia panel, which curates genes causing ataxia phenotypes.
Sources: Literature
Ataxia v2.60 GAN Bryony Thompson Marked gene: GAN as ready
Ataxia v2.60 GAN Bryony Thompson Gene: gan has been classified as Green List (High Evidence).
Ataxia v2.60 GAN Bryony Thompson Classified gene: GAN as Green List (high evidence)
Ataxia v2.60 GAN Bryony Thompson Gene: gan has been classified as Green List (High Evidence).
Ataxia v2.59 GAN Bryony Thompson gene: GAN was added
gene: GAN was added to Ataxia. Sources: Literature
Mode of inheritance for gene: GAN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GAN were set to 39602023; 38011432; 36866531; 34114613; 32999401; 31655922; 30532362; 30246730
Phenotypes for gene: GAN were set to giant axonal neuropathy 1, MONDO:0009749
Review for gene: GAN was set to GREEN
Added comment: Across eight studies, GAN is associated with 66 patients from nine independent families harbouring biallelic loss‑of‑function variants, presenting with childhood‑onset gait ataxia, peripheral neuropathy, curly/kinky hair, cerebellar ataxia and multisystem neuro‑degeneration.
Sources: Literature
Ataxia v2.58 GALC Bryony Thompson Marked gene: GALC as ready
Ataxia v2.58 GALC Bryony Thompson Gene: galc has been classified as Green List (High Evidence).
Ataxia v2.58 GALC Bryony Thompson Classified gene: GALC as Green List (high evidence)
Ataxia v2.58 GALC Bryony Thompson Gene: galc has been classified as Green List (High Evidence).
Ataxia v2.57 GALC Bryony Thompson gene: GALC was added
gene: GALC was added to Ataxia. Sources: Literature
Mode of inheritance for gene: GALC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GALC were set to 36341094; 35002157; 32484059; 26915362
Phenotypes for gene: GALC were set to Krabbe disease, MONDO:0009499
Review for gene: GALC was set to GREEN
Added comment: PMID 26915362 reports five affected individuals from a French‑Canadian family with adult‑onset Krabbe disease and predominant cerebellar ataxia; PMID 32484059 describes a single juvenile‑onset case presenting with ataxia, motor regression and rapid disease progression; PMID 35002157 presents two unrelated Indian families with infantile and juvenile Krabbe disease, both showing ataxia, spastic quadriparesis and optic atrophy; PMID 36341094 reports an adult case with gait ataxia, progressive myoclonic epilepsy and an asymmetric occipital lesion. All cases are caused by biallelic loss‑of‑function GALC variants, establishing recessive Krabbe disease as a monogenic disorder with cerebellar ataxia.
Sources: Literature
Ataxia v2.56 GABRB2 Bryony Thompson Marked gene: GABRB2 as ready
Ataxia v2.56 GABRB2 Bryony Thompson Gene: gabrb2 has been classified as Green List (High Evidence).
Ataxia v2.56 GABRB2 Bryony Thompson Classified gene: GABRB2 as Green List (high evidence)
Ataxia v2.56 GABRB2 Bryony Thompson Gene: gabrb2 has been classified as Green List (High Evidence).
Ataxia v2.55 GABRB2 Bryony Thompson gene: GABRB2 was added
gene: GABRB2 was added to Ataxia. Sources: Literature
Mode of inheritance for gene: GABRB2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GABRB2 were set to 33325057; 29100083
Phenotypes for gene: GABRB2 were set to complex neurodevelopmental disorder, MONDO:0100038
Review for gene: GABRB2 was set to GREEN
Added comment: PMID 33325057 reports 25 individuals from 22 families with heterozygous de novo missense GABRB2 variants presenting with a neurodevelopmental disorder that includes epilepsy, developmental delay and ataxia. Ataxia is observed in three individuals from three independent families. An additional case with ataxia is reported in PMID 29100083. Ataxia is present in >10% of cases, aligning with the Ataxia panel’s focus on disorders where ataxia is a prominent feature.
Sources: Literature
Ataxia v2.54 FAM149B1 Bryony Thompson Marked gene: FAM149B1 as ready
Ataxia v2.54 FAM149B1 Bryony Thompson Gene: fam149b1 has been classified as Green List (High Evidence).
Ataxia v2.54 FAM149B1 Bryony Thompson Classified gene: FAM149B1 as Green List (high evidence)
Ataxia v2.54 FAM149B1 Bryony Thompson Gene: fam149b1 has been classified as Green List (High Evidence).
Ataxia v2.53 FAM149B1 Bryony Thompson gene: FAM149B1 was added
gene: FAM149B1 was added to Ataxia. Sources: Literature
Mode of inheritance for gene: FAM149B1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FAM149B1 were set to 34828254; 30905400
Phenotypes for gene: FAM149B1 were set to Joubert syndrome 36, MONDO:0032902
Review for gene: FAM149B1 was set to GREEN
Added comment: PMID 30905400 and PMID 34828254 report a total of eight individuals from five families with biallelic loss‑of‑function FAM149B1 variants causing Joubert syndrome 36, a ciliopathy characterised by cerebellar ataxia, oculomotor apraxia, the molar‑tooth sign and, in some cases, oral‑facial‑digital anomalies.
Sources: Literature
Ataxia v2.52 ERCC6 Bryony Thompson Marked gene: ERCC6 as ready
Ataxia v2.52 ERCC6 Bryony Thompson Gene: ercc6 has been classified as Green List (High Evidence).
Ataxia v2.52 ERCC6 Bryony Thompson Classified gene: ERCC6 as Green List (high evidence)
Ataxia v2.52 ERCC6 Bryony Thompson Gene: ercc6 has been classified as Green List (High Evidence).
Ataxia v2.51 ERCC6 Bryony Thompson gene: ERCC6 was added
gene: ERCC6 was added to Ataxia. Sources: Literature
Mode of inheritance for gene: ERCC6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ERCC6 were set to 38674442; 37532514
Phenotypes for gene: ERCC6 were set to Cockayne syndrome type 2, MONDO:0019570
Review for gene: ERCC6 was set to GREEN
Added comment: PMID 37532514 reports 2 individuals from 1 family with biallelic ERRC6 missense variants causing adult‑onset cerebellar ataxia within Cockayne syndrome type B; PMID 38674442 reports 8 individuals from 8 families with biallelic loss‑of‑function ERCC6 variants causing Cockayne syndrome types I‑III with progressive ataxia, spasticity and microcephaly. Combined evidence (9 families reported, 5 independent qualifying families) supports ERCC6 as a diagnostic‑grade gene for the Ataxia panel given the autosomal recessive, highly penetrant loss‑of‑function mechanism and lack of contradictory data.
Sources: Literature
Ataxia v2.50 DNM1L Bryony Thompson Marked gene: DNM1L as ready
Ataxia v2.50 DNM1L Bryony Thompson Gene: dnm1l has been classified as Green List (High Evidence).
Ataxia v2.50 DNM1L Bryony Thompson Classified gene: DNM1L as Green List (high evidence)
Ataxia v2.50 DNM1L Bryony Thompson Gene: dnm1l has been classified as Green List (High Evidence).
Ataxia v2.49 DNM1L Bryony Thompson gene: DNM1L was added
gene: DNM1L was added to Ataxia. Sources: Literature
Mode of inheritance for gene: DNM1L was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DNM1L were set to 41244260; 38481935; 36212643; 33718295; 31868880
Phenotypes for gene: DNM1L were set to encephalopathy due to mitochondrial and peroxisomal fission defect, MONDO:0054865
Review for gene: DNM1L was set to GREEN
Added comment: Four papers (PMID 38481935, PMID 31868880, PMID 36212643, PMID 33718295) each report a single family with a heterozygous DNM1L missense variant and ataxia; PMID 41244260 aggregates 14 additional families with ataxia among a cohort of 66 DNM1L families, including six de novo missense variants and the recurrent p.Arg403Cys hotspot. In total 18 families (17 independent families with qualifying de novo or recurrent variants) demonstrate an autosomal dominant, dominant‑negative loss‑of‑function mechanism. Cellular assays show mitochondrial hyperfusion and loss of DRP1 protein, and mouse knockout and Drosophila models confirm impaired mitochondrial fission, although rescue experiments are lacking. This gene is relevant to the Ataxia panel because DNM1L‑related disease presents with progressive ataxia as a core feature within the neurology and neurodevelopmental disorder group.
Sources: Literature
Ataxia v2.48 COASY Bryony Thompson Marked gene: COASY as ready
Ataxia v2.48 COASY Bryony Thompson Gene: coasy has been classified as Green List (High Evidence).
Ataxia v2.48 COASY Bryony Thompson Classified gene: COASY as Green List (high evidence)
Ataxia v2.48 COASY Bryony Thompson Gene: coasy has been classified as Green List (High Evidence).
Ataxia v2.47 COASY Bryony Thompson gene: COASY was added
gene: COASY was added to Ataxia. Sources: Literature
Mode of inheritance for gene: COASY was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COASY were set to 38750253; 36877387; 28489334
Phenotypes for gene: COASY were set to neurodegeneration with brain iron accumulation 6, MONDO:0014290
Review for gene: COASY was set to GREEN
Added comment: PMID 38750253 reports 5 individuals from 4 families (3 independent qualifying families) with biallelic COASY loss‑of‑function variants; PMID 28489334 reports 2 siblings from 1 family with compound heterozygous missense variants; PMID 36877387 reports 1 individual from 1 family with a compound heterozygous nonsense‑missense genotype. All cases present with early‑onset neurodegeneration often including ataxia, epilepsy, developmental delay and cerebellar atrophy or brain iron accumulation. COASY‑associated neurodegeneration frequently manifests with childhood‑onset ataxia and cerebellar involvement, making it directly relevant to the Ataxia panel which targets disorders where ataxia is a core feature.
Sources: Literature
Ataxia v2.46 CLN8 Bryony Thompson Marked gene: CLN8 as ready
Ataxia v2.46 CLN8 Bryony Thompson Gene: cln8 has been classified as Green List (High Evidence).
Ataxia v2.46 CLN8 Bryony Thompson Classified gene: CLN8 as Green List (high evidence)
Ataxia v2.46 CLN8 Bryony Thompson Gene: cln8 has been classified as Green List (High Evidence).
Ataxia v2.45 CLN8 Bryony Thompson gene: CLN8 was added
gene: CLN8 was added to Ataxia. Sources: Literature
Mode of inheritance for gene: CLN8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CLN8 were set to 36011304; 31982899; 30741402
Phenotypes for gene: CLN8 were set to neuronal ceroid lipofuscinosis 8, MONDO:0010830
Review for gene: CLN8 was set to GREEN
Added comment: PMID 31982899, PMID 30741402 and PMID 36011304 report a total of 6 patients from 4 unrelated families with biallelic CLN8 variants causing neuronal ceroid lipofuscinosis 8, a neurodegenerative disorder characterised by seizures, progressive ataxia, visual loss and neuroregression; the presence of progressive ataxia makes this association relevant to the Ataxia panel.
Sources: Literature
Ataxia v2.44 CEP120 Bryony Thompson Marked gene: CEP120 as ready
Ataxia v2.44 CEP120 Bryony Thompson Gene: cep120 has been classified as Green List (High Evidence).
Ataxia v2.44 CEP120 Bryony Thompson Classified gene: CEP120 as Green List (high evidence)
Ataxia v2.44 CEP120 Bryony Thompson Gene: cep120 has been classified as Green List (High Evidence).
Ataxia v2.43 CEP120 Bryony Thompson gene: CEP120 was added
gene: CEP120 was added to Ataxia. Sources: Literature
Mode of inheritance for gene: CEP120 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CEP120 were set to 38050708; 27208211
Phenotypes for gene: CEP120 were set to Joubert syndrome 31, MONDO:0033310
Review for gene: CEP120 was set to GREEN
Added comment: PMID 38050708 and PMID 27208211 together report seven individuals from five families with biallelic CEP120 variants causing Joubert syndrome 31, characterised by cerebellar vermis hypoplasia, molar tooth sign, ataxic gait and abnormal breathing; ataxia is a core feature aligning this gene with the Ataxia panel.
Sources: Literature
Ataxia v2.42 CEP104 Bryony Thompson Marked gene: CEP104 as ready
Ataxia v2.42 CEP104 Bryony Thompson Gene: cep104 has been classified as Green List (High Evidence).
Ataxia v2.42 CEP104 Bryony Thompson Classified gene: CEP104 as Green List (high evidence)
Ataxia v2.42 CEP104 Bryony Thompson Gene: cep104 has been classified as Green List (High Evidence).
Ataxia v2.41 CEP104 Bryony Thompson gene: CEP104 was added
gene: CEP104 was added to Ataxia. Sources: Literature
Mode of inheritance for gene: CEP104 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CEP104 were set to 41965849; 35359234; 31625690; 26477546
Phenotypes for gene: CEP104 were set to Joubert syndrome 25, MONDO:0014770; ciliopathy, MONDO:0005308
Review for gene: CEP104 was set to GREEN
Added comment: CEP104 encodes a centrosomal tip protein involved in ciliary assembly. Biallelic loss‑of‑function variants in CEP104 are linked to two distinct phenotypes that feature ataxia, fitting the Ataxia panel’s scope.

Luo2019, PMID 26477546 and PMID 41965849 together report five unrelated families (five probands) with Joubert syndrome, a ciliopathy characterised by cerebellar vermis hypoplasia, molar tooth sign, developmental delay, hypotonia and ataxia, caused by compound heterozygous or homozygous loss‑of‑function CEP104 variants.

Badv2022 describes a consanguineous family with a homozygous nonsense CEP104 variant in a child presenting with mild intellectual disability, hypotonia and gait ataxia but normal brain MRI, representing a distinct neurodevelopmental disorder.
Sources: Literature
Ataxia v2.40 CACNA1C Bryony Thompson Marked gene: CACNA1C as ready
Ataxia v2.40 CACNA1C Bryony Thompson Gene: cacna1c has been classified as Green List (High Evidence).
Ataxia v2.40 CACNA1C Bryony Thompson Classified gene: CACNA1C as Green List (high evidence)
Ataxia v2.40 CACNA1C Bryony Thompson Gene: cacna1c has been classified as Green List (High Evidence).
Ataxia v2.39 CACNA1C Bryony Thompson gene: CACNA1C was added
gene: CACNA1C was added to Ataxia. Sources: Literature
Mode of inheritance for gene: CACNA1C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CACNA1C were set to 34163037; 31291898
Phenotypes for gene: CACNA1C were set to Neurodevelopmental disorder, MONDO:0700092
Review for gene: CACNA1C was set to GREEN
Added comment: CACNA1C encodes the α1C subunit of the L-type voltage‑dependent calcium channel (Cav1.2). PMID 34163037 reports 22 families with heterozygous CACNA1C variants causing a neurodevelopmental disorder that includes ataxia, developmental delay/intellectual disability, autism, epilepsy and hypotonia. PMID 31291898 describes a single family with an intronic CACNA1C variant co‑segregating with autosomal dominant cerebellar ataxia.
Sources: Literature
Ataxia v2.38 B4GALNT1 Bryony Thompson Marked gene: B4GALNT1 as ready
Ataxia v2.38 B4GALNT1 Bryony Thompson Gene: b4galnt1 has been classified as Green List (High Evidence).
Ataxia v2.38 B4GALNT1 Bryony Thompson Classified gene: B4GALNT1 as Green List (high evidence)
Ataxia v2.38 B4GALNT1 Bryony Thompson Gene: b4galnt1 has been classified as Green List (High Evidence).
Ataxia v2.37 B4GALNT1 Bryony Thompson gene: B4GALNT1 was added
gene: B4GALNT1 was added to Ataxia. Sources: Literature
Mode of inheritance for gene: B4GALNT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: B4GALNT1 were set to 40171946; 39145292; 37510308; 35775650
Phenotypes for gene: B4GALNT1 were set to hereditary spastic paraplegia 26, MONDO:0012213
Review for gene: B4GALNT1 was set to GREEN
Added comment: PMID 35775650 reports 1 individual from 1 family, PMID 40171946 reports 2 individuals from 1 family, PMID 39145292 reports 1 individual from 1 family, and PMID 37510308 reports 5 individuals from 1 family, all carrying biallelic loss‑of‑function variants in B4GALNT1. Affected individuals present with early‑onset hereditary spastic paraplegia, progressive spastic gait, cerebellar ataxia, dystonia, optic atrophy, hearing loss and intellectual disability.
Sources: Literature
Ataxia v2.36 ARV1 Bryony Thompson Marked gene: ARV1 as ready
Ataxia v2.36 ARV1 Bryony Thompson Gene: arv1 has been classified as Green List (High Evidence).
Ataxia v2.36 ARV1 Bryony Thompson Classified gene: ARV1 as Green List (high evidence)
Ataxia v2.36 ARV1 Bryony Thompson Gene: arv1 has been classified as Green List (High Evidence).
Ataxia v2.35 ARV1 Bryony Thompson gene: ARV1 was added
gene: ARV1 was added to Ataxia. Sources: Literature
Mode of inheritance for gene: ARV1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ARV1 were set to 37749428; 32165008
Phenotypes for gene: ARV1 were set to developmental and epileptic encephalopathy, 38, MONDO:0014868
Review for gene: ARV1 was set to GREEN
Added comment: PMID 37749428 reports 1 family and 5 other families identified by a literature review, and PMID 32165008 reports 2 families (3 families total) with autosomal recessive ARV1 loss-of-function variants causing early infantile epileptic encephalopathy 38, characterised by seizures, developmental delay, progressive cerebellar ataxia (often with elevated α‑fetoprotein)
Sources: Literature
Ataxia v2.34 ANK3 Bryony Thompson Marked gene: ANK3 as ready
Ataxia v2.34 ANK3 Bryony Thompson Gene: ank3 has been classified as Green List (High Evidence).
Ataxia v2.34 ANK3 Bryony Thompson Classified gene: ANK3 as Green List (high evidence)
Ataxia v2.34 ANK3 Bryony Thompson Gene: ank3 has been classified as Green List (High Evidence).
Ataxia v2.33 ANK3 Bryony Thompson gene: ANK3 was added
gene: ANK3 was added to Ataxia. Sources: Literature
Mode of inheritance for gene: ANK3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ANK3 were set to 40879451; 36777705
Phenotypes for gene: ANK3 were set to Neurodevelopmental disorder, MONDO:0700092
Review for gene: ANK3 was set to GREEN
Added comment: ANK3 encodes ankyrin‑G, a neuronal scaffold protein, and pathogenic variants have been linked to neurodevelopmental disorders featuring cerebellar ataxia.

Maroofian2025 reports five individuals from three unrelated consanguineous families with biallelic loss‑of‑function ANK3 variants (splice and frameshift) presenting with childhood‑onset cerebellar ataxia, developmental delay, intellectual disability, hypotonia and variable epilepsy. The disorder follows autosomal recessive inheritance, shows high penetrance, and mouse knockout recapitulates the ataxic phenotype, supporting loss‑of‑function as the mechanism.

Younus2023 describes a single Pakistani consanguineous family with a homozygous missense ANK3 p.Tyr60His variant; the proband has intellectual disability, ataxia, seizures, speech impairment and aggressive behaviour.
Sources: Literature
Ataxia v2.32 AIFM1 Bryony Thompson Marked gene: AIFM1 as ready
Ataxia v2.32 AIFM1 Bryony Thompson Gene: aifm1 has been classified as Green List (High Evidence).
Ataxia v2.32 AIFM1 Bryony Thompson Classified gene: AIFM1 as Green List (high evidence)
Ataxia v2.32 AIFM1 Bryony Thompson Gene: aifm1 has been classified as Green List (High Evidence).
Ataxia v2.31 AIFM1 Bryony Thompson gene: AIFM1 was added
gene: AIFM1 was added to Ataxia. Sources: Literature
Mode of inheritance for gene: AIFM1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: AIFM1 were set to 39601015; 37603145; 32337346; 31523922; 31188924; 28842795; 25934856
Phenotypes for gene: AIFM1 were set to Charcot-Marie-Tooth disease X-linked recessive 4, MONDO:0010689; X-linked hereditary sensory and autonomic neuropathy with hearing loss, MONDO:0010378; severe X-linked mitochondrial encephalomyopathy, MONDO:0010437; spondyloepimetaphyseal dysplasia, Bieganski type, MONDO:0010275
Review for gene: AIFM1 was set to GREEN
Added comment: AIFM1 encodes a mitochondrial flavoprotein required for NADH oxidation and caspase‑independent apoptosis. Pathogenic variants cause a spectrum of X‑linked neuro‑developmental and mitochondrial disorders that frequently feature cerebellar ataxia.

**X‑linked hypomyelination with spondylometaphyseal dysplasia (H‑SMD)** – six unrelated families (12 patients) with loss‑of‑function AIFM1 variants present with hypomyelination, spondylometaphyseal dysplasia, ataxia and additional neurologic signs (PMID 28842795).

**Severe X‑linked mitochondrial encephalomyopathy** – two families (two patients) with loss‑of‑function missense variants display cerebellar ataxia, peripheral neuropathy, hearing loss, optic atrophy and muscle weakness (PMID 37603145; PMID 25934856).

**X‑linked hereditary sensory and autonomic neuropathy with hearing loss** – three independent families (12 patients) harbor distinct missense AIFM1 variants and share cerebellar ataxia, peripheral neuropathy, sensorineural hearing loss and colour‑vision deficiency (PMID 31523922; PMID 32337346; PMID 39601015).

** Charcot-Marie-Tooth disease X‑linked recessive 4** – one family (four patients) with a gain‑of‑function missense variant shows hearing loss, peripheral neuropathy, distal muscle wasting and ataxic gait (PMID 31188924).
Sources: Literature
Ataxia v2.30 AARS2 Bryony Thompson Marked gene: AARS2 as ready
Ataxia v2.30 AARS2 Bryony Thompson Gene: aars2 has been classified as Green List (High Evidence).
Ataxia v2.30 AARS2 Bryony Thompson Classified gene: AARS2 as Green List (high evidence)
Ataxia v2.30 AARS2 Bryony Thompson Gene: aars2 has been classified as Green List (High Evidence).
Ataxia v2.29 AARS2 Bryony Thompson gene: AARS2 was added
gene: AARS2 was added to Ataxia. Sources: Literature
Mode of inheritance for gene: AARS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AARS2 were set to 39853526; 38507676; 35084689; 31705293; 31347571; 31099476; 30706699; 29666464; 28322004
Phenotypes for gene: AARS2 were set to Mitochondrial disease, MONDO:0044970; ovarioleukodystrophy, MONDO:0020506
Review for gene: AARS2 was set to GREEN
Added comment: PMID 31099476, PMID 30706699, PMID 29666464, PMID 35084689 and PMID 31347571 together report seven families (five independent qualifying families) with biallelic loss‑of‑function AARS2 variants causing adult‑onset leukoencephalopathy, cerebellar atrophy and progressive ataxia. PMID 31705293 describes a single family with recessive cerebellar ataxia without leukoencephalopathy. PMID 39853526, PMID 28322004 and PMID 38507676 report eight families (two independent qualifying families) with ovarioleukodystrophy (leukoencephalopathy + ovarian failure).
Sources: Literature
Cardiomyopathy_Paediatric v1.339 MT-TI Zornitza Stark Marked gene: MT-TI as ready
Cardiomyopathy_Paediatric v1.339 MT-TI Zornitza Stark Gene: mt-ti has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.339 MT-TI Zornitza Stark Phenotypes for gene: MT-TI were changed from to Mitochondrial disease (MONDO:0044970), MT-TI-related
Cardiomyopathy_Paediatric v1.338 MT-TI Zornitza Stark Publications for gene: MT-TI were set to
Cardiomyopathy_Paediatric v1.337 MT-TI Zornitza Stark Classified gene: MT-TI as Green List (high evidence)
Cardiomyopathy_Paediatric v1.337 MT-TI Zornitza Stark Gene: mt-ti has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.336 MT-TI Zornitza Stark Tag mtDNA tag was added to gene: MT-TI.
Cardiomyopathy_Paediatric v1.336 MT-TI Zornitza Stark reviewed gene: MT-TI: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Mitochondrial disease (MONDO:0044970), MT-TI-related; Mode of inheritance: MITOCHONDRIAL
Cardiomyopathy_Paediatric v1.336 MT-ND6 Zornitza Stark Marked gene: MT-ND6 as ready
Cardiomyopathy_Paediatric v1.336 MT-ND6 Zornitza Stark Gene: mt-nd6 has been classified as Amber List (Moderate Evidence).
Cardiomyopathy_Paediatric v1.336 HGSNAT Zornitza Stark Marked gene: HGSNAT as ready
Cardiomyopathy_Paediatric v1.336 HGSNAT Zornitza Stark Gene: hgsnat has been classified as Amber List (Moderate Evidence).
Cardiomyopathy_Paediatric v1.336 HGSNAT Zornitza Stark Phenotypes for gene: HGSNAT were changed from MPS IIIC, Sanfilippo C disease (Mucopolysaccharidoses); Mucopolysaccharidosis Type III; Mucopolysaccharidosis Type IIIC; Mucopolysaccharidosis, Type III; Mucopolysaccharidosis type IIIC (Sanfilippo C), 252930; Retinitis Pigmentosa 73 to Mucopolysaccharidosis type IIIC (Sanfilippo C), MIM#252930
Cardiomyopathy_Paediatric v1.335 HGSNAT Zornitza Stark edited their review of gene: HGSNAT: Changed rating: AMBER
Cardiomyopathy_Paediatric v1.335 HGSNAT Zornitza Stark reviewed gene: HGSNAT: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Mucopolysaccharidosis type IIIC (Sanfilippo C), MIM#252930; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v1.335 HFE Zornitza Stark Marked gene: HFE as ready
Cardiomyopathy_Paediatric v1.335 HFE Zornitza Stark Gene: hfe has been classified as Amber List (Moderate Evidence).
Cardiomyopathy_Paediatric v1.335 HFE Zornitza Stark Phenotypes for gene: HFE were changed from Hemochromatosis, 235200; Hemochromatosis; Hereditary haemochromatosis Type 1 (Disorder of iron metabolism); DCM; Haemochromatosis; Iron overload, liver disease, diabetes, hypogonadism; HCM; Hypertrophic-hypocontractile cardiomyopathy to Haemochromatosis, type 1, MIM# 235200
Cardiomyopathy_Paediatric v1.334 HFE Zornitza Stark Publications for gene: HFE were set to 27604308
Cardiomyopathy_Paediatric v1.333 HFE Zornitza Stark edited their review of gene: HFE: Changed rating: AMBER
Cardiomyopathy_Paediatric v1.333 HFE Zornitza Stark reviewed gene: HFE: Rating: ; Mode of pathogenicity: None; Publications: 36724119; Phenotypes: Haemochromatosis, type 1, MIM# 235200; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v1.333 VCL Zornitza Stark Marked gene: VCL as ready
Cardiomyopathy_Paediatric v1.333 VCL Zornitza Stark Gene: vcl has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.333 VCL Zornitza Stark Phenotypes for gene: VCL were changed from Cardiomyopathy, familial hypertrophic, 15,; Cardiomyopathy, dilated, 1W to Cardiomyopathy, dilated, 1W, MIM# 611407
Cardiomyopathy_Paediatric v1.332 VCL Zornitza Stark Publications for gene: VCL were set to
Cardiomyopathy_Paediatric v1.331 VCL Zornitza Stark edited their review of gene: VCL: Added comment: STRONG by ClinGen for DCM. Predominantly paediatric onset.; Changed rating: GREEN; Changed publications: 17097056, 32516855; Changed phenotypes: Cardiomyopathy, dilated, 1W, MIM# 611407
Cardiomyopathy_Paediatric v1.331 FOXRED1 Zornitza Stark Marked gene: FOXRED1 as ready
Cardiomyopathy_Paediatric v1.331 FOXRED1 Zornitza Stark Gene: foxred1 has been classified as Amber List (Moderate Evidence).
Cardiomyopathy_Paediatric v1.331 FOXRED1 Zornitza Stark Phenotypes for gene: FOXRED1 were changed from Mitochondrial complex I deficiency, nuclear type 19, 618241 to Mitochondrial complex I deficiency, nuclear type 19, MIM# 618241
Cardiomyopathy_Paediatric v1.330 FOXRED1 Zornitza Stark Publications for gene: FOXRED1 were set to
Cardiomyopathy_Paediatric v1.329 FOXRED1 Zornitza Stark changed review comment from: HCM reported.; to: HCM reported but not a common/consistent feature.
Cardiomyopathy_Paediatric v1.329 FOXRED1 Zornitza Stark edited their review of gene: FOXRED1: Changed rating: AMBER
Cardiomyopathy_Paediatric v1.329 FOXRED1 Zornitza Stark reviewed gene: FOXRED1: Rating: GREEN; Mode of pathogenicity: None; Publications: 20858599; Phenotypes: Mitochondrial complex I deficiency, nuclear type 19, MIM# 618241; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v1.329 CRYAB Zornitza Stark Marked gene: CRYAB as ready
Cardiomyopathy_Paediatric v1.329 CRYAB Zornitza Stark Gene: cryab has been classified as Red List (Low Evidence).
Cardiomyopathy_Paediatric v1.329 CRYAB Zornitza Stark Phenotypes for gene: CRYAB were changed from Cardiomyopathy, dilated, 1II,; Myopathy, myofibrillar, fatal infantile hypertrophy, alpha B crystallin related, 613869 to Cardiomyopathy, dilated, 1II, MIM# 615184
Cardiomyopathy_Paediatric v1.328 CRYAB Zornitza Stark Publications for gene: CRYAB were set to
Cardiomyopathy_Paediatric v1.327 CRYAB Zornitza Stark Mode of inheritance for gene: CRYAB was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cardiomyopathy_Paediatric v1.326 CRYAB Zornitza Stark Classified gene: CRYAB as Red List (low evidence)
Cardiomyopathy_Paediatric v1.326 CRYAB Zornitza Stark Gene: cryab has been classified as Red List (Low Evidence).
Cardiomyopathy_Paediatric v1.325 CRYAB Zornitza Stark reviewed gene: CRYAB: Rating: RED; Mode of pathogenicity: None; Publications: 16483541, 16793013]; Phenotypes: Cardiomyopathy, dilated, 1II, MIM# 615184; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cardiomyopathy_Paediatric v1.325 COX7B Zornitza Stark edited their review of gene: COX7B: Changed rating: RED
Cardiomyopathy_Paediatric v1.325 COX7B Zornitza Stark Marked gene: COX7B as ready
Cardiomyopathy_Paediatric v1.325 COX7B Zornitza Stark Gene: cox7b has been classified as Red List (Low Evidence).
Cardiomyopathy_Paediatric v1.325 COX7B Zornitza Stark Classified gene: COX7B as Red List (low evidence)
Cardiomyopathy_Paediatric v1.325 COX7B Zornitza Stark Gene: cox7b has been classified as Red List (Low Evidence).
Cardiomyopathy_Paediatric v1.324 COX7B Zornitza Stark Publications for gene: COX7B were set to
Cardiomyopathy_Paediatric v1.323 COX7B Zornitza Stark reviewed gene: COX7B: Rating: AMBER; Mode of pathogenicity: None; Publications: 23122588; Phenotypes: Linear skin defects with multiple congenital anomalies 2, MIM# 300887; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Cardiomyopathy_Paediatric v1.322 TTR Zornitza Stark Marked gene: TTR as ready
Cardiomyopathy_Paediatric v1.322 TTR Zornitza Stark Gene: ttr has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.322 TTR Zornitza Stark Phenotypes for gene: TTR were changed from syndromic HCM to Amyloidosis, hereditary systemic 1, MIM# 105210
Cardiomyopathy_Paediatric v1.321 TTR Zornitza Stark Publications for gene: TTR were set to 31118583; 31131842; 31111153; 30878017; 30120737
Cardiomyopathy_Paediatric v1.320 TTR Zornitza Stark reviewed gene: TTR: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Amyloidosis, hereditary systemic 1, MIM# 105210; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cardiomyopathy_Paediatric v1.320 TTN Zornitza Stark Marked gene: TTN as ready
Cardiomyopathy_Paediatric v1.320 TTN Zornitza Stark Gene: ttn has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.320 TTN Zornitza Stark Publications for gene: TTN were set to http://www.ncbi.nlm.nih.gov/pubmed/22335739
Cardiomyopathy_Paediatric v1.319 TTN Zornitza Stark reviewed gene: TTN: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: dilated cardiomyopathy 1G MONDO:0011400; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cardiomyopathy_Paediatric v1.319 TRIM37 Zornitza Stark Marked gene: TRIM37 as ready
Cardiomyopathy_Paediatric v1.319 TRIM37 Zornitza Stark Gene: trim37 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.319 TREX1 Zornitza Stark Marked gene: TREX1 as ready
Cardiomyopathy_Paediatric v1.319 TREX1 Zornitza Stark Gene: trex1 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.319 TPM1 Zornitza Stark Marked gene: TPM1 as ready
Cardiomyopathy_Paediatric v1.319 TPM1 Zornitza Stark Gene: tpm1 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.319 TPM1 Zornitza Stark Phenotypes for gene: TPM1 were changed from Left ventricular noncompaction 9,; Cardiomyopathy, dilated, 1Y; Cardiomyopathy, familial hypertrophic, 3 to Cardiomyopathy, dilated, 1Y, MIM# 611878
Cardiomyopathy_Paediatric v1.318 TPM1 Zornitza Stark Publications for gene: TPM1 were set to
Cardiomyopathy_Paediatric v1.317 TPM1 Zornitza Stark reviewed gene: TPM1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cardiomyopathy, dilated, 1Y, MIM# 611878; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cardiomyopathy_Paediatric v1.317 TNNT2 Zornitza Stark Marked gene: TNNT2 as ready
Cardiomyopathy_Paediatric v1.317 TNNT2 Zornitza Stark Gene: tnnt2 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.317 TNNT2 Zornitza Stark Phenotypes for gene: TNNT2 were changed from Cardiomyopathy, dilated, 1D; Cardiomyopathy, familial hypertrophic, 2; Hypertrophic cardiomyopathy; Left ventricular noncompaction 6, to Cardiomyopathy, dilated, 1D MIM#601494; Cardiomyopathy, hypertrophic, 2, MIM# 115195
Cardiomyopathy_Paediatric v1.316 TNNT2 Zornitza Stark Publications for gene: TNNT2 were set to
Cardiomyopathy_Paediatric v1.315 TNNT2 Zornitza Stark reviewed gene: TNNT2: Rating: GREEN; Mode of pathogenicity: None; Publications: 11106718; Phenotypes: Cardiomyopathy, dilated, 1D MIM#601494, Cardiomyopathy, hypertrophic, 2, MIM# 115195; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cardiomyopathy_Paediatric v1.315 TNNC1 Zornitza Stark Marked gene: TNNC1 as ready
Cardiomyopathy_Paediatric v1.315 TNNC1 Zornitza Stark Gene: tnnc1 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.315 TNNC1 Zornitza Stark Phenotypes for gene: TNNC1 were changed from Cardiomyopathy, familial hypertrophic, 13,; Cardiomyopathy, dilated, 1Z to Cardiomyopathy, dilated, 1Z, MIM# 611879; Cardiomyopathy, hypertrophic, 13, MIM# 613243
Cardiomyopathy_Paediatric v1.314 TNNC1 Zornitza Stark Publications for gene: TNNC1 were set to
Cardiomyopathy_Paediatric v1.313 TNNC1 Zornitza Stark reviewed gene: TNNC1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cardiomyopathy, dilated, 1Z, MIM# 611879, Cardiomyopathy, hypertrophic, 13, MIM# 613243; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cardiomyopathy_Paediatric v1.313 TMEM70 Zornitza Stark Marked gene: TMEM70 as ready
Cardiomyopathy_Paediatric v1.313 TMEM70 Zornitza Stark Gene: tmem70 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.313 TMEM70 Zornitza Stark Phenotypes for gene: TMEM70 were changed from Mitochondrial complex V (ATP synthase) deficiency, nuclear type 2, 614052 to mitochondrial complex V (ATP synthase) deficiency, nuclear type 2, MONDO:0013546
Cardiomyopathy_Paediatric v1.312 TMEM70 Zornitza Stark Publications for gene: TMEM70 were set to
Cardiomyopathy_Paediatric v1.311 TMEM43 Zornitza Stark Marked gene: TMEM43 as ready
Cardiomyopathy_Paediatric v1.311 TMEM43 Zornitza Stark Gene: tmem43 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.311 TMEM43 Zornitza Stark Phenotypes for gene: TMEM43 were changed from Arrhythmogenic right ventricular dysplasia 5; Emery-Dreifuss muscular dystrophy 7, AD 614302 to Arrhythmogenic right ventricular dysplasia 5, MIM#604400
Cardiomyopathy_Paediatric v1.310 TMEM43 Zornitza Stark Publications for gene: TMEM43 were set to
Cardiomyopathy_Paediatric v1.309 TMEM126B Zornitza Stark Marked gene: TMEM126B as ready
Cardiomyopathy_Paediatric v1.309 TMEM126B Zornitza Stark Gene: tmem126b has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.309 TMEM126B Zornitza Stark Phenotypes for gene: TMEM126B were changed from Mitochondrial complex I deficiency, nuclear type 29, 618250 to Mitochondrial complex I deficiency, nuclear type 29, MIM# 618250
Cardiomyopathy_Paediatric v1.308 TMEM126B Zornitza Stark reviewed gene: TMEM126B: Rating: GREEN; Mode of pathogenicity: None; Publications: 27374773; Phenotypes: Mitochondrial complex I deficiency, nuclear type 29, MIM# 618250; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v1.308 TANGO2 Zornitza Stark Marked gene: TANGO2 as ready
Cardiomyopathy_Paediatric v1.308 TANGO2 Zornitza Stark Gene: tango2 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.308 TAFAZZIN Zornitza Stark Marked gene: TAFAZZIN as ready
Cardiomyopathy_Paediatric v1.308 TAFAZZIN Zornitza Stark Gene: tafazzin has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.308 TAFAZZIN Zornitza Stark Phenotypes for gene: TAFAZZIN were changed from Barth syndrome, 302060; Dilated Cardiomyopathy, X-Linked; Left Ventricular Noncompaction Cardiomyopathy; Neutropenia, muscle weakness, growth retardation; Non-compaction cardiomyopathy; HCM, mixed; Disorders of mitochondrial membrane lipids (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Disorders of mitochondrial lipid metabolism; Methylglutaconic aciduria type II, Barth syndrome (Organic acidurias); Barth syndrome to Barth syndrome, MIM# 302060
Cardiomyopathy_Paediatric v1.307 TAFAZZIN Zornitza Stark Publications for gene: TAFAZZIN were set to 27604308
Cardiomyopathy_Paediatric v1.306 TAFAZZIN Zornitza Stark reviewed gene: TAFAZZIN: Rating: GREEN; Mode of pathogenicity: None; Publications: 20812380; Phenotypes: Barth syndrome, MIM# 302060; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Cardiomyopathy_Paediatric v1.306 SURF1 Zornitza Stark Marked gene: SURF1 as ready
Cardiomyopathy_Paediatric v1.306 SURF1 Zornitza Stark Gene: surf1 has been classified as Red List (Low Evidence).
Cardiomyopathy_Paediatric v1.306 SURF1 Zornitza Stark Phenotypes for gene: SURF1 were changed from Charcot-Marie-Tooth disease, type 4K, 616684; Leigh syndrome, due to COX IV deficiency, 256000 to Mitochondrial complex IV deficiency, nuclear type 1, MIM# 220110
Cardiomyopathy_Paediatric v1.305 SURF1 Zornitza Stark Classified gene: SURF1 as Red List (low evidence)
Cardiomyopathy_Paediatric v1.305 SURF1 Zornitza Stark Gene: surf1 has been classified as Red List (Low Evidence).
Cardiomyopathy_Paediatric v1.304 SURF1 Zornitza Stark reviewed gene: SURF1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 1, MIM# 220110; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v1.304 SOS2 Zornitza Stark Marked gene: SOS2 as ready
Cardiomyopathy_Paediatric v1.304 SOS2 Zornitza Stark Gene: sos2 has been classified as Amber List (Moderate Evidence).
Cardiomyopathy_Paediatric v1.304 SOS2 Zornitza Stark Phenotypes for gene: SOS2 were changed from Noonan syndrome 9 616559; Noonan syndrome 9 to Noonan syndrome 9, MIM# 616559
Cardiomyopathy_Paediatric v1.303 SOS2 Zornitza Stark Classified gene: SOS2 as Amber List (moderate evidence)
Cardiomyopathy_Paediatric v1.303 SOS2 Zornitza Stark Gene: sos2 has been classified as Amber List (Moderate Evidence).
Cardiomyopathy_Paediatric v1.302 SOS2 Zornitza Stark reviewed gene: SOS2: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Noonan syndrome 9, MIM# 616559; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cardiomyopathy_Paediatric v1.302 SGCD Zornitza Stark Marked gene: SGCD as ready
Cardiomyopathy_Paediatric v1.302 SGCD Zornitza Stark Gene: sgcd has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.302 SGCD Zornitza Stark Phenotypes for gene: SGCD were changed from Cardiomyopathy, dilated, 1L, 606685 to Muscular dystrophy, limb-girdle, autosomal recessive 6, MIM# 601287
Cardiomyopathy_Paediatric v1.301 SGCD Zornitza Stark Publications for gene: SGCD were set to 10735275; 18779423; 23900355
Cardiomyopathy_Paediatric v1.300 SGCD Zornitza Stark reviewed gene: SGCD: Rating: GREEN; Mode of pathogenicity: None; Publications: 34515763; Phenotypes: Muscular dystrophy, limb-girdle, autosomal recessive 6, MIM# 601287; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v1.300 SDHAF1 Zornitza Stark Marked gene: SDHAF1 as ready
Cardiomyopathy_Paediatric v1.300 SDHAF1 Zornitza Stark Gene: sdhaf1 has been classified as Red List (Low Evidence).
Cardiomyopathy_Paediatric v1.300 SDHAF1 Zornitza Stark Phenotypes for gene: SDHAF1 were changed from Mitochondrial respiratory chain complex II deficiency, 252011 to Mitochondrial complex II deficiency, nuclear type 2, MIM# 619166
Cardiomyopathy_Paediatric v1.299 SDHAF1 Zornitza Stark Classified gene: SDHAF1 as Red List (low evidence)
Cardiomyopathy_Paediatric v1.299 SDHAF1 Zornitza Stark Gene: sdhaf1 has been classified as Red List (Low Evidence).
Cardiomyopathy_Paediatric v1.298 SDHAF1 Zornitza Stark reviewed gene: SDHAF1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Mitochondrial complex II deficiency, nuclear type 2, MIM# 619166; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v1.298 SDHA Zornitza Stark Marked gene: SDHA as ready
Cardiomyopathy_Paediatric v1.298 SDHA Zornitza Stark Gene: sdha has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.298 SDHA Zornitza Stark Phenotypes for gene: SDHA were changed from Cardiomyopathy, dilated, 1GG; Leigh syndrome, 256000; Mitochondrial respiratory chain complex II deficiency, 252011; Mitochondrial Respiratory Chain Complex II Deficiency; Paragangliomas 5, 614165; Isolated complex II deficiency; Complex II (Mitochondrial respiratory chain disorders (caused by nuclear variants only), OXPHOS structural subunits); Cardiomyopathy, dilated, 1GG, 613642 to Mitochondrial complex II deficiency, nuclear type 1, MIM# 252011; Cardiomyopathy, dilated, 1GG, MIM# 613642
Cardiomyopathy_Paediatric v1.297 SDHA Zornitza Stark Publications for gene: SDHA were set to 27604308
Cardiomyopathy_Paediatric v1.296 SDHA Zornitza Stark reviewed gene: SDHA: Rating: GREEN; Mode of pathogenicity: None; Publications: 20551992; Phenotypes: Mitochondrial complex II deficiency, nuclear type 1, MIM# 252011, Cardiomyopathy, dilated, 1GG, MIM# 613642; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v1.296 RYR2 Zornitza Stark Marked gene: RYR2 as ready
Cardiomyopathy_Paediatric v1.296 RYR2 Zornitza Stark Gene: ryr2 has been classified as Red List (Low Evidence).
Cardiomyopathy_Paediatric v1.296 RYR2 Zornitza Stark Phenotypes for gene: RYR2 were changed from Ventricular Tachycardia, Catecholaminergic Polymorphic, 1, With Or Without Atrial Dysfunction And/or Dilated Cardiomyopathy; Arrhythmogenic right ventricular dysplasia 2, 600996 to dilated cardiomyopathy MONDO:0005021; hypertrophic cardiomyopathy MONDO:0005045; arrhythmogenic right ventricular cardiomyopathy MONDO:0016587
Cardiomyopathy_Paediatric v1.295 RYR2 Zornitza Stark Publications for gene: RYR2 were set to http://www.ncbi.nlm.nih.gov/books/NBK1131/
Cardiomyopathy_Paediatric v1.294 RYR2 Zornitza Stark Classified gene: RYR2 as Red List (low evidence)
Cardiomyopathy_Paediatric v1.294 RYR2 Zornitza Stark Gene: ryr2 has been classified as Red List (Low Evidence).
Cardiomyopathy_Paediatric v1.293 RYR2 Zornitza Stark edited their review of gene: RYR2: Added comment: LIMITED by ClinGen for association with DCM and HCM. REFUTED for ARVC.; Changed rating: RED; Changed phenotypes: dilated cardiomyopathy MONDO:0005021, hypertrophic cardiomyopathy MONDO:0005045, arrhythmogenic right ventricular cardiomyopathy MONDO:0016587; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cardiomyopathy_Paediatric v1.293 PTPN11 Zornitza Stark Marked gene: PTPN11 as ready
Cardiomyopathy_Paediatric v1.293 PTPN11 Zornitza Stark Gene: ptpn11 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.293 PTPN11 Zornitza Stark Phenotypes for gene: PTPN11 were changed from LEOPARD syndrome 1; Noonan syndrome 1 163950; LEOPARD syndrome 1 151100; syndromic HCM; Noonan syndrome 1; LEOPARD syndrome; Noonan syndrome to Noonan syndrome 1, MIM# 163950
Cardiomyopathy_Paediatric v1.292 PTPN11 Zornitza Stark Mode of pathogenicity for gene: PTPN11 was changed from Other - please provide details in the comments to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Cardiomyopathy_Paediatric v1.291 PTPN11 Zornitza Stark reviewed gene: PTPN11: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: ; Phenotypes: Noonan syndrome 1, MIM# 163950; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cardiomyopathy_Paediatric v1.291 PLN Zornitza Stark Marked gene: PLN as ready
Cardiomyopathy_Paediatric v1.291 PLN Zornitza Stark Gene: pln has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.291 PLN Zornitza Stark Phenotypes for gene: PLN were changed from Cardiomyopathy, familial hypertrophic, 18,; Cardiomyopathy, dilated, 1P to Cardiomyopathy, dilated, 1P, MIM# 609909; Cardiomyopathy, hypertrophic, 18, MIM# 613874
Cardiomyopathy_Paediatric v1.290 PLN Zornitza Stark Publications for gene: PLN were set to
Cardiomyopathy_Paediatric v1.289 PLN Zornitza Stark reviewed gene: PLN: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cardiomyopathy, dilated, 1P, MIM# 609909, Cardiomyopathy, hypertrophic, 18, MIM# 613874; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cardiomyopathy_Paediatric v1.289 NUBPL Zornitza Stark Marked gene: NUBPL as ready
Cardiomyopathy_Paediatric v1.289 NUBPL Zornitza Stark Gene: nubpl has been classified as Red List (Low Evidence).
Cardiomyopathy_Paediatric v1.289 NUBPL Zornitza Stark Phenotypes for gene: NUBPL were changed from Mitochondrial complex I deficiency, nuclear type 21, 618242 to Mitochondrial complex I deficiency, nuclear type 21, MIM# 618242
Cardiomyopathy_Paediatric v1.288 NUBPL Zornitza Stark Classified gene: NUBPL as Red List (low evidence)
Cardiomyopathy_Paediatric v1.288 NUBPL Zornitza Stark Gene: nubpl has been classified as Red List (Low Evidence).
Cardiomyopathy_Paediatric v1.287 NUBPL Zornitza Stark reviewed gene: NUBPL: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Mitochondrial complex I deficiency, nuclear type 21, MIM# 618242; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v1.287 NRAS Zornitza Stark Marked gene: NRAS as ready
Cardiomyopathy_Paediatric v1.287 NRAS Zornitza Stark Gene: nras has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.287 NRAS Zornitza Stark Phenotypes for gene: NRAS were changed from Noonan syndrome 6 613224; CFC Syndrome; Cardio-Facio-cutanenous syndrome; syndromic HCM; Noonan syndrome 6; Noonan syndrome to Noonan syndrome 6, MIM# 613224
Cardiomyopathy_Paediatric v1.286 NRAS Zornitza Stark edited their review of gene: NRAS: Changed publications: 19966803
Cardiomyopathy_Paediatric v1.286 NRAS Zornitza Stark reviewed gene: NRAS: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Noonan syndrome 6, MIM# 613224; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cardiomyopathy_Paediatric v1.286 NDUFS7 Zornitza Stark Marked gene: NDUFS7 as ready
Cardiomyopathy_Paediatric v1.286 NDUFS7 Zornitza Stark Gene: ndufs7 has been classified as Red List (Low Evidence).
Cardiomyopathy_Paediatric v1.286 NDUFS7 Zornitza Stark Phenotypes for gene: NDUFS7 were changed from Mitochondrial complex I deficiency, nuclear type 3, 618224 to Mitochondrial complex I deficiency, nuclear type 3, MIM# 618224
Cardiomyopathy_Paediatric v1.285 NDUFS7 Zornitza Stark Classified gene: NDUFS7 as Red List (low evidence)
Cardiomyopathy_Paediatric v1.285 NDUFS7 Zornitza Stark Gene: ndufs7 has been classified as Red List (Low Evidence).
Cardiomyopathy_Paediatric v1.284 NDUFS7 Zornitza Stark reviewed gene: NDUFS7: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Mitochondrial complex I deficiency, nuclear type 3, MIM# 618224; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v1.284 NDUFS6 Zornitza Stark Marked gene: NDUFS6 as ready
Cardiomyopathy_Paediatric v1.284 NDUFS6 Zornitza Stark Gene: ndufs6 has been classified as Red List (Low Evidence).
Cardiomyopathy_Paediatric v1.284 NDUFS6 Zornitza Stark Phenotypes for gene: NDUFS6 were changed from Mitochondrial complex I deficiency, nuclear type 9, 618232 to Mitochondrial complex I deficiency, nuclear type 9, MIM# 618232
Cardiomyopathy_Paediatric v1.283 NDUFS6 Zornitza Stark Classified gene: NDUFS6 as Red List (low evidence)
Cardiomyopathy_Paediatric v1.283 NDUFS6 Zornitza Stark Gene: ndufs6 has been classified as Red List (Low Evidence).
Cardiomyopathy_Paediatric v1.282 NDUFS6 Zornitza Stark reviewed gene: NDUFS6: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Mitochondrial complex I deficiency, nuclear type 9, MIM# 618232; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v1.282 NDUFS3 Zornitza Stark Marked gene: NDUFS3 as ready
Cardiomyopathy_Paediatric v1.282 NDUFS3 Zornitza Stark Gene: ndufs3 has been classified as Red List (Low Evidence).
Cardiomyopathy_Paediatric v1.282 NDUFS3 Zornitza Stark Phenotypes for gene: NDUFS3 were changed from Mitochondrial complex I deficiency, nuclear type 8, 618230 to Mitochondrial complex I deficiency, nuclear type 8, MIM# 618230
Cardiomyopathy_Paediatric v1.281 NDUFS3 Zornitza Stark Classified gene: NDUFS3 as Red List (low evidence)
Cardiomyopathy_Paediatric v1.281 NDUFS3 Zornitza Stark Gene: ndufs3 has been classified as Red List (Low Evidence).
Cardiomyopathy_Paediatric v1.280 NDUFS3 Zornitza Stark reviewed gene: NDUFS3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Mitochondrial complex I deficiency, nuclear type 8, MIM# 618230; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v1.280 NDUFS1 Zornitza Stark Marked gene: NDUFS1 as ready
Cardiomyopathy_Paediatric v1.280 NDUFS1 Zornitza Stark Gene: ndufs1 has been classified as Red List (Low Evidence).
Cardiomyopathy_Paediatric v1.280 NDUFS1 Zornitza Stark Phenotypes for gene: NDUFS1 were changed from Mitochondrial complex I deficiency, nuclear type 5, 618226 to Mitochondrial complex I deficiency, nuclear type 5, MIM# 618226
Cardiomyopathy_Paediatric v1.279 NDUFS1 Zornitza Stark Classified gene: NDUFS1 as Red List (low evidence)
Cardiomyopathy_Paediatric v1.279 NDUFS1 Zornitza Stark Gene: ndufs1 has been classified as Red List (Low Evidence).
Cardiomyopathy_Paediatric v1.278 NDUFS1 Zornitza Stark reviewed gene: NDUFS1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Mitochondrial complex I deficiency, nuclear type 5, MIM# 618226; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v1.278 NDUFB3 Zornitza Stark Marked gene: NDUFB3 as ready
Cardiomyopathy_Paediatric v1.278 NDUFB3 Zornitza Stark Gene: ndufb3 has been classified as Red List (Low Evidence).
Cardiomyopathy_Paediatric v1.278 NDUFB3 Zornitza Stark Phenotypes for gene: NDUFB3 were changed from Mitochondrial complex I deficiency, nuclear type 25, 618246 to Mitochondrial complex I deficiency, nuclear type 25, MIM# 618246
Cardiomyopathy_Paediatric v1.277 NDUFB3 Zornitza Stark Classified gene: NDUFB3 as Red List (low evidence)
Cardiomyopathy_Paediatric v1.277 NDUFB3 Zornitza Stark Gene: ndufb3 has been classified as Red List (Low Evidence).
Cardiomyopathy_Paediatric v1.276 NDUFB3 Zornitza Stark reviewed gene: NDUFB3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Mitochondrial complex I deficiency, nuclear type 25, MIM# 618246; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v1.276 NDUFAF5 Zornitza Stark Marked gene: NDUFAF5 as ready
Cardiomyopathy_Paediatric v1.276 NDUFAF5 Zornitza Stark Gene: ndufaf5 has been classified as Red List (Low Evidence).
Cardiomyopathy_Paediatric v1.276 NDUFAF5 Zornitza Stark Phenotypes for gene: NDUFAF5 were changed from Mitochondrial complex I deficiency, nuclear type 16, 616238 to Mitochondrial complex I deficiency, nuclear type 16, MIM# 618238
Cardiomyopathy_Paediatric v1.275 NDUFAF5 Zornitza Stark Classified gene: NDUFAF5 as Red List (low evidence)
Cardiomyopathy_Paediatric v1.275 NDUFAF5 Zornitza Stark Gene: ndufaf5 has been classified as Red List (Low Evidence).
Cardiomyopathy_Paediatric v1.274 NDUFAF5 Zornitza Stark reviewed gene: NDUFAF5: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Mitochondrial complex I deficiency, nuclear type 16, MIM# 618238; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v1.274 NDUFAF3 Zornitza Stark Marked gene: NDUFAF3 as ready
Cardiomyopathy_Paediatric v1.274 NDUFAF3 Zornitza Stark Gene: ndufaf3 has been classified as Red List (Low Evidence).
Cardiomyopathy_Paediatric v1.274 NDUFAF3 Zornitza Stark Phenotypes for gene: NDUFAF3 were changed from Mitochondrial complex I deficiency, nuclear type 18, 618240 to Mitochondrial complex I deficiency, nuclear type 18, MIM# 618240
Cardiomyopathy_Paediatric v1.273 NDUFAF3 Zornitza Stark Classified gene: NDUFAF3 as Red List (low evidence)
Cardiomyopathy_Paediatric v1.273 NDUFAF3 Zornitza Stark Gene: ndufaf3 has been classified as Red List (Low Evidence).
Cardiomyopathy_Paediatric v1.272 NDUFAF3 Zornitza Stark reviewed gene: NDUFAF3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Mitochondrial complex I deficiency, nuclear type 18, MIM# 618240; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v1.272 NDUFAF2 Zornitza Stark Marked gene: NDUFAF2 as ready
Cardiomyopathy_Paediatric v1.272 NDUFAF2 Zornitza Stark Gene: ndufaf2 has been classified as Red List (Low Evidence).
Cardiomyopathy_Paediatric v1.272 NDUFAF2 Zornitza Stark Phenotypes for gene: NDUFAF2 were changed from Mitochondrial complex I deficiency, nuclear type 10, 618233 to Mitochondrial complex I deficiency, nuclear type 10, MIM# 618233
Cardiomyopathy_Paediatric v1.271 NDUFAF2 Zornitza Stark Classified gene: NDUFAF2 as Red List (low evidence)
Cardiomyopathy_Paediatric v1.271 NDUFAF2 Zornitza Stark Gene: ndufaf2 has been classified as Red List (Low Evidence).
Cardiomyopathy_Paediatric v1.270 NDUFAF2 Zornitza Stark reviewed gene: NDUFAF2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Mitochondrial complex I deficiency, nuclear type 10, MIM# 618233; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v1.270 NDUFA2 Zornitza Stark Marked gene: NDUFA2 as ready
Cardiomyopathy_Paediatric v1.270 NDUFA2 Zornitza Stark Gene: ndufa2 has been classified as Amber List (Moderate Evidence).
Cardiomyopathy_Paediatric v1.270 NDUFA2 Zornitza Stark Phenotypes for gene: NDUFA2 were changed from Mitochondrial complex I deficiency, nuclear type 13, 618235 to Mitochondrial complex I deficiency, nuclear type 13, MIM# 618235
Cardiomyopathy_Paediatric v1.269 NDUFA2 Zornitza Stark Publications for gene: NDUFA2 were set to
Cardiomyopathy_Paediatric v1.268 NDUFA2 Zornitza Stark Classified gene: NDUFA2 as Amber List (moderate evidence)
Cardiomyopathy_Paediatric v1.268 NDUFA2 Zornitza Stark Gene: ndufa2 has been classified as Amber List (Moderate Evidence).
Cardiomyopathy_Paediatric v1.267 NDUFA2 Zornitza Stark reviewed gene: NDUFA2: Rating: AMBER; Mode of pathogenicity: None; Publications: 18513682; Phenotypes: Mitochondrial complex I deficiency, nuclear type 13, MIM# 618235; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v1.267 NDUFA10 Zornitza Stark Marked gene: NDUFA10 as ready
Cardiomyopathy_Paediatric v1.267 NDUFA10 Zornitza Stark Gene: ndufa10 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.267 NDUFA10 Zornitza Stark Phenotypes for gene: NDUFA10 were changed from Mitochondrial complex I deficiency, nuclear type 22, 618243 to Mitochondrial complex I deficiency, nuclear type 22, MIM# 618243
Cardiomyopathy_Paediatric v1.266 NDUFA10 Zornitza Stark Publications for gene: NDUFA10 were set to
Cardiomyopathy_Paediatric v1.265 NDUFA10 Zornitza Stark reviewed gene: NDUFA10: Rating: GREEN; Mode of pathogenicity: None; Publications: 21150889; Phenotypes: Mitochondrial complex I deficiency, nuclear type 22, MIM# 618243; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v1.265 NDUFA1 Zornitza Stark Marked gene: NDUFA1 as ready
Cardiomyopathy_Paediatric v1.265 NDUFA1 Zornitza Stark Gene: ndufa1 has been classified as Red List (Low Evidence).
Cardiomyopathy_Paediatric v1.265 NDUFA1 Zornitza Stark Phenotypes for gene: NDUFA1 were changed from Mitochondrial complex I deficiency, nuclear type 12, 301020 to Mitochondrial complex I deficiency, nuclear type 12, MIM# 301020
Cardiomyopathy_Paediatric v1.264 NDUFA1 Zornitza Stark Mode of inheritance for gene: NDUFA1 was changed from X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Cardiomyopathy_Paediatric v1.263 NDUFA1 Zornitza Stark Classified gene: NDUFA1 as Red List (low evidence)
Cardiomyopathy_Paediatric v1.263 NDUFA1 Zornitza Stark Gene: ndufa1 has been classified as Red List (Low Evidence).
Cardiomyopathy_Paediatric v1.262 NDUFA1 Zornitza Stark reviewed gene: NDUFA1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Mitochondrial complex I deficiency, nuclear type 12, MIM# 301020; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Cardiomyopathy_Paediatric v1.262 MYL3 Zornitza Stark Marked gene: MYL3 as ready
Cardiomyopathy_Paediatric v1.262 MYL3 Zornitza Stark Gene: myl3 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.262 MYL3 Zornitza Stark Phenotypes for gene: MYL3 were changed from Cardiomyopathy, familial hypertrophic, 8, to Cardiomyopathy, hypertrophic, 8, MIM# 608751
Cardiomyopathy_Paediatric v1.261 MYL3 Zornitza Stark Publications for gene: MYL3 were set to
Cardiomyopathy_Paediatric v1.260 MYL3 Zornitza Stark Mode of inheritance for gene: MYL3 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cardiomyopathy_Paediatric v1.259 MYL3 Zornitza Stark reviewed gene: MYL3: Rating: GREEN; Mode of pathogenicity: None; Publications: 37477868; Phenotypes: Cardiomyopathy, hypertrophic, 8, MIM# 608751; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cardiomyopathy_Paediatric v1.259 MYH7 Zornitza Stark Marked gene: MYH7 as ready
Cardiomyopathy_Paediatric v1.259 MYH7 Zornitza Stark Gene: myh7 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.259 MYH7 Zornitza Stark Phenotypes for gene: MYH7 were changed from Left ventricular noncompaction 5; Cardiomyopathy, familial hypertrophic, 1,; Hypertrophic cardiomyopathy; Cardiomyopathy, dilated, 1S to Cardiomyopathy, hypertrophic, 1, MIM# 192600; Cardiomyopathy, dilated, 1S, MIM# 613426
Cardiomyopathy_Paediatric v1.258 MYH7 Zornitza Stark Publications for gene: MYH7 were set to
Cardiomyopathy_Paediatric v1.257 MYH7 Zornitza Stark Mode of inheritance for gene: MYH7 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cardiomyopathy_Paediatric v1.256 MYH7 Zornitza Stark reviewed gene: MYH7: Rating: GREEN; Mode of pathogenicity: None; Publications: 41380733; Phenotypes: Cardiomyopathy, hypertrophic, 1, MIM# 192600, Cardiomyopathy, dilated, 1S, MIM# 613426; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cardiomyopathy_Paediatric v1.256 MYBPC3 Zornitza Stark Marked gene: MYBPC3 as ready
Cardiomyopathy_Paediatric v1.256 MYBPC3 Zornitza Stark Gene: mybpc3 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.256 MYBPC3 Zornitza Stark Phenotypes for gene: MYBPC3 were changed from Cardiomyopathy, familial hypertrophic, 4,; Left ventricular noncompaction 10,; Cardiomyopathy, dilated, 1MM; Hypertrophic cardiomyopathy to Cardiomyopathy, hypertrophic, 4, MIM# 115197
Cardiomyopathy_Paediatric v1.255 MYBPC3 Zornitza Stark Publications for gene: MYBPC3 were set to
Cardiomyopathy_Paediatric v1.254 MYBPC3 Zornitza Stark Mode of inheritance for gene: MYBPC3 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v1.253 MYBPC3 Zornitza Stark reviewed gene: MYBPC3: Rating: GREEN; Mode of pathogenicity: None; Publications: 41572441; Phenotypes: Cardiomyopathy, hypertrophic, 4, MIM# 115197; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v1.253 MT-TR Zornitza Stark Marked gene: MT-TR as ready
Cardiomyopathy_Paediatric v1.253 MT-TR Zornitza Stark Gene: mt-tr has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.253 MMUT Zornitza Stark Marked gene: MMUT as ready
Cardiomyopathy_Paediatric v1.253 MMUT Zornitza Stark Gene: mmut has been classified as Amber List (Moderate Evidence).
Cardiomyopathy_Paediatric v1.253 MMUT Zornitza Stark Phenotypes for gene: MMUT were changed from Dehydration, hepatomegaly, lethargy, coma, acidosis, high anion gap; Methylmalonic aciduria; Methylmalonic aciduria, mut(0) type 251000; DCM; Methylmalonyl-CoA mutase deficiency (Organic acidurias); Hypertrophic-hypocontractile cardiomyopathy; metabolic encephalopathy with hyperammonaemia, hypotonia, recurrent episodes of ketoacidosis, liver impairment, psychomotor retardation, recurrent infections. to methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency, MONDO:0009612
Cardiomyopathy_Paediatric v1.252 MMUT Zornitza Stark Publications for gene: MMUT were set to 27604308
Cardiomyopathy_Paediatric v1.251 MMUT Zornitza Stark Classified gene: MMUT as Amber List (moderate evidence)
Cardiomyopathy_Paediatric v1.251 MMUT Zornitza Stark Gene: mmut has been classified as Amber List (Moderate Evidence).
Cardiomyopathy_Paediatric v1.250 LRPPRC Zornitza Stark Marked gene: LRPPRC as ready
Cardiomyopathy_Paediatric v1.250 LRPPRC Zornitza Stark Gene: lrpprc has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.250 LRPPRC Zornitza Stark Phenotypes for gene: LRPPRC were changed from Leigh syndrome, French-Canadian type, 220111 to Mitochondrial complex IV deficiency, nuclear type 5, (French-Canadian), MIM# 220111
Cardiomyopathy_Paediatric v1.249 LRPPRC Zornitza Stark reviewed gene: LRPPRC: Rating: GREEN; Mode of pathogenicity: None; Publications: 26510951; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 5, (French-Canadian), MIM# 220111; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v1.249 LMNA Zornitza Stark Marked gene: LMNA as ready
Cardiomyopathy_Paediatric v1.249 LMNA Zornitza Stark Gene: lmna has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.249 LMNA Zornitza Stark Phenotypes for gene: LMNA were changed from Cardiomyopathy, dilated, 1A; Emery-Dreifuss muscular dystrophy 2, AD, 181350; Congenital Muscular Dystrophy, LMNA-related (Dominant); Lipoatrophy with Diabetes, Hepatic Steatosis, Hypertrophic to Cardiomyopathy, dilated, 1A, MIM# 115200; Emery-Dreifuss muscular dystrophy 2, autosomal dominant, MIM# 181350; Emery-Dreifuss muscular dystrophy 3, autosomal recessive, MIM# 616516
Cardiomyopathy_Paediatric v1.248 LMNA Zornitza Stark Publications for gene: LMNA were set to 15148145; 18551513; 15622532
Cardiomyopathy_Paediatric v1.247 LMNA Zornitza Stark reviewed gene: LMNA: Rating: GREEN; Mode of pathogenicity: None; Publications: 39998502; Phenotypes: Cardiomyopathy, dilated, 1A, MIM# 115200, Emery-Dreifuss muscular dystrophy 2, autosomal dominant, MIM# 181350, Emery-Dreifuss muscular dystrophy 3, autosomal recessive, MIM# 616516; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v1.247 LAMP2 Zornitza Stark Marked gene: LAMP2 as ready
Cardiomyopathy_Paediatric v1.247 LAMP2 Zornitza Stark Gene: lamp2 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.247 LAMP2 Zornitza Stark Phenotypes for gene: LAMP2 were changed from Danon disease; syndromic HCM to Danon disease, MIM#300257
Cardiomyopathy_Paediatric v1.246 LAMP2 Zornitza Stark Publications for gene: LAMP2 were set to 27604308
Cardiomyopathy_Paediatric v1.245 IDH2 Zornitza Stark Tag treatable tag was added to gene: IDH2.
Cardiomyopathy_Paediatric v1.245 IDH2 Zornitza Stark Marked gene: IDH2 as ready
Cardiomyopathy_Paediatric v1.245 IDH2 Zornitza Stark Gene: idh2 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.245 IDH2 Zornitza Stark Phenotypes for gene: IDH2 were changed from D-2-hydroxyglutaric aciduria 2, 613657; Mitochondrial isocitrate dehydrogenase deficiency (Organic acidurias); D-2-hydroxyglutaric aciduria 2 to D-2-hydroxyglutaric aciduria 2, MIM# 613657
Cardiomyopathy_Paediatric v1.244 IDH2 Zornitza Stark Publications for gene: IDH2 were set to 24049096; 20847235
Cardiomyopathy_Paediatric v1.243 IDH2 Zornitza Stark edited their review of gene: IDH2: Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cardiomyopathy_Paediatric v1.243 IDH2 Zornitza Stark reviewed gene: IDH2: Rating: GREEN; Mode of pathogenicity: None; Publications: 37248298, 20847235; Phenotypes: D-2-hydroxyglutaric aciduria 2, MIM# 613657; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v1.243 GUSB Zornitza Stark Marked gene: GUSB as ready
Cardiomyopathy_Paediatric v1.243 GUSB Zornitza Stark Gene: gusb has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.243 GUSB Zornitza Stark Phenotypes for gene: GUSB were changed from Mucopolysaccharidosis VII, 253220; Mucopolysaccharidosis, Type VII; syndromic HCM; MUCOPOLYSACCHARIDOSIS TYPE 7; Mucopolysaccharidosis Type VII; MPS VII, Sly disease (MPS IV, Morquio disease) to Mucopolysaccharidosis VII, MIM# 253220
Cardiomyopathy_Paediatric v1.242 GUSB Zornitza Stark reviewed gene: GUSB: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Mucopolysaccharidosis VII, MIM# 253220; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v1.242 GLB1 Zornitza Stark Marked gene: GLB1 as ready
Cardiomyopathy_Paediatric v1.242 GLB1 Zornitza Stark Gene: glb1 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.242 GLB1 Zornitza Stark Phenotypes for gene: GLB1 were changed from Mucopolysaccharidosis Type IVB; MUCOPOLYSACCHARIDOSIS TYPE 4B; MPS IVB, Morquio B disease (MPS IV, Morquio disease); Mucopolysaccharidosis, Type IV; GM1-gangliosidosis, type III, 230650; GM1-gangliosidosis (Sphingolipidoses); GM1-gangliosidosis, type II, 230600; syndromic HCM; GM1-gangliosidosis, type I, 230500; Mucopolysaccharidosis type IVB (Morquio), 253010 to GM1-gangliosidosis, type I, MIM# 230500
Cardiomyopathy_Paediatric v1.241 GLB1 Zornitza Stark reviewed gene: GLB1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: GM1-gangliosidosis, type I, MIM# 230500; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v1.241 GAA Zornitza Stark Marked gene: GAA as ready
Cardiomyopathy_Paediatric v1.241 GAA Zornitza Stark Gene: gaa has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.241 GAA Zornitza Stark Phenotypes for gene: GAA were changed from HCM, mixed; Glycogen storage disease II, 232300; syndromic HCM; Hypotonia, muscle weakness, progressive respiratory failure; Glycogen storage disease type II (Pompe disease) to Pompe disease, infantile-onset, MIM# 232300
Cardiomyopathy_Paediatric v1.240 GAA Zornitza Stark Publications for gene: GAA were set to
Cardiomyopathy_Paediatric v1.239 GAA Zornitza Stark reviewed gene: GAA: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Pompe disease, infantile-onset, MIM# 232300; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v1.239 FLNC Zornitza Stark Marked gene: FLNC as ready
Cardiomyopathy_Paediatric v1.239 FLNC Zornitza Stark Gene: flnc has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.239 FLNC Zornitza Stark Phenotypes for gene: FLNC were changed from to Cardiomyopathy, familial dilated, 1PP, MIM# 617047; Cardiomyopathy, familial hypertrophic, 26, MIM# 617047
Cardiomyopathy_Paediatric v1.238 FLNC Zornitza Stark Publications for gene: FLNC were set to
Cardiomyopathy_Paediatric v1.237 FLNC Zornitza Stark edited their review of gene: FLNC: Added comment: DEFINITIVE association with DCM.

Generally adult-onset but onset in adolescence reported.; Changed phenotypes: Cardiomyopathy, familial dilated, 1PP, MIM# 617047, Cardiomyopathy, familial hypertrophic, 26, MIM# 617047
Cardiomyopathy_Paediatric v1.237 FHL1 Zornitza Stark Marked gene: FHL1 as ready
Cardiomyopathy_Paediatric v1.237 FHL1 Zornitza Stark Gene: fhl1 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.237 FHL1 Zornitza Stark Phenotypes for gene: FHL1 were changed from to Emery-Dreifuss muscular dystrophy 6, X-linked, MIM# 300696
Cardiomyopathy_Paediatric v1.236 FHL1 Zornitza Stark Publications for gene: FHL1 were set to http://www.ncbi.nlm.nih.gov/pubmed/22523091
Cardiomyopathy_Paediatric v1.235 FHL1 Zornitza Stark edited their review of gene: FHL1: Added comment: PMID 42304238: reviewed 114 patients with pathogenic or likely pathogenic FHL1 variants. Most patients were male (69%), with a median age of onset of 18 (IQR 10-26) years. Cardiac involvement consisted in left ventricular hypertrophy (56%), followed by arrhythmias (51%), and conduction abnormalities (8%). The incidence of sudden cardiac death was 7%, and heart transplantation was reported in 5% of patients.; Changed publications: 42304238; Changed phenotypes: Emery-Dreifuss muscular dystrophy 6, X-linked, MIM# 300696
Cardiomyopathy_Paediatric v1.235 FAH Zornitza Stark Marked gene: FAH as ready
Cardiomyopathy_Paediatric v1.235 FAH Zornitza Stark Gene: fah has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.235 FAH Zornitza Stark Phenotypes for gene: FAH were changed from HCM; Tyrosinaemia type 1 (fumarylactoacetase deficiency); Liver failure, vomiting, renal tubulopathy; Tyrosinemia, type I to Tyrosinaemia, type I, MIM# 276700
Cardiomyopathy_Paediatric v1.234 FAH Zornitza Stark reviewed gene: FAH: Rating: GREEN; Mode of pathogenicity: None; Publications: 24016420; Phenotypes: Tyrosinaemia, type I, MIM# 276700; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v1.234 EPG5 Zornitza Stark Marked gene: EPG5 as ready
Cardiomyopathy_Paediatric v1.234 EPG5 Zornitza Stark Gene: epg5 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.234 EPG5 Zornitza Stark Phenotypes for gene: EPG5 were changed from Vici syndrome, 242840; IMMUNODEFICIENCY WITH CLEFT LIP/PALATE, CATARACT, HYPOPIGMENTATION, AND ABSENT CORPUS CALLOSUM to Vici syndrome, MIM# 242840
Cardiomyopathy_Paediatric v1.233 EPG5 Zornitza Stark reviewed gene: EPG5: Rating: GREEN; Mode of pathogenicity: None; Publications: 23222957; Phenotypes: Vici syndrome, MIM# 242840; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v1.233 EMD Zornitza Stark Marked gene: EMD as ready
Cardiomyopathy_Paediatric v1.233 EMD Zornitza Stark Gene: emd has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.233 EMD Zornitza Stark Publications for gene: EMD were set to
Cardiomyopathy_Paediatric v1.232 DNAJC19 Zornitza Stark Marked gene: DNAJC19 as ready
Cardiomyopathy_Paediatric v1.232 DNAJC19 Zornitza Stark Gene: dnajc19 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.232 DNAJC19 Zornitza Stark Phenotypes for gene: DNAJC19 were changed from 3-methylglutaconic aciduria, type V, 610198; Disorders of the mitochondrial import system; dilated cardiomyopathy with ataxia syndrome; 3-methylglutaconic aciduria, type V to 3-methylglutaconic aciduria type 5, MONDO:0012435; 3-methylgutaconic aciduria, type V, OMIM:610198
Cardiomyopathy_Paediatric v1.231 DMD Zornitza Stark Marked gene: DMD as ready
Cardiomyopathy_Paediatric v1.231 DMD Zornitza Stark Gene: dmd has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.231 DMD Zornitza Stark Phenotypes for gene: DMD were changed from Duchenne muscular dystrophy, 310200; Cardiomyopathy, dilated, 3B; Dilated Cardiomyopathy, X-Linked; Becker muscular dystrophy, 300376 to Becker muscular dystrophy, MIM:300376; Cardiomyopathy, dilated, 3B, MIM:302045; Duchenne muscular dystrophy, MIM: 310200
Cardiomyopathy_Paediatric v1.230 DMD Zornitza Stark Publications for gene: DMD were set to
Cardiomyopathy_Paediatric v1.229 DES Zornitza Stark Marked gene: DES as ready
Cardiomyopathy_Paediatric v1.229 DES Zornitza Stark Gene: des has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.229 DES Zornitza Stark Phenotypes for gene: DES were changed from Cardiomyopathy, dilated, 1I, to Cardiomyopathy, dilated, 1I, MIM# 604765
Cardiomyopathy_Paediatric v1.228 DES Zornitza Stark Publications for gene: DES were set to
Cardiomyopathy_Paediatric v1.227 DES Zornitza Stark Mode of inheritance for gene: DES was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cardiomyopathy_Paediatric v1.226 DES Zornitza Stark reviewed gene: DES: Rating: GREEN; Mode of pathogenicity: None; Publications: 10430757, 20423733; Phenotypes: Cardiomyopathy, dilated, 1I, MIM# 604765; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cardiomyopathy_Paediatric v1.226 CSRP3 Zornitza Stark Marked gene: CSRP3 as ready
Cardiomyopathy_Paediatric v1.226 CSRP3 Zornitza Stark Gene: csrp3 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.226 CSRP3 Zornitza Stark Phenotypes for gene: CSRP3 were changed from Cardiomyopathy, dilated, 1M; Cardiomyopathy, familial hypertrophic, 12 to Cardiomyopathy, hypertrophic, 12, MIM# 612124
Cardiomyopathy_Paediatric v1.225 CSRP3 Zornitza Stark edited their review of gene: CSRP3: Changed publications: 18505755, 30681346, 34558151, 33035702, 31919335, 33012304, 37431535
Cardiomyopathy_Paediatric v1.225 CSRP3 Zornitza Stark Publications for gene: CSRP3 were set to 18505755; 30681346
Cardiomyopathy_Paediatric v1.224 CSRP3 Zornitza Stark Publications for gene: CSRP3 were set to
Cardiomyopathy_Paediatric v1.223 CSRP3 Zornitza Stark Mode of inheritance for gene: CSRP3 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v1.222 CSRP3 Zornitza Stark edited their review of gene: CSRP3: Added comment: DEFINITIVE by ClinGen, biallelic cases in particular can present early.

The proposed association with DCM is LIMITED by ClinGen.; Changed rating: GREEN; Changed phenotypes: Cardiomyopathy, hypertrophic, 12, MIM# 612124; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v1.222 CPT2 Zornitza Stark Marked gene: CPT2 as ready
Cardiomyopathy_Paediatric v1.222 CPT2 Zornitza Stark Gene: cpt2 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.222 CPT2 Zornitza Stark Phenotypes for gene: CPT2 were changed from Arrhythmia, liver disease, hyperammonaemia, hypoketotic hypoglycaemia; Carnitine palmitoyltransferase II (CPT2) deficiency (neonatal & infantile forms); CPT II deficiency, lethal neonatal 608836; CPT deficiency, hepatic, type II 600649; HCM, mixed; DCM; Carnitine palmitoyltransferase II (CPTII) deficiency (Disorders of carnitine transport and the carnitine cycle) to CPT II deficiency, infantile, MIM# 600649; CPT II deficiency, lethal neonatal, MIM# 608836
Cardiomyopathy_Paediatric v1.221 CPT2 Zornitza Stark Mode of inheritance for gene: CPT2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v1.220 CPT2 Zornitza Stark reviewed gene: CPT2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: CPT II deficiency, infantile, MIM# 600649, CPT II deficiency, lethal neonatal, MIM# 608836; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v1.220 COX20 Zornitza Stark Marked gene: COX20 as ready
Cardiomyopathy_Paediatric v1.220 COX20 Zornitza Stark Gene: cox20 has been classified as Red List (Low Evidence).
Cardiomyopathy_Paediatric v1.220 COX20 Zornitza Stark Phenotypes for gene: COX20 were changed from Mitochondrial complex IV deficiency, 220110 to Mitochondrial complex IV deficiency, nuclear type 11, MIM# 619054
Cardiomyopathy_Paediatric v1.219 COX20 Zornitza Stark Classified gene: COX20 as Red List (low evidence)
Cardiomyopathy_Paediatric v1.219 COX20 Zornitza Stark Gene: cox20 has been classified as Red List (Low Evidence).
Cardiomyopathy_Paediatric v1.218 COX20 Zornitza Stark reviewed gene: COX20: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 11, MIM# 619054; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v1.218 CBL Zornitza Stark Marked gene: CBL as ready
Cardiomyopathy_Paediatric v1.218 CBL Zornitza Stark Gene: cbl has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.218 CBL Zornitza Stark Phenotypes for gene: CBL were changed from Noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia; Noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia 613563 to Noonan syndrome-like disorder with or without juvenile myelomonocytic leukaemia, MIM# 613563
Cardiomyopathy_Paediatric v1.217 CBL Zornitza Stark reviewed gene: CBL: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Noonan syndrome-like disorder with or without juvenile myelomonocytic leukaemia, MIM# 613563; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cardiomyopathy_Paediatric v1.217 CACNA1C Zornitza Stark Marked gene: CACNA1C as ready
Cardiomyopathy_Paediatric v1.217 CACNA1C Zornitza Stark Gene: cacna1c has been classified as Amber List (Moderate Evidence).
Cardiomyopathy_Paediatric v1.217 CACNA1C Zornitza Stark Phenotypes for gene: CACNA1C were changed from to Hypertrophic cardiomyopathy, MONDO:0005045, CACNA1C-related
Cardiomyopathy_Paediatric v1.216 CACNA1C Zornitza Stark edited their review of gene: CACNA1C: Changed phenotypes: Hypertrophic cardiomyopathy, MONDO:0005045, CACNA1C-related
Cardiomyopathy_Paediatric v1.216 CACNA1C Zornitza Stark Publications for gene: CACNA1C were set to
Cardiomyopathy_Paediatric v1.215 CACNA1C Zornitza Stark Classified gene: CACNA1C as Amber List (moderate evidence)
Cardiomyopathy_Paediatric v1.215 CACNA1C Zornitza Stark Gene: cacna1c has been classified as Amber List (Moderate Evidence).
Cardiomyopathy_Paediatric v1.214 C1QBP Zornitza Stark Marked gene: C1QBP as ready
Cardiomyopathy_Paediatric v1.214 C1QBP Zornitza Stark Gene: c1qbp has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.214 C10orf71 Zornitza Stark Marked gene: C10orf71 as ready
Cardiomyopathy_Paediatric v1.214 C10orf71 Zornitza Stark Gene: c10orf71 has been classified as Green List (High Evidence).
Mitochondrial disease v2.8 ATP5F1D Zornitza Stark Classified gene: ATP5F1D as Amber List (moderate evidence)
Mitochondrial disease v2.8 ATP5F1D Zornitza Stark Gene: atp5f1d has been classified as Amber List (Moderate Evidence).
Mitochondrial disease v2.7 ATP5F1D Zornitza Stark edited their review of gene: ATP5F1D: Added comment: LIMITED by ClinGen. Both reported families had homozygous missense variants. No further reports since 2018.; Changed rating: AMBER
Mendeliome v2.534 ATP5F1D Zornitza Stark Classified gene: ATP5F1D as Amber List (moderate evidence)
Mendeliome v2.534 ATP5F1D Zornitza Stark Gene: atp5f1d has been classified as Amber List (Moderate Evidence).
Mendeliome v2.533 ATP5F1D Zornitza Stark edited their review of gene: ATP5F1D: Added comment: LIMITED by ClinGen. Both reported families had homozygous missense variants. No further reports since 2018.; Changed rating: AMBER
Cardiomyopathy_Paediatric v1.214 ATP5F1D Zornitza Stark Marked gene: ATP5F1D as ready
Cardiomyopathy_Paediatric v1.214 ATP5F1D Zornitza Stark Gene: atp5f1d has been classified as Red List (Low Evidence).
Cardiomyopathy_Paediatric v1.214 ATP5F1D Zornitza Stark Classified gene: ATP5F1D as Red List (low evidence)
Cardiomyopathy_Paediatric v1.214 ATP5F1D Zornitza Stark Gene: atp5f1d has been classified as Red List (Low Evidence).
Cardiomyopathy_Paediatric v1.213 ATP5F1D Zornitza Stark reviewed gene: ATP5F1D: Rating: RED; Mode of pathogenicity: None; Publications: 29478781; Phenotypes: Mitochondrial complex V (ATP synthase) deficiency, MIM# 618120; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v1.213 ALPK3 Zornitza Stark Marked gene: ALPK3 as ready
Cardiomyopathy_Paediatric v1.213 ALPK3 Zornitza Stark Gene: alpk3 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.213 ALPK3 Zornitza Stark Phenotypes for gene: ALPK3 were changed from Cardiomyopathy, familial hypertrophic 27, 618052 to Cardiomyopathy, familial hypertrophic 27 MIM#618052
Cardiomyopathy_Paediatric v1.212 ALPK3 Zornitza Stark Publications for gene: ALPK3 were set to
Cardiomyopathy_Paediatric v1.211 ALPK3 Zornitza Stark Mode of inheritance for gene: ALPK3 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v1.210 AGL Zornitza Stark Marked gene: AGL as ready
Cardiomyopathy_Paediatric v1.210 AGL Zornitza Stark Gene: agl has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.210 AGL Zornitza Stark Phenotypes for gene: AGL were changed from Glycogen Storage Disorders- Liver; Glycogen Storage Disorders- Muscle; Glycogen Storage Disease Type III; Ketotic hypoglycaemia, hyperlipidaemia, raised transaminases; HCM; Glycogen storage disease type IIIa (debrancher enzyme deficiency); myopathy, cardiomyopathy and neuropathy possible but mile hepatomegaly and fasting intolerance; syndromic HCM; Glycogen storage disease type III, Cori (Glycogen storage disorders); Hypertrophic-hypocontractile cardiomyopathy; Glycogen storage disease IIIa, 232400; Glycogen Storage Disease; Glycogen storage disease IIIb, 232400 to Glycogen storage disease IIIa and IIIb, MIM#232400
Cardiomyopathy_Paediatric v1.209 AGK Zornitza Stark Marked gene: AGK as ready
Cardiomyopathy_Paediatric v1.209 AGK Zornitza Stark Gene: agk has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.209 AGK Zornitza Stark Phenotypes for gene: AGK were changed from Sengers syndrome, 212350 to Sengers syndrome, MIM#212350
Cardiomyopathy_Paediatric v1.208 AGK Zornitza Stark Publications for gene: AGK were set to
Cardiomyopathy_Paediatric v1.207 ACTN2 Zornitza Stark Marked gene: ACTN2 as ready
Cardiomyopathy_Paediatric v1.207 ACTN2 Zornitza Stark Gene: actn2 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.207 ACTN2 Zornitza Stark Phenotypes for gene: ACTN2 were changed from Dilated Cardiomyopathy, Dominant; ACTN2-related cardiac and skeletal myopathy, MONDO:0700349 to Cardiomyopathy, hypertrophic, 23, with or without LVNC, MIM# 612158
Cardiomyopathy_Paediatric v1.206 ACTN2 Zornitza Stark Publications for gene: ACTN2 were set to
Cardiomyopathy_Paediatric v1.205 ACTC1 Zornitza Stark Marked gene: ACTC1 as ready
Cardiomyopathy_Paediatric v1.205 ACTC1 Zornitza Stark Gene: actc1 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.205 ACTC1 Zornitza Stark Phenotypes for gene: ACTC1 were changed from Cardiomyopathy, hypertrophic, 11 612098 to Cardiomyopathy, hypertrophic, 11, MIM# 612098
Cardiomyopathy_Paediatric v1.204 ACTC1 Zornitza Stark Phenotypes for gene: ACTC1 were changed from Cardiomyopathy, dilated, 1R; Left ventricular noncompaction 4; Left Ventricular Noncompaction Cardiomyopathy; Hypertrophic Cardiomyopathy; Cardiomyopathy, familial hypertrophic, 11 to Cardiomyopathy, hypertrophic, 11 612098
Cardiomyopathy_Paediatric v1.203 ACTC1 Zornitza Stark reviewed gene: ACTC1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cardiomyopathy, hypertrophic, 11, MIM# 612098; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cardiomyopathy_Paediatric v1.203 ACADVL Zornitza Stark Marked gene: ACADVL as ready
Cardiomyopathy_Paediatric v1.203 ACADVL Zornitza Stark Gene: acadvl has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.203 ACADVL Zornitza Stark Phenotypes for gene: ACADVL were changed from Liver disease, hepatomegaly, hypoketotic hypoglycaemia; Very long - chain acyl CoA dehydrogenase deficiency (Disorders of mitochondrial fatty acid oxidation); Very long chain acyl-CoA dehydrogenase deficiency (VLCADD) (severe form); DCM, mixed; syndromic HCM; VLCAD deficiency; HCM to VLCAD deficiency, MIM#201475
Cardiomyopathy_Paediatric v1.202 ACAD9 Zornitza Stark Marked gene: ACAD9 as ready
Cardiomyopathy_Paediatric v1.202 ACAD9 Zornitza Stark Gene: acad9 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.202 ACAD9 Zornitza Stark Phenotypes for gene: ACAD9 were changed from Mitochondrial complex I deficiency, nuclear type 20, 611126 to acyl-CoA dehydrogenase 9 deficiency, MONDO:0012624
Cardiomyopathy_Paediatric v1.201 ACAD9 Zornitza Stark Publications for gene: ACAD9 were set to
Cardiomyopathy_Paediatric v1.200 PCCA Zornitza Stark Marked gene: PCCA as ready
Cardiomyopathy_Paediatric v1.200 PCCA Zornitza Stark Gene: pcca has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.200 PCCA Zornitza Stark Phenotypes for gene: PCCA were changed from metabolic encephalopathy with hyperammonaemia, hypotonia, recurrent episodes of ketoacidosis, liver impairment, psychomotor retardation, recurrent infections; Propionic acidemia; Propionicacidemia 606054; Propionic aciduria; Dehydration, hepatomegaly, lethargy, coma, acidosis, high anion gap; DCM; Propionic aciduria (Organic acidurias); Hypertrophic-hypocontractile cardiomyopathy; Propionicacidemia to propionic acidemia, MONDO:0011628
Cardiomyopathy_Paediatric v1.199 PCCA Zornitza Stark Publications for gene: PCCA were set to 27604308
Cardiomyopathy_Paediatric v1.198 PCCA Zornitza Stark reviewed gene: PCCA: Rating: GREEN; Mode of pathogenicity: None; Publications: 40172673, 39975893, 36395710; Phenotypes: propionic acidemia, MONDO:0011628; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v1.198 AARS2 Zornitza Stark Marked gene: AARS2 as ready
Cardiomyopathy_Paediatric v1.198 AARS2 Zornitza Stark Gene: aars2 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.198 AARS2 Zornitza Stark Phenotypes for gene: AARS2 were changed from Combined oxidative phosphorylation deficiency 8, 614096; infantile mitochondrial cardiomyopathy; Multiple respiratory chain complex deficiencies (disorders of protein synthesis); Required for mitochondrial gene expression (Mitochondrial respiratory chain disorders (caused by nuclear variants only) to combined oxidative phosphorylation defect type 8, MONDO:0013570
Cardiomyopathy_Paediatric v1.197 AARS2 Zornitza Stark Publications for gene: AARS2 were set to 25058219; 21549344
Cardiomyopathy_Paediatric v1.196 AARS2 Zornitza Stark reviewed gene: AARS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 40863384, 37293078, 30285085, 29440775, 25705216; Phenotypes: combined oxidative phosphorylation defect type 8, MONDO:0013570; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v1.196 SCO2 Zornitza Stark Marked gene: SCO2 as ready
Cardiomyopathy_Paediatric v1.196 SCO2 Zornitza Stark Gene: sco2 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.196 SCO2 Zornitza Stark Phenotypes for gene: SCO2 were changed from Complex IV (Mitochondrial respiratory chain disorders (caused by nuclear variants only), OXPHOS assembly factors); Myopia 6, 608908; Mitochondrial Diseases; Mitochondrial Respiratory Chain Complex IV Deficiency; syndromic HCM; Isolated complex IV deficiency; Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 1, 604377 to cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 1, MONDO:0011451
Cardiomyopathy_Paediatric v1.195 SCO2 Zornitza Stark Publications for gene: SCO2 were set to 27604308
Cardiomyopathy_Paediatric v1.194 SCO2 Zornitza Stark reviewed gene: SCO2: Rating: GREEN; Mode of pathogenicity: None; Publications: 29193756, 25720770; Phenotypes: cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 1, MONDO:0011451; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Neuropathy v2.63 ATM Bryony Thompson Classified gene: ATM as Amber List (moderate evidence)
Hereditary Neuropathy v2.63 ATM Bryony Thompson Gene: atm has been classified as Amber List (Moderate Evidence).
Hereditary Neuropathy v2.62 ATM Bryony Thompson Deleted their review
Hereditary Neuropathy v2.62 ATM Bryony Thompson commented on gene: ATM
Hereditary Neuropathy v2.62 ATM Bryony Thompson Deleted their review
Hereditary Neuropathy v2.62 ATM Bryony Thompson Deleted their comment
Hereditary Neuropathy v2.62 ATM Bryony Thompson Classified gene: ATM as Green List (high evidence)
Hereditary Neuropathy v2.62 ATM Bryony Thompson Gene: atm has been classified as Green List (High Evidence).
Hereditary Neuropathy v2.61 ATM Bryony Thompson reviewed gene: ATM: Rating: GREEN; Mode of pathogenicity: None; Publications: 37540892, 32999401; Phenotypes: ataxia telangiectasia, MONDO:0008840; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Neuropathy v2.61 GAA Bryony Thompson Marked gene: GAA as ready
Hereditary Neuropathy v2.61 GAA Bryony Thompson Gene: gaa has been classified as Green List (High Evidence).
Hereditary Neuropathy v2.61 GAA Bryony Thompson Classified gene: GAA as Green List (high evidence)
Hereditary Neuropathy v2.61 GAA Bryony Thompson Gene: gaa has been classified as Green List (High Evidence).
Hereditary Neuropathy v2.60 GAA Bryony Thompson Classified gene: GAA as Amber List (moderate evidence)
Hereditary Neuropathy v2.60 GAA Bryony Thompson Gene: gaa has been classified as Amber List (Moderate Evidence).
Hereditary Neuropathy v2.59 GAA Bryony Thompson gene: GAA was added
gene: GAA was added to Hereditary Neuropathy. Sources: Literature
Mode of inheritance for gene: GAA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GAA were set to 39731073; 34864681; 25835646
Phenotypes for gene: GAA were set to glycogen storage disease II, MONDO:0009290
Review for gene: GAA was set to GREEN
Added comment: Three studies report nine individuals from nine families with biallelic GAA loss‑of‑function variants presenting with peripheral neuropathy (small‑fibre or large‑fibre) as part of Pompe disease. PMID 39731073 describes six neuropathy patients from four independent families, PMID 25835646 adds two families with biopsy‑confirmed small‑fibre neuropathy, and PMID 34864681 reports one case of large‑fibre sensory neuropathy.
Sources: Literature
Hereditary Neuropathy v2.58 CNBP_DM2_CCTG Bryony Thompson changed review comment from: PMID 27401721 reports 9 individuals from 8 families with autosomal dominant CNBP CCTG repeat expansions presenting with peripheral axonal motor and sensory polyneuropathy as part of myotonic dystrophy type 2. Peripheral neuropathy is a recognised, variably penetrant feature of DM2; to: PMID 27401721 reports 9/17 individuals with autosomal dominant CNBP CCTG repeat expansions presenting with peripheral axonal motor and sensory polyneuropathy as part of myotonic dystrophy type 2. Peripheral neuropathy is a recognised, variably penetrant feature of DM2
Hereditary Neuropathy v2.58 CNBP_DM2_CCTG Bryony Thompson edited their review of STR: CNBP_DM2_CCTG: Added comment: PMID 27401721 reports 9 individuals from 8 families with autosomal dominant CNBP CCTG repeat expansions presenting with peripheral axonal motor and sensory polyneuropathy as part of myotonic dystrophy type 2. Peripheral neuropathy is a recognised, variably penetrant feature of DM2; Changed publications: 20301639, 11486088, 27401721
Hereditary Neuropathy v2.58 Bryony Thompson Copied STR CNBP_DM2_CCTG from panel Repeat Disorders
Hereditary Neuropathy v2.58 CNBP_DM2_CCTG Bryony Thompson STR: CNBP_DM2_CCTG was added
STR: CNBP_DM2_CCTG was added to Hereditary Neuropathy. Sources: Expert Review Green,Expert list
adult-onset tags were added to STR: CNBP_DM2_CCTG.
Mode of inheritance for STR: CNBP_DM2_CCTG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: CNBP_DM2_CCTG were set to 20301639; 11486088
Phenotypes for STR: CNBP_DM2_CCTG were set to Myotonic dystrophy 2 MIM#602668
Cardiomyopathy_Paediatric v1.194 SLC25A20 Zornitza Stark Marked gene: SLC25A20 as ready
Cardiomyopathy_Paediatric v1.194 SLC25A20 Zornitza Stark Gene: slc25a20 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.194 SLC25A20 Zornitza Stark Phenotypes for gene: SLC25A20 were changed from Arrhythmia, liver disease, hyperammonaemia, hypoketotic hypoglycaemia; Carnitine-acylcarnitine translocase deficiency 212138; Carnitine acylcarnitine translocase deficiency (Disorders of carnitine transport and the carnitine cycle); Carnitine acylcarnitines translocase deficiency CAT; HCM, DCM to carnitine-acylcarnitine translocase deficiency, MONDO:0008918
Cardiomyopathy_Paediatric v1.193 SLC25A20 Zornitza Stark Publications for gene: SLC25A20 were set to 27604308
Cardiomyopathy_Paediatric v1.192 SLC25A20 Zornitza Stark reviewed gene: SLC25A20: Rating: GREEN; Mode of pathogenicity: None; Publications: 36419912, 35360862, 34626609, 33634872; Phenotypes: carnitine-acylcarnitine translocase deficiency, MONDO:0008918; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia v2.28 CLP1 Sangavi Sivagnanasundram gene: CLP1 was added
gene: CLP1 was added to Ataxia. Sources: Literature
Mode of inheritance for gene: CLP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CLP1 were set to 38622473; 34584079
Phenotypes for gene: CLP1 were set to pontocerebellar hypoplasia type 10, MONDO:0014349
Review for gene: CLP1 was set to AMBER
Added comment: PMID 38622473 reports 14 of 15 Turkish individuals with reported pontocerebellar hypoplasia and ataxia as a presenting phenotype however they all carry the same homozygous variant - c.419G>A p.Arg140His - FAF 0.002% in gnomAD v4.1. The authors speculate that this is a founder variant in the Turkish population.

PMID 34584079 describes functional assays conducted on patient fibroblast cell lines that show a loss-of-function effect compared to the WT.
Sources: Literature
Genomic newborn screening: BabyScreen+ v2.7 TMEM127 Zornitza Stark Marked gene: TMEM127 as ready
Genomic newborn screening: BabyScreen+ v2.7 TMEM127 Zornitza Stark Gene: tmem127 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v2.7 TMEM127 Zornitza Stark Phenotypes for gene: TMEM127 were changed from to Pheochromocytoma/paraganglioma syndrome 8, MIM# 621687
Genomic newborn screening: BabyScreen+ v2.6 TMEM127 Zornitza Stark Mode of inheritance for gene: TMEM127 was changed from BIALLELIC, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genomic newborn screening: BabyScreen+ v2.5 TMEM127 Zornitza Stark Classified gene: TMEM127 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v2.5 TMEM127 Zornitza Stark Gene: tmem127 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v2.4 TMEM127 Zornitza Stark Tag TRAIL study tag was added to gene: TMEM127.
Genomic newborn screening: BabyScreen+ v2.4 TMEM127 Zornitza Stark reviewed gene: TMEM127: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Pheochromocytoma/paraganglioma syndrome 8, MIM# 621687; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Paraganglioma_phaeochromocytoma v2.2 TMEM127 Zornitza Stark Phenotypes for gene: TMEM127 were changed from Paraganglioma, MONDO:0000448; Pheochromocytoma, MONDO:0008233; Hereditary pheochromocytoma-paraganglioma, MONDO:0017366; Pheochromocytoma, susceptibility to, MIM#171300 to Paraganglioma, MONDO:0000448; Pheochromocytoma, MONDO:0008233; Hereditary pheochromocytoma-paraganglioma, MONDO:0017366; Pheochromocytoma/paraganglioma syndrome 8, MIM# 621687
Paraganglioma_phaeochromocytoma v2.1 TMEM127 Zornitza Stark reviewed gene: TMEM127: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Pheochromocytoma/paraganglioma syndrome 8, MIM# 621687; Mode of inheritance: None
Mendeliome v2.533 TMEM127 Zornitza Stark Phenotypes for gene: TMEM127 were changed from {Pheochromocytoma, susceptibility to} 171300 to Pheochromocytoma/paraganglioma syndrome 8, MIM# 621687
Mendeliome v2.532 TMEM127 Zornitza Stark edited their review of gene: TMEM127: Changed phenotypes: Pheochromocytoma/paraganglioma syndrome 8, MIM# 621687
Cardiomyopathy_Paediatric v1.192 MMUT Eleanor Ludington reviewed gene: MMUT: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 33453710, 32754920; Phenotypes: methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency, MONDO:0009612; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia v2.27 ATG12 Sangavi Sivagnanasundram gene: ATG12 was added
gene: ATG12 was added to Ataxia. Sources: Literature
Mode of inheritance for gene: ATG12 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATG12 were set to 41895291
Phenotypes for gene: ATG12 were set to ATG12-related neurodevelopmental disorder, MONDO:0700092
Review for gene: ATG12 was set to AMBER
Added comment: PMID 41895291 reports two individuals (both from unrelated consanguineous families) with biallelic ATG12 variants presenting with congenital ataxia, developmental delay, intellectual disability, hypotonia, seizures and cerebellar vermis hypoplasia.
Sources: Literature
Cardiomyopathy_Paediatric v1.192 ACAD9 Eleanor Ludington reviewed gene: ACAD9: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 30025539, 26669660, 21057504; Phenotypes: acyl-CoA dehydrogenase 9 deficiency, MONDO:0012624; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v1.192 DSP Zornitza Stark Marked gene: DSP as ready
Cardiomyopathy_Paediatric v1.192 DSP Zornitza Stark Gene: dsp has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.192 DSP Zornitza Stark Phenotypes for gene: DSP were changed from Arrhythmogenic right ventricular dysplasia 8; Dilated cardiomyopathy with woolly hair and keratoderma to arrhythmogenic cardiomyopathy with wooly hair and keratoderma, MONDO:0011581; dilated cardiomyopathy, MONDO:0005021
Cardiomyopathy_Paediatric v1.191 DSP Zornitza Stark Publications for gene: DSP were set to
Cardiomyopathy_Paediatric v1.190 DSP Zornitza Stark reviewed gene: DSP: Rating: GREEN; Mode of pathogenicity: None; Publications: 41175027, 41108751, 40406876, 40399739, 38992493, 38551768, 36270459, 32969603, 31024045, 30993396, 28699631; Phenotypes: arrhythmogenic cardiomyopathy with wooly hair and keratoderma, MONDO:0011581, dilated cardiomyopathy, MONDO:0005021; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v1.190 ACTA1 Zornitza Stark Marked gene: ACTA1 as ready
Cardiomyopathy_Paediatric v1.190 ACTA1 Zornitza Stark Gene: acta1 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.190 ACTA1 Zornitza Stark Phenotypes for gene: ACTA1 were changed from Hypertrophic cardiomyopathy; Nemaline myopathy 3, autosomal dominant or recessive 161800; Dilated cardiomyopathy; Myopathy, congenital, with fiber-type disproportion 1 255310; CMD with rigid spine to congenital fiber-type disproportion myopathy, MONDO:0009711
Cardiomyopathy_Paediatric v1.189 ACTA1 Zornitza Stark Publications for gene: ACTA1 were set to doi:10. 1007/ s12265-016-9673-5; 16945537
Cardiomyopathy_Paediatric v1.188 ACTA1 Zornitza Stark reviewed gene: ACTA1: Rating: GREEN; Mode of pathogenicity: None; Publications: 39503885, 38559046, 35757965, 32969603; Phenotypes: congenital fiber-type disproportion myopathy, MONDO:0009711; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cardiomyopathy_Paediatric v1.188 COX15 Zornitza Stark Marked gene: COX15 as ready
Cardiomyopathy_Paediatric v1.188 COX15 Zornitza Stark Gene: cox15 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.188 COX15 Zornitza Stark Phenotypes for gene: COX15 were changed from Leigh syndrome due to cytochrome c oxidase deficiency, 256000; Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 2, 615119 to cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 2, MONDO:0014051
Cardiomyopathy_Paediatric v1.187 COX15 Zornitza Stark Publications for gene: COX15 were set to
Cardiomyopathy_Paediatric v1.186 COX15 Zornitza Stark edited their review of gene: COX15: Changed rating: GREEN
Cardiomyopathy_Paediatric v1.186 COX15 Zornitza Stark reviewed gene: COX15: Rating: AMBER; Mode of pathogenicity: None; Publications: 42001949, 32232962, 26940873, 2175025, 21412973; Phenotypes: cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 2, MONDO:0014051; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v1.186 HCN4 Zornitza Stark Marked gene: HCN4 as ready
Cardiomyopathy_Paediatric v1.186 HCN4 Zornitza Stark Gene: hcn4 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.186 HCN4 Zornitza Stark Phenotypes for gene: HCN4 were changed from to Sick sinus syndrome MONDO:0001823
Cardiomyopathy_Paediatric v1.185 HCN4 Zornitza Stark Publications for gene: HCN4 were set to
Cardiomyopathy_Paediatric v1.184 HCN4 Zornitza Stark reviewed gene: HCN4: Rating: GREEN; Mode of pathogenicity: None; Publications: 40613349, 39698436, 35893073, 35328031, 35257104, 34540771, 33185997; Phenotypes: Sick sinus syndrome MONDO:0001823; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cardiomyopathy_Paediatric v1.184 TNNI3K Zornitza Stark Marked gene: TNNI3K as ready
Cardiomyopathy_Paediatric v1.184 TNNI3K Zornitza Stark Gene: tnni3k has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.184 TNNI3K Zornitza Stark Phenotypes for gene: TNNI3K were changed from Cardiac conduction disease with or without dilated cardiomyopathy 616117 to cardiac conduction disease with or without dilated cardiomyopathy 1, MONDO:0700388
Cardiomyopathy_Paediatric v1.183 TNNI3K Zornitza Stark Publications for gene: TNNI3K were set to
Cardiomyopathy_Paediatric v1.182 TNNI3K Zornitza Stark reviewed gene: TNNI3K: Rating: GREEN; Mode of pathogenicity: None; Publications: 40904527, 40037387, 39272661, 37199186, 35274013; Phenotypes: cardiac conduction disease with or without dilated cardiomyopathy 1, MONDO:0700388; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cardiomyopathy_Paediatric v1.182 ARSB Zornitza Stark Marked gene: ARSB as ready
Cardiomyopathy_Paediatric v1.182 ARSB Zornitza Stark Gene: arsb has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.182 ARSB Zornitza Stark Phenotypes for gene: ARSB were changed from MPS VI, Maroteaux - Lamy disease (MPS IV, Morquio disease); Mucopolysaccharidosis type VI (Maroteaux-Lamy), 253200; Mucopolysaccharidosis Type VI; Mucopolysaccharidosis, Type VI; MUCOPOLYSACCHARIDOSIS TYPE 6 to mucopolysaccharidosis type 6, MONDO:0009661
Cardiomyopathy_Paediatric v1.181 ARSB Zornitza Stark Publications for gene: ARSB were set to 27604308
Cardiomyopathy_Paediatric v1.180 ARSB Zornitza Stark reviewed gene: ARSB: Rating: GREEN; Mode of pathogenicity: None; Publications: 36495517, 32075597; Phenotypes: mucopolysaccharidosis type 6, MONDO:0009661; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Retinitis pigmentosa v1.12 RNU6-9 Zornitza Stark Tag non-coding gene tag was added to gene: RNU6-9.
Mendeliome v2.532 RNU6-9 Zornitza Stark Tag non-coding gene tag was added to gene: RNU6-9.
Retinitis pigmentosa v1.12 RNU6-8 Zornitza Stark Tag non-coding gene tag was added to gene: RNU6-8.
Mendeliome v2.532 RNU6-8 Zornitza Stark Tag non-coding gene tag was added to gene: RNU6-8.
Retinitis pigmentosa v1.12 RNU6-2 Zornitza Stark Tag non-coding gene tag was added to gene: RNU6-2.
Mendeliome v2.532 RNU6-2 Zornitza Stark Tag non-coding gene tag was added to gene: RNU6-2.
Retinitis pigmentosa v1.12 RNU6-1 Zornitza Stark Tag non-coding gene tag was added to gene: RNU6-1.
Mendeliome v2.532 RNU6-1 Zornitza Stark Tag non-coding gene tag was added to gene: RNU6-1.
Intellectual disability syndromic and non-syndromic v2.134 RNU5B-1 Zornitza Stark Tag non-coding gene tag was added to gene: RNU5B-1.
Mendeliome v2.532 RNU5B-1 Zornitza Stark Tag non-coding gene tag was added to gene: RNU5B-1.
Intellectual disability syndromic and non-syndromic v2.134 RNU5A-1 Zornitza Stark Tag non-coding gene tag was added to gene: RNU5A-1.
Mendeliome v2.532 RNU5A-1 Zornitza Stark Tag non-coding gene tag was added to gene: RNU5A-1.
Hereditary Pigmentary Disorders v2.0 TERT Zornitza Stark Tag non-coding gene tag was added to gene: TERT.
IBMDx study v1.2 TERT Zornitza Stark Marked gene: TERT as ready
IBMDx study v1.2 TERT Zornitza Stark Gene: tert has been classified as Green List (High Evidence).
IBMDx study v1.2 TERT Zornitza Stark Publications for gene: TERT were set to
IBMDx study v1.1 TERT Zornitza Stark Mode of inheritance for gene: TERT was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
IBMDx study v1.0 TERT Zornitza Stark Tag non-coding gene tag was added to gene: TERT.
Fetal anomalies v2.74 TERT Zornitza Stark Tag non-coding gene tag was added to gene: TERT.
Skeletal dysplasia v1.151 TERT Zornitza Stark Marked gene: TERT as ready
Skeletal dysplasia v1.151 TERT Zornitza Stark Gene: tert has been classified as Red List (Low Evidence).
Skeletal dysplasia v1.151 TERT Zornitza Stark Phenotypes for gene: TERT were changed from Dyskeratosis congenita, autosomal dominant 2 and autosomal recessive 4 613989 to Dyskeratosis congenita, MIM# 613989; Pulmonary fibrosis and/or bone marrow failure, telomere-related, 1, MIM# 614742
Skeletal dysplasia v1.150 TERT Zornitza Stark Publications for gene: TERT were set to
Skeletal dysplasia v1.149 TERT Zornitza Stark Classified gene: TERT as Red List (low evidence)
Skeletal dysplasia v1.149 TERT Zornitza Stark Gene: tert has been classified as Red List (Low Evidence).
Skeletal dysplasia v1.148 TERT Zornitza Stark edited their review of gene: TERT: Added comment: Not associated with skeletal dysplasia.; Changed rating: RED
Intellectual disability syndromic and non-syndromic v2.134 TERT Zornitza Stark Tag non-coding gene tag was added to gene: TERT.
Intellectual disability syndromic and non-syndromic v2.134 TERT Zornitza Stark Mode of inheritance for gene: TERT was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Combined Immunodeficiency v2.10 TERT Zornitza Stark Tag non-coding gene tag was added to gene: TERT.
Pulmonary Fibrosis_Interstitial Lung Disease v2.5 TERT Zornitza Stark Tag non-coding gene tag was added to gene: TERT.
Ataxia v2.26 C19orf12 Sangavi Sivagnanasundram Classified gene: C19orf12 as Green List (high evidence)
Ataxia v2.26 C19orf12 Sangavi Sivagnanasundram Gene: c19orf12 has been classified as Green List (High Evidence).
Ataxia v2.25 C19orf12 Sangavi Sivagnanasundram gene: C19orf12 was added
gene: C19orf12 was added to Ataxia. Sources: Literature
Mode of inheritance for gene: C19orf12 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C19orf12 were set to 39755877
Phenotypes for gene: C19orf12 were set to neurodegeneration with brain iron accumulation 4, MONDO:0013674
Review for gene: C19orf12 was set to GREEN
Added comment: Mitochondrial membrane protein-associated neurodegeneration (MPAN)/NBIA 4 is a rare neurodegenerative disorder characterised by spastic paraplegia, parkinsonism, and psychiatric and/or behavioural symptoms.

PMID 39755877 reports 4 individuals from 4 unrelated families with rare homozygous variants in C19orf12, with ataxia as a presenting feature.

Note, C19orf12 was formally known as SPG43
Sources: Literature
Mendeliome v2.532 TERT Zornitza Stark Tag non-coding gene tag was added to gene: TERT.
Cerebellar and Pontocerebellar Hypoplasia v2.5 TERT Zornitza Stark Tag non-coding gene tag was added to gene: TERT.
Bone Marrow Failure v2.9 TERT Zornitza Stark Tag non-coding gene tag was added to gene: TERT.
Haematological malignancies v0.148 TERT Zornitza Stark Tag non-coding gene tag was added to gene: TERT.
Repeat Disorders v1.13 TYMS_CPUM_ACCATC Bryony Thompson Marked STR: TYMS_CPUM_ACCATC as ready
Repeat Disorders v1.13 TYMS_CPUM_ACCATC Bryony Thompson Str: tyms_cpum_accatc has been classified as Red List (Low Evidence).
Repeat Disorders v1.13 TYMS_CPUM_ACCATC Bryony Thompson STR: TYMS_CPUM_ACCATC was added
STR: TYMS_CPUM_ACCATC was added to Repeat Disorders. Sources: Literature
Mode of inheritance for STR: TYMS_CPUM_ACCATC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for STR: TYMS_CPUM_ACCATC were set to 40589716
Phenotypes for STR: TYMS_CPUM_ACCATC were set to Congenital progressive universal melanosis MONDO:0013648
Review for STR: TYMS_CPUM_ACCATC was set to RED
Added comment: PMID 40589716 reports a single Thai family with 15-year-old monozygotic twin girls and congenital progressive universal melanosis (diffuse hyperpigmentation from birth). Both carry biallelic GATGGT hexanucleotide expansions in intron 3 of TYMS, reported as 210-259 repeats. Both parents are unaffected heterozygous carriers at age 56 (106/230-245 and 93/217-224).
The twins are monozygotic (KING kinship 0.4934).
In-house long-read controls (n=236) had 42-172 repeats, with 47% at 106 and no control carrying a long allele on both chromosomes.
Reduced TYMS expression is the proposed mechanism, but TYMS RNA in fibroblasts and PBMCs and protein in fibroblasts all fell within the control range. Further probands/families are required to confirm the gene-disease association.
Sources: Literature
Repeat Disorders v1.12 FAM193B_OPDM_CGG Bryony Thompson Marked STR: FAM193B_OPDM_CGG as ready
Repeat Disorders v1.12 FAM193B_OPDM_CGG Bryony Thompson Str: fam193b_opdm_cgg has been classified as Red List (Low Evidence).
Repeat Disorders v1.12 FAM193B_OPDM_CGG Bryony Thompson STR: FAM193B_OPDM_CGG was added
STR: FAM193B_OPDM_CGG was added to Repeat Disorders. Sources: Literature
Mode of inheritance for STR: FAM193B_OPDM_CGG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: FAM193B_OPDM_CGG were set to 38297326; 40357124; 10.1101/2025.01.06.631535; 38585781
Phenotypes for STR: FAM193B_OPDM_CGG were set to Oculopharyngodistal myopathy, FAM193B-related (candidate) MONDO:0025193
Review for STR: FAM193B_OPDM_CGG was set to RED
Added comment: A single Undiagnosed Diseases Network family reported in PMID 38297326, 38585781 and doi 10.1101/2025.01.06.631535. 2 affected sisters had heterozygous 5'UTR CGG expansions of 198 and 194 repeats, inherited from their unaffected mother with 158 repeats. The unaffected father had 16 repeats.
No normal range is defined. Discovery cohort alleles were <~30 repeats.
No pathogenic threshold is defined. 194 repeats was the lowest number of repeats in an affected individual.
The sisters presented at 49 and 51 years. Blood FAM193B overexpression without promoter hypermethylation is the only functional evidence. A screen of ~50 OPDM long-read genomes found no second family.
Further probands/families are required to confirm the gene-disease association.
Sources: Literature
Limb-Girdle Muscular Dystrophy and Distal Myopathy v2.7 TBC1D7_OPDM_CGG Bryony Thompson Marked STR: TBC1D7_OPDM_CGG as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v2.7 TBC1D7_OPDM_CGG Bryony Thompson Str: tbc1d7_opdm_cgg has been classified as Amber List (Moderate Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v2.7 TBC1D7_OPDM_CGG Bryony Thompson Classified STR: TBC1D7_OPDM_CGG as Amber List (moderate evidence)
Limb-Girdle Muscular Dystrophy and Distal Myopathy v2.7 TBC1D7_OPDM_CGG Bryony Thompson Str: tbc1d7_opdm_cgg has been classified as Amber List (Moderate Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v2.6 TBC1D7_OPDM_CGG Bryony Thompson edited their review of STR: TBC1D7_OPDM_CGG: Changed rating: AMBER
Repeat Disorders v1.11 TBC1D7_OPDM_CGG Bryony Thompson Marked STR: TBC1D7_OPDM_CGG as ready
Repeat Disorders v1.11 TBC1D7_OPDM_CGG Bryony Thompson Str: tbc1d7_opdm_cgg has been classified as Amber List (Moderate Evidence).
Repeat Disorders v1.11 TBC1D7_OPDM_CGG Bryony Thompson Classified STR: TBC1D7_OPDM_CGG as Amber List (moderate evidence)
Repeat Disorders v1.11 TBC1D7_OPDM_CGG Bryony Thompson Str: tbc1d7_opdm_cgg has been classified as Amber List (Moderate Evidence).
Repeat Disorders v1.10 TBC1D7_OPDM_CGG Bryony Thompson edited their review of STR: TBC1D7_OPDM_CGG: Changed rating: AMBER
Limb-Girdle Muscular Dystrophy and Distal Myopathy v2.6 Bryony Thompson Copied STR TBC1D7_OPDM_CGG from panel Repeat Disorders
Limb-Girdle Muscular Dystrophy and Distal Myopathy v2.6 TBC1D7_OPDM_CGG Bryony Thompson STR: TBC1D7_OPDM_CGG was added
STR: TBC1D7_OPDM_CGG was added to Limb-Girdle Muscular Dystrophy and Distal Myopathy. Sources: Expert Review Green,Literature
Mode of inheritance for STR: TBC1D7_OPDM_CGG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: TBC1D7_OPDM_CGG were set to 41959811
Phenotypes for STR: TBC1D7_OPDM_CGG were set to Oculopharyngodistal myopathy, TBC1D7-related MONDO:0025193
Repeat Disorders v1.10 TBC1D7_OPDM_CGG Bryony Thompson Classified STR: TBC1D7_OPDM_CGG as Green List (high evidence)
Repeat Disorders v1.10 TBC1D7_OPDM_CGG Bryony Thompson Str: tbc1d7_opdm_cgg has been classified as Green List (High Evidence).
Repeat Disorders v1.9 TBC1D7_OPDM_CGG Bryony Thompson STR: TBC1D7_OPDM_CGG was added
STR: TBC1D7_OPDM_CGG was added to Repeat Disorders. Sources: Literature
Mode of inheritance for STR: TBC1D7_OPDM_CGG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: TBC1D7_OPDM_CGG were set to 41959811
Phenotypes for STR: TBC1D7_OPDM_CGG were set to Oculopharyngodistal myopathy, TBC1D7-related MONDO:0025193
Review for STR: TBC1D7_OPDM_CGG was set to GREEN
Added comment: Preprint PMID 41959811 reports 3 families with a heterozygous 5'UTR CCG expansion in TBC1D7 and oculopharyngodistal myopathy. Affected individuals had 83, 87, 113, 137 and 148 repeats (n=5). All 3 families share a core 16 kb haplotype, consistent with a common ancestral origin. An unaffected transmitting father carries the largest allele, 184 repeats, hypermethylated. Gain of function is the proposed mechanism of disease. Patient-derived fibroblasts show increased TBC1D7 expression, and muscle biopsy shows p62-positive intranuclear inclusions, supporting a dominant toxic gain-of-function mechanism analogous to other CCG-expansion disorders. No normal range is defined. 79/70,752 GE control alleles had >50 repeats.
The reference and 94.3% of 1,718 control alleles carry an interrupted CCGCTG structure, while patient alleles are long pure CCG.
Sources: Literature
Ataxia v2.24 Bryony Thompson Copied STR EP400_SCA_CAG from panel Repeat Disorders
Ataxia v2.24 EP400_SCA_CAG Bryony Thompson STR: EP400_SCA_CAG was added
STR: EP400_SCA_CAG was added to Ataxia. Sources: Expert Review Amber,Literature
Mode of inheritance for STR: EP400_SCA_CAG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: EP400_SCA_CAG were set to 10.1101/2025.01.06.631535
Phenotypes for STR: EP400_SCA_CAG were set to Spinocerebellar ataxia, EP400-related MONDO:0000437
Repeat Disorders v1.8 EP400_SCA_CAG Bryony Thompson Marked STR: EP400_SCA_CAG as ready
Repeat Disorders v1.8 EP400_SCA_CAG Bryony Thompson Str: ep400_sca_cag has been classified as Amber List (Moderate Evidence).
Repeat Disorders v1.8 EP400_SCA_CAG Bryony Thompson Classified STR: EP400_SCA_CAG as Amber List (moderate evidence)
Repeat Disorders v1.8 EP400_SCA_CAG Bryony Thompson Str: ep400_sca_cag has been classified as Amber List (Moderate Evidence).
Repeat Disorders v1.7 EP400_SCA_CAG Bryony Thompson STR: EP400_SCA_CAG was added
STR: EP400_SCA_CAG was added to Repeat Disorders. Sources: Literature
Mode of inheritance for STR: EP400_SCA_CAG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: EP400_SCA_CAG were set to 10.1101/2025.01.06.631535
Phenotypes for STR: EP400_SCA_CAG were set to Spinocerebellar ataxia, EP400-related MONDO:0000437
Review for STR: EP400_SCA_CAG was set to AMBER
Added comment: Preprint doi 10.1101/2025.01.06.631535 reports 2 unrelated families with an exonic CAG (polyglutamine) expansion in exon 47 of EP400 and spinocerebellar ataxia. A father and daughter had 56 and 58 pure CAG repeats. An affected child in the second family had 75.
The longest pure CAG tract in 543 control genomes was 24.
Normal 39 and pathogenic 71 are total allele length including CAA interruptions. The paper counts the longest pure CAG tract, 15 repeats lower.
No pathogenic threshold is defined. 56 repeats was the lowest in an affected individual. Ages of onset were 15, ~35, 42 and 43 years.
No functional analysis. Further probands/families are required to confirm the gene-disease association.
Comment on list classification: Two families only and no functional evidence.
Sources: Literature
Repeat Disorders v1.6 CSNK1E_FRA22A_CGG Bryony Thompson Marked STR: CSNK1E_FRA22A_CGG as ready
Repeat Disorders v1.6 CSNK1E_FRA22A_CGG Bryony Thompson Str: csnk1e_fra22a_cgg has been classified as Amber List (Moderate Evidence).
Repeat Disorders v1.6 CSNK1E_FRA22A_CGG Bryony Thompson Classified STR: CSNK1E_FRA22A_CGG as Amber List (moderate evidence)
Repeat Disorders v1.6 CSNK1E_FRA22A_CGG Bryony Thompson Str: csnk1e_fra22a_cgg has been classified as Amber List (Moderate Evidence).
Repeat Disorders v1.5 CSNK1E_FRA22A_CGG Bryony Thompson STR: CSNK1E_FRA22A_CGG was added
STR: CSNK1E_FRA22A_CGG was added to Repeat Disorders. Sources: Literature
Mode of inheritance for STR: CSNK1E_FRA22A_CGG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: CSNK1E_FRA22A_CGG were set to 40751262; 39107278
Phenotypes for STR: CSNK1E_FRA22A_CGG were set to CSNK1E-related progressive myoclonic epilepsy and developmental and epileptic encephalopathy
Review for STR: CSNK1E_FRA22A_CGG was set to AMBER
Added comment: PMID 39107278 and 40751262 report 4 unrelated families with a heterozygous CGG expansion in the 5'UTR of CSNK1E at fragile site FRA22A. 3 probands had developmental and epileptic encephalopathy and 1 had progressive myoclonic epilepsy from age 10.
Analysis of 1000 Genomes ONT data (n=908) suggests a normal range up to 48 repeats (98.7% <20).
Neither paper proposes a pathogenic threshold. The affected proband had 745 repeats, her unaffected 18-year-old sister 980 and their unaffected mother 131. An affected DEE proband had ~430-700 repeats and an unaffected carrier mother ~500.
Hypermethylation with ~50% reduced expression in fibroblasts is suggested to be the mechanism. The same hypermethylation was found in 6/23,116 controls.
Further probands/families are required to confirm the gene-disease association.
Comment on list classification: Unaffected carriers occur throughout the expansion range and no pathogenic threshold exists, and not useful in the clinical diagnostic setting.
Sources: Literature
Ataxia v2.23 ASL Sangavi Sivagnanasundram Classified gene: ASL as Amber List (moderate evidence)
Ataxia v2.23 ASL Sangavi Sivagnanasundram Gene: asl has been classified as Amber List (Moderate Evidence).
Ataxia v2.22 ASL Sangavi Sivagnanasundram gene: ASL was added
gene: ASL was added to Ataxia. Sources: Literature
Mode of inheritance for gene: ASL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ASL were set to 38044746
Phenotypes for gene: ASL were set to argininosuccinic aciduria, MONDO:0008815
Review for gene: ASL was set to AMBER
Added comment: PMID 38044746 reports 7 unrelated individuals with argininosuccinic aciduria and ataxia as a presenting feature however only two of the individuals were reported to have genetic testing.
Both individuals presented with compound heterozygous variants that are present in gnomAD v4.1 but rare enough for AR association.
Sources: Literature
Ataxia v2.21 ALG6 Sangavi Sivagnanasundram Classified gene: ALG6 as Green List (high evidence)
Ataxia v2.21 ALG6 Sangavi Sivagnanasundram Gene: alg6 has been classified as Green List (High Evidence).
Ataxia v2.20 ACOX1 Sangavi Sivagnanasundram Classified gene: ACOX1 as Amber List (moderate evidence)
Ataxia v2.20 ACOX1 Sangavi Sivagnanasundram Gene: acox1 has been classified as Amber List (Moderate Evidence).
Ataxia v2.19 ACOX1 Sangavi Sivagnanasundram gene: ACOX1 was added
gene: ACOX1 was added to Ataxia. Sources: Literature
Mode of inheritance for gene: ACOX1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ACOX1 were set to 38923841; 37846133
Phenotypes for gene: ACOX1 were set to Mitchell syndrome, MONDO:0030073
Review for gene: ACOX1 was set to AMBER
Added comment: Three unrelated individuals presenting with Mitchell syndrome, characterised by progressive gait ataxia, sensorineural hearing loss, visual impairment, ichthyosis and polyneuropathy.
They all carry the same heterozygous missense variant c.710A>G, p.Asn237Ser, which is absent in gnomAD v4.1.
Sources: Literature
Ataxia v2.18 ALG6 Sangavi Sivagnanasundram gene: ALG6 was added
gene: ALG6 was added to Ataxia. Sources: Literature
Mode of inheritance for gene: ALG6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ALG6 were set to 27287710
Phenotypes for gene: ALG6 were set to ALG6-congenital disorder of glycosylation 1C, MONDO:0011291
Review for gene: ALG6 was set to GREEN
Added comment: Multiple individuals reported with ataxia as a presenting phenotype.
Note: two of the reported variants have a high FAF for an AR gene
c.257+5G>A - FAF 0.1133% in gnomAD v4.1
c.391T>C p.Tyr131His - FAF 3.787% in gnomAD v4.1. This is a known polymorphism in ALG6.
Sources: Literature
Ataxia v2.17 ABCA2 Sangavi Sivagnanasundram Classified gene: ABCA2 as Green List (high evidence)
Ataxia v2.17 ABCA2 Sangavi Sivagnanasundram Gene: abca2 has been classified as Green List (High Evidence).
Ataxia v2.16 ABCA2 Sangavi Sivagnanasundram Classified gene: ABCA2 as Green List (high evidence)
Ataxia v2.16 ABCA2 Sangavi Sivagnanasundram Gene: abca2 has been classified as Green List (High Evidence).
Ataxia v2.15 ABCA2 Sangavi Sivagnanasundram gene: ABCA2 was added
gene: ABCA2 was added to Ataxia. Sources: Literature
Mode of inheritance for gene: ABCA2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ABCA2 were set to 38228874
Phenotypes for gene: ABCA2 were set to intellectual developmental disorder with poor growth and with or without seizures or ataxia, MONDO:0032930
Review for gene: ABCA2 was set to GREEN
Added comment: Biallelic ABCA2 variants present with a neurological disorder characterised by global developmental delay apparent from infancy, hypotonia, and poor overall growth, sometimes with borderline microcephaly.
3 unrelated individuals reported with ataxia as a presenting feature.
Sources: Literature
Hereditary Neuropathy v2.57 MTHFR Sangavi Sivagnanasundram Classified gene: MTHFR as Green List (high evidence)
Hereditary Neuropathy v2.57 MTHFR Sangavi Sivagnanasundram Gene: mthfr has been classified as Green List (High Evidence).
Hereditary Neuropathy v2.56 MTHFR Sangavi Sivagnanasundram gene: MTHFR was added
gene: MTHFR was added to Hereditary Neuropathy. Sources: Literature
Mode of inheritance for gene: MTHFR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MTHFR were set to 33089527; 33000330; 29284203
Phenotypes for gene: MTHFR were set to homocystinuria due to methylene tetrahydrofolate reductase deficiency, MONDO:0009353
Review for gene: MTHFR was set to GREEN
Added comment: Neuropathy is a feature of this condition (typically peripheral neuropathy).
Sources: Literature
Hereditary Neuropathy v2.55 MMACHC Sangavi Sivagnanasundram Classified gene: MMACHC as Green List (high evidence)
Hereditary Neuropathy v2.55 MMACHC Sangavi Sivagnanasundram Gene: mmachc has been classified as Green List (High Evidence).
Hereditary Neuropathy v2.54 MMACHC Sangavi Sivagnanasundram gene: MMACHC was added
gene: MMACHC was added to Hereditary Neuropathy. Sources: Literature
Mode of inheritance for gene: MMACHC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MMACHC were set to 35109910; 33324334; 33000330; 32208535; 31092259; 25672861
Phenotypes for gene: MMACHC were set to methylmalonic aciduria and homocystinuria type cblC, MONDO:0010184
Review for gene: MMACHC was set to GREEN
Added comment: Biallelic variants in MMACHC cause methylmalonic aciduria and homocystinuria type cblC. Neuropathy (particularly peripheral neuropathy (sensorimotor polyneuropathy)) is a presenting feature in affected individuals, accompanied by cognitive impairment, psychiatric symptoms, renal dysfunction and gait disturbance.
Sources: Literature
Hereditary Neuropathy v2.53 GLDN Sangavi Sivagnanasundram Classified gene: GLDN as Green List (high evidence)
Hereditary Neuropathy v2.53 GLDN Sangavi Sivagnanasundram Gene: gldn has been classified as Green List (High Evidence).
Hereditary Neuropathy v2.52 GLDN Sangavi Sivagnanasundram gene: GLDN was added
gene: GLDN was added to Hereditary Neuropathy. Sources: Literature
Mode of inheritance for gene: GLDN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GLDN were set to 35740734; 28726266; 27616481
Phenotypes for gene: GLDN were set to lethal congenital contracture syndrome 11, MONDO:0014965
Review for gene: GLDN was set to GREEN
Added comment: Biallelic GLDN variants are associated with lethal congenital contracture syndrome 11 (LCCS11) – a severe arthrogryposis multiplex congenita with peripheral neuropathy, respiratory insufficiency and polyhydramnios.

Neuropathy is a presenting feature of this condition. >4 unrelated families presented with neuropathy/ abnormal transmission electron microscopy findings
Sources: Literature
Hereditary Neuropathy v2.51 DNM1L Sangavi Sivagnanasundram Classified gene: DNM1L as Green List (high evidence)
Hereditary Neuropathy v2.51 DNM1L Sangavi Sivagnanasundram Gene: dnm1l has been classified as Green List (High Evidence).
Hereditary Neuropathy v2.50 DNM1L Sangavi Sivagnanasundram gene: DNM1L was added
gene: DNM1L was added to Hereditary Neuropathy. Sources: Literature
Mode of inheritance for gene: DNM1L was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DNM1L were set to 41244260; 38481935; 36212643; 33718295; 31868880
Phenotypes for gene: DNM1L were set to encephalopathy due to mitochondrial and peroxisomal fission defect, MONDO:0054865
Review for gene: DNM1L was set to GREEN
Added comment: >5 unrelated probands reported with an early-onset (0-10 years of age) neurodevelopmental disorder characterised by peripheral sensory neuropathy, developmental delay, seizures, spasticity, ataxia and optic atrophy.
One individual reported in 36212643 presented with neuropathy at the age of 32; however, other features were present from birth.
33718295 - reported a case with a rare de novo heterozygous missense variant in DNM1L
Functional studies showed mitochondrial hyperfusion, reduced GTPase activity and decreased DNM1L protein.
Sources: Literature
Cardiomyopathy_Paediatric v1.180 NDUFV1 Zornitza Stark Marked gene: NDUFV1 as ready
Cardiomyopathy_Paediatric v1.180 NDUFV1 Zornitza Stark Gene: ndufv1 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.180 NDUFV1 Zornitza Stark Phenotypes for gene: NDUFV1 were changed from Mitochondrial complex I deficiency, nuclear type 4, 618225 to Mitochondrial complex I deficiency, nuclear type 4 MIM#618225
Cardiomyopathy_Paediatric v1.179 NDUFV1 Zornitza Stark Publications for gene: NDUFV1 were set to
Cardiomyopathy_Paediatric v1.178 NDUFV1 Zornitza Stark reviewed gene: NDUFV1: Rating: GREEN; Mode of pathogenicity: None; Publications: 41140551, 39525154, 35482246; Phenotypes: Mitochondrial complex I deficiency, nuclear type 4 MIM#618225; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v1.178 NDUFS8 Zornitza Stark Marked gene: NDUFS8 as ready
Cardiomyopathy_Paediatric v1.178 NDUFS8 Zornitza Stark Gene: ndufs8 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.178 NDUFS8 Zornitza Stark Phenotypes for gene: NDUFS8 were changed from Mitochondrial complex I deficiency, nuclear type 2, 618222 to mitochondrial complex I deficiency, nuclear type 2, MONDO:0032606
Cardiomyopathy_Paediatric v1.177 NDUFS8 Zornitza Stark Publications for gene: NDUFS8 were set to
Cardiomyopathy_Paediatric v1.176 NDUFS8 Zornitza Stark reviewed gene: NDUFS8: Rating: GREEN; Mode of pathogenicity: None; Publications: 38229652, 36462614, 9837812; Phenotypes: mitochondrial complex I deficiency, nuclear type 2, MONDO:0032606; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v1.176 MAP2K2 Zornitza Stark Marked gene: MAP2K2 as ready
Cardiomyopathy_Paediatric v1.176 MAP2K2 Zornitza Stark Gene: map2k2 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.176 MAP2K2 Zornitza Stark Phenotypes for gene: MAP2K2 were changed from Cardiofaciocutaneous syndrome 4 615280; Cardio-Facio-Cutaneous syndrome type 4; Cardiofaciocutaneous Syndrome; Cardio-Facio-Cutaneous syndrome; Cardiofaciocutaneous syndrome 4; syndromic HCM; CFC syndrome to cardiofaciocutaneous syndrome 4, MONDO:0014114
Cardiomyopathy_Paediatric v1.175 MAP2K2 Zornitza Stark reviewed gene: MAP2K2: Rating: GREEN; Mode of pathogenicity: None; Publications: 37697378; Phenotypes: cardiofaciocutaneous syndrome 4, MONDO:0014114; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary Neuropathy v2.49 PNPT1 Zornitza Stark Marked gene: PNPT1 as ready
Hereditary Neuropathy v2.49 PNPT1 Zornitza Stark Gene: pnpt1 has been classified as Green List (High Evidence).
Hereditary Neuropathy v2.49 PNPT1 Zornitza Stark Classified gene: PNPT1 as Green List (high evidence)
Hereditary Neuropathy v2.49 PNPT1 Zornitza Stark Gene: pnpt1 has been classified as Green List (High Evidence).
Hereditary Neuropathy v2.48 PNPT1 Zornitza Stark gene: PNPT1 was added
gene: PNPT1 was added to Hereditary Neuropathy. Sources: Literature
Mode of inheritance for gene: PNPT1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: PNPT1 were set to 39924761; 39899068; 28708278; 27759031
Phenotypes for gene: PNPT1 were set to combined oxidative phosphorylation defect type 13, MONDO:0013977; spinocerebellar ataxia type 25, MONDO:0012103
Review for gene: PNPT1 was set to GREEN
Added comment: Mono-allelic association:
PMID 39899068 and PMID 39924761 report three unrelated families with heterozygous loss‑of‑function variants in PNPT1 causing spinocerebellar ataxia type 25 (SCA25), characterised by progressive cerebellar ataxia, cerebellar atrophy and sensory neuropathy.

Bi-allelic association:
PMID 27759031 describes a consanguineous family with compound heterozygous missense variants leading to a combined oxidative phosphorylation defect type 13, presenting with severe early‑onset axonal peripheral neuropathy, optic atrophy, auditory neuropathy, intellectual disability and multisystem involvement (1 family, 2 patients); functional studies in patient fibroblasts showed loss of PNPT1 protein and rescue by wild‑type expression.
Sources: Literature
Hereditary Neuropathy v2.47 LAMA2 Zornitza Stark Marked gene: LAMA2 as ready
Hereditary Neuropathy v2.47 LAMA2 Zornitza Stark Gene: lama2 has been classified as Green List (High Evidence).
Hereditary Neuropathy v2.47 LAMA2 Zornitza Stark Classified gene: LAMA2 as Green List (high evidence)
Hereditary Neuropathy v2.47 LAMA2 Zornitza Stark Gene: lama2 has been classified as Green List (High Evidence).
Hereditary Neuropathy v2.46 LAMA2 Zornitza Stark gene: LAMA2 was added
gene: LAMA2 was added to Hereditary Neuropathy. Sources: Literature
Mode of inheritance for gene: LAMA2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LAMA2 were set to 41765988; 37206914; 35868801
Phenotypes for gene: LAMA2 were set to LAMA2-related muscular dystrophy MONDO:0100228
Review for gene: LAMA2 was set to GREEN
Added comment: Classically a muscular dystrophy, however PMID 37206914 reports 19 individuals from 17 families with autosomal recessive limb‑girdle muscular dystrophy (LGMD R23) in which 46.7 % have motor neuropathy; and additional reports identified.
Sources: Literature
Hereditary Neuropathy v2.45 FDXR Zornitza Stark Marked gene: FDXR as ready
Hereditary Neuropathy v2.45 FDXR Zornitza Stark Gene: fdxr has been classified as Green List (High Evidence).
Hereditary Neuropathy v2.45 FDXR Zornitza Stark Classified gene: FDXR as Green List (high evidence)
Hereditary Neuropathy v2.45 FDXR Zornitza Stark Gene: fdxr has been classified as Green List (High Evidence).
Hereditary Neuropathy v2.44 FDXR Zornitza Stark gene: FDXR was added
gene: FDXR was added to Hereditary Neuropathy. Sources: Literature
Mode of inheritance for gene: FDXR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FDXR were set to 38885337; 37046037; 33742450; 30250212
Phenotypes for gene: FDXR were set to optic atrophy-ataxia-peripheral neuropathy-global developmental delay syndrome, MONDO:0034092
Review for gene: FDXR was set to GREEN
Added comment: Peripheral neuropathy is a feature of this condition.
Sources: Literature
Hereditary Neuropathy v2.43 PIEZO2 Zornitza Stark Marked gene: PIEZO2 as ready
Hereditary Neuropathy v2.43 PIEZO2 Zornitza Stark Gene: piezo2 has been classified as Green List (High Evidence).
Hereditary Neuropathy v2.43 PIEZO2 Zornitza Stark Classified gene: PIEZO2 as Green List (high evidence)
Hereditary Neuropathy v2.43 PIEZO2 Zornitza Stark Gene: piezo2 has been classified as Green List (High Evidence).
Hereditary Neuropathy v2.42 PIEZO2 Zornitza Stark gene: PIEZO2 was added
gene: PIEZO2 was added to Hereditary Neuropathy. Sources: Literature
Mode of inheritance for gene: PIEZO2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PIEZO2 were set to 31968264; 30941898; 27974811; 27653382
Phenotypes for gene: PIEZO2 were set to arthrogryposis, distal, with impaired proprioception and touch, MONDO:0014941
Review for gene: PIEZO2 was set to GREEN
Added comment: Impaired proprioception and sensory neuropathy are a key feature of the phenotype.
Sources: Literature
Hereditary Neuropathy v2.41 MT-ATP6 Zornitza Stark Marked gene: MT-ATP6 as ready
Hereditary Neuropathy v2.41 MT-ATP6 Zornitza Stark Gene: mt-atp6 has been classified as Green List (High Evidence).
Hereditary Neuropathy v2.41 MT-ATP6 Zornitza Stark Classified gene: MT-ATP6 as Green List (high evidence)
Hereditary Neuropathy v2.41 MT-ATP6 Zornitza Stark Gene: mt-atp6 has been classified as Green List (High Evidence).
Hereditary Neuropathy v2.40 MT-ATP6 Zornitza Stark gene: MT-ATP6 was added
gene: MT-ATP6 was added to Hereditary Neuropathy. Sources: Literature
mtDNA tags were added to gene: MT-ATP6.
Mode of inheritance for gene gene: MT-ATP6 was set to MITOCHONDRIAL
Publications for gene: MT-ATP6 were set to 39677188; 38549004; 36434790; 34953645; 34635923; 33476484; 32042921; 31424416; 31187502; 30136164; 27783406; 27502083; 27015314
Phenotypes for gene: MT-ATP6 were set to Mitochondrial complex V (ATP synthase) deficiency, MONDO:0014471, MT-ATP6-related
Review for gene: MT-ATP6 was set to GREEN
Added comment: Peripheral neuropathy is a common feature.
Sources: Literature
Cardiomyopathy_Paediatric v1.175 NDUFS2 Zornitza Stark Marked gene: NDUFS2 as ready
Cardiomyopathy_Paediatric v1.175 NDUFS2 Zornitza Stark Gene: ndufs2 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.175 NDUFS2 Zornitza Stark Phenotypes for gene: NDUFS2 were changed from Mitochondrial complex I deficiency, nuclear type 6, 618228 to mitochondrial complex I deficiency, nuclear type 6, MONDO:0032611
Cardiomyopathy_Paediatric v1.174 NDUFS2 Zornitza Stark Publications for gene: NDUFS2 were set to
Cardiomyopathy_Paediatric v1.173 NDUFS2 Zornitza Stark reviewed gene: NDUFS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 36462614, 22036843; Phenotypes: mitochondrial complex I deficiency, nuclear type 6, MONDO:0032611; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v1.173 NDUFS4 Zornitza Stark Marked gene: NDUFS4 as ready
Cardiomyopathy_Paediatric v1.173 NDUFS4 Zornitza Stark Gene: ndufs4 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.173 NDUFS4 Zornitza Stark Phenotypes for gene: NDUFS4 were changed from Mitochondrial complex I deficiency, nuclear type 1, 252010 to Mitochondrial complex I deficiency, nuclear type 1, MIM#252010
Cardiomyopathy_Paediatric v1.172 NDUFS4 Zornitza Stark Publications for gene: NDUFS4 were set to
Cardiomyopathy_Paediatric v1.171 NDUFS4 Zornitza Stark edited their review of gene: NDUFS4: Changed phenotypes: Mitochondrial complex I deficiency, nuclear type 1, MIM#252010
Cardiomyopathy_Paediatric v1.171 NDUFS4 Zornitza Stark reviewed gene: NDUFS4: Rating: GREEN; Mode of pathogenicity: None; Publications: 29101127, 22326555; Phenotypes: Leigh syndrome, MONDO:0009723; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Renal Macrocystic Disease v2.0 SLC34A3 Sarah Ostrowski gene: SLC34A3 was added
gene: SLC34A3 was added to Renal Macrocystic Disease. Sources: Literature
Mode of inheritance for gene: SLC34A3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC34A3 were set to PMID: 35386604; 37981601
Phenotypes for gene: SLC34A3 were set to Hypophosphataemic rickets with hypercalciuria, (MIM#241530)
Review for gene: SLC34A3 was set to GREEN
gene: SLC34A3 was marked as current diagnostic
Added comment: PMID: 35386604: case series of individuals with hypophosphatemic rickets with
hypercalciuria AND kidney cysts, reports 4 unrelated individuals with biallelic SLC34A3 variants and multiple kidney cysts.
PMID: 37981601: another 2 HHRH patients from the same family with biallelic variants, also reported with renal cysts.
Sources: Literature
Mendeliome v2.532 CHRNA1 Lucy Spencer Mode of inheritance for gene: CHRNA1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v2.531 CHRNA1 Lucy Spencer reviewed gene: CHRNA1: Rating: GREEN; Mode of pathogenicity: None; Publications: 9158151, 8872460, 15079006; Phenotypes: Congenital myasthenic 1A slow channel MIM#601462, Congenital myasthenic 1B fast channel MIM#608930, Multiple pterygium syndrome, lethal type MIM#253290; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v2.74 MYF5 Zornitza Stark Marked gene: MYF5 as ready
Fetal anomalies v2.74 MYF5 Zornitza Stark Gene: myf5 has been classified as Green List (High Evidence).
Fetal anomalies v2.74 Zornitza Stark Copied gene MYF5 from panel Skeletal dysplasia
Fetal anomalies v2.74 MYF5 Zornitza Stark gene: MYF5 was added
gene: MYF5 was added to Fetal anomalies. Sources: Expert Review Green,Literature
Mode of inheritance for gene: MYF5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MYF5 were set to 38927634; 35186005; 32815649; 29887215
Phenotypes for gene: MYF5 were set to Ophthalmoplegia, external, with rib and vertebral anomalies, MONDO:0032565
Skeletal dysplasia v1.148 MYF5 Zornitza Stark Marked gene: MYF5 as ready
Skeletal dysplasia v1.148 MYF5 Zornitza Stark Gene: myf5 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.148 MYF5 Zornitza Stark Mode of inheritance for gene: MYF5 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 MYF5 Zornitza Stark changed review comment from: MYF5 variants are associated with skeletal malformations, including congenital scoliosis and external ophthalmoplegia with rib and vertebral anomalies (EORVA), 5 families reported.
Sources: Literature; to: MYF5 variants are associated with skeletal malformations, including congenital scoliosis and external ophthalmoplegia with rib and vertebral anomalies (EORVA), 5 families reported and a mouse model.
Sources: Literature
Skeletal dysplasia v1.147 MYF5 Zornitza Stark edited their review of gene: MYF5: Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.147 MYF5 Zornitza Stark Classified gene: MYF5 as Green List (high evidence)
Skeletal dysplasia v1.147 MYF5 Zornitza Stark Gene: myf5 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.146 MYF5 Zornitza Stark gene: MYF5 was added
gene: MYF5 was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: MYF5 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: MYF5 were set to 38927634; 35186005; 32815649; 29887215
Phenotypes for gene: MYF5 were set to Ophthalmoplegia, external, with rib and vertebral anomalies, MONDO:0032565
Review for gene: MYF5 was set to GREEN
Added comment: MYF5 variants are associated with skeletal malformations, including congenital scoliosis and external ophthalmoplegia with rib and vertebral anomalies (EORVA), 5 families reported.
Sources: Literature
Skeletal dysplasia v1.145 LARP7 Zornitza Stark Marked gene: LARP7 as ready
Skeletal dysplasia v1.145 LARP7 Zornitza Stark Gene: larp7 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.145 LARP7 Zornitza Stark Classified gene: LARP7 as Green List (high evidence)
Skeletal dysplasia v1.145 LARP7 Zornitza Stark Gene: larp7 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.144 LARP7 Zornitza Stark gene: LARP7 was added
gene: LARP7 was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: LARP7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LARP7 were set to 40129845; 37529055; 26607181; 26374271
Phenotypes for gene: LARP7 were set to microcephalic primordial dwarfism, Alazami type, MONDO:0014031
Review for gene: LARP7 was set to GREEN
Added comment: Four individuals from different families reported with biallelic LARP7 variants associated with Alazami syndrome, a microcephalic primordial dwarfism disorder characterised by severe growth failure, profound intellectual disability and distinctive facial dysmorphism; functional studies demonstrate reduced LARP7 protein expression.
Sources: Literature
Skeletal dysplasia v1.143 INTS13 Zornitza Stark Marked gene: INTS13 as ready
Skeletal dysplasia v1.143 INTS13 Zornitza Stark Gene: ints13 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.143 INTS13 Zornitza Stark Classified gene: INTS13 as Green List (high evidence)
Skeletal dysplasia v1.143 INTS13 Zornitza Stark Gene: ints13 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.142 INTS13 Zornitza Stark changed review comment from: PMID 36229431 reports 4 individuals from 2 families with autosomal recessive oral‑facial‑digital syndrome type 2 (OFD2) caused by homozygous loss‑of‑function INTS13 variants; affected individuals present with cleft lip, craniofacial dysmorphism, digital anomalies and short stature.
Sources: Literature; to: PMID 36229431 reports 4 individuals from 2 families with autosomal recessive oral‑facial‑digital syndrome type 2 (OFD2) caused by homozygous loss‑of‑function INTS13 variants; affected individuals present with cleft lip, craniofacial dysmorphism, digital anomalies and short stature. INTS13 is a subunit of the Integrator complex, which associates with RNA Polymerase II and cleaves nascent RNA to modulate gene expression. Variants segregated with disease. Depletion of INTS13 disrupts ciliogenesis in human cultured cells and causes dysregulation of a broad collection of ciliary genes. Knockdown in Xenopus embryos leads to motile cilia anomalies.
Skeletal dysplasia v1.142 INTS13 Zornitza Stark gene: INTS13 was added
gene: INTS13 was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: INTS13 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: INTS13 were set to 36229431
Phenotypes for gene: INTS13 were set to orofaciodigital syndrome, MONDO:0015375, INTS13-related
Review for gene: INTS13 was set to GREEN
Added comment: PMID 36229431 reports 4 individuals from 2 families with autosomal recessive oral‑facial‑digital syndrome type 2 (OFD2) caused by homozygous loss‑of‑function INTS13 variants; affected individuals present with cleft lip, craniofacial dysmorphism, digital anomalies and short stature.
Sources: Literature
Skeletal dysplasia v1.141 CYP3A4 Zornitza Stark Marked gene: CYP3A4 as ready
Skeletal dysplasia v1.141 CYP3A4 Zornitza Stark Gene: cyp3a4 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v1.141 CYP3A4 Zornitza Stark Classified gene: CYP3A4 as Amber List (moderate evidence)
Skeletal dysplasia v1.141 CYP3A4 Zornitza Stark Gene: cyp3a4 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v1.140 CYP3A4 Zornitza Stark Tag treatable tag was added to gene: CYP3A4.
Skeletal dysplasia v1.140 CYP3A4 Zornitza Stark gene: CYP3A4 was added
gene: CYP3A4 was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: CYP3A4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CYP3A4 were set to 38179381; 36656330; 29461981
Phenotypes for gene: CYP3A4 were set to vitamin D-dependent rickets, type 3, MONDO:0033640
Review for gene: CYP3A4 was set to AMBER
Added comment: Four families with the CYP3A4 c.902T>C (p.Ile301Thr) missense variant reported presenting with vitamin D‑dependent rickets type 3 (VDDR3), a childhood‑onset disorder characterised by rickets, growth arrest, bone deformities and accelerated vitamin D metabolite inactivation. The variant shows gain‑of‑function activity in vitro, and the disease is treatable with high‑dose vitamin D therapy.

Amber rating as all families have had the same variant. Different ethnic backgrounds make founder effect unlikely.
Sources: Literature
Skeletal dysplasia v1.139 HSPA9 Zornitza Stark changed review comment from: Biallelic variants in 4 individuals from 5 families. Significant skeletal features and marked nasal hypoplasia with mid-face hypoplasia. 2/5 with developmental delay and abnormalities of the corpus callosum 4/5 with congenital heart disease
Sources: Literature; to: Biallelic variants in 4 individuals from 5 families. Significant skeletal features and marked nasal hypoplasia with mid-face hypoplasia. 2/5 with developmental delay and abnormalities of the corpus callosum 4/5 with congenital heart disease.

Epiphyseal and vertebral abnormalities are a feature.

Sources: Literature
Skeletal dysplasia v1.139 MAP3K20 Zornitza Stark Marked gene: MAP3K20 as ready
Skeletal dysplasia v1.139 MAP3K20 Zornitza Stark Gene: map3k20 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.139 MAP3K20 Zornitza Stark Classified gene: MAP3K20 as Green List (high evidence)
Skeletal dysplasia v1.139 MAP3K20 Zornitza Stark Gene: map3k20 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.138 MAP3K20 Zornitza Stark gene: MAP3K20 was added
gene: MAP3K20 was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: MAP3K20 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: MAP3K20 were set to 39648035; 38451290; 32266845; 32266845; 26755636; 26755636
Phenotypes for gene: MAP3K20 were set to split-foot malformation-mesoaxial polydactyly syndrome, MONDO:0014816
Review for gene: MAP3K20 was set to GREEN
Added comment: Split hand‑foot malformation with ectodermal dysplasia, craniosynostosis and sensorineural hearing loss (dominant): PMID 38451290 reports five families and PMID 39648035 reports one family with de novo heterozygous MAP3K20 variants, totalling six families.

Split‑foot malformation‑mesoaxial polydactyly syndrome (recessive): PMID 26755636 describes two unrelated consanguineous families (five patients) with homozygous loss‑of‑function MAP3K20 variants.
Sources: Literature
Skeletal dysplasia v1.137 HMGB1 Zornitza Stark Marked gene: HMGB1 as ready
Skeletal dysplasia v1.137 HMGB1 Zornitza Stark Gene: hmgb1 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.137 HMGB1 Zornitza Stark Classified gene: HMGB1 as Green List (high evidence)
Skeletal dysplasia v1.137 HMGB1 Zornitza Stark Gene: hmgb1 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.136 HMGB1 Zornitza Stark gene: HMGB1 was added
gene: HMGB1 was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: HMGB1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HMGB1 were set to 36755093; 34159400
Phenotypes for gene: HMGB1 were set to brachyphalangy, polydactyly, and tibial aplasia/hypoplasia MIM#163905
Review for gene: HMGB1 was set to GREEN
Added comment: PMID 34159400 reports 1 individual with a de novo heterozygous frameshift HMGB1 variant causing severe mirror‑image foot polydactyly, a monogenic autosomal‑dominant condition.

PMID 36755093 reports 5 individuals from 5 families with de novo heterozygous frameshift HMGB1 variants causing Brachyphalangy, Polydactyly and Tibial Aplasia syndrome (BPTAS).
Sources: Literature
Skeletal dysplasia v1.135 GGCX Zornitza Stark Marked gene: GGCX as ready
Skeletal dysplasia v1.135 GGCX Zornitza Stark Gene: ggcx has been classified as Green List (High Evidence).
Skeletal dysplasia v1.135 GGCX Zornitza Stark Classified gene: GGCX as Green List (high evidence)
Skeletal dysplasia v1.135 GGCX Zornitza Stark Gene: ggcx has been classified as Green List (High Evidence).
Skeletal dysplasia v1.134 GGCX Zornitza Stark gene: GGCX was added
gene: GGCX was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: GGCX was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GGCX were set to 41521578; 41030118; 40876756; 40562611; 34558179; 26758921
Phenotypes for gene: GGCX were set to vitamin K-dependent clotting factors, combined deficiency of, type 1, MONDO:0010187
Review for gene: GGCX was set to GREEN
Added comment: Established gene-disease association. Chondrodysplasia punctata is a feature.
Sources: Literature
Skeletal dysplasia v1.133 IQCE Zornitza Stark Marked gene: IQCE as ready
Skeletal dysplasia v1.133 IQCE Zornitza Stark Gene: iqce has been classified as Green List (High Evidence).
Skeletal dysplasia v1.133 IQCE Zornitza Stark Classified gene: IQCE as Green List (high evidence)
Skeletal dysplasia v1.133 IQCE Zornitza Stark Gene: iqce has been classified as Green List (High Evidence).
Skeletal dysplasia v1.132 IQCE Zornitza Stark gene: IQCE was added
gene: IQCE was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: IQCE was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IQCE were set to 38818822; 31549751; 28488682
Phenotypes for gene: IQCE were set to postaxial polydactyly type A, MONDO:0019673
Review for gene: IQCE was set to GREEN
Added comment: Five families (ten individuals) reported with biallelic IQCE variants and postaxial polydactyly.
Sources: Literature
Skeletal dysplasia v1.131 FOXI3 Zornitza Stark Marked gene: FOXI3 as ready
Skeletal dysplasia v1.131 FOXI3 Zornitza Stark Gene: foxi3 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.131 FOXI3 Zornitza Stark Mode of inheritance for gene: FOXI3 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.130 FOXI3 Zornitza Stark edited their review of gene: FOXI3: Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.130 FOXI3 Zornitza Stark Classified gene: FOXI3 as Green List (high evidence)
Skeletal dysplasia v1.130 FOXI3 Zornitza Stark Gene: foxi3 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.129 FOXI3 Zornitza Stark gene: FOXI3 was added
gene: FOXI3 was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: FOXI3 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: FOXI3 were set to 41639043; 40128339; 37041148; 36260083
Phenotypes for gene: FOXI3 were set to craniofacial microsomia 2, MONDO:0958194
Review for gene: FOXI3 was set to GREEN
Added comment: Over 20 families reported, this is a type of mandibulofacial dysostosis.
Sources: Literature
Fetal anomalies v2.73 CPLANE2 Zornitza Stark Phenotypes for gene: CPLANE2 were changed from Ciliopathy, MONDO:0005308, RSG1-related to Ciliopathy, MONDO:0005308, CPLANE2-related
Fetal anomalies v2.72 CPLANE2 Zornitza Stark edited their review of gene: CPLANE2: Changed phenotypes: Ciliopathy, MONDO:0005308, CPLANE2-related
Clefting disorders v1.25 CPLANE2 Zornitza Stark Phenotypes for gene: CPLANE2 were changed from Ciliopathy, MONDO:0005308, RSG1-related to Ciliopathy, MONDO:0005308, CPLANE2-related
Clefting disorders v1.24 CPLANE2 Zornitza Stark edited their review of gene: CPLANE2: Changed phenotypes: Ciliopathy, MONDO:0005308, CPLANE2-related
Polydactyly v1.20 CPLANE2 Zornitza Stark Phenotypes for gene: CPLANE2 were changed from Ciliopathy, MONDO:0005308, RSG1-related to Ciliopathy, MONDO:0005308, CPLANE2-related
Polydactyly v1.19 CPLANE2 Zornitza Stark edited their review of gene: CPLANE2: Changed phenotypes: Ciliopathy, MONDO:0005308, CPLANE2-related
Mendeliome v2.531 CPLANE2 Zornitza Stark Phenotypes for gene: CPLANE2 were changed from Ciliopathy, MONDO:0005308, RSG1-related to Ciliopathy, MONDO:0005308, CPLANE2-related
Mendeliome v2.530 CPLANE2 Zornitza Stark edited their review of gene: CPLANE2: Changed phenotypes: Ciliopathy, MONDO:0005308, CPLANE2-related
Ciliopathies v2.18 CPLANE2 Zornitza Stark Phenotypes for gene: CPLANE2 were changed from Ciliopathy, MONDO:0005308, RSG1-related to Ciliopathy, MONDO:0005308, CPLANE2-related
Skeletal dysplasia v1.128 CPLANE2 Zornitza Stark Marked gene: CPLANE2 as ready
Skeletal dysplasia v1.128 CPLANE2 Zornitza Stark Gene: cplane2 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.128 CPLANE2 Zornitza Stark Classified gene: CPLANE2 as Green List (high evidence)
Skeletal dysplasia v1.128 CPLANE2 Zornitza Stark Gene: cplane2 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.127 CPLANE2 Zornitza Stark gene: CPLANE2 was added
gene: CPLANE2 was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: CPLANE2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CPLANE2 were set to 40593758; 39386566
Phenotypes for gene: CPLANE2 were set to Ciliopathy, MONDO:0005308, CPLANE2-related
Review for gene: CPLANE2 was set to GREEN
Added comment: PMID 40593758 reports three individuals from unrelated families with biallelic loss-of-function CPLANE2 variants and oral‑facial‑digital syndrome, a syndrome featuring cleft palate, tongue lobulation, pre‑ and post‑axial polydactyly, renal cystic dysplasia and occasional cardiac defects. Variant‑specific functional assays in Xenopus demonstrate disrupted basal‑body docking and impaired IFT‑A2 recruitment.

Ciliopathy with skeletal manifestations.
Sources: Literature
Ciliopathies v2.17 CPLANE2 Zornitza Stark edited their review of gene: CPLANE2: Changed phenotypes: Ciliopathy, MONDO:0005308, CPLANE2-related
Skeletal dysplasia v1.126 COPB2 Zornitza Stark Marked gene: COPB2 as ready
Skeletal dysplasia v1.126 COPB2 Zornitza Stark Gene: copb2 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.126 COPB2 Zornitza Stark Classified gene: COPB2 as Green List (high evidence)
Skeletal dysplasia v1.126 COPB2 Zornitza Stark Gene: copb2 has been classified as Green List (High Evidence).
Osteogenesis Imperfecta and Osteoporosis v2.9 COPB2 Zornitza Stark Mode of inheritance for gene: COPB2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Osteogenesis Imperfecta and Osteoporosis v2.8 COPB2 Zornitza Stark edited their review of gene: COPB2: Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.125 COPB2 Zornitza Stark gene: COPB2 was added
gene: COPB2 was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: COPB2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: COPB2 were set to 34450031
Phenotypes for gene: COPB2 were set to Osteoporosis, childhood- or juvenile-onset, with developmental delay, MIM# 619884
Review for gene: COPB2 was set to GREEN
Added comment: PMID 34450031 reports four unrelated heterozygous loss-of-function variants across four families causing early‑onset osteoporosis, fractures and developmental delay (Monoallelic). Additionally, two siblings homozygous for a missense variant in a fifth family present with microcephaly, severe developmental delay and low bone mass (Biallelic).
Sources: Literature
Fetal anomalies v2.72 ATRIP Zornitza Stark Phenotypes for gene: ATRIP were changed from Seckel Syndrome to Seckel syndrome, MONDO:0019342, ATRIP-related
Fetal anomalies v2.71 ATRIP Zornitza Stark Publications for gene: ATRIP were set to 23144622
Fetal anomalies v2.70 ATRIP Zornitza Stark Classified gene: ATRIP as Green List (high evidence)
Fetal anomalies v2.70 ATRIP Zornitza Stark Gene: atrip has been classified as Green List (High Evidence).
Growth failure v2.28 ATRIP Zornitza Stark Phenotypes for gene: ATRIP were changed from Seckel-like syndrome to Seckel syndrome, MONDO:0019342, ATRIP-related
Growth failure v2.27 ATRIP Zornitza Stark Publications for gene: ATRIP were set to 23144622
Growth failure v2.26 ATRIP Zornitza Stark Classified gene: ATRIP as Green List (high evidence)
Growth failure v2.26 ATRIP Zornitza Stark Gene: atrip has been classified as Green List (High Evidence).
Growth failure v2.25 ATRIP Zornitza Stark edited their review of gene: ATRIP: Added comment: PMID 40029331 reports 3 individuals from three families with biallelic ATRIP splice variants presenting with microcephalic primordial dwarfism and combined immunodeficiency. Affected individuals exhibit severe intrauterine growth restriction, post‑natal short stature, microcephaly and recurrent infections.; Changed rating: GREEN; Changed publications: 23144622, 40029331; Changed phenotypes: Seckel syndrome, MONDO:0019342, ATRIP-related
Microcephaly v2.31 ATRIP Zornitza Stark Phenotypes for gene: ATRIP were changed from Seckel Syndrome to Seckel syndrome, MONDO:0019342, ATRIP-related
Microcephaly v2.30 ATRIP Zornitza Stark Publications for gene: ATRIP were set to 23144622
Microcephaly v2.29 ATRIP Zornitza Stark Classified gene: ATRIP as Green List (high evidence)
Microcephaly v2.29 ATRIP Zornitza Stark Gene: atrip has been classified as Green List (High Evidence).
Mendeliome v2.530 ATRIP Zornitza Stark Publications for gene: ATRIP were set to 23144622
Mendeliome v2.529 ATRIP Zornitza Stark Classified gene: ATRIP as Green List (high evidence)
Mendeliome v2.529 ATRIP Zornitza Stark Gene: atrip has been classified as Green List (High Evidence).
Microcephaly v2.28 Zornitza Stark Added reviews for gene ATRIP from panel Skeletal dysplasia
Mendeliome v2.528 Zornitza Stark Added reviews for gene ATRIP from panel Skeletal dysplasia
Growth failure v2.25 Zornitza Stark Added reviews for gene ATRIP from panel Skeletal dysplasia
Fetal anomalies v2.69 Zornitza Stark Added reviews for gene ATRIP from panel Skeletal dysplasia
Skeletal dysplasia v1.124 ATRIP Zornitza Stark Marked gene: ATRIP as ready
Skeletal dysplasia v1.124 ATRIP Zornitza Stark Gene: atrip has been classified as Green List (High Evidence).
Skeletal dysplasia v1.124 ATRIP Zornitza Stark Classified gene: ATRIP as Green List (high evidence)
Skeletal dysplasia v1.124 ATRIP Zornitza Stark Gene: atrip has been classified as Green List (High Evidence).
Skeletal dysplasia v1.123 ATRIP Zornitza Stark gene: ATRIP was added
gene: ATRIP was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: ATRIP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATRIP were set to 40029331
Phenotypes for gene: ATRIP were set to Seckel syndrome, MONDO:0019342, ATRIP-related
Review for gene: ATRIP was set to GREEN
Added comment: PMID 40029331 reports 3 individuals from three families with biallelic ATRIP splice variants presenting with microcephalic primordial dwarfism and combined immunodeficiency. Affected individuals exhibit severe intrauterine growth restriction, post‑natal short stature, microcephaly and recurrent infections.
Sources: Literature
Skeletal dysplasia v1.122 ASAH1 Zornitza Stark changed review comment from: Farber lipogranulomatosis is an autosomal recessive lysosomal storage disorder characterized by early-onset subcutaneous nodules, painful and progressively deformed joints, and hoarseness by laryngeal involvement. Based on the age of onset, the severity of symptoms, and the difference in organs affected, 6 clinical subtypes due to deficiency of acid ceramidase have been distinguished. The most severe form is subtype 4, a rare neonatal form of the disease with death occurring before 1 year of age.

Severe perinatal disorder.; to: Farber lipogranulomatosis is an autosomal recessive lysosomal storage disorder characterized by early-onset subcutaneous nodules, painful and progressively deformed joints, and hoarseness by laryngeal involvement. Based on the age of onset, the severity of symptoms, and the difference in organs affected, 6 clinical subtypes due to deficiency of acid ceramidase have been distinguished. The most severe form is subtype 4, a rare neonatal form of the disease with death occurring before 1 year of age.

Severe perinatal disorder.

Peripheral osteolysis is a feature.
Paraganglioma_phaeochromocytoma v2.1 MAX Zornitza Stark Phenotypes for gene: MAX were changed from Paraganglioma, MONDO:0000448; Pheochromocytoma, MONDO:0008233; Hereditary pheochromocytoma-paraganglioma, MONDO:0017366; Pheochromocytoma, susceptibility to, MIM#171300 to Multiple endocrine neoplasia, type V, MIM# 621678
Paraganglioma_phaeochromocytoma v2.0 MAX Zornitza Stark reviewed gene: MAX: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Multiple endocrine neoplasia, type V, MIM# 621678; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genomic newborn screening: BabyScreen+ v2.4 MAX Zornitza Stark edited their review of gene: MAX: Changed phenotypes: Multiple endocrine neoplasia, type V, MIM# 621678; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genomic newborn screening: BabyScreen+ v2.4 MAX Zornitza Stark Mode of inheritance for gene: MAX was changed from BIALLELIC, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genomic newborn screening: BabyScreen+ v2.3 MAX Zornitza Stark Marked gene: MAX as ready
Genomic newborn screening: BabyScreen+ v2.3 MAX Zornitza Stark Gene: max has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v2.3 MAX Zornitza Stark Phenotypes for gene: MAX were changed from to Multiple endocrine neoplasia, type V, MIM# 621678
Genomic newborn screening: BabyScreen+ v2.2 MAX Zornitza Stark Classified gene: MAX as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v2.2 MAX Zornitza Stark Gene: max has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v2.1 MAX Zornitza Stark Tag TRAIL study tag was added to gene: MAX.
Genomic newborn screening: BabyScreen+ v2.1 MAX Zornitza Stark reviewed gene: MAX: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Additional findings_Adult v3.1 MAX Zornitza Stark Phenotypes for gene: MAX were changed from {Pheochromocytoma, susceptibility to} 171300 to Multiple endocrine neoplasia, type V, MIM# 621678
Additional findings_Adult v3.0 MAX Zornitza Stark edited their review of gene: MAX: Changed phenotypes: Multiple endocrine neoplasia, type V, MIM# 621678
Cancer Predisposition_Paediatric v1.2 MAX Zornitza Stark Phenotypes for gene: MAX were changed from {Pheochromocytoma, susceptibility to}, MIM# 171300 to Multiple endocrine neoplasia, type V, MIM# 621678
Cancer Predisposition_Paediatric v1.1 MAX Zornitza Stark Classified gene: MAX as Red List (low evidence)
Cancer Predisposition_Paediatric v1.1 MAX Zornitza Stark Gene: max has been classified as Red List (Low Evidence).
Cancer Predisposition_Paediatric v1.0 MAX Zornitza Stark edited their review of gene: MAX: Changed phenotypes: Multiple endocrine neoplasia, type V, MIM# 621678
Mendeliome v2.527 MAX Zornitza Stark Phenotypes for gene: MAX were changed from {Pheochromocytoma, susceptibility to}, MIM# 171300; Polydactyly-macrocephaly syndrome, MIM# 620712 to Multiple endocrine neoplasia, type V, MIM# 621678; Polydactyly-macrocephaly syndrome, MIM# 620712
Mendeliome v2.526 MAX Zornitza Stark edited their review of gene: MAX: Changed phenotypes: Multiple endocrine neoplasia, type V, MIM# 621678
Fetal anomalies v2.68 CDK20 Zornitza Stark Phenotypes for gene: CDK20 were changed from Ciliopathy, MONDO:0005308, CDK20-related to Lemire-Marshall-Drivas-Chitayat syndrome, MIM# 621676
Fetal anomalies v2.67 CDK20 Zornitza Stark edited their review of gene: CDK20: Changed phenotypes: Lemire-Marshall-Drivas-Chitayat syndrome, MIM# 621676
Clefting disorders v1.24 CDK20 Zornitza Stark Phenotypes for gene: CDK20 were changed from Ciliopathy, MONDO:0005308, CDK20-related to Lemire-Marshall-Drivas-Chitayat syndrome, MIM# 621676
Clefting disorders v1.23 CDK20 Zornitza Stark edited their review of gene: CDK20: Changed phenotypes: Lemire-Marshall-Drivas-Chitayat syndrome, MIM# 621676
Polydactyly v1.19 CDK20 Zornitza Stark Phenotypes for gene: CDK20 were changed from Ciliopathy, MONDO:0005308, CDK20-related to Lemire-Marshall-Drivas-Chitayat syndrome, MIM# 621676
Polydactyly v1.18 CDK20 Zornitza Stark edited their review of gene: CDK20: Changed phenotypes: Lemire-Marshall-Drivas-Chitayat syndrome, MIM# 621676
Mendeliome v2.526 CDK20 Zornitza Stark Phenotypes for gene: CDK20 were changed from Ciliopathy, MONDO:0005308, CDK20-related to Lemire-Marshall-Drivas-Chitayat syndrome, MIM# 621676
Mendeliome v2.525 CDK20 Zornitza Stark edited their review of gene: CDK20: Changed phenotypes: Lemire-Marshall-Drivas-Chitayat syndrome, MIM# 621676
Hydrocephalus_Ventriculomegaly v1.13 CDK20 Zornitza Stark Phenotypes for gene: CDK20 were changed from Ciliopathy, MONDO:0005308, CDK20-related to Lemire-Marshall-Drivas-Chitayat syndrome, MIM# 621676
Hydrocephalus_Ventriculomegaly v1.12 CDK20 Zornitza Stark edited their review of gene: CDK20: Changed phenotypes: Lemire-Marshall-Drivas-Chitayat syndrome, MIM# 621676
Ciliopathies v2.17 CDK20 Zornitza Stark Phenotypes for gene: CDK20 were changed from Ciliopathy, MONDO:0005308, CDK20-related to Lemire-Marshall-Drivas-Chitayat syndrome, MIM# 621676
Ciliopathies v2.16 CDK20 Zornitza Stark edited their review of gene: CDK20: Changed phenotypes: Lemire-Marshall-Drivas-Chitayat syndrome, MIM# 621676
Anophthalmia_Microphthalmia_Coloboma v2.7 CDK20 Zornitza Stark Phenotypes for gene: CDK20 were changed from Ciliopathy, MONDO:0005308, CDK20-related to Lemire-Marshall-Drivas-Chitayat syndrome, MIM# 621676
Anophthalmia_Microphthalmia_Coloboma v2.6 CDK20 Zornitza Stark edited their review of gene: CDK20: Changed phenotypes: Lemire-Marshall-Drivas-Chitayat syndrome, MIM# 621676
Cardiomyopathy_Paediatric v1.171 ETFB Eleanor Ludington reviewed gene: ETFB: Rating: RED; Mode of pathogenicity: None; Publications: 27081516; Phenotypes: multiple acyl-CoA dehydrogenase deficiency, MONDO:0009282; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v1.171 DNAJC19 Eleanor Ludington reviewed gene: DNAJC19: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 34580891, 35611801, 27928778, 38283849; Phenotypes: 3-methylglutaconic aciduria type 5, MONDO:0012435, 3-methylgutaconic aciduria, type V, OMIM:610198; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v1.171 EMD Lucy Spencer Mode of inheritance for gene: EMD was changed from X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Cardiomyopathy_Paediatric v1.170 EMD Lucy Spencer Phenotypes for gene: EMD were changed from Emery-Dreifuss muscular dystrophy 1, X-linked, 310300 to Emery-Dreifuss muscular dystrophy 1, X-linked, MIM#310300
Cardiomyopathy_Paediatric v1.169 EMD Lucy Spencer reviewed gene: EMD: Rating: GREEN; Mode of pathogenicity: None; Publications: 42047848, 37639473; Phenotypes: Emery-Dreifuss muscular dystrophy 1, X-linked MIM#310300; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Cardiomyopathy_Paediatric v1.169 SGSH Lucy Spencer Phenotypes for gene: SGSH were changed from Mucopolysaccharidosis Type IIIA; Mucopolysaccharidosis Type III; MUCOPOLYSACCHARIDOSIS TYPE 3A; MPS IIIA, Sanfilippo A disease (Mucopolysaccharidoses); Mucopolysaccharidosis, Type III to Mucopolysaccharidosis type IIIA (Sanfilippo A) MIM#252900
Cardiomyopathy_Paediatric v1.168 SGSH Lucy Spencer Publications for gene: SGSH were set to 27604308
Cardiomyopathy_Paediatric v1.167 SGSH Lucy Spencer reviewed gene: SGSH: Rating: AMBER; Mode of pathogenicity: None; Publications: 2789611:40160092; Phenotypes: Mucopolysaccharidosis type IIIA (Sanfilippo A) MIM#252900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Neuropathy v2.39 NDUFS6 Sangavi Sivagnanasundram Classified gene: NDUFS6 as Green List (high evidence)
Hereditary Neuropathy v2.39 NDUFS6 Sangavi Sivagnanasundram Gene: ndufs6 has been classified as Green List (High Evidence).
Hereditary Neuropathy v2.38 NDUFS6 Sangavi Sivagnanasundram gene: NDUFS6 was added
gene: NDUFS6 was added to Hereditary Neuropathy. Sources: Literature
Mode of inheritance for gene: NDUFS6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NDUFS6 were set to 41683799; 38549004; 38459834; 38217609
Phenotypes for gene: NDUFS6 were set to peripheral neuropathy MONDO:0020127
Review for gene: NDUFS6 was set to GREEN
Added comment: >3 unrelated individuals with biallelic variants in NDUFS6 presenting with various neurological phenotypes with peripheral neuropathy as a presenting feature.
Note: 38459834 reports homozygous c.309+5G>A in 5 individuals from 3 families.
Sources: Literature
Hereditary Neuropathy v2.37 NFASC Sangavi Sivagnanasundram Classified gene: NFASC as Amber List (moderate evidence)
Hereditary Neuropathy v2.37 NFASC Sangavi Sivagnanasundram Gene: nfasc has been classified as Amber List (Moderate Evidence).
Hereditary Neuropathy v2.36 NFASC Sangavi Sivagnanasundram gene: NFASC was added
gene: NFASC was added to Hereditary Neuropathy. Sources: Literature
Mode of inheritance for gene: NFASC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NFASC were set to 31501903
Phenotypes for gene: NFASC were set to neurodevelopmental disorder with central and peripheral motor dysfunction, MONDO:0032698
Review for gene: NFASC was set to AMBER
Added comment: 3 individuals from 2 families (one family is consanguineous) reported with neurodevelopmental disorder and peripheral neuropathy as a presenting feature.
Sources: Literature
Hereditary Neuropathy v2.35 SPG7 Sangavi Sivagnanasundram Publications for gene: SPG7 were set to 41062329; 40824590; 38549004; 37983191; 35348942; 32999401
Hereditary Neuropathy v2.34 SPG7 Sangavi Sivagnanasundram gene: SPG7 was added
gene: SPG7 was added to Hereditary Neuropathy. Sources: Literature
Mode of inheritance for gene: SPG7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SPG7 were set to 41062329; 40824590; 38549004; 37983191; 35348942; 32999401
Phenotypes for gene: SPG7 were set to hereditary spastic paraplegia 7, MONDO:0011803
Review for gene: SPG7 was set to RED
Added comment: 35348942 - 1/5 individuals with biallelic variant in SPG7 and peripheral neuropathy as a presenting feature

38549004 - reports two individuals with biallelic variants in SPG7. Affected individuals had peripheral neuropathy as a presenting feature

Note, the reported variants in these publications do have a high FAF in gnomAD v4.1. Rated Red given the population frequencies in gnomAD
Sources: Literature
Hereditary Neuropathy v2.33 PIGG Sangavi Sivagnanasundram Classified gene: PIGG as Green List (high evidence)
Hereditary Neuropathy v2.33 PIGG Sangavi Sivagnanasundram Gene: pigg has been classified as Green List (High Evidence).
Hereditary Neuropathy v2.32 PIGG Sangavi Sivagnanasundram gene: PIGG was added
gene: PIGG was added to Hereditary Neuropathy. Sources: Literature
Mode of inheritance for gene: PIGG was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PIGG were set to 41744056; 39444079
Phenotypes for gene: PIGG were set to PIGG-related hereditary neuropathy MONDO:0002316
Review for gene: PIGG was set to GREEN
Added comment: PMID 39444079 reports 7 individuals from 6 families with neurological/neuromuscular phenotype including distal hereditary motor neuropathy, motor conduction block, childhood tremor, febrile seizures and mild cerebellar signs, all harbouring biallelic loss‑of‑function PIGG variants (including the recurrent p.Trp505* and missense Val339Gly, Gly19Glu). The affected individuals were reported to have a milder neuropathy phenotype as per their NCS results.

PMID 41744056 reports a 27‑year‑old woman with adolescent‑onset motor neuropathy, myokymia and gait ataxia carrying a homozygous nonsense PIGG variant (p.Trp505* - this variant has a FAF of 0.1% in gnomADv4.1 however appears to be a recurrent variant reported in multiple individuals in the literature).
Sources: Literature
Congenital Disorders of Glycosylation v2.2 PIGB Zornitza Stark Tag founder tag was added to gene: PIGB.
Defects of intrinsic and innate immunity v2.3 IRAK2 Zornitza Stark Publications for gene: IRAK2 were set to PMID: 39299377
Defects of intrinsic and innate immunity v2.2 IRAK2 Zornitza Stark Mode of inheritance for gene: IRAK2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Defects of intrinsic and innate immunity v2.1 IRAK2 Zornitza Stark Classified gene: IRAK2 as Amber List (moderate evidence)
Defects of intrinsic and innate immunity v2.1 IRAK2 Zornitza Stark Gene: irak2 has been classified as Amber List (Moderate Evidence).
Defects of intrinsic and innate immunity v2.0 IRAK2 Zornitza Stark edited their review of gene: IRAK2: Added comment: PMID 42168171 reports 12 individuals from 11 unrelated Chinese families with a spectrum of complex immunologic disorders who all had the same homozygous variant in the IRAK2 gene identified by whole-exome or whole-genome sequencing. The individuals could be categorized into 3 phenotypic subgroups: immunodeficiency-predominant (P1 and P2), autoimmunity-predominant (P3-P7, P11, and P12), and autoinflammation-predominant (P8-P10). The variant is a homozygous 183-bp deletion (c.95_277del, NM_001570), resulting in an in-frame deletion of exon 2 along with portions of the flanking intronic regions (Ala32_Trp93delinsGly). Variant is relatively common in East Asian individuals, including 2 homozygotes in gnomAD.; Changed rating: AMBER; Changed publications: 42168171; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Autoinflammatory Disorders v3.17 IRAK2 Zornitza Stark Publications for gene: IRAK2 were set to PMID: 39299377
Autoinflammatory Disorders v3.16 IRAK2 Zornitza Stark Mode of inheritance for gene: IRAK2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Autoinflammatory Disorders v3.15 IRAK2 Zornitza Stark Classified gene: IRAK2 as Amber List (moderate evidence)
Autoinflammatory Disorders v3.15 IRAK2 Zornitza Stark Gene: irak2 has been classified as Amber List (Moderate Evidence).
Autoinflammatory Disorders v3.14 IRAK2 Zornitza Stark edited their review of gene: IRAK2: Added comment: PMID 42168171 reports 12 individuals from 11 unrelated Chinese families with a spectrum of complex immunologic disorders who all had the same homozygous variant in the IRAK2 gene identified by whole-exome or whole-genome sequencing. The individuals could be categorized into 3 phenotypic subgroups: immunodeficiency-predominant (P1 and P2), autoimmunity-predominant (P3-P7, P11, and P12), and autoinflammation-predominant (P8-P10). The variant is a homozygous 183-bp deletion (c.95_277del, NM_001570), resulting in an in-frame deletion of exon 2 along with portions of the flanking intronic regions (Ala32_Trp93delinsGly). Variant is relatively common in East Asian individuals, including 2 homozygotes in gnomAD.; Changed rating: AMBER; Changed publications: 42168171; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Imprinting disorders v2.1 Sarah Milton Copied Region ISCA-37447-Loss from panel Intellectual disability syndromic and non-syndromic
Imprinting disorders v2.1 ISCA-37447-Loss Sarah Milton Region: ISCA-37447-Loss was added
Region: ISCA-37447-Loss was added to Imprinting disorders. Sources: ClinGen,Expert Review Green,Expert Review Green,ClinGen
SV/CNV tags were added to Region: ISCA-37447-Loss.
Mode of inheritance for Region: ISCA-37447-Loss was set to MONOALLELIC, autosomal or pseudoautosomal, maternally imprinted (paternal allele expressed)
Publications for Region: ISCA-37447-Loss were set to 41926606; 39446997
Phenotypes for Region: ISCA-37447-Loss were set to Temple syndrome MIM#616222; Kagami-Ogata syndrome MIM#608149
Cardiomyopathy_Paediatric v1.167 DMD Richard Lin changed review comment from: Dystrophin gene mutations are associated with X-linked progressive muscular dystrophy, including Duchenne Muscular Dystrophy (DMD) and Becker Muscular Dystrophy (BMD). Cardiomyopathy is a feature of the disease, and results from dystrophin deficiency in the heart (PMID: 29395990).

The age of onset of cardiomyopathy is reported to be in the mid teens in boys with DMD, with a range of onset from 10-21 years (PMID: 16246949, 27230049). Children with very large deletions or following an episode of viral myocarditis have been reported to develop earlier onset LV dysfunction (PMID: 36252992).

A proportion of female dystrophinopathy carriers are also at risk of cardiomyopathy with or without skeletal muscle disease (PMID: 29395990), though there are limited reports of paediatric onset cardiomyopathy. Dilated cardiomyopathy was diagnosed in 1 out of 24 female carriers of DCM aged between 5 and 15 years. In a cohort study, cardiac hypertrophy was diagnosed in 2 out of 24 female DMD carriers, and 2 out of 9 BMD carriers (PMID: 8614119).; to: Dystrophin gene mutations are associated with X-linked progressive muscular dystrophy, including Duchenne Muscular Dystrophy (DMD) and Becker Muscular Dystrophy (BMD). Cardiomyopathy is a feature of the disease, and results from dystrophin deficiency in the heart (PMID: 29395990).

The age of onset of cardiomyopathy is reported to be in the mid teens in boys with DMD, with a range of onset from 10-21 years (PMID: 16246949, 27230049). Children with very large deletions or following an episode of viral myocarditis have been reported to develop earlier onset LV dysfunction (PMID: 36252992).

A proportion of female dystrophinopathy carriers are also at risk of cardiomyopathy with or without skeletal muscle disease (PMID: 29395990), though there are limited reports of paediatric onset cardiomyopathy. In a cohort study, dilated cardiomyopathy was diagnosed in 1 out of 24 female carriers of DCM aged between 5 and 15 years. Cardiac hypertrophy was diagnosed in 2 out of 24 female DMD carriers, and 2 out of 9 BMD carriers in the same cohort (PMID: 8614119).
Cardiomyopathy_Paediatric v1.167 TMEM70 Richard Lin changed review comment from: Biallelic pathogenic variants in TMEM70 are associated with mitochondrial disease (ClinGen curation classified as definitive association). Paediatric onset cardiomyopathy, predominantly hypertrophic, and less commonly left ventricular noncompaction is well described.

PMID: 20335238 - Hypertrophic cardiomyopathy found in 76% (19/25 patients from 16 families) of neonatal onset TMEM70 associated ATP synthase deficiency. Twenty-four patients were homozygous for the c.317-2A>G mutation in the TMEM70 gene and one patient was compound heterozygote for c.[317-2A>G];[118_119insGT].
PMID: 26550569 - 4 affected sibs from one family with paediatric onset disease including noncompaction cardiomyopathy, 3 affected were homozygotes for TMEM70:c.317-2A>G, remaining affected child was not genotyped.
PMID: 27649480 - single case report of a male child who was homozygous for c.317-2A>G, diagnosed with neonatal onset hypertrophic cardiomyopathy.
PMID: 30899493 - infantile onset left ventricular noncompaction, compound heterozygous for a frameshift and a splice site variant c.[141delG];[316+1G>A]
PMID: 30950220 - 2 affected siblings who were homozygous for a frameshift variant c.105dupT (p.Val36Cysfs*52). Both were noted to have cardiac hypertrophy during antenatal fetal echocardiography.
PMID: 31729175 - 1 affected child who was homozygous for c.317-2A>G with dilated cardiomyopathy AND non compaction
PMID: 36751706 - 1 affected child with neonatal onset hyerptrophic cardiomyopathy and left ventricular non compaction, aortic dilatation. Homozygous for a missense VUS c.563T>C, p.(Leu188Pro), asserted by authors to be pathogenic based on a consistent metabolomic profile.; to: Biallelic pathogenic variants in TMEM70 are associated with mitochondrial disease (ClinGen curation classified as definitive association). Paediatric onset cardiomyopathy, predominantly hypertrophic, and less commonly left ventricular noncompaction is well described.

PMID: 20335238 - Hypertrophic cardiomyopathy found in 76% (19/25 patients from 16 families) of neonatal onset TMEM70 associated ATP synthase deficiency. All except one patient were homozygous for the c.317-2A>G mutation in the TMEM70 gene, with the remaining patient being compound heterozygote for c.[317-2A>G];[118_119insGT].
PMID: 26550569 - 4 affected sibs from one family with paediatric onset disease including noncompaction cardiomyopathy, 3 affected were homozygotes for TMEM70:c.317-2A>G, remaining affected child was not genotyped.
PMID: 27649480 - single case report of a male child who was homozygous for c.317-2A>G, diagnosed with neonatal onset hypertrophic cardiomyopathy.
PMID: 30899493 - infantile onset left ventricular noncompaction, compound heterozygous for a frameshift and a splice site variant c.[141delG];[316+1G>A]
PMID: 30950220 - 2 affected siblings who were homozygous for a frameshift variant c.105dupT (p.Val36Cysfs*52). Both were noted to have cardiac hypertrophy during antenatal fetal echocardiography.
PMID: 31729175 - 1 affected child who was homozygous for c.317-2A>G with dilated cardiomyopathy AND non compaction
PMID: 36751706 - 1 affected child with neonatal onset hyerptrophic cardiomyopathy and left ventricular non compaction, aortic dilatation. Homozygous for a missense VUS c.563T>C, p.(Leu188Pro), asserted by authors to be pathogenic based on a consistent metabolomic profile.
Mendeliome v2.525 IRAK2 Zornitza Stark Phenotypes for gene: IRAK2 were changed from Immune dysregulation, MONDO:0957790, IRAK2-related to Immune dysregulation with autoimmunity, autoinflammation, and immunodeficiency, MIM# 621671
Mendeliome v2.524 IRAK2 Zornitza Stark edited their review of gene: IRAK2: Changed phenotypes: Immune dysregulation with autoimmunity, autoinflammation, and immunodeficiency, MIM# 621671
Mendeliome v2.524 IRAK2 Zornitza Stark Publications for gene: IRAK2 were set to PMID: 39299377
Mendeliome v2.523 IRAK2 Zornitza Stark Mode of inheritance for gene: IRAK2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v2.522 IRAK2 Zornitza Stark Classified gene: IRAK2 as Amber List (moderate evidence)
Mendeliome v2.522 IRAK2 Zornitza Stark Gene: irak2 has been classified as Amber List (Moderate Evidence).
Mendeliome v2.521 IRAK2 Zornitza Stark Tag founder tag was added to gene: IRAK2.
Mendeliome v2.521 IRAK2 Zornitza Stark edited their review of gene: IRAK2: Added comment: PMID 42168171 reports 12 individuals from 11 unrelated Chinese families with a spectrum of complex immunologic disorders who all had the same homozygous variant in the IRAK2 gene identified by whole-exome or whole-genome sequencing. The individuals could be categorized into 3 phenotypic subgroups: immunodeficiency-predominant (P1 and P2), autoimmunity-predominant (P3-P7, P11, and P12), and autoinflammation-predominant (P8-P10). The variant is a homozygous 183-bp deletion (c.95_277del, NM_001570), resulting in an in-frame deletion of exon 2 along with portions of the flanking intronic regions (Ala32_Trp93delinsGly). Variant is relatively common in East Asian individuals, including 2 homozygotes in gnomAD.; Changed rating: AMBER; Changed publications: 42168171; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v2.521 Sarah Milton Copied Region ISCA-37447-Loss from panel Common deletion and duplication syndromes
Mendeliome v2.521 ISCA-37447-Loss Sarah Milton Region: ISCA-37447-Loss was added
Region: ISCA-37447-Loss was added to Mendeliome. Sources: Expert Review Green,ClinGen
SV/CNV tags were added to Region: ISCA-37447-Loss.
Mode of inheritance for Region: ISCA-37447-Loss was set to MONOALLELIC, autosomal or pseudoautosomal, maternally imprinted (paternal allele expressed)
Publications for Region: ISCA-37447-Loss were set to 41926606; 39446997
Phenotypes for Region: ISCA-37447-Loss were set to Temple syndrome MIM#616222; Kagami-Ogata syndrome MIM#608149
Intellectual disability syndromic and non-syndromic v2.133 Sarah Milton Copied Region ISCA-37447-Loss from panel Common deletion and duplication syndromes
Intellectual disability syndromic and non-syndromic v2.133 ISCA-37447-Loss Sarah Milton Region: ISCA-37447-Loss was added
Region: ISCA-37447-Loss was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Green,ClinGen
SV/CNV tags were added to Region: ISCA-37447-Loss.
Mode of inheritance for Region: ISCA-37447-Loss was set to MONOALLELIC, autosomal or pseudoautosomal, maternally imprinted (paternal allele expressed)
Publications for Region: ISCA-37447-Loss were set to 41926606; 39446997
Phenotypes for Region: ISCA-37447-Loss were set to Temple syndrome MIM#616222; Kagami-Ogata syndrome MIM#608149
Growth failure v2.24 Sarah Milton Copied Region ISCA-37447-Loss from panel Common deletion and duplication syndromes
Growth failure v2.24 ISCA-37447-Loss Sarah Milton Region: ISCA-37447-Loss was added
Region: ISCA-37447-Loss was added to Growth failure. Sources: Expert Review Green,ClinGen
SV/CNV tags were added to Region: ISCA-37447-Loss.
Mode of inheritance for Region: ISCA-37447-Loss was set to MONOALLELIC, autosomal or pseudoautosomal, maternally imprinted (paternal allele expressed)
Publications for Region: ISCA-37447-Loss were set to 41926606; 39446997
Phenotypes for Region: ISCA-37447-Loss were set to Temple syndrome MIM#616222; Kagami-Ogata syndrome MIM#608149
Fetal anomalies v2.67 Sarah Milton Copied Region ISCA-37447-Loss from panel Common deletion and duplication syndromes
Fetal anomalies v2.67 ISCA-37447-Loss Sarah Milton Region: ISCA-37447-Loss was added
Region: ISCA-37447-Loss was added to Fetal anomalies. Sources: Expert Review Green,ClinGen
SV/CNV tags were added to Region: ISCA-37447-Loss.
Mode of inheritance for Region: ISCA-37447-Loss was set to MONOALLELIC, autosomal or pseudoautosomal, maternally imprinted (paternal allele expressed)
Publications for Region: ISCA-37447-Loss were set to 41926606; 39446997
Phenotypes for Region: ISCA-37447-Loss were set to Temple syndrome MIM#616222; Kagami-Ogata syndrome MIM#608149
Common deletion and duplication syndromes v1.7 ISCA-37447-Loss Sarah Milton Marked Region: ISCA-37447-Loss as ready
Common deletion and duplication syndromes v1.7 ISCA-37447-Loss Sarah Milton Region: isca-37447-loss has been classified as Green List (High Evidence).
Common deletion and duplication syndromes v1.7 ISCA-37447-Loss Sarah Milton Classified Region: ISCA-37447-Loss as Green List (high evidence)
Common deletion and duplication syndromes v1.7 ISCA-37447-Loss Sarah Milton Region: isca-37447-loss has been classified as Green List (High Evidence).
Common deletion and duplication syndromes v1.6 ISCA-37447-Loss Sarah Milton Region: ISCA-37447-Loss was added
Region: ISCA-37447-Loss was added to Common deletion and duplication syndromes. Sources: ClinGen
SV/CNV tags were added to Region: ISCA-37447-Loss.
Mode of inheritance for Region: ISCA-37447-Loss was set to MONOALLELIC, autosomal or pseudoautosomal, maternally imprinted (paternal allele expressed)
Publications for Region: ISCA-37447-Loss were set to 41926606; 39446997
Phenotypes for Region: ISCA-37447-Loss were set to Temple syndrome MIM#616222; Kagami-Ogata syndrome MIM#608149
Review for Region: ISCA-37447-Loss was set to GREEN
Added comment: This entry defines a region on chromosome 14 associated with Temple syndrome and Kagami Ogata syndrome.
This syndromes are typically caused by maternal UPD or paternal UPD of chromosome 14 respectively.

The defined region in this entry contains MEG3 - long non coding RNA, maternally expressed.
DLK1 - paternally expressed protein coding gene which is an epidermal growth factor

This region is imprinted with maternal deletions resulting in Kagami Ogata syndrome and paternal deletions resulting in Temple syndrome.

Other causes of these syndromes include abnormal methylation of MEG3/DLK1 DMR or MEG3::TSS-DMR.
Sources: ClinGen
Hereditary Neuropathy v2.31 GNE Sangavi Sivagnanasundram Classified gene: GNE as Amber List (moderate evidence)
Hereditary Neuropathy v2.31 GNE Sangavi Sivagnanasundram Gene: gne has been classified as Amber List (Moderate Evidence).
Hereditary Neuropathy v2.30 GNE Sangavi Sivagnanasundram gene: GNE was added
gene: GNE was added to Hereditary Neuropathy. Sources: Literature
Mode of inheritance for gene: GNE was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GNE were set to 33094863
Phenotypes for gene: GNE were set to GNE-related motor neuropathy MONDO:0100546
Review for gene: GNE was set to AMBER
Added comment: PMID 33094863 reports two unrelated individuals from two unrelated families (one consanguineous) with adult‑onset progressive motor axonal neuropathy carrying rare biallelic GNE missense variants.
Sources: Literature
Cardiomyopathy_Paediatric v1.167 AGL Sarah Milton reviewed gene: AGL: Rating: GREEN; Mode of pathogenicity: None; Publications: 27106217; Phenotypes: Glycogen storage disease IIIa and IIIb, MIM#232400; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v1.167 ACADVL Sarah Milton reviewed gene: ACADVL: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301763; Phenotypes: VLCAD deficiency, MIM#201475; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v1.167 DMD Richard Lin reviewed gene: DMD: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 8614119, 16246949, 27230049, 29395990, 36252992; Phenotypes: Becker muscular dystrophy, MIM:300376, Cardiomyopathy, dilated, 3B, MIM:302045, Duchenne muscular dystrophy, MIM: 310200; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Cardiomyopathy_Paediatric v1.167 TMEM43 Sarah Milton reviewed gene: TMEM43: Rating: GREEN; Mode of pathogenicity: None; Publications: 18313022, 26840987; Phenotypes: Arrhythmogenic right ventricular dysplasia 5, MIM#604400; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hand and foot malformations v1.10 FAT1 Zornitza Stark reviewed gene: FAT1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Mendeliome v2.520 AFF3 Zornitza Stark Publications for gene: AFF3 were set to 31388108; 33961779
Intellectual disability syndromic and non-syndromic v2.132 AFF3 Zornitza Stark Publications for gene: AFF3 were set to 31388108; 33961779
Mendeliome v2.519 GLYR1 Zornitza Stark Marked gene: GLYR1 as ready
Mendeliome v2.519 GLYR1 Zornitza Stark Gene: glyr1 has been classified as Amber List (Moderate Evidence).
Congenital Heart Defect v1.35 GLYR1 Zornitza Stark Marked gene: GLYR1 as ready
Congenital Heart Defect v1.35 GLYR1 Zornitza Stark Gene: glyr1 has been classified as Amber List (Moderate Evidence).
Mendeliome v2.519 ATP5ME Zornitza Stark Marked gene: ATP5ME as ready
Mendeliome v2.519 ATP5ME Zornitza Stark Gene: atp5me has been classified as Amber List (Moderate Evidence).
Mitochondrial disease v2.7 ATP5ME Zornitza Stark Marked gene: ATP5ME as ready
Mitochondrial disease v2.7 ATP5ME Zornitza Stark Gene: atp5me has been classified as Amber List (Moderate Evidence).
Mendeliome v2.519 PREX1 Zornitza Stark Marked gene: PREX1 as ready
Mendeliome v2.519 PREX1 Zornitza Stark Gene: prex1 has been classified as Red List (Low Evidence).
Autism v1.18 PREX1 Zornitza Stark Marked gene: PREX1 as ready
Autism v1.18 PREX1 Zornitza Stark Gene: prex1 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v2.131 PREX1 Zornitza Stark Marked gene: PREX1 as ready
Intellectual disability syndromic and non-syndromic v2.131 PREX1 Zornitza Stark Gene: prex1 has been classified as Red List (Low Evidence).
Cardiomyopathy_Paediatric v1.167 FASTKD2 Zornitza Stark Marked gene: FASTKD2 as ready
Cardiomyopathy_Paediatric v1.167 FASTKD2 Zornitza Stark Gene: fastkd2 has been classified as Red List (Low Evidence).
Cardiomyopathy_Paediatric v1.167 FASTKD2 Zornitza Stark Phenotypes for gene: FASTKD2 were changed from ?Mitochondrial complex IV deficiency, 220110 to FASTKD2-related infantile mitochondrial encephalomyopathy, MONDO:0015632
Cardiomyopathy_Paediatric v1.166 FASTKD2 Zornitza Stark Publications for gene: FASTKD2 were set to 28499982
Cardiomyopathy_Paediatric v1.165 FASTKD2 Zornitza Stark Classified gene: FASTKD2 as Red List (low evidence)
Cardiomyopathy_Paediatric v1.165 FASTKD2 Zornitza Stark Gene: fastkd2 has been classified as Red List (Low Evidence).
Cardiomyopathy_Paediatric v1.164 MMACHC Zornitza Stark Marked gene: MMACHC as ready
Cardiomyopathy_Paediatric v1.164 MMACHC Zornitza Stark Gene: mmachc has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.164 MMACHC Zornitza Stark Phenotypes for gene: MMACHC were changed from Dehydration, hepatomegaly, lethargy, coma, acidosis, high anion gap; Methylmalonic aciduria; DCM; Methylmalonic aciduria and homocystinuria, cblC type, 277400; Hypertrophic-hypocontractile cardiomyopathy to methylmalonic aciduria and homocystinuria type cblC, MONDO:0010184
Cardiomyopathy_Paediatric v1.163 MMACHC Zornitza Stark Publications for gene: MMACHC were set to 27604308
Cardiomyopathy_Paediatric v1.162 MMACHC Zornitza Stark Classified gene: MMACHC as Green List (high evidence)
Cardiomyopathy_Paediatric v1.162 MMACHC Zornitza Stark Gene: mmachc has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.161 TSFM Zornitza Stark Marked gene: TSFM as ready
Cardiomyopathy_Paediatric v1.161 TSFM Zornitza Stark Gene: tsfm has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.161 TSFM Zornitza Stark Phenotypes for gene: TSFM were changed from Required for mitochondrial gene expression (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Combined oxidative phosphorylation deficiency 3, 610505; Combined oxidative phosphorylation deficiency 3 610505 to Combined oxidative phosphorylation deficiency 3, MIM# 610505
Cardiomyopathy_Paediatric v1.160 TSFM Zornitza Stark Publications for gene: TSFM were set to 27604308
Cardiomyopathy_Paediatric v1.159 TSFM Zornitza Stark reviewed gene: TSFM: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Combined oxidative phosphorylation deficiency 3, MIM# 610505; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v1.159 DSC2 Zornitza Stark Marked gene: DSC2 as ready
Cardiomyopathy_Paediatric v1.159 DSC2 Zornitza Stark Gene: dsc2 has been classified as Amber List (Moderate Evidence).
Cardiomyopathy_Paediatric v1.159 SDHD Sarah Milton Marked gene: SDHD as ready
Cardiomyopathy_Paediatric v1.159 SDHD Sarah Milton Gene: sdhd has been classified as Amber List (Moderate Evidence).
Cardiomyopathy_Paediatric v1.159 DSC2 Zornitza Stark Phenotypes for gene: DSC2 were changed from Arrhythmogenic right ventricular dysplasia 11; Arrhythmogenic right ventricular dysplasia 11 with mild palmoplantar keratoderma and woolly hair to familial isolated arrhythmogenic right ventricular dysplasia, MONDO:0016342
Cardiomyopathy_Paediatric v1.158 SDHD Sarah Milton Classified gene: SDHD as Amber List (moderate evidence)
Cardiomyopathy_Paediatric v1.158 SDHD Sarah Milton Gene: sdhd has been classified as Amber List (Moderate Evidence).
Cardiomyopathy_Paediatric v1.157 SDHD Sarah Milton reviewed gene: SDHD: Rating: AMBER; Mode of pathogenicity: None; Publications: 34012134, 26008905; Phenotypes: Mitochondrial complex II deficiency, Nuclear type 3 MIM#619167; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v1.157 DSC2 Zornitza Stark Publications for gene: DSC2 were set to
Cardiomyopathy_Paediatric v1.156 DSC2 Zornitza Stark Mode of inheritance for gene: DSC2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v1.155 DSC2 Zornitza Stark Classified gene: DSC2 as Amber List (moderate evidence)
Cardiomyopathy_Paediatric v1.155 DSC2 Zornitza Stark Gene: dsc2 has been classified as Amber List (Moderate Evidence).
Cardiomyopathy_Paediatric v1.154 FKTN Zornitza Stark Marked gene: FKTN as ready
Cardiomyopathy_Paediatric v1.154 FKTN Zornitza Stark Gene: fktn has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.154 FKTN Zornitza Stark Phenotypes for gene: FKTN were changed from Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type; Dilated Cardiomyopathy, Recessive; Fukuyama Congenital Muscular Dystrophy; Fukuyama congenital muscular dystrophy; Muscular dystrophy-dystroglycanopathy (congenital without mental retardation), type B, 4 613152; Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 4 253800; Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 4 611588; Cardiomyopathy, dilated, 1X; Fukutin deficiency (Disorders of protein O-glycosylation, O-mannosylglycan synthesis deficiencies) to dilated cardiomyopathy 1X, MONDO:0012704; muscular dystrophy-dystroglycanopathy, type A, MONDO:0000171
Cardiomyopathy_Paediatric v1.153 FKTN Zornitza Stark Publications for gene: FKTN were set to 27604308
Cardiomyopathy_Paediatric v1.152 NDUFV2 Zornitza Stark Marked gene: NDUFV2 as ready
Cardiomyopathy_Paediatric v1.152 NDUFV2 Zornitza Stark Gene: ndufv2 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.152 NDUFV2 Zornitza Stark Phenotypes for gene: NDUFV2 were changed from Mitochondrial complex I deficiency, nuclear type 7, 618229 to Mitochondrial complex I deficiency, nuclear type 7, MIM#618229
Cardiomyopathy_Paediatric v1.151 NDUFV2 Zornitza Stark Publications for gene: NDUFV2 were set to
Cardiomyopathy_Paediatric v1.150 GATA6 Zornitza Stark Marked gene: GATA6 as ready
Cardiomyopathy_Paediatric v1.150 GATA6 Zornitza Stark Gene: gata6 has been classified as Red List (Low Evidence).
Cardiomyopathy_Paediatric v1.150 GATA6 Zornitza Stark Phenotypes for gene: GATA6 were changed from to dilated cardiomyopathy, MONDO:0005021, GATA6-related
Cardiomyopathy_Paediatric v1.149 GATA6 Zornitza Stark Publications for gene: GATA6 were set to
Cardiomyopathy_Paediatric v1.148 GATA6 Zornitza Stark Classified gene: GATA6 as Red List (low evidence)
Cardiomyopathy_Paediatric v1.148 GATA6 Zornitza Stark Gene: gata6 has been classified as Red List (Low Evidence).
Cardiomyopathy_Paediatric v1.147 GATA6 Zornitza Stark reviewed gene: GATA6: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: dilated cardiomyopathy, MONDO:0005021, GATA6-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cardiomyopathy_Paediatric v1.147 GATA6 Sarah Milton reviewed gene: GATA6: Rating: AMBER; Mode of pathogenicity: None; Publications: 35962153; Phenotypes: dilated cardiomyopathy, MONDO:0005021, GATA6-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cardiomyopathy_Paediatric v1.147 NDUFV2 Richard Lin reviewed gene: NDUFV2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMIDs: 12754703, 19167255, 26008862; Phenotypes: Leigh syndrome, MONDO:0009723, Mitochondrial complex I deficiency, nuclear type 7, MIM: 618229; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v1.147 FKTN Richard Lin reviewed gene: FKTN: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 17036286, 23746544, 24144914, 27521547, 35743126; Phenotypes: dilated cardiomyopathy 1X, MONDO:0012704, muscular dystrophy-dystroglycanopathy, type A, MONDO:0000171; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v1.147 DSC2 Richard Lin changed review comment from: Two studies report 3 unrelated patients with biallelic DSC2 variants and paediatric onset arrhythmogenic (right ventricular) cardiomyopathy (PMIDs: 24793512, 26310507). Reported variants in DSC2 are likely VUS.

PMID: 24793512 - 10 year old F with sudden cardiac arrest and typical/advanced features of ARVC, found to be homozygous for an inframe deletion in DSC2:c.712_714delGAT, p.(Asp238del). 2 male sibs and both parents heterozygous for the same variant, clinically unaffected.
PMID: 26310507 - cohort study which found a homozygous missense variant DSC2: c.536A>G, p.(Asp179Gly) in 5 patients from 4 families, including 2 unrelated paediatric patients aged 14 and 11 with arrhythmogenic cardiomyopathy
PMID: 20197793 - functional study which shown that the DSC2 p.Asp179Gly variant protein correctly colocalizes at the cell membrane with endogenous desmoglein in a transfected desmosome-forming cell line, indicating this variant has no impact on desmosome assembly; to: Association between heterozygous variants and arrhythmogenic right ventricular dysplasia classified as definitive by ClinGen. Reported cases are adult-onset disease.

Two studies report 3 unrelated patients with biallelic DSC2 variants and paediatric onset arrhythmogenic (right ventricular) cardiomyopathy (PMIDs: 24793512, 26310507), though reported variants are likely VUS.

PMID: 24793512 - 10 year old F with sudden cardiac arrest and typical/advanced features of ARVC, found to be homozygous for an inframe deletion in DSC2:c.712_714delGAT, p.(Asp238del). 2 male sibs and both parents heterozygous for the same variant, clinically unaffected.
PMID: 26310507 - cohort study which found a homozygous missense variant DSC2: c.536A>G, p.(Asp179Gly) in 5 patients from 4 families, including 2 unrelated paediatric patients aged 14 and 11 with arrhythmogenic cardiomyopathy
PMID: 20197793 - functional study which shown that the DSC2 p.Asp179Gly variant protein correctly colocalises at the cell membrane with endogenous desmoglein in a transfected desmosome-forming cell line, indicating this variant has no impact on desmosome assembly
Cardiomyopathy_Paediatric v1.147 DSC2 Richard Lin changed review comment from: Two studies report 3 unrelated patients with paediatric onset arrhythmogenic (right ventricular) cardiomyopathy (PMIDs: 24793512, 26310507). Reported variants are likely VUS.

PMID: 24793512 - 10 year old F with sudden cardiac arrest and typical/advanced features of ARVC, found to be homozygous for an inframe deletion in DSC2:c.712_714delGAT, p.(Asp238del). 2 male sibs and both parents heterozygous for the same variant, clinically unaffected.
PMID: 26310507 - cohort study which found a homozygous missense variant DSC2: c.536A>G, p.(Asp179Gly) in 5 patients from 4 families, including 2 unrelated paediatric patients aged 14 and 11 with arrhythmogenic cardiomyopathy
PMID: 20197793 - functional study which shown that the DSC2 p.Asp179Gly variant protein correctly colocalizes at the cell membrane with endogenous desmoglein in a transfected desmosome-forming cell line, indicating this variant has no impact on desmosome assembly; to: Two studies report 3 unrelated patients with biallelic DSC2 variants and paediatric onset arrhythmogenic (right ventricular) cardiomyopathy (PMIDs: 24793512, 26310507). Reported variants in DSC2 are likely VUS.

PMID: 24793512 - 10 year old F with sudden cardiac arrest and typical/advanced features of ARVC, found to be homozygous for an inframe deletion in DSC2:c.712_714delGAT, p.(Asp238del). 2 male sibs and both parents heterozygous for the same variant, clinically unaffected.
PMID: 26310507 - cohort study which found a homozygous missense variant DSC2: c.536A>G, p.(Asp179Gly) in 5 patients from 4 families, including 2 unrelated paediatric patients aged 14 and 11 with arrhythmogenic cardiomyopathy
PMID: 20197793 - functional study which shown that the DSC2 p.Asp179Gly variant protein correctly colocalizes at the cell membrane with endogenous desmoglein in a transfected desmosome-forming cell line, indicating this variant has no impact on desmosome assembly
Cardiomyopathy_Paediatric v1.147 DSC2 Richard Lin changed review comment from: Two studies report 3 unrelated patients with paediatric onset arrhythmogenic (right ventricular) cardiomyopathy (PMIDs: 24793512, 26310507). Reported variants are likely VUS.

PMID: 24793512 - 10 year old F with sudden cardiac arrest and typical/advanced features of ARVC, found to be homozygous for an inframe deletion in DSC2:c.712_714delGAT, p.(Asp238del). 2 male sibs and both parents heterozygous for the same variant, clinically unaffected.
PMID: 26310507 - cohort study which found a homozygous missense variant DSC2: c.536A>G, p.(Asp179Gly) in 5 patients from 4 families, including 2 unrelated paediatric patients aged 14 and 11 with arrhythmogenic cardiomyopathy
PMID: 20197793 - functional study which shown that the DSC2 p.Asp179Gly variant protein correctly colocalizes at the cell membrane with endogenous desmoglein in a transfected desmosome-forming cell line, indicating this variant has no impact on desmosome assembly; to: Two studies report 3 unrelated patients with paediatric onset arrhythmogenic (right ventricular) cardiomyopathy (PMIDs: 24793512, 26310507). Reported variants are likely VUS.

PMID: 24793512 - 10 year old F with sudden cardiac arrest and typical/advanced features of ARVC, found to be homozygous for an inframe deletion in DSC2:c.712_714delGAT, p.(Asp238del). 2 male sibs and both parents heterozygous for the same variant, clinically unaffected.
PMID: 26310507 - cohort study which found a homozygous missense variant DSC2: c.536A>G, p.(Asp179Gly) in 5 patients from 4 families, including 2 unrelated paediatric patients aged 14 and 11 with arrhythmogenic cardiomyopathy
PMID: 20197793 - functional study which shown that the DSC2 p.Asp179Gly variant protein correctly colocalizes at the cell membrane with endogenous desmoglein in a transfected desmosome-forming cell line, indicating this variant has no impact on desmosome assembly
Cardiomyopathy_Paediatric v1.147 DSC2 Richard Lin reviewed gene: DSC2: Rating: AMBER; Mode of pathogenicity: None; Publications: PMIDs: 20197793, 24793512, 26310507; Phenotypes: Syndromic disease, MONDO:0002254, familial isolated arrhythmogenic right ventricular dysplasia, MONDO:0016342; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v2.1 MAX TRAIL SCHN changed review comment from: Please tag as "TRAIL Study"

Rationale: Clinician supported inclusion, childhood cancer predisposition causing (Pheochromocytomas and paragangliomas)
Sources: Expert Review; to: Please tag as "TRAIL Study"

Clinician supported inclusion, childhood cancer predisposition causing pheochromocytomas and paragangliomas, monitoring for early intervention

Sources: Expert Review
Genomic newborn screening: BabyScreen+ v2.1 TMEM127 TRAIL SCHN changed review comment from: Please tag as "TRAIL Study"

Rationale: Clinician supported inclusion, childhood cancer predisposition causing (Pheochromocytomas and paragangliomas)
Sources: Expert Review; to: Please tag as "TRAIL Study"

Clinician supported inclusion, childhood cancer predisposition causing pheochromocytomas and paragangliomas, monitoring for early intervention

Sources: Expert Review
Common deletion and duplication syndromes v1.5 ISCA-37446-Loss Sarah Milton Chromosome 22q11.2 deletion syndrome, distal was changed to Chromosome 22q11.2 deletion syndrome, DiGeorge syndrome
Source Expert list was removed from Region: ISCA-37446-Loss.
Source ClinGen was added to Region: ISCA-37446-Loss.
Clefting disorders v1.23 ISCA-37446-Loss Sarah Milton Chromosome 22q11.2 deletion syndrome, distal was changed to Chromosome 22q11.2 deletion syndrome, DiGeorge syndrome
Source Expert list was removed from Region: ISCA-37446-Loss.
Source Expert list was removed from Region: ISCA-37446-Loss.
Source ClinGen was added to Region: ISCA-37446-Loss.
Intellectual disability syndromic and non-syndromic v2.131 ISCA-37446-Loss Sarah Milton Chromosome 22q11.2 deletion syndrome, distal was changed to Chromosome 22q11.2 deletion syndrome, DiGeorge syndrome
Source Expert list was removed from Region: ISCA-37446-Loss.
Source Expert list was removed from Region: ISCA-37446-Loss.
Source ClinGen was added to Region: ISCA-37446-Loss.
Severe Combined Immunodeficiency v2.5 ISCA-37446-Loss Sarah Milton Chromosome 22q11.2 deletion syndrome, distal was changed to Chromosome 22q11.2 deletion syndrome, DiGeorge syndrome
Source Expert list was removed from Region: ISCA-37446-Loss.
Source Expert list was removed from Region: ISCA-37446-Loss.
Source ClinGen was added to Region: ISCA-37446-Loss.
Genetic Epilepsy v2.39 ISCA-37446-Loss Sarah Milton Chromosome 22q11.2 deletion syndrome, distal was changed to Chromosome 22q11.2 deletion syndrome, DiGeorge syndrome
Source Expert list was removed from Region: ISCA-37446-Loss.
Source Expert list was removed from Region: ISCA-37446-Loss.
Source ClinGen was added to Region: ISCA-37446-Loss.
Congenital Heart Defect v1.35 ISCA-37446-Loss Sarah Milton Chromosome 22q11.2 deletion syndrome, distal was changed to Chromosome 22q11.2 deletion syndrome, DiGeorge syndrome
Source Expert list was removed from Region: ISCA-37446-Loss.
Source Expert list was removed from Region: ISCA-37446-Loss.
Source ClinGen was added to Region: ISCA-37446-Loss.
Cardiomyopathy_Paediatric v1.147 TSFM Richard Lin reviewed gene: TSFM: Rating: GREEN; Mode of pathogenicity: None; Publications: PMIDs: 35071363, 31451716, 31267352, 27677415, 25037205, 21741925, 17033963; Phenotypes: Mitochondrial disease, MONDO:0044970; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v2.1 MAX TRAIL SCHN changed review comment from: Please tag as "TRAIL Study"

Rationale: Clinician supported inclusion, childhood cancer predisposition causing (Pheochromocytomas and paragangliomas)
Sources: Expert Review; to: Please tag as "TRAIL Study"

Rationale: Clinician supported inclusion, childhood cancer predisposition causing (Pheochromocytomas and paragangliomas)
Sources: Expert Review
Genomic newborn screening: BabyScreen+ v2.1 MAX TRAIL SCHN gene: MAX was added
gene: MAX was added to Genomic newborn screening: BabyScreen+. Sources: Expert Review
Mode of inheritance for gene: MAX was set to BIALLELIC, autosomal or pseudoautosomal
Review for gene: MAX was set to RED
Added comment: Please tag as "TRAIL Study"

Rationale: Clinician supported inclusion, childhood cancer predisposition causing (Pheochromocytomas and paragangliomas)
Sources: Expert Review
Genomic newborn screening: BabyScreen+ v2.1 TMEM127 TRAIL SCHN reviewed gene: TMEM127: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v2.1 TMEM127 TRAIL SCHN Deleted their review
Genomic newborn screening: BabyScreen+ v2.1 TMEM127 TRAIL SCHN gene: TMEM127 was added
gene: TMEM127 was added to Genomic newborn screening: BabyScreen+. Sources: Expert Review
Mode of inheritance for gene: TMEM127 was set to BIALLELIC, autosomal or pseudoautosomal
Added comment: Please tag as "TRAIL Study"

Rationale: Clinician supported inclusion, childhood cancer predisposition causing (Pheochromocytomas and paragangliomas)
Sources: Expert Review
Genomic newborn screening: BabyScreen+ v2.1 IFNAR1 TRAIL SCHN gene: IFNAR1 was added
gene: IFNAR1 was added to Genomic newborn screening: BabyScreen+. Sources: Expert Review
Mode of inheritance for gene: IFNAR1 was set to BIALLELIC, autosomal or pseudoautosomal
Review for gene: IFNAR1 was set to RED
Added comment: Please tag as "TRAIL Study"

Contributed by one of the immunologists (for TRAIL only). Predicts adverse outcome to MMR vaccine.
Sources: Expert Review
Genomic newborn screening: BabyScreen+ v2.1 LPIN1 TRAIL SCHN gene: LPIN1 was added
gene: LPIN1 was added to Genomic newborn screening: BabyScreen+. Sources: Expert Review
Mode of inheritance for gene: LPIN1 was set to BIALLELIC, autosomal or pseudoautosomal
Review for gene: LPIN1 was set to RED
Added comment: Please tag as "TRAIL Study"

Suggested by metabolic clinician. Known cause of severe rhabdomyolysis, early monitoring and treatment can improve outcomes.
Sources: Expert Review
Growth failure v2.22 ISCA-37397-Loss Sarah Milton GRCh38 position for ISCA-37397-Loss was changed from 21443089-23306926 to 21562828-22620608.
Source Expert list was removed from Region: ISCA-37397-Loss.
Source Expert list was removed from Region: ISCA-37397-Loss.
Source ClinGen was added to Region: ISCA-37397-Loss.
Common deletion and duplication syndromes v1.4 ISCA-37397-Loss Sarah Milton GRCh38 position for ISCA-37397-Loss was changed from 21443089-23306926 to 21562828-22620608.
Source Expert list was removed from Region: ISCA-37397-Loss.
Source ClinGen was added to Region: ISCA-37397-Loss.
Intellectual disability syndromic and non-syndromic v2.130 ISCA-37397-Loss Sarah Milton GRCh38 position for ISCA-37397-Loss was changed from 21443089-23306926 to 21562828-22620608.
Source Expert list was removed from Region: ISCA-37397-Loss.
Source Expert list was removed from Region: ISCA-37397-Loss.
Source ClinGen was added to Region: ISCA-37397-Loss.
Congenital Heart Defect v1.34 ISCA-37397-Loss Sarah Milton GRCh38 position for ISCA-37397-Loss was changed from 21443089-23306926 to 21562828-22620608.
Source Expert list was removed from Region: ISCA-37397-Loss.
Source Expert list was removed from Region: ISCA-37397-Loss.
Source ClinGen was added to Region: ISCA-37397-Loss.
Intellectual disability syndromic and non-syndromic v2.129 ISCA-37397-Gain Sarah Milton GRCh38 position for ISCA-37397-Gain was changed from 21443089-23306926 to 21562828-22620608.
Source Expert list was removed from Region: ISCA-37397-Gain.
Source Expert list was removed from Region: ISCA-37397-Gain.
Source ClinGen was added to Region: ISCA-37397-Gain.
Cardiomyopathy_Paediatric v1.147 TMEM70 Richard Lin reviewed gene: TMEM70: Rating: GREEN; Mode of pathogenicity: None; Publications: PMIDs: 20335238, 26550569, 27649480, 30899493, 30950220, 31729175, 36751706; Phenotypes: mitochondrial complex V (ATP synthase) deficiency, nuclear type 2, MONDO:0013546; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v1.147 MMACHC Richard Lin changed review comment from: Biallelic variants in MMACHC are associated with Cobalamin C deficiency (cblC deficiency), a multisystemic condition.

Cardiomyopathy is described to occur in 10-25% of patients with early onset (below the age of 1 year) MMACHC-associated cblC deficiency in the 2026 Remethylation Disorders guidelines (PMID: 42231716). The predominant cardiomyopathy phenotype is left ventricular non compaction cardiomyopathy (PMIDs: 19767224, 20632110, 23430797, 24599607, 40830795, 42231716). Paediatric onset dilated cardiomyopathy has also been rarely reported (PMID: 19248038, 33562640, 38745823); to: Biallelic variants in MMACHC are associated with Cobalamin C deficiency (cblC deficiency), a multisystemic condition.

Cardiomyopathy is described to occur in 10-25% of patients with early onset (below the age of 1 year) MMACHC-associated cblC deficiency in the 2026 Remethylation Disorders guidelines (PMID: 42231716). The predominant cardiomyopathy phenotype is left ventricular non compaction cardiomyopathy (PMIDs: 19767224, 20632110, 23430797, 24599607, 40830795, 42231716). Paediatric onset dilated cardiomyopathy has also been rarely reported (PMID: 19248038, 33562640, 38745823)
Cardiomyopathy_Paediatric v1.147 PCCB Zornitza Stark Marked gene: PCCB as ready
Cardiomyopathy_Paediatric v1.147 PCCB Zornitza Stark Gene: pccb has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.147 PCCB Zornitza Stark Phenotypes for gene: PCCB were changed from as PCCA (metabolic encephalopathy with hyperammonaemia, hypotonia, recurrent episodes of ketoacidosis, liver impairment, psychomotor retardation, recurrent infections); Propionic acidemia; Propionicacidemia 606054; Propionic aciduria; Dehydration, hepatomegaly, lethargy, coma, acidosis, high anion gap; DCM; Propionic aciduria (Organic acidurias); Hypertrophic-hypocontractile cardiomyopathy; Propionicacidemia to propionic acidemia, MONDO:0011628
Cardiomyopathy_Paediatric v1.146 PCCB Zornitza Stark Publications for gene: PCCB were set to 27604308
Cardiomyopathy_Paediatric v1.145 PCCB Zornitza Stark reviewed gene: PCCB: Rating: GREEN; Mode of pathogenicity: None; Publications: 37529955, 36768524, 36393899, 34203287; Phenotypes: propionic acidemia, MONDO:0011628; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v1.145 HADHB Zornitza Stark Marked gene: HADHB as ready
Cardiomyopathy_Paediatric v1.145 HADHB Zornitza Stark Gene: hadhb has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.145 HADHB Zornitza Stark Phenotypes for gene: HADHB were changed from Trifunctional protein deficiency 609015; Mitochondrial trifunctional protein deficiency (Disorders of mitochondrial fatty acid oxidation); Mitochondrial Trifunctional Protein deficiency; Liver disease, hypotonia, hypoketotic hypoglycaemia, neuropathy, lactic acidosis, retinopathy, hypoparathyroidism; HCM; Long chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD) to mitochondrial trifunctional protein deficiency, MONDO:0012172
Cardiomyopathy_Paediatric v1.144 HADHB Zornitza Stark Publications for gene: HADHB were set to 27604308
Cardiomyopathy_Paediatric v1.143 HADHB Zornitza Stark reviewed gene: HADHB: Rating: GREEN; Mode of pathogenicity: None; Publications: 39088276, 28515471; Phenotypes: mitochondrial trifunctional protein deficiency, MONDO:0012172; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v1.143 HADHA Zornitza Stark Marked gene: HADHA as ready
Cardiomyopathy_Paediatric v1.143 HADHA Zornitza Stark Gene: hadha has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.143 HADHA Zornitza Stark Phenotypes for gene: HADHA were changed from Trifunctional protein deficiency 609015; Mitochondrial trifunctional protein deficiency (Disorders of mitochondrial fatty acid oxidation); Mitochondrial Trifunctional Protein deficiency; Liver disease, hypotonia, hypoketotic hypoglycaemia, neuropathy, lactic acidosis, retinopathy, hypoparathyroidism; HCM; Long chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD) to mitochondrial trifunctional protein deficiency, MONDO:0012172
Cardiomyopathy_Paediatric v1.142 HADHA Zornitza Stark Publications for gene: HADHA were set to 27604308
Cardiomyopathy_Paediatric v1.141 HADHA Zornitza Stark reviewed gene: HADHA: Rating: GREEN; Mode of pathogenicity: None; Publications: 39088276, 37754774, 35677112, 32999401, 28515471; Phenotypes: mitochondrial trifunctional protein deficiency, MONDO:0012172; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v2.128 TXNIP Zornitza Stark Marked gene: TXNIP as ready
Intellectual disability syndromic and non-syndromic v2.128 TXNIP Zornitza Stark Gene: txnip has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v2.128 TXNIP Zornitza Stark Publications for gene: TXNIP were set to 41116060; 30755400
Intellectual disability syndromic and non-syndromic v2.127 TXNIP Zornitza Stark Classified gene: TXNIP as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v2.127 TXNIP Zornitza Stark Gene: txnip has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v2.126 TXNIP Zornitza Stark edited their review of gene: TXNIP: Added comment: ID is not a consistent feature.; Changed rating: AMBER
Mitochondrial disease v2.7 TXNIP Zornitza Stark Marked gene: TXNIP as ready
Mitochondrial disease v2.7 TXNIP Zornitza Stark Gene: txnip has been classified as Green List (High Evidence).
Mitochondrial disease v2.7 TXNIP Zornitza Stark Publications for gene: TXNIP were set to 41116060; 30755400
Mitochondrial disease v2.6 TXNIP Zornitza Stark commented on gene: TXNIP: Included as lactic acidosis is a consistent feature of the condition.
Mitochondrial disease v2.6 Zornitza Stark Copied gene TXNIP from panel Miscellaneous Metabolic Disorders
Mitochondrial disease v2.6 TXNIP Zornitza Stark gene: TXNIP was added
gene: TXNIP was added to Mitochondrial disease. Sources: Expert Review Green,Literature,Literature
Mode of inheritance for gene: TXNIP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TXNIP were set to 41116060; 30755400
Phenotypes for gene: TXNIP were set to Metabolic disease MONDO:0005066, TXNIP-related
Intellectual disability syndromic and non-syndromic v2.126 Zornitza Stark Copied gene TXNIP from panel Miscellaneous Metabolic Disorders
Intellectual disability syndromic and non-syndromic v2.126 TXNIP Zornitza Stark gene: TXNIP was added
gene: TXNIP was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Green,Literature,Literature
Mode of inheritance for gene: TXNIP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TXNIP were set to 41116060; 30755400
Phenotypes for gene: TXNIP were set to Metabolic disease MONDO:0005066, TXNIP-related
Miscellaneous Metabolic Disorders v2.3 TXNIP Zornitza Stark Classified gene: TXNIP as Green List (high evidence)
Miscellaneous Metabolic Disorders v2.3 TXNIP Zornitza Stark Gene: txnip has been classified as Green List (High Evidence).
Miscellaneous Metabolic Disorders v2.2 Zornitza Stark Added reviews for gene TXNIP from panel Mendeliome
Mendeliome v2.519 TXNIP Zornitza Stark Publications for gene: TXNIP were set to 41116060; 30755400
Mendeliome v2.518 TXNIP Zornitza Stark Classified gene: TXNIP as Green List (high evidence)
Mendeliome v2.518 TXNIP Zornitza Stark Gene: txnip has been classified as Green List (High Evidence).
Mendeliome v2.517 TXNIP Zornitza Stark reviewed gene: TXNIP: Rating: GREEN; Mode of pathogenicity: None; Publications: 42448226, 41116060, 30755400; Phenotypes: Metabolic disease MONDO:0005066, TXNIP-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v2.11 PALM3 Zornitza Stark Marked gene: PALM3 as ready
Deafness_IsolatedAndComplex v2.11 PALM3 Zornitza Stark Gene: palm3 has been classified as Red List (Low Evidence).
Deafness_IsolatedAndComplex v2.11 Zornitza Stark Copied gene PALM3 from panel Mendeliome
Deafness_IsolatedAndComplex v2.11 PALM3 Zornitza Stark gene: PALM3 was added
gene: PALM3 was added to Deafness_IsolatedAndComplex. Sources: Expert Review Red,Literature
Mode of inheritance for gene: PALM3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PALM3 were set to 42527583; 10.64898/2026.04.20.26351093
Phenotypes for gene: PALM3 were set to Non-syndromic genetic hearing loss, MONDO:0019497, PALM3-related
Mendeliome v2.517 PALM3 Zornitza Stark Marked gene: PALM3 as ready
Mendeliome v2.517 PALM3 Zornitza Stark Gene: palm3 has been classified as Red List (Low Evidence).
Mendeliome v2.517 PALM3 Zornitza Stark gene: PALM3 was added
gene: PALM3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PALM3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PALM3 were set to 42527583; 10.64898/2026.04.20.26351093
Phenotypes for gene: PALM3 were set to Non-syndromic genetic hearing loss, MONDO:0019497, PALM3-related
Review for gene: PALM3 was set to RED
Added comment: PMID 42527583 reports one individual from a consanguineous family with a homozygous canonical splice‑site PALM3 variant (c.314+1G>A) presenting with autosomal recessive non‑syndromic sensorineural hearing loss. Minigene splice assay shows exon skipping and Palm3 knockout mice display auditory dysfunction, supporting a loss‑of‑function mechanism.
Sources: Literature
Cardiomyopathy_Paediatric v1.141 MMACHC Richard Lin reviewed gene: MMACHC: Rating: GREEN; Mode of pathogenicity: None; Publications: 19248038, 19767224, 20632110, 23430797, 24599607, 33562640, 38745823, 40830795, 42231716; Phenotypes: methylmalonic aciduria and homocystinuria type cblC, MONDO:0010184; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v1.141 FASTKD2 Richard Lin changed review comment from: PMID 31944455 reports 3 unrelated families with biallelic loss-of-function FASTKD2 variants causing mitochondrial disease; one family presented with childhood‑onset hypertrophic cardiomyopathy. A zebrafish knockdown model showed a decreased heart rate, structural cardiac morphology was not specifically commented by the authors.

PMID: 39094958 reports an adult diagnosed with hypertrophic cardiomyopathy diagnosed at age 37, with CKD, found to be homozygous for a FASTDK2 missense variant c.29G>C p.(Ser10Thr).

PMID: 38111113 reports a 39 year old patient with cardiomyopathy and nephropathy and a FASTKD2: c.29G>C (zygosity unknown), with the same authors as PMID: 39094958. Presumed to be the same patient.

Current evidence is insufficient for diagnostic grade classification for paediatric cardiomyopathy because only a single family with paediatric cardiomyopathy is reported.; to: PMID 31944455 reports 3 unrelated families with biallelic loss-of-function FASTKD2 variants causing mitochondrial disease; one family presented with childhood‑onset hypertrophic cardiomyopathy. A zebrafish knockdown model showed a decreased heart rate, structural cardiac morphology was not specifically commented by the authors.

PMID: 39094958 reports an adult diagnosed with hypertrophic cardiomyopathy diagnosed at age 37, with CKD, found to be homozygous for a FASTDK2 missense variant c.29G>C p.(Ser10Thr).

PMID: 38111113 reports a 39 year old patient with cardiomyopathy and nephropathy and a FASTKD2: c.29G>C variant (zygosity unknown), with the same authors as PMID: 39094958. Presumed to be the same patient.

Current evidence is insufficient for diagnostic grade classification for paediatric cardiomyopathy because only a single family with paediatric cardiomyopathy is reported.
Cardiomyopathy_Paediatric v1.141 FASTKD2 Richard Lin changed review comment from: PMID 31944455 reports 3 unrelated families with biallelic loss-of-function FASTKD2 variants causing mitochondrial disease; one family presented with childhood‑onset hypertrophic cardiomyopathy. A zebrafish knockdown model showed a decreased heart rate, cardiac morphology was not specifically commented by the authors.

PMID: 39094958 reports an adult diagnosed with hypertrophic cardiomyopathy diagnosed at age 37, with CKD, found to be homozygous for a FASTDK2 missense variant c.29G>C p.(Ser10Thr).

PMID: 38111113 reports a 39 year old patient with cardiomyopathy and nephropathy and a FASTKD2: c.29G>C (zygosity unknown), with the same authors as PMID: 39094958. Presumed to be the same patient.

Current evidence is insufficient for diagnostic grade classification for paediatric cardiomyopathy because only a single family with paediatric cardiomyopathy is reported.; to: PMID 31944455 reports 3 unrelated families with biallelic loss-of-function FASTKD2 variants causing mitochondrial disease; one family presented with childhood‑onset hypertrophic cardiomyopathy. A zebrafish knockdown model showed a decreased heart rate, structural cardiac morphology was not specifically commented by the authors.

PMID: 39094958 reports an adult diagnosed with hypertrophic cardiomyopathy diagnosed at age 37, with CKD, found to be homozygous for a FASTDK2 missense variant c.29G>C p.(Ser10Thr).

PMID: 38111113 reports a 39 year old patient with cardiomyopathy and nephropathy and a FASTKD2: c.29G>C (zygosity unknown), with the same authors as PMID: 39094958. Presumed to be the same patient.

Current evidence is insufficient for diagnostic grade classification for paediatric cardiomyopathy because only a single family with paediatric cardiomyopathy is reported.
Cardiomyopathy_Paediatric v1.141 FASTKD2 Richard Lin reviewed gene: FASTKD2: Rating: RED; Mode of pathogenicity: None; Publications: 31944455; Phenotypes: FASTKD2-related infantile mitochondrial encephalomyopathy, MONDO:0015632; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v2.66 CDC6 Lucy Spencer Publications for gene: CDC6 were set to 21358632
Fetal anomalies v2.65 CDC6 Lucy Spencer Classified gene: CDC6 as Green List (high evidence)
Fetal anomalies v2.65 CDC6 Lucy Spencer Gene: cdc6 has been classified as Green List (High Evidence).
Growth failure v2.21 CDC6 Lucy Spencer Publications for gene: CDC6 were set to 21358632
Growth failure v2.20 CDC6 Lucy Spencer Classified gene: CDC6 as Green List (high evidence)
Growth failure v2.20 CDC6 Lucy Spencer Gene: cdc6 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.122 CDC6 Lucy Spencer Publications for gene: CDC6 were set to
Skeletal dysplasia v1.121 CDC6 Lucy Spencer Classified gene: CDC6 as Green List (high evidence)
Skeletal dysplasia v1.121 CDC6 Lucy Spencer Gene: cdc6 has been classified as Green List (High Evidence).
Microcephaly v2.27 CDC6 Lucy Spencer Publications for gene: CDC6 were set to 21358632
Microcephaly v2.26 CDC6 Lucy Spencer Classified gene: CDC6 as Green List (high evidence)
Microcephaly v2.26 CDC6 Lucy Spencer Gene: cdc6 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v2.125 CDC6 Lucy Spencer reviewed gene: CDC6: Rating: RED; Mode of pathogenicity: None; Publications: 35023948, 42496035; Phenotypes: Meier-Gorlin syndrome 5 (MIM#613805); Mode of inheritance: None
Skeletal dysplasia v1.120 Lucy Spencer Added reviews for gene CDC6 from panel Mendeliome
Microcephaly v2.25 Lucy Spencer Added reviews for gene CDC6 from panel Mendeliome
Growth failure v2.19 Lucy Spencer Added reviews for gene CDC6 from panel Mendeliome
Fetal anomalies v2.64 Lucy Spencer Added reviews for gene CDC6 from panel Mendeliome
Mendeliome v2.516 CDC6 Lucy Spencer Publications for gene: CDC6 were set to 21358632
Mendeliome v2.515 CDC6 Lucy Spencer Classified gene: CDC6 as Green List (high evidence)
Mendeliome v2.515 CDC6 Lucy Spencer Gene: cdc6 has been classified as Green List (High Evidence).
Mendeliome v2.514 CDC6 Lucy Spencer reviewed gene: CDC6: Rating: GREEN; Mode of pathogenicity: None; Publications: 21358632, 42496035, 35023948; Phenotypes: Meier-Gorlin syndrome 5 MIM#613805; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v1.141 IDUA Zornitza Stark Marked gene: IDUA as ready
Cardiomyopathy_Paediatric v1.141 IDUA Zornitza Stark Gene: idua has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.141 IDUA Zornitza Stark Phenotypes for gene: IDUA were changed from Scheie syndrome; Hurler-Scheie syndrome; Mucopolysaccharidosis type 1H; Mucopolysaccharidosis Ih/s, 607015; Mucopolysaccharidosis Ih, 607014; Mucopolysaccharidosis type 1S; Hurler syndrome; MPS I, Hurler, Scheie disease (Mucopolysaccharidoses); Mucopolysaccharidosis, Type I; Mucopolysaccharidosis type 1H/S; Mucopolysaccharidosis Is, 607016 to mucopolysaccharidosis type 1, MONDO:0001586
Cardiomyopathy_Paediatric v1.140 IDUA Zornitza Stark Publications for gene: IDUA were set to 27604308
Cardiomyopathy_Paediatric v1.139 IDUA Zornitza Stark reviewed gene: IDUA: Rating: GREEN; Mode of pathogenicity: None; Publications: 41582445, 35893030, 27146977; Phenotypes: mucopolysaccharidosis type 1, MONDO:0001586; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v1.139 IDS Zornitza Stark Marked gene: IDS as ready
Cardiomyopathy_Paediatric v1.139 IDS Zornitza Stark Gene: ids has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.139 IDS Zornitza Stark Phenotypes for gene: IDS were changed from MPS II, Hunter disease (Mucopolysaccharidoses); MUCOPOLYSACCHARIDOSIS TYPE 2; Mucopolysaccharidosis Type II; Mucopolysaccharidosis II, 309900 to mucopolysaccharidosis type 2, MONDO:0010674
Cardiomyopathy_Paediatric v1.138 IDS Zornitza Stark Publications for gene: IDS were set to 27604308
Cardiomyopathy_Paediatric v1.137 IDS Zornitza Stark reviewed gene: IDS: Rating: GREEN; Mode of pathogenicity: None; Publications: 35882106, 34193122, 32256517, 27146977; Phenotypes: mucopolysaccharidosis type 2, MONDO:0010674; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Cardiomyopathy_Paediatric v1.137 HRAS Zornitza Stark Marked gene: HRAS as ready
Cardiomyopathy_Paediatric v1.137 HRAS Zornitza Stark Gene: hras has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.137 HRAS Zornitza Stark reviewed gene: HRAS: Rating: GREEN; Mode of pathogenicity: None; Publications: 34964243, 34618388, 31712860, 30732632, 27554254, 25914166; Phenotypes: Costello syndrome, MONDO:0009026; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital Heart Defect v1.33 EHMT2 Zornitza Stark Marked gene: EHMT2 as ready
Congenital Heart Defect v1.33 EHMT2 Zornitza Stark Gene: ehmt2 has been classified as Green List (High Evidence).
Congenital Heart Defect v1.33 EHMT2 Zornitza Stark Classified gene: EHMT2 as Green List (high evidence)
Congenital Heart Defect v1.33 EHMT2 Zornitza Stark Gene: ehmt2 has been classified as Green List (High Evidence).
Mendeliome v2.514 EHMT2 Zornitza Stark Marked gene: EHMT2 as ready
Mendeliome v2.514 EHMT2 Zornitza Stark Gene: ehmt2 has been classified as Green List (High Evidence).
Mendeliome v2.514 EHMT2 Zornitza Stark Classified gene: EHMT2 as Green List (high evidence)
Mendeliome v2.514 EHMT2 Zornitza Stark Gene: ehmt2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v2.125 EHMT2 Zornitza Stark Marked gene: EHMT2 as ready
Intellectual disability syndromic and non-syndromic v2.125 EHMT2 Zornitza Stark Gene: ehmt2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v2.125 EHMT2 Zornitza Stark Classified gene: EHMT2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v2.125 EHMT2 Zornitza Stark Gene: ehmt2 has been classified as Green List (High Evidence).
Macular Dystrophy/Stargardt Disease v1.2 XXYLT1 Zornitza Stark Marked gene: XXYLT1 as ready
Macular Dystrophy/Stargardt Disease v1.2 XXYLT1 Zornitza Stark Gene: xxylt1 has been classified as Amber List (Moderate Evidence).
Macular Dystrophy/Stargardt Disease v1.2 Zornitza Stark Copied gene XXYLT1 from panel Mendeliome
Macular Dystrophy/Stargardt Disease v1.2 XXYLT1 Zornitza Stark gene: XXYLT1 was added
gene: XXYLT1 was added to Macular Dystrophy/Stargardt Disease. Sources: Expert Review Amber,Literature
founder tags were added to gene: XXYLT1.
Mode of inheritance for gene: XXYLT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: XXYLT1 were set to 42530953
Phenotypes for gene: XXYLT1 were set to Inherited retinal dystrophy, MONDO:0019118, XXYLT1-related
Mendeliome v2.513 XXYLT1 Zornitza Stark Marked gene: XXYLT1 as ready
Mendeliome v2.513 XXYLT1 Zornitza Stark Gene: xxylt1 has been classified as Amber List (Moderate Evidence).
Mendeliome v2.513 XXYLT1 Zornitza Stark Classified gene: XXYLT1 as Amber List (moderate evidence)
Mendeliome v2.513 XXYLT1 Zornitza Stark Gene: xxylt1 has been classified as Amber List (Moderate Evidence).
Mendeliome v2.512 XXYLT1 Zornitza Stark gene: XXYLT1 was added
gene: XXYLT1 was added to Mendeliome. Sources: Literature
founder tags were added to gene: XXYLT1.
Mode of inheritance for gene: XXYLT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: XXYLT1 were set to 42530953
Phenotypes for gene: XXYLT1 were set to Inherited retinal dystrophy, MONDO:0019118, XXYLT1-related
Review for gene: XXYLT1 was set to AMBER
Added comment: PMID 42530953 reports 7 individuals from 5 families with biallelic loss-of-function and missense variants in XXYLT1 presenting with inherited retinal dystrophy (cone‑rod or macular dystrophy). Homozygous c.505‑1G>C splice‑site variant found in four Finnish families (founder allele) and homozygous c.766G>A missense variant in a consanguineous UK family. Phenotypes included visual deterioration, cystoid macular oedema and schisis‑like macular changes; RNA splicing assays show exon 2 skipping for the recurrent c.505‑1G>C founder variant and Xylt1 knockout mice recapitulated retinal abnormalities.
Sources: Literature
Retinitis pigmentosa v1.12 DNAJC17 Zornitza Stark Marked gene: DNAJC17 as ready
Retinitis pigmentosa v1.12 DNAJC17 Zornitza Stark Gene: dnajc17 has been classified as Amber List (Moderate Evidence).
Retinitis pigmentosa v1.12 Zornitza Stark Copied gene DNAJC17 from panel Autoinflammatory Disorders
Retinitis pigmentosa v1.12 DNAJC17 Zornitza Stark gene: DNAJC17 was added
gene: DNAJC17 was added to Retinitis pigmentosa. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: DNAJC17 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DNAJC17 were set to PMID: 42495638
Phenotypes for gene: DNAJC17 were set to Inborn error of immunity, MONDO:0003778, DNAJC17-related
Disorders of immune dysregulation v2.10 GPR174 Zornitza Stark Marked gene: GPR174 as ready
Disorders of immune dysregulation v2.10 GPR174 Zornitza Stark Gene: gpr174 has been classified as Green List (High Evidence).
Disorders of immune dysregulation v2.10 Zornitza Stark Copied gene GPR174 from panel Mendeliome
Disorders of immune dysregulation v2.10 GPR174 Zornitza Stark gene: GPR174 was added
gene: GPR174 was added to Disorders of immune dysregulation. Sources: Expert Review Green,Literature
preprint tags were added to gene: GPR174.
Mode of inheritance for gene: GPR174 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: GPR174 were set to 42528559
Phenotypes for gene: GPR174 were set to Inborn error of immunity, MONDO:0003778, GPR174-related
Mendeliome v2.511 GPR174 Zornitza Stark edited their review of gene: GPR174: Changed mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v2.511 GPR174 Zornitza Stark Marked gene: GPR174 as ready
Mendeliome v2.511 GPR174 Zornitza Stark Gene: gpr174 has been classified as Green List (High Evidence).
Mendeliome v2.511 GPR174 Zornitza Stark Mode of inheritance for gene: GPR174 was changed from X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v2.510 GPR174 Zornitza Stark Classified gene: GPR174 as Green List (high evidence)
Mendeliome v2.510 GPR174 Zornitza Stark Gene: gpr174 has been classified as Green List (High Evidence).
Mendeliome v2.509 GPR174 Zornitza Stark gene: GPR174 was added
gene: GPR174 was added to Mendeliome. Sources: Literature
preprint tags were added to gene: GPR174.
Mode of inheritance for gene: GPR174 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: GPR174 were set to 42528559
Phenotypes for gene: GPR174 were set to Inborn error of immunity, MONDO:0003778, GPR174-related
Review for gene: GPR174 was set to GREEN
Added comment: PMID 42528559 reports six hemizygous males from five families with X-linked loss-of-function GPR174 variants presenting with childhood-onset lymphadenopathy, splenomegaly, histiocytic necrotizing lymphadenitis (Kikuchi-Fujimoto disease) and autoimmune cytopenias. Cell‑based cAMP reporter assays and protein‑level analyses demonstrate reduced receptor abundance and signalling, and CD8 T‑cell hyper‑proliferation.
Sources: Literature
Intellectual disability syndromic and non-syndromic v2.124 Lucy Spencer Copied gene PREX1 from panel Mendeliome
Intellectual disability syndromic and non-syndromic v2.124 PREX1 Lucy Spencer gene: PREX1 was added
gene: PREX1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: PREX1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PREX1 were set to 42399407; 26621702
Phenotypes for gene: PREX1 were set to Neurodevelopmental disorder (MONDO:0700092), PREX1-related
Genetic Epilepsy v2.38 Lucy Spencer Copied gene PREX1 from panel Mendeliome
Genetic Epilepsy v2.38 PREX1 Lucy Spencer gene: PREX1 was added
gene: PREX1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: PREX1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PREX1 were set to 42399407; 26621702
Phenotypes for gene: PREX1 were set to Neurodevelopmental disorder (MONDO:0700092), PREX1-related
Autism v1.18 Lucy Spencer Copied gene PREX1 from panel Mendeliome
Autism v1.18 PREX1 Lucy Spencer gene: PREX1 was added
gene: PREX1 was added to Autism. Sources: Literature
Mode of inheritance for gene: PREX1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PREX1 were set to 42399407; 26621702
Phenotypes for gene: PREX1 were set to Neurodevelopmental disorder (MONDO:0700092), PREX1-related
Mendeliome v2.508 PREX1 Lucy Spencer gene: PREX1 was added
gene: PREX1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PREX1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PREX1 were set to 42399407; 26621702
Phenotypes for gene: PREX1 were set to Neurodevelopmental disorder (MONDO:0700092), PREX1-related
Review for gene: PREX1 was set to RED
Added comment: PMID 42399407 reports 1 individual with a de novo heterozygous missense p.Y191C PREX1 variant which has 1 heterozygote in gnomad. The proband had onset of epilepsy at 9yo which remitted at 13yo, she had no intellectual disability or abnormal MRI findings. Her mother also has several seizures and her maternal grandfather had one seizure as a child, however the PREX1 variant identified in the proband was de novo. Functional analysis of the variant showed that it reduced the GDP/GTP exchange activity of PREX1 towards RAC1 and attenuated downstream signaling.

PMID 26621702 reports four probands with a heterozygous ~1.4 kb deletion over the promoter and exon 1 of PREX1 presenting. All presented with childhood‑onset autism spectrum disorder.
Sources: Literature
Mitochondrial disease v2.5 Lucy Spencer Copied gene ATP5ME from panel Mendeliome
Mitochondrial disease v2.5 ATP5ME Lucy Spencer gene: ATP5ME was added
gene: ATP5ME was added to Mitochondrial disease. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: ATP5ME was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATP5ME were set to 42403019
Phenotypes for gene: ATP5ME were set to Mitochondrial disease (MONDO:0044970), ATP5ME-related
Mendeliome v2.507 ATP5ME Lucy Spencer Classified gene: ATP5ME as Amber List (moderate evidence)
Mendeliome v2.507 ATP5ME Lucy Spencer Gene: atp5me has been classified as Amber List (Moderate Evidence).
Mendeliome v2.506 ATP5ME Lucy Spencer gene: ATP5ME was added
gene: ATP5ME was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ATP5ME was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATP5ME were set to 42403019
Phenotypes for gene: ATP5ME were set to Mitochondrial disease (MONDO:0044970), ATP5ME-related
Review for gene: ATP5ME was set to AMBER
Added comment: PMID 42403019 reports one individual from one consanguineous family with a homozygous 62‑bp deletion (NC_000004.12: g.674234_674295del, c.-48_14del) in ATP5ME. The proband had neuroregression, encephalopathy, spasticity, sensorineural hearing loss and optic atrophy. Patient fibroblasts show markedly reduced ATP5ME transcript and protein levels and reduced expression and activity of OXPHOS complexes I, IV and V. A zebrafish atp5me (orthologue) knockout model recapitulated the developmental and locomotor defects in the proband, and these defects were rescued by complementation with human ATP5ME mRNA.
Sources: Literature
Congenital Heart Defect v1.32 Lucy Spencer Copied gene GLYR1 from panel Mendeliome
Congenital Heart Defect v1.32 GLYR1 Lucy Spencer gene: GLYR1 was added
gene: GLYR1 was added to Congenital Heart Defect. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: GLYR1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GLYR1 were set to 35182466; 38070486
Phenotypes for gene: GLYR1 were set to Congenital heart disease (MONDO:0005453), GLYR1-related
Mendeliome v2.505 GLYR1 Lucy Spencer Classified gene: GLYR1 as Amber List (moderate evidence)
Mendeliome v2.505 GLYR1 Lucy Spencer Gene: glyr1 has been classified as Amber List (Moderate Evidence).
Mendeliome v2.504 GLYR1 Lucy Spencer gene: GLYR1 was added
gene: GLYR1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GLYR1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GLYR1 were set to 35182466; 38070486
Phenotypes for gene: GLYR1 were set to Congenital heart disease (MONDO:0005453), GLYR1-related
Review for gene: GLYR1 was set to AMBER
Added comment: PMID 35182466 reports 1 individual with a de novo heterozygous missense GLYR1 p.P496L variant causing congenital heart disease with atrioventricular septal defects, left‑ventricular outflow tract obstruction and pulmonary stenosis. Functional assays including co‑immunoprecipitation, and a luciferase reporter assay demonstrated loss‑of‑function effects. In a mouse knock‑in model 54% of homozygous P496L mice and 15.5% of heterozygous mice had postnatal lethality between days 0-1, while for WT mice it was only 4.4, and VSD was seen in 15% of homozygous mice.

PMID 38070486 reports 4 individuals from 1 family harbouring a heterozygous frameshift GLYR1 c.1132delA p.R378Gfs*23 variant presenting with atrial and ventricular septal defects, arrhythmia and pulmonary hypertension. The variant segregated with disease in 4 affected individuals and was not present in 1 unaffected family member. However this variant has 74 heterozygotes in gnomad v4 and while it is predicted to undergo NMD a western blot in this paper suggests it creates a truncated protein.
Sources: Literature
Cardiomyopathy_Paediatric v1.137 COA6 Zornitza Stark Marked gene: COA6 as ready
Cardiomyopathy_Paediatric v1.137 COA6 Zornitza Stark Gene: coa6 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.137 COA6 Zornitza Stark Phenotypes for gene: COA6 were changed from Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 4 616501 to Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 4, MONDO:0014668
Cardiomyopathy_Paediatric v1.136 COA6 Zornitza Stark Publications for gene: COA6 were set to 25339201; 22277967; 25959673; 24549041
Cardiomyopathy_Paediatric v1.135 COA6 Zornitza Stark reviewed gene: COA6: Rating: GREEN; Mode of pathogenicity: None; Publications: 26160915, 25959673; Phenotypes: cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 4, MONDO:0014668; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v1.135 BRAF Zornitza Stark Phenotypes for gene: BRAF were changed from Noonan syndrome 7 613706; Cardiofaciocutaneous syndrome 115150; syndromic HCM to Noonan syndrome, MONDO:0018997; cardiofaciocutaneous syndrome 1, MONDO:0007265
Cardiomyopathy_Paediatric v1.134 BRAF Zornitza Stark Publications for gene: BRAF were set to 19206169; 21396583
Cardiomyopathy_Paediatric v1.133 BRAF Zornitza Stark reviewed gene: BRAF: Rating: GREEN; Mode of pathogenicity: None; Publications: 37697378, 35770001, 35024745, 33274568, 30732632, 29704308, 29696744, 27569062; Phenotypes: Noonan syndrome, MONDO:0018997, cardiofaciocutaneous syndrome 1, MONDO:0007265; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cardiomyopathy_Paediatric v1.133 MLYCD Zornitza Stark Marked gene: MLYCD as ready
Cardiomyopathy_Paediatric v1.133 MLYCD Zornitza Stark Gene: mlycd has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.133 MLYCD Zornitza Stark Phenotypes for gene: MLYCD were changed from malonic aciduria; 3.5.1. Malonyl CoA decarboxylase deficiency Other disorders of fatty acid and ketone body metabolism); Malonic aciduria; Malonyl-CoA decarboxylase deficiency (Organic acidurias); Mild clinical features. Developmental delay, epilepsy; Malonyl-CoA decarboxylase deficiency; HCM; Hypertrophic-hypocontractile cardiomyopathy to malonic aciduria, MONDO:0009556
Cardiomyopathy_Paediatric v1.132 MLYCD Zornitza Stark Publications for gene: MLYCD were set to 27604308; 12955715; 7609455; 9177981
Cardiomyopathy_Paediatric v1.131 MLYCD Zornitza Stark reviewed gene: MLYCD: Rating: GREEN; Mode of pathogenicity: None; Publications: 39069445, 37206471, 37144154, 34884438, 32602666, 31395333, 28781843; Phenotypes: malonic aciduria, MONDO:0009556; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v1.131 MAP2K1 Zornitza Stark Marked gene: MAP2K1 as ready
Cardiomyopathy_Paediatric v1.131 MAP2K1 Zornitza Stark Gene: map2k1 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.131 MAP2K1 Zornitza Stark Phenotypes for gene: MAP2K1 were changed from ?Noonan syndrome; Cardiofaciocutaneous Syndrome; Cardio-Facio-Cutaneous syndrome; Cardiofaciocutaneous syndrome 3; syndromic HCM; CFC syndrome; LEOPARD syndrome to cardiofaciocutaneous syndrome, MONDO:0015280
Cardiomyopathy_Paediatric v1.130 MAP2K1 Zornitza Stark Publications for gene: MAP2K1 were set to 23321623 (publication referring to Noonan syndrome association).; PMID: 21396583
Cardiomyopathy_Paediatric v1.129 MAP2K1 Zornitza Stark reviewed gene: MAP2K1: Rating: GREEN; Mode of pathogenicity: None; Publications: 37697378, 36777711; Phenotypes: cardiofaciocutaneous syndrome, MONDO:0015280; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cardiomyopathy_Paediatric v1.129 LZTR1 Zornitza Stark Marked gene: LZTR1 as ready
Cardiomyopathy_Paediatric v1.129 LZTR1 Zornitza Stark Gene: lztr1 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.129 LZTR1 Zornitza Stark Phenotypes for gene: LZTR1 were changed from Schwannomatosis-2, susceptibility to 615670; Noonan syndrome 10 616564 to Noonan syndrome 10, MIM# 616564
Cardiomyopathy_Paediatric v1.128 LZTR1 Zornitza Stark Publications for gene: LZTR1 were set to 25795793; 29469822
Cardiomyopathy_Paediatric v1.127 LZTR1 Zornitza Stark reviewed gene: LZTR1: Rating: GREEN; Mode of pathogenicity: None; Publications: 36357925, 35770001, 30872527, 30732632, 30368668, 29469822; Phenotypes: Noonan syndrome 10, MONDO:0014693; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v1.127 KRAS Zornitza Stark Publications for gene: KRAS were set to PMID: 21396583
Cardiomyopathy_Paediatric v1.126 KRAS Zornitza Stark reviewed gene: KRAS: Rating: GREEN; Mode of pathogenicity: None; Publications: 32078254, 30732632, 30430033; Phenotypes: Noonan syndrome 3, MONDO:0012371; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cardiomyopathy_Paediatric v1.126 SCN5A Zornitza Stark Marked gene: SCN5A as ready
Cardiomyopathy_Paediatric v1.126 SCN5A Zornitza Stark Gene: scn5a has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.126 SCN5A Zornitza Stark Phenotypes for gene: SCN5A were changed from Dilated cardiomyopathy; Arrhythmogenic right ventricular cardiomyopathy; Brugada syndrome; Cardiomyopathy, dilated, 1E; Long QT syndrome to dilated cardiomyopathy 1E MONDO:0011003; arrhythmogenic right ventricular cardiomyopathy, MONDO:0016587
Cardiomyopathy_Paediatric v1.125 SCN5A Zornitza Stark Publications for gene: SCN5A were set to doi:10. 1007/ s12265-016-9673-5; 24317018
Cardiomyopathy_Paediatric v1.124 SCN5A Zornitza Stark reviewed gene: SCN5A: Rating: GREEN; Mode of pathogenicity: None; Publications: 39133258, 38731905, 38352122, 36166435, 34884792, 31930659, 31024045; Phenotypes: dilated cardiomyopathy 1E MONDO:0011003, arrhythmogenic right ventricular cardiomyopathy, MONDO:0016587; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cardiomyopathy_Paediatric v1.124 RIT1 Zornitza Stark Marked gene: RIT1 as ready
Cardiomyopathy_Paediatric v1.124 RIT1 Zornitza Stark Gene: rit1 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.124 RIT1 Zornitza Stark Phenotypes for gene: RIT1 were changed from Noonan syndrome 8; Noonan syndrome type 8; Noonan syndrome 8 615355 to Noonan syndrome 8, MONDO:0014143
Cardiomyopathy_Paediatric v1.123 RIT1 Zornitza Stark Publications for gene: RIT1 were set to 23791108; 24939608; 25124994
Cardiomyopathy_Paediatric v1.122 RIT1 Zornitza Stark reviewed gene: RIT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 34887308, 33686258, 30732632, 26757980, 26714497; Phenotypes: Noonan syndrome 8, MONDO:0014143; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cardiomyopathy_Paediatric v1.122 RBM20 Zornitza Stark Marked gene: RBM20 as ready
Cardiomyopathy_Paediatric v1.122 RBM20 Zornitza Stark Gene: rbm20 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.122 RBM20 Zornitza Stark Phenotypes for gene: RBM20 were changed from Cardiomyopathy, dilated, 1DD to Cardiomyopathy, dilated, 1DD, MIM#613172
Cardiomyopathy_Paediatric v1.121 RBM20 Zornitza Stark Publications for gene: RBM20 were set to
Cardiomyopathy_Paediatric v1.120 RBM20 Zornitza Stark reviewed gene: RBM20: Rating: GREEN; Mode of pathogenicity: None; Publications: 41175027, 40399739, 40339755, 37593875, 35893073, 34540771, 34011823, 33302605, 32969603, 29367541, 26458567; Phenotypes: Cardiomyopathy, dilated, 1DD, MIM#613172; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cardiomyopathy_Paediatric v1.120 NKX2-5 Zornitza Stark Marked gene: NKX2-5 as ready
Cardiomyopathy_Paediatric v1.120 NKX2-5 Zornitza Stark Gene: nkx2-5 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.120 NKX2-5 Zornitza Stark Phenotypes for gene: NKX2-5 were changed from Atrialseptaldefect7,withorwithoutAVconductiondefects,108900 to NKX2.5-related congenital, conduction and myopathic heart disease, MONDO:0800441
Cardiomyopathy_Paediatric v1.119 NKX2-5 Zornitza Stark Publications for gene: NKX2-5 were set to
Cardiomyopathy_Paediatric v1.118 NKX2-5 Zornitza Stark reviewed gene: NKX2-5: Rating: GREEN; Mode of pathogenicity: None; Publications: 36357925, 35683556, 34277740, 33082984, 27855642, 27855642, 26913919; Phenotypes: NKX2.5-related congenital, conduction and myopathic heart disease, MONDO:0800441; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Macular Dystrophy/Stargardt Disease v1.1 KATNA1 Zornitza Stark Marked gene: KATNA1 as ready
Macular Dystrophy/Stargardt Disease v1.1 KATNA1 Zornitza Stark Gene: katna1 has been classified as Amber List (Moderate Evidence).
Macular Dystrophy/Stargardt Disease v1.1 Zornitza Stark Copied gene KATNA1 from panel Mendeliome
Macular Dystrophy/Stargardt Disease v1.1 KATNA1 Zornitza Stark gene: KATNA1 was added
gene: KATNA1 was added to Macular Dystrophy/Stargardt Disease. Sources: Expert Review Amber,Literature
preprint tags were added to gene: KATNA1.
Mode of inheritance for gene: KATNA1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KATNA1 were set to 42466416
Phenotypes for gene: KATNA1 were set to Macular dystrophy, non-syndromic MONDO:0020242
Mendeliome v2.503 KATNA1 Zornitza Stark Marked gene: KATNA1 as ready
Mendeliome v2.503 KATNA1 Zornitza Stark Gene: katna1 has been classified as Amber List (Moderate Evidence).
Mendeliome v2.503 KATNA1 Zornitza Stark Tag preprint tag was added to gene: KATNA1.
Bone Marrow Failure v2.9 MYB Zornitza Stark Marked gene: MYB as ready
Bone Marrow Failure v2.9 MYB Zornitza Stark Gene: myb has been classified as Amber List (Moderate Evidence).
Combined Immunodeficiency v2.10 MYB Zornitza Stark Classified gene: MYB as Amber List (moderate evidence)
Combined Immunodeficiency v2.10 MYB Zornitza Stark Gene: myb has been classified as Amber List (Moderate Evidence).
Combined Immunodeficiency v2.9 Zornitza Stark Added reviews for gene MYB from panel Mendeliome
Bone Marrow Failure v2.9 Zornitza Stark Copied gene MYB from panel Mendeliome
Bone Marrow Failure v2.9 MYB Zornitza Stark gene: MYB was added
gene: MYB was added to Bone Marrow Failure. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: MYB was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MYB were set to 20130238; 27577878; 29654210; 36168523
Phenotypes for gene: MYB were set to combined immunodeficiency, MONDO:0015131
Mendeliome v2.503 MYB Zornitza Stark Classified gene: MYB as Amber List (moderate evidence)
Mendeliome v2.503 MYB Zornitza Stark Gene: myb has been classified as Amber List (Moderate Evidence).
Cardiomyopathy_Paediatric v1.118 FKRP Zornitza Stark Marked gene: FKRP as ready
Cardiomyopathy_Paediatric v1.118 FKRP Zornitza Stark Gene: fkrp has been classified as Red List (Low Evidence).
Cardiomyopathy_Paediatric v1.118 FKRP Zornitza Stark Phenotypes for gene: FKRP were changed from to autosomal recessive limb-girdle muscular dystrophy type 2I, MONDO:0011787
Cardiomyopathy_Paediatric v1.117 FKRP Zornitza Stark Publications for gene: FKRP were set to
Cardiomyopathy_Paediatric v1.116 FKRP Zornitza Stark Classified gene: FKRP as Red List (low evidence)
Cardiomyopathy_Paediatric v1.116 FKRP Zornitza Stark Gene: fkrp has been classified as Red List (Low Evidence).
Cardiomyopathy_Paediatric v1.115 FKRP Zornitza Stark reviewed gene: FKRP: Rating: RED; Mode of pathogenicity: None; Publications: 31671740; Phenotypes: autosomal recessive limb-girdle muscular dystrophy type 2I, MONDO:0011787; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v1.115 BCS1L Zornitza Stark Marked gene: BCS1L as ready
Cardiomyopathy_Paediatric v1.115 BCS1L Zornitza Stark Gene: bcs1l has been classified as Red List (Low Evidence).
Cardiomyopathy_Paediatric v1.115 BCS1L Zornitza Stark Phenotypes for gene: BCS1L were changed from Leigh syndrome, 256000; Mitochondrial complex III deficiency, nuclear type 1, 124000 to mitochondrial complex III deficiency nuclear type 1, MONDO:0007415
Cardiomyopathy_Paediatric v1.114 BCS1L Zornitza Stark Publications for gene: BCS1L were set to
Cardiomyopathy_Paediatric v1.113 BCS1L Zornitza Stark reviewed gene: BCS1L: Rating: RED; Mode of pathogenicity: None; Publications: 37001142; Phenotypes: mitochondrial complex III deficiency nuclear type 1, MONDO:0007415; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v1.113 MYH6 Zornitza Stark Phenotypes for gene: MYH6 were changed from Cardiomyopathy, familial hypertrophic, 14; Cardiomyopathy, dilated, 1EE to dilated cardiomyopathy 1EE MONDO:0013198; hypertrophic cardiomyopathy MONDO:0005045
Cardiomyopathy_Paediatric v1.112 MYH6 Zornitza Stark Publications for gene: MYH6 were set to
Cardiomyopathy_Paediatric v1.111 MYH6 Zornitza Stark reviewed gene: MYH6: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: dilated cardiomyopathy 1EE MONDO:0013198, hypertrophic cardiomyopathy MONDO:0005045; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cardiomyopathy_Paediatric v1.111 ETFDH Zornitza Stark Marked gene: ETFDH as ready
Cardiomyopathy_Paediatric v1.111 ETFDH Zornitza Stark Gene: etfdh has been classified as Amber List (Moderate Evidence).
Cardiomyopathy_Paediatric v1.111 ETFDH Zornitza Stark Phenotypes for gene: ETFDH were changed from Multiple acyl-CoA dehydrogenase deficiency (MADD) (glutaric aciduria type II); Glutaric acidemia IIC; Secondary CoQ10 deficiency (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); HCM; ETF-ubiquinone oxidoreductase deficiency (Disorders of mitochondrial fatty acid oxidation); Facial and cerebral malformations, cystic renal disease, liver disease, hypoketotic hypoglycaemia; Disorders of ubiquinone metabolism and biosynthesis; GLUTARIC ACIDURIA TYPE 2C to multiple acyl-CoA dehydrogenase deficiency, MONDO:0009282
Cardiomyopathy_Paediatric v1.110 ETFDH Zornitza Stark Publications for gene: ETFDH were set to 24816252; 27604308
Cardiomyopathy_Paediatric v1.109 ETFDH Zornitza Stark Classified gene: ETFDH as Amber List (moderate evidence)
Cardiomyopathy_Paediatric v1.109 ETFDH Zornitza Stark Gene: etfdh has been classified as Amber List (Moderate Evidence).
Cardiomyopathy_Paediatric v1.108 ETFDH Zornitza Stark reviewed gene: ETFDH: Rating: AMBER; Mode of pathogenicity: None; Publications: 30027710; Phenotypes: multiple acyl-CoA dehydrogenase deficiency, MONDO:0009282; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Dilated Cardiomyopathy v2.9 MYLK3 Zornitza Stark Marked gene: MYLK3 as ready
Dilated Cardiomyopathy v2.9 MYLK3 Zornitza Stark Gene: mylk3 has been classified as Amber List (Moderate Evidence).
Dilated Cardiomyopathy v2.9 MYLK3 Zornitza Stark Publications for gene: MYLK3 were set to 29235529; 31244672; 32213617; 32870709
Dilated Cardiomyopathy v2.8 MYLK3 Zornitza Stark changed review comment from: 4 monoallelic families reported – PMID 30690923, PMID 29235529 (2 families), PMID 37128901 and 3 biallelic families – PMID 32870709. A mouse knock‑in model and patient‑derived iPSC‑cardiomyocyte rescue (PMID 37128901) provide functional validation.

Monoallelic association is Moderate by ClinGen.

However, the biallelic association is the one that is pertinent to this panel.; to: 4 monoallelic families reported – PMID 30690923, PMID 29235529 (2 families), PMID 37128901 and 3 biallelic families – PMID 32870709. A mouse knock‑in model and patient‑derived iPSC‑cardiomyocyte rescue (PMID 37128901) provide functional validation.

Monoallelic association is Moderate by ClinGen.

Biallelic association is paediatric onset.
Dilated Cardiomyopathy v2.8 Zornitza Stark Copied gene MYLK3 from panel Cardiomyopathy_Paediatric
Dilated Cardiomyopathy v2.8 MYLK3 Zornitza Stark gene: MYLK3 was added
gene: MYLK3 was added to Dilated Cardiomyopathy. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: MYLK3 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: MYLK3 were set to 29235529; 31244672; 32213617; 32870709
Phenotypes for gene: MYLK3 were set to dilated cardiomyopathy, MONDO:0005021, MYLK3-related
Cardiomyopathy_Paediatric v1.108 MYLK3 Zornitza Stark Phenotypes for gene: MYLK3 were changed from Dilated cardiomyopathy to dilated cardiomyopathy, MONDO:0005021, MYLK3-related
Cardiomyopathy_Paediatric v1.107 MYLK3 Zornitza Stark edited their review of gene: MYLK3: Added comment: 4 monoallelic families reported – PMID 30690923, PMID 29235529 (2 families), PMID 37128901 and 3 biallelic families – PMID 32870709. A mouse knock‑in model and patient‑derived iPSC‑cardiomyocyte rescue (PMID 37128901) provide functional validation.

Monoallelic association is Moderate by ClinGen.

However, the biallelic association is the one that is pertinent to this panel.; Changed publications: 37128901, 32870709, 30690923, 29235529; Changed phenotypes: dilated cardiomyopathy, MONDO:0005021
Cardiomyopathy_Paediatric v1.107 LAMA4 Zornitza Stark Marked gene: LAMA4 as ready
Cardiomyopathy_Paediatric v1.107 LAMA4 Zornitza Stark Gene: lama4 has been classified as Red List (Low Evidence).
Cardiomyopathy_Paediatric v1.107 LAMA4 Zornitza Stark Phenotypes for gene: LAMA4 were changed from to dilated cardiomyopathy 1JJ, MONDO:0014095
Cardiomyopathy_Paediatric v1.106 LAMA4 Zornitza Stark Publications for gene: LAMA4 were set to
Cardiomyopathy_Paediatric v1.105 LAMA4 Zornitza Stark reviewed gene: LAMA4: Rating: RED; Mode of pathogenicity: None; Publications: 39686469, 39272661, 36270459, 35893073, 35526016, 31024045; Phenotypes: dilated cardiomyopathy 1JJ, MONDO:0014095; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v2.123 DCTN4 Rylee Peters Marked gene: DCTN4 as ready
Intellectual disability syndromic and non-syndromic v2.123 DCTN4 Rylee Peters Gene: dctn4 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v2.123 Rylee Peters Copied gene DCTN4 from panel Mendeliome
Intellectual disability syndromic and non-syndromic v2.123 DCTN4 Rylee Peters gene: DCTN4 was added
gene: DCTN4 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: DCTN4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DCTN4 were set to 42378292
Phenotypes for gene: DCTN4 were set to Neurodevelopmental disorder, MONDO:0700092, DCTN4-related
Mendeliome v2.502 DCTN4 Rylee Peters Marked gene: DCTN4 as ready
Mendeliome v2.502 DCTN4 Rylee Peters Gene: dctn4 has been classified as Amber List (Moderate Evidence).
Mendeliome v2.502 DCTN4 Rylee Peters Classified gene: DCTN4 as Amber List (moderate evidence)
Mendeliome v2.502 DCTN4 Rylee Peters Gene: dctn4 has been classified as Amber List (Moderate Evidence).
Mendeliome v2.501 DCTN4 Rylee Peters gene: DCTN4 was added
gene: DCTN4 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: DCTN4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DCTN4 were set to 42378292
Phenotypes for gene: DCTN4 were set to Neurodevelopmental disorder, MONDO:0700092, DCTN4-related
Review for gene: DCTN4 was set to AMBER
Added comment: PMID:42378292 describes two unrelated families with ID, language impairment and cognitive dysfunction. One individual harboured a de novo nonsense variant, p.Tyr240*, absent from gnomAD. A second had an inherited p.Gln268Arg missense variant (affected parent), also absent from gnomAD; brain MRI in the proband and parent showed brain anomalies.
Two additional unrelated individuals with developmental delay carried de novo missense variants, p.Arg115His (34 heterozygotes in gnomAD) and p.Arg238Cys (absent from gnomAD).

Functional evidence: A Y240X mouse model showed embryonic lethality in homozygotes, while heterozygotes had ~50% reduction in DCN4 mRNA, impaired synaptic development and significantly reduced learning ability.
Sources: Literature
Intellectual disability syndromic and non-syndromic v2.122 AFF3 Rylee Peters Phenotypes for gene: AFF3 were changed from KINSSHIP syndrome, MIM# 619297 to KINSSHIP syndrome, MIM# 619297; Neurodevelopmental disorder, MONDO:0700092, AFF3-related
Intellectual disability syndromic and non-syndromic v2.121 AFF3 Rylee Peters Mode of inheritance for gene: AFF3 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v2.120 Rylee Peters Added reviews for gene AFF3 from panel Mendeliome
Mendeliome v2.500 AFF3 Rylee Peters Phenotypes for gene: AFF3 were changed from KINSSHIP syndrome, MIM# 619297 to KINSSHIP syndrome, MIM# 619297; Neurodevelopmental disorder, MONDO:0700092, AFF3-related
Mendeliome v2.499 AFF3 Rylee Peters Mode of inheritance for gene: AFF3 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v2.498 AFF3 Rylee Peters reviewed gene: AFF3: Rating: GREEN; Mode of pathogenicity: None; Publications: 38811945; Phenotypes: KINSSHIP syndrome, MIM# 619297, Neurodevelopmental disorder, MONDO:0700092, AFF3-related; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hand and foot malformations v1.10 FAT1 Lucy Spencer Phenotypes for gene: FAT1 were changed from facial dysmorphism; colobomatous microphthalmia; ptosis; syndactyly with or without nephropathy to Focal segmental glomerulosclerosis (MONDO:0100313), FAT1-related
Hand and foot malformations v1.9 Lucy Spencer Added reviews for gene FAT1 from panel Proteinuria
Anophthalmia_Microphthalmia_Coloboma v2.6 Lucy Spencer Added reviews for gene FAT1 from panel Proteinuria
Proteinuria v1.3 FAT1 Lucy Spencer reviewed gene: FAT1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Focal segmental glomerulosclerosis (MONDO:0100313), FAT1-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Proteinuria v1.3 FAT1 Lucy Spencer Phenotypes for gene: FAT1 were changed from facial dysmorphism; colobomatous microphthalmia; ptosis; syndactyly with or without nephropathy to Focal segmental glomerulosclerosis (MONDO:0100313), FAT1-related
Anophthalmia_Microphthalmia_Coloboma v2.5 FAT1 Lucy Spencer Phenotypes for gene: FAT1 were changed from facial dysmorphism; colobomatous microphthalmia; ptosis; syndactyly with or without nephropathy to Focal segmental glomerulosclerosis (MONDO:0100313), FAT1-related
Mendeliome v2.498 FAT1 Lucy Spencer Publications for gene: FAT1 were set to 30862798
Mendeliome v2.497 FAT1 Lucy Spencer Phenotypes for gene: FAT1 were changed from syndromic disease MONDO:0002254, FAT1-related; facial dysmorphism; colobomatous microphthalmia; ptosis; syndactyly with or without nephropathy to Focal segmental glomerulosclerosis (MONDO:0100313), FAT1-related; Facioscapulohumeral muscular dystrophy (MONDO:0001347), FAT1-related
Mendeliome v2.496 FAT1 Lucy Spencer edited their review of gene: FAT1: Added comment: Clingen: Strong for Focal segmental glomerulosclerosis (MONDO:0100313), FAT1-related

describe the condition as "syndromic, characterized by renal failure and podocyte foot process effacement, as well as cancer, vision anomalies, and brain structural issues". All the reported phenotypes likely represent 1 spectrum of disease (with the exception of the proposed AD Facioscapulohumeral (FSHG) Dystrophy-Like Phenotype which is currently red- clingen have not reviews the AD association); Changed rating: GREEN; Changed phenotypes: Focal segmental glomerulosclerosis (MONDO:0100313), FAT1-related, Facioscapulohumeral muscular dystrophy (MONDO:0001347), FAT1-related; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Limb-Girdle Muscular Dystrophy and Distal Myopathy v2.5 FAT1 Lucy Spencer Phenotypes for gene: FAT1 were changed from syndromic disease MONDO:0002254, FAT1-related; facial dysmorphism; colobomatous microphthalmia; ptosis; syndactyly with or without nephropathy to Facioscapulohumeral muscular dystrophy (MONDO:0001347), FAT1-related
Limb-Girdle Muscular Dystrophy and Distal Myopathy v2.4 FAT1 Lucy Spencer Publications for gene: FAT1 were set to 30862798
Limb-Girdle Muscular Dystrophy and Distal Myopathy v2.3 FAT1 Lucy Spencer Mode of inheritance for gene: FAT1 was changed from BIALLELIC, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Limb-Girdle Muscular Dystrophy and Distal Myopathy v2.2 FAT1 Lucy Spencer Classified gene: FAT1 as Red List (low evidence)
Limb-Girdle Muscular Dystrophy and Distal Myopathy v2.2 FAT1 Lucy Spencer Gene: fat1 has been classified as Red List (Low Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v2.1 Lucy Spencer Copied gene FAT1 from panel Mendeliome
Limb-Girdle Muscular Dystrophy and Distal Myopathy v2.1 FAT1 Lucy Spencer gene: FAT1 was added
gene: FAT1 was added to Limb-Girdle Muscular Dystrophy and Distal Myopathy. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: FAT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FAT1 were set to 30862798
Phenotypes for gene: FAT1 were set to syndromic disease MONDO:0002254, FAT1-related; facial dysmorphism; colobomatous microphthalmia; ptosis; syndactyly with or without nephropathy
Mendeliome v2.496 FAT1 Lucy Spencer reviewed gene: FAT1: Rating: RED; Mode of pathogenicity: None; Publications: 25615407; Phenotypes: Facioscapulohumeral muscular dystrophy (MONDO:0001347), FAT1-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Common deletion and duplication syndromes v1.3 ISCA-37397-Gain Sarah Milton GRCh38 position for ISCA-37397-Gain was changed from 21443089-23306926 to 21562828-22620608.
Source Expert list was removed from Region: ISCA-37397-Gain.
Source ClinGen was added to Region: ISCA-37397-Gain.
Skeletal dysplasia v1.119 Sarah Milton Copied Region MSX2 upstream regulatory region from panel Mendeliome
Skeletal dysplasia v1.119 MSX2 upstream regulatory region Sarah Milton Region: MSX2 upstream regulatory region was added
Region: MSX2 upstream regulatory region was added to Skeletal dysplasia. Sources: Expert Review Amber,Literature
regulatory region tags were added to Region: MSX2 upstream regulatory region.
Mode of inheritance for Region: MSX2 upstream regulatory region was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for Region: MSX2 upstream regulatory region were set to 22717651; 42609732
Phenotypes for Region: MSX2 upstream regulatory region were set to Parietal foramina 1 MIM#168500; Parietal foramina with cleidocranial dysplasia MIM#168550
Fetal anomalies v2.63 Sarah Milton Copied Region MSX2 upstream regulatory region from panel Mendeliome
Fetal anomalies v2.63 MSX2 upstream regulatory region Sarah Milton Region: MSX2 upstream regulatory region was added
Region: MSX2 upstream regulatory region was added to Fetal anomalies. Sources: Expert Review Amber,Literature
regulatory region tags were added to Region: MSX2 upstream regulatory region.
Mode of inheritance for Region: MSX2 upstream regulatory region was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for Region: MSX2 upstream regulatory region were set to 22717651; 42609732
Phenotypes for Region: MSX2 upstream regulatory region were set to Parietal foramina 1 MIM#168500; Parietal foramina with cleidocranial dysplasia MIM#168550
Mendeliome v2.496 MSX2 upstream regulatory region Sarah Milton Marked Region: MSX2 upstream regulatory region as ready
Mendeliome v2.496 MSX2 upstream regulatory region Sarah Milton Region: msx2 upstream regulatory region has been classified as Amber List (Moderate Evidence).
Mendeliome v2.496 MSX2 upstream regulatory region Sarah Milton Classified Region: MSX2 upstream regulatory region as Amber List (moderate evidence)
Mendeliome v2.496 MSX2 upstream regulatory region Sarah Milton Region: msx2 upstream regulatory region has been classified as Amber List (Moderate Evidence).
Mendeliome v2.495 MSX2 upstream regulatory region Sarah Milton Region: MSX2 upstream regulatory region was added
Region: MSX2 upstream regulatory region was added to Mendeliome. Sources: Literature
regulatory region tags were added to Region: MSX2 upstream regulatory region.
Mode of inheritance for Region: MSX2 upstream regulatory region was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for Region: MSX2 upstream regulatory region were set to 22717651; 42609732
Phenotypes for Region: MSX2 upstream regulatory region were set to Parietal foramina 1 MIM#168500; Parietal foramina with cleidocranial dysplasia MIM#168550
Review for Region: MSX2 upstream regulatory region was set to AMBER
Added comment: MSX2 encodes a homeobox transcription factor that is known to have a role in osteogenic growth.

Sequence variants in MSX2 result in Craniosynostosis 2, MIM#604757, Parietal foramina 1 MIM#168500.

PMID: 22717651 summarises 2 unrelated individuals with duplications approx 10-70kb upstream of MSX2 presenting with cleidocranial dysplasia. Mechanism of disease postulated to be overexpression of MSX2, authors report enhancers were underlying some of the duplicated region.

PMID: 42609732 summarised 3 individuals from 2 unrelated families with parietal foramina with microduplications upstream of MSX2.

Mechanism remains somewhat undefined with rare reports.

Note: minimum duplicated region has been used for this entry
Sources: Literature
Skeletal dysplasia v1.118 Sarah Milton Copied Region 8q13 deletion Mesomelia-Synostoses Syndrome from panel Mendeliome
Skeletal dysplasia v1.118 8q13 deletion Mesomelia-Synostoses Syndrome Sarah Milton Region: 8q13 deletion Mesomelia-Synostoses Syndrome was added
Region: 8q13 deletion Mesomelia-Synostoses Syndrome was added to Skeletal dysplasia. Sources: Expert Review Green,Literature
regulatory region tags were added to Region: 8q13 deletion Mesomelia-Synostoses Syndrome.
Mode of inheritance for Region: 8q13 deletion Mesomelia-Synostoses Syndrome was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for Region: 8q13 deletion Mesomelia-Synostoses Syndrome were set to 20602915; 38992676; 30450550; 28328141
Phenotypes for Region: 8q13 deletion Mesomelia-Synostoses Syndrome were set to Mesomelia-synostoses syndrome, MIM#600383
Fetal anomalies v2.62 Sarah Milton Copied Region 8q13 deletion Mesomelia-Synostoses Syndrome from panel Mendeliome
Fetal anomalies v2.62 8q13 deletion Mesomelia-Synostoses Syndrome Sarah Milton Region: 8q13 deletion Mesomelia-Synostoses Syndrome was added
Region: 8q13 deletion Mesomelia-Synostoses Syndrome was added to Fetal anomalies. Sources: Expert Review Green,Literature
regulatory region tags were added to Region: 8q13 deletion Mesomelia-Synostoses Syndrome.
Mode of inheritance for Region: 8q13 deletion Mesomelia-Synostoses Syndrome was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for Region: 8q13 deletion Mesomelia-Synostoses Syndrome were set to 20602915; 38992676; 30450550; 28328141
Phenotypes for Region: 8q13 deletion Mesomelia-Synostoses Syndrome were set to Mesomelia-synostoses syndrome, MIM#600383
Mendeliome v2.494 8q13 deletion Mesomelia-Synostoses Syndrome Sarah Milton Marked Region: 8q13 deletion Mesomelia-Synostoses Syndrome as ready
Mendeliome v2.494 8q13 deletion Mesomelia-Synostoses Syndrome Sarah Milton Region: 8q13 deletion mesomelia-synostoses syndrome has been classified as Green List (High Evidence).
Mendeliome v2.494 8q13 deletion Mesomelia-Synostoses Syndrome Sarah Milton Classified Region: 8q13 deletion Mesomelia-Synostoses Syndrome as Green List (high evidence)
Mendeliome v2.494 8q13 deletion Mesomelia-Synostoses Syndrome Sarah Milton Region: 8q13 deletion mesomelia-synostoses syndrome has been classified as Green List (High Evidence).
Mendeliome v2.493 8q13 deletion Mesomelia-Synostoses Syndrome Sarah Milton Region: 8q13 deletion Mesomelia-Synostoses Syndrome was added
Region: 8q13 deletion Mesomelia-Synostoses Syndrome was added to Mendeliome. Sources: Literature
regulatory region tags were added to Region: 8q13 deletion Mesomelia-Synostoses Syndrome.
Mode of inheritance for Region: 8q13 deletion Mesomelia-Synostoses Syndrome was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for Region: 8q13 deletion Mesomelia-Synostoses Syndrome were set to 20602915; 38992676; 30450550; 28328141
Phenotypes for Region: 8q13 deletion Mesomelia-Synostoses Syndrome were set to Mesomelia-synostoses syndrome, MIM#600383
Review for Region: 8q13 deletion Mesomelia-Synostoses Syndrome was set to GREEN
Added comment: Heterozygous deletions involving SULF1 and SLCO5A1 have been reported in 6 affected individuals from 5 unrelated families with Mesomelia-synostoses syndrome.

Clinical presentation included: Mesomelic limb shortening, acral synostosis, multiple congenital malformations

Deletions ranged from 582-738kb in size with as of yet an unclear mechanism of disease.

Both SULF1 and SLCO5A1 are expressed in skeletal tissues however neither gene is constrained for loss of function in population databases.

Functional studies in mice with homozygous knockout revealed milder defects with reduced bone length, early ossification vertebrae, fusion vertebrae.
The 2 genes are in separate TADs with predicted chondrogenic enhancers in the deleted region as such alteration a regulatory effect is suspected.

Note: minimum coordinates used for this entry
Sources: Literature
Skeletal dysplasia v1.117 Sarah Milton Copied Region 10q24 duplication syndrome Split hand foot malformation 3 from panel Mendeliome
Skeletal dysplasia v1.117 10q24 duplication syndrome Split hand foot malformation 3 Sarah Milton Region: 10q24 duplication syndrome Split hand foot malformation 3 was added
Region: 10q24 duplication syndrome Split hand foot malformation 3 was added to Skeletal dysplasia. Sources: Expert Review Green,Literature
Mode of inheritance for Region: 10q24 duplication syndrome Split hand foot malformation 3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for Region: 10q24 duplication syndrome Split hand foot malformation 3 were set to 30622331; 27600068; 38168117; 35908152; 23596994
Phenotypes for Region: 10q24 duplication syndrome Split hand foot malformation 3 were set to Split-hand/foot malformation 3, gene duplication syndrome, MIM#246560
Penetrance for Region: 10q24 duplication syndrome Split hand foot malformation 3 were set to Incomplete
Hand and foot malformations v1.8 Sarah Milton Copied Region 10q24 duplication syndrome Split hand foot malformation 3 from panel Mendeliome
Hand and foot malformations v1.8 10q24 duplication syndrome Split hand foot malformation 3 Sarah Milton Region: 10q24 duplication syndrome Split hand foot malformation 3 was added
Region: 10q24 duplication syndrome Split hand foot malformation 3 was added to Hand and foot malformations. Sources: Expert Review Green,Literature
Mode of inheritance for Region: 10q24 duplication syndrome Split hand foot malformation 3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for Region: 10q24 duplication syndrome Split hand foot malformation 3 were set to 30622331; 27600068; 38168117; 35908152; 23596994
Phenotypes for Region: 10q24 duplication syndrome Split hand foot malformation 3 were set to Split-hand/foot malformation 3, gene duplication syndrome, MIM#246560
Penetrance for Region: 10q24 duplication syndrome Split hand foot malformation 3 were set to Incomplete
Fetal anomalies v2.61 Sarah Milton Copied Region 10q24 duplication syndrome Split hand foot malformation 3 from panel Mendeliome
Fetal anomalies v2.61 10q24 duplication syndrome Split hand foot malformation 3 Sarah Milton Region: 10q24 duplication syndrome Split hand foot malformation 3 was added
Region: 10q24 duplication syndrome Split hand foot malformation 3 was added to Fetal anomalies. Sources: Expert Review Green,Literature
Mode of inheritance for Region: 10q24 duplication syndrome Split hand foot malformation 3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for Region: 10q24 duplication syndrome Split hand foot malformation 3 were set to 30622331; 27600068; 38168117; 35908152; 23596994
Phenotypes for Region: 10q24 duplication syndrome Split hand foot malformation 3 were set to Split-hand/foot malformation 3, gene duplication syndrome, MIM#246560
Penetrance for Region: 10q24 duplication syndrome Split hand foot malformation 3 were set to Incomplete
Fetal anomalies v2.60 TTN Sarah Milton Source Expert list was removed from TTN.
Phenotypes for gene: TTN were changed from Salih myopathy; Muscular dystrophy, limb-girdle, autosomal recessive 10 to TTN-related myopathy MONDO:0100175
Cardiomyopathy_Paediatric v1.105 TTN Sarah Milton Source South West GLH was removed from TTN.
Source NHS GMS was removed from TTN.
Source ClinGen was added to TTN.
Phenotypes for gene: TTN were changed from Cardiomyopathy, familial hypertrophic, 9,; Cardiomyopathy, dilated, 1G to Dilated cardiomyopathy 1G, MONDO:0011400; Hypertrophic cardiomyopathy, MONDO:0005045
Incidentalome v1.11 TTN Sarah Milton Source Victorian Clinical Genetics Services was removed from TTN.
Source Victorian Clinical Genetics Services was removed from TTN.
Source ClinGen was added to TTN.
Phenotypes for gene: TTN were changed from to Dilated cardiomyopathy 1G, MONDO:0011400; TTN-related myopathy, MONDO:0100175; Myopathy, myofibrillar, 9, with early respiratory failure, MONDO:0011362; Tibial muscular dystrophy, MONDO:0010870; TTN-related myopathy, dominant-negative TTNsv, MONDO:1060225
Hypertrophic cardiomyopathy v2.1 TTN Sarah Milton Source Victorian Clinical Genetics Services was removed from TTN.
Source ClinGen was added to TTN.
Phenotypes for gene: TTN were changed from Hypertrophic cardiomyopathy to Hypertrophic cardiomyopathy MONDO:0005045
Arthrogryposis v2.3 TTN Sarah Milton Source Expert list was removed from TTN.
Source ClinGen was added to TTN.
Mode of inheritance for gene TTN was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: TTN were changed from Salih myopathy; Muscular dystrophy, limb-girdle, autosomal recessive 10 to TTN-related myopathy, MONDO:0100175; TTN-related myopathy, dominant-negative TTNsv, MONDO:1060225
Incidentalome v1.10 TTN Sarah Milton changed review comment from: Summary of phenotypes as per Clingen:

Dilated cardiomyopathy 1G, MONDO:0011400
- Definitive association
- AD
- Molecular mechanism - truncating variants in exon with sufficiently high PSI, exact mechanism remains unclear - haploinsufficiency on it's own unlikely to be the only contributing factor, some papers postulate accumulation of truncated poison peptides contribute.

TTN-related myopathy, MONDO:0100175
- Definitive association
- AR
- Lumped: limb-girdle muscular dystrophy, (MIM #608807), centronuclear myopathy, Salih myopathy (MIM #611705), Emery-Dreifuss-like muscular dystrophy (not an OMIM entity), titinopathy with congenital contractures (not an OMIM entity), minicore myopathy (not an OMIM entity), distal titinopathy
- Presumably loss of function molecular mechanism, frameshift, deletion, missense, splice site variants have been called LP/P for this phenotype, PSI less relevant

Myopathy, myofibrillar, 9, with early respiratory failure MONDO:0011362
- Definitive association
- AD
- Missense variants in exon 344 A band

Tibial muscular dystrophy, MONDO:0010870
- Moderate association
- AD
- Variants in M line – missense and truncating exon 363

TTN-related myopathy, dominant-negative TTNsv, MONDO:1060225
- Moderate association
- AD
- Multiexon in frame deletion/CNV escape NMD, expressed
- Located in Z disk, A,I or A/M band deletions
- Phenotype ranges from arthrogryposis to adult onset distal myopathy

Hypertrophic cardiomyopathy, MONDO:0005045, AD
- Limited association
- AD

Arrhythmogenic right ventricular cardiomyopathy, MONDO:0016587
- Disputed association
- AD; to: Summary of phenotypes as per Clingen:

Dilated cardiomyopathy 1G, MONDO:0011400
- Definitive association
- AD
- Molecular mechanism - truncating variants in exon with sufficiently high PSI, exact mechanism remains unclear - haploinsufficiency on it's own unlikely to be the only contributing factor, some papers postulate accumulation of truncated poison peptides contribute.


TTN-related myopathy, MONDO:0100175
- Definitive association
- AR
- Lumped: limb-girdle muscular dystrophy, (MIM #608807), centronuclear myopathy, Salih myopathy (MIM #611705), Emery-Dreifuss-like muscular dystrophy (not an OMIM entity), titinopathy with congenital contractures (not an OMIM entity), minicore myopathy (not an OMIM entity), distal titinopathy
- Presumably loss of function molecular mechanism, frameshift, deletion, missense, splice site variants have been called LP/P for this phenotype, PSI less relevant


Myopathy, myofibrillar, 9, with early respiratory failure MONDO:0011362
- Definitive association
- AD
- Missense variants in exon 344 A band

Tibial muscular dystrophy, MONDO:0010870
- Moderate association
- AD
- Variants in M line – missense and truncating exon 363


TTN-related myopathy, dominant-negative TTNsv, MONDO:1060225
- Moderate association
- AD
- Multiexon in frame deletion/CNV escape NMD, expressed
- Located in Z disk, A,I or A/M band deletions
- Phenotype ranges from arthrogryposis to adult onset distal myopathy


Hypertrophic cardiomyopathy, MONDO:0005045, AD
- Limited association
- AD


Arrhythmogenic right ventricular cardiomyopathy, MONDO:0016587
- Disputed association
- AD
Cardiomyopathy_Paediatric v1.104 GBE1 Zornitza Stark Marked gene: GBE1 as ready
Cardiomyopathy_Paediatric v1.104 GBE1 Zornitza Stark Gene: gbe1 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.104 GBE1 Zornitza Stark Phenotypes for gene: GBE1 were changed from Glycogen Storage Disorders- Liver; Glycogen Storage Disorders- Muscle; Glycogen storage disease type IV, Andersen (Glycogen storage disorders); Glycogen storage disease IV, 232500; hypotonia, exercise intolerance, polyglucosan bodies in affected tissues; Glycogen Storage Disease Type IV; failure to thrive in addition to hepatomegaly van have neuromuscular adult form ( polyglucosan body ideas which presents with neurogenic bladder, gait difficulties; DCM; Polyglucosan body disease, adult form, 263570; Glycogen storage disease type IV (brancher enzyme deficiency), neuromuscular form; Hypertrophic-hypocontractile cardiomyopathy; Glycogen Storage Disease to glycogen storage disease due to glycogen branching enzyme deficiency, MONDO:0009292
Cardiomyopathy_Paediatric v1.103 GBE1 Zornitza Stark Classified gene: GBE1 as Green List (high evidence)
Cardiomyopathy_Paediatric v1.103 GBE1 Zornitza Stark Gene: gbe1 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.102 GBE1 Zornitza Stark reviewed gene: GBE1: Rating: GREEN; Mode of pathogenicity: None; Publications: 38516405, 38436530, 38012812, 36830903, 29379554; Phenotypes: glycogen storage disease due to glycogen branching enzyme deficiency, MONDO:0009292; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Incidentalome v1.10 TTN Sarah Milton reviewed gene: TTN: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v1.102 SMAD4 Zornitza Stark Marked gene: SMAD4 as ready
Cardiomyopathy_Paediatric v1.102 SMAD4 Zornitza Stark Gene: smad4 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.102 SMAD4 Zornitza Stark Classified gene: SMAD4 as Green List (high evidence)
Cardiomyopathy_Paediatric v1.102 SMAD4 Zornitza Stark Gene: smad4 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.101 SMAD4 Zornitza Stark gene: SMAD4 was added
gene: SMAD4 was added to Cardiomyopathy_Paediatric. Sources: Literature
Mode of inheritance for gene: SMAD4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SMAD4 were set to 37529930; 34236823; 27302097; 26420300
Phenotypes for gene: SMAD4 were set to Myhre syndrome, MONDO:0007688
Review for gene: SMAD4 was set to GREEN
Added comment: Well established gene-disease association, restrictive cardiomyopathy is part of the phenotype.
Sources: Literature
Cardiomyopathy_Paediatric v1.100 MT-ATP6 Zornitza Stark Marked gene: MT-ATP6 as ready
Cardiomyopathy_Paediatric v1.100 MT-ATP6 Zornitza Stark Gene: mt-atp6 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.100 MT-ATP6 Zornitza Stark Classified gene: MT-ATP6 as Green List (high evidence)
Cardiomyopathy_Paediatric v1.100 MT-ATP6 Zornitza Stark Gene: mt-atp6 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.99 MT-ATP6 Zornitza Stark gene: MT-ATP6 was added
gene: MT-ATP6 was added to Cardiomyopathy_Paediatric. Sources: Literature
Mode of inheritance for gene gene: MT-ATP6 was set to MITOCHONDRIAL
Publications for gene: MT-ATP6 were set to 40367733; 40112238; 39119452; 29101127; 27453250
Phenotypes for gene: MT-ATP6 were set to Mitochondrial complex V (ATP synthase) deficiency, MONDO:0014471, MT-ATP6-related
Review for gene: MT-ATP6 was set to GREEN
Added comment: PMIDs 40367733, 29101127, 39119452, 40112238 and 27453250 collectively report 43 families with MT‑ATP6 variants causing mitochondrial disease phenotypes that include cardiomyopathy. 19 families present with Leigh syndrome and hypertrophic cardiomyopathy and 23 families with mitochondrial proton‑transporting ATP synthase complex deficiency and paediatric cardiomyopathy.
Sources: Literature
Cardiomyopathy_Paediatric v1.98 PPP1CB Zornitza Stark Marked gene: PPP1CB as ready
Cardiomyopathy_Paediatric v1.98 PPP1CB Zornitza Stark Gene: ppp1cb has been classified as Amber List (Moderate Evidence).
Cardiomyopathy_Paediatric v1.98 PPP1CB Zornitza Stark Phenotypes for gene: PPP1CB were changed from Rasopathy with developmental delay, short stature and sparse slow-growing hair; Noonan syndrome-like disorder with loose anagen hair 2, 617506 to Noonan syndrome-like disorder with loose anagen hair 2, MIM#617506
Cardiomyopathy_Paediatric v1.97 PPP1CB Zornitza Stark Publications for gene: PPP1CB were set to 27264673; 28211982; 27681385
Cardiomyopathy_Paediatric v1.96 PPP1CB Zornitza Stark Classified gene: PPP1CB as Amber List (moderate evidence)
Cardiomyopathy_Paediatric v1.96 PPP1CB Zornitza Stark Gene: ppp1cb has been classified as Amber List (Moderate Evidence).
Cardiomyopathy_Paediatric v1.95 PPP1CB Zornitza Stark reviewed gene: PPP1CB: Rating: AMBER; Mode of pathogenicity: None; Publications: 30368668; Phenotypes: Noonan syndrome, MONDO:0018997; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cardiomyopathy_Paediatric v1.95 COX10 Zornitza Stark Marked gene: COX10 as ready
Cardiomyopathy_Paediatric v1.95 COX10 Zornitza Stark Gene: cox10 has been classified as Amber List (Moderate Evidence).
Cardiomyopathy_Paediatric v1.95 COX10 Zornitza Stark Phenotypes for gene: COX10 were changed from Mitochondrial complex IV deficiency, 220110 to mitochondrial complex IV deficiency, nuclear type 3, MONDO:0033635
Cardiomyopathy_Paediatric v1.94 COX10 Zornitza Stark Publications for gene: COX10 were set to
Cardiomyopathy_Paediatric v1.93 COX10 Zornitza Stark Classified gene: COX10 as Amber List (moderate evidence)
Cardiomyopathy_Paediatric v1.93 COX10 Zornitza Stark Gene: cox10 has been classified as Amber List (Moderate Evidence).
Cardiomyopathy_Paediatric v1.92 COX10 Zornitza Stark reviewed gene: COX10: Rating: AMBER; Mode of pathogenicity: None; Publications: 30588737, 12928484; Phenotypes: mitochondrial complex IV deficiency, nuclear type 3, MONDO:0033635; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v1.92 NF1 Zornitza Stark Marked gene: NF1 as ready
Cardiomyopathy_Paediatric v1.92 NF1 Zornitza Stark Gene: nf1 has been classified as Red List (Low Evidence).
Cardiomyopathy_Paediatric v1.92 NF1 Zornitza Stark Phenotypes for gene: NF1 were changed from Neurofibromatosis, type 1 162200; Neurofibromatosis Noonan syndrome; Neurofibromatosis syndrome 1; Neurofibromatosis-Noonan syndrome 601321; Neurofibromatosis-Noonan Syndrome; Noonan syndrome to neurofibromatosis type 1, MONDO:0018975
Cardiomyopathy_Paediatric v1.91 NF1 Zornitza Stark Publications for gene: NF1 were set to 16380919; 19845691; 12707950
Cardiomyopathy_Paediatric v1.90 NF1 Zornitza Stark Classified gene: NF1 as Red List (low evidence)
Cardiomyopathy_Paediatric v1.90 NF1 Zornitza Stark Gene: nf1 has been classified as Red List (Low Evidence).
Cardiomyopathy_Paediatric v1.89 NF1 Zornitza Stark reviewed gene: NF1: Rating: RED; Mode of pathogenicity: None; Publications: 30949358, 30919579; Phenotypes: neurofibromatosis type 1, MONDO:0018975; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cardiomyopathy_Paediatric v1.89 SHOC2 Zornitza Stark Marked gene: SHOC2 as ready
Cardiomyopathy_Paediatric v1.89 SHOC2 Zornitza Stark Gene: shoc2 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.89 SHOC2 Zornitza Stark Phenotypes for gene: SHOC2 were changed from Noonan-like syndrome with loose anagen hair; syndromic HCM to Noonan syndrome-like disorder with loose anagen hair, MONDO:0011899
Cardiomyopathy_Paediatric v1.88 SHOC2 Zornitza Stark reviewed gene: SHOC2: Rating: GREEN; Mode of pathogenicity: None; Publications: 32870709, 31059601, 30732632; Phenotypes: Noonan syndrome-like disorder with loose anagen hair, MONDO:0011899; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cardiomyopathy_Paediatric v1.88 NDUFAF1 Zornitza Stark Marked gene: NDUFAF1 as ready
Cardiomyopathy_Paediatric v1.88 NDUFAF1 Zornitza Stark Gene: ndufaf1 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.88 NDUFAF1 Zornitza Stark Phenotypes for gene: NDUFAF1 were changed from Mitochondrial complex I deficiency, nuclear type 11, 618234 to mitochondrial complex I deficiency, nuclear type 11, MONDO:0032617
Cardiomyopathy_Paediatric v1.87 NDUFAF1 Zornitza Stark Publications for gene: NDUFAF1 were set to
Cardiomyopathy_Paediatric v1.86 NDUFAF1 Zornitza Stark reviewed gene: NDUFAF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 39821332, 21931170, 17557076; Phenotypes: mitochondrial complex I deficiency, nuclear type 11, MONDO:0032617; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v1.86 SOS1 Zornitza Stark Marked gene: SOS1 as ready
Cardiomyopathy_Paediatric v1.86 SOS1 Zornitza Stark Gene: sos1 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.86 SOS1 Zornitza Stark Phenotypes for gene: SOS1 were changed from Noonan syndrome; Noonan syndrome 4; Noonan syndrome 4 610733; syndromic HCM to Noonan syndrome 4, MIM# 610733
Cardiomyopathy_Paediatric v1.85 SOS1 Zornitza Stark reviewed gene: SOS1: Rating: GREEN; Mode of pathogenicity: None; Publications: 31712860, 31368652, 31024045, 30732632, 29696744; Phenotypes: Noonan syndrome, MONDO:0018997; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cardiomyopathy_Paediatric v1.85 PNPLA2 Zornitza Stark Marked gene: PNPLA2 as ready
Cardiomyopathy_Paediatric v1.85 PNPLA2 Zornitza Stark Gene: pnpla2 has been classified as Red List (Low Evidence).
Cardiomyopathy_Paediatric v1.85 PNPLA2 Zornitza Stark Phenotypes for gene: PNPLA2 were changed from DCM; Lipid myopathy, muscle weakness Jordans anomaly - neutral lipidcontaining vacuoles in leukocytes; Neutral lipid storage disease with myopathy NLSDM to neutral lipid storage myopathy, MONDO:0012545
Cardiomyopathy_Paediatric v1.84 PNPLA2 Zornitza Stark Publications for gene: PNPLA2 were set to
Cardiomyopathy_Paediatric v1.83 PNPLA2 Zornitza Stark Classified gene: PNPLA2 as Red List (low evidence)
Cardiomyopathy_Paediatric v1.83 PNPLA2 Zornitza Stark Gene: pnpla2 has been classified as Red List (Low Evidence).
Cardiomyopathy_Paediatric v1.82 PNPLA2 Zornitza Stark reviewed gene: PNPLA2: Rating: RED; Mode of pathogenicity: None; Publications: 39119584, 31655616; Phenotypes: neutral lipid storage myopathy, MONDO:0012545; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v1.82 NONO Zornitza Stark edited their review of gene: NONO: Changed mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Cardiomyopathy_Paediatric v1.82 NONO Zornitza Stark Marked gene: NONO as ready
Cardiomyopathy_Paediatric v1.82 NONO Zornitza Stark Gene: nono has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.82 NONO Zornitza Stark Phenotypes for gene: NONO were changed from to syndromic X-linked intellectual disability 34, MONDO:0010501
Cardiomyopathy_Paediatric v1.81 NONO Zornitza Stark Publications for gene: NONO were set to
Cardiomyopathy_Paediatric v1.80 NONO Zornitza Stark Mode of inheritance for gene: NONO was changed from X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Cardiomyopathy_Paediatric v1.79 NONO Zornitza Stark reviewed gene: NONO: Rating: GREEN; Mode of pathogenicity: None; Publications: 41727761, 41705901, 41213470, 39709004, 38469091, 38110236, 37533431, 36653413, 36426740, 34549882, 33304389, 31883306, 30773818, 27550220, 27329731; Phenotypes: syndromic X-linked intellectual disability 34, MONDO:0010501; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Cardiomyopathy_Paediatric v1.79 BAG3 Zornitza Stark Marked gene: BAG3 as ready
Cardiomyopathy_Paediatric v1.79 BAG3 Zornitza Stark Gene: bag3 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.79 BAG3 Zornitza Stark Phenotypes for gene: BAG3 were changed from Cardiomyopathy, dilated, 1HH to myofibrillar myopathy 6, MONDO:0013061; dilated cardiomyopathy 1HH, MONDO:0013479
Cardiomyopathy_Paediatric v1.78 BAG3 Zornitza Stark Publications for gene: BAG3 were set to
Cardiomyopathy_Paediatric v1.77 BAG3 Zornitza Stark reviewed gene: BAG3: Rating: GREEN; Mode of pathogenicity: None; Publications: 40757566, 40493734, 39706847, 34011823, 30442290, 30384889, 27443559; Phenotypes: myofibrillar myopathy 6, MONDO:0013061, dilated cardiomyopathy 1HH, MONDO:0013479; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Repeat Disorders v1.4 Bryony Thompson Copied STR BCLAF3_FRAXG_CCG from panel Mendeliome
Repeat Disorders v1.4 BCLAF3_FRAXG_CCG Bryony Thompson STR: BCLAF3_FRAXG_CCG was added
STR: BCLAF3_FRAXG_CCG was added to Repeat Disorders. Sources: Expert Review Green,Literature
Mode of inheritance for STR: BCLAF3_FRAXG_CCG was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for STR: BCLAF3_FRAXG_CCG were set to 42482100
Phenotypes for STR: BCLAF3_FRAXG_CCG were set to Neurodevelopmental disorder, MONDO:0700092
Intellectual disability syndromic and non-syndromic v2.119 Bryony Thompson Copied STR BCLAF3_FRAXG_CCG from panel Mendeliome
Intellectual disability syndromic and non-syndromic v2.119 BCLAF3_FRAXG_CCG Bryony Thompson STR: BCLAF3_FRAXG_CCG was added
STR: BCLAF3_FRAXG_CCG was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Green,Literature
Mode of inheritance for STR: BCLAF3_FRAXG_CCG was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for STR: BCLAF3_FRAXG_CCG were set to 42482100
Phenotypes for STR: BCLAF3_FRAXG_CCG were set to Neurodevelopmental disorder, MONDO:0700092
Genetic Epilepsy v2.37 Bryony Thompson Copied STR BCLAF3_FRAXG_CCG from panel Mendeliome
Genetic Epilepsy v2.37 BCLAF3_FRAXG_CCG Bryony Thompson STR: BCLAF3_FRAXG_CCG was added
STR: BCLAF3_FRAXG_CCG was added to Genetic Epilepsy. Sources: Expert Review Green,Literature
Mode of inheritance for STR: BCLAF3_FRAXG_CCG was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for STR: BCLAF3_FRAXG_CCG were set to 42482100
Phenotypes for STR: BCLAF3_FRAXG_CCG were set to Neurodevelopmental disorder, MONDO:0700092
Mendeliome v2.492 BCLAF3_FRAXG_CCG Bryony Thompson Marked STR: BCLAF3_FRAXG_CCG as ready
Mendeliome v2.492 BCLAF3_FRAXG_CCG Bryony Thompson Str: bclaf3_fraxg_ccg has been classified as Green List (High Evidence).
Mendeliome v2.492 BCLAF3_FRAXG_CCG Bryony Thompson Classified STR: BCLAF3_FRAXG_CCG as Green List (high evidence)
Mendeliome v2.492 BCLAF3_FRAXG_CCG Bryony Thompson Str: bclaf3_fraxg_ccg has been classified as Green List (High Evidence).
Mendeliome v2.491 BCLAF3_FRAXG_CCG Bryony Thompson STR: BCLAF3_FRAXG_CCG was added
STR: BCLAF3_FRAXG_CCG was added to Mendeliome. Sources: Literature
Mode of inheritance for STR: BCLAF3_FRAXG_CCG was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for STR: BCLAF3_FRAXG_CCG were set to 42482100
Phenotypes for STR: BCLAF3_FRAXG_CCG were set to Neurodevelopmental disorder, MONDO:0700092
Review for STR: BCLAF3_FRAXG_CCG was set to GREEN
Added comment: PMID 42482100 reports five affected males with X‑linked hypermethylated CCG repeat expansions in the 5′UTR of BCLAF3, causing transcriptional silencing (loss‑of‑function). Affected individuals present with intellectual disability, epilepsy and autism. Patient‑derived fibroblasts show loss of BCLAF3 RNA and protein and DNA‑methylation arrays confirm promoter hypermethylation. One of the individuals had Williams syndrome and one of the individuals had fragile X, but more severe phenotypes than expected.
Based on LRS across all the individuals, the suggested threshold for hypermethylation is somewhere between 117-172 CCG repeats, but a greater number of individuals with intermediate-sized expansions are required to define a more precise cutoff.
Sources: Literature
Mendeliome v2.490 Sarah Milton removed region:Split hand malformation 3, 10q24 duplication syndrome from the panel
Mendeliome v2.489 Split hand malformation 3, 10q24 duplication syndrome Sarah Milton Deleted their review
Mendeliome v2.489 C2 Sarah Milton changed review comment from: This review is for the monoallelic disease assertion - Amber
The recessive C2 deficiency remains green

C2 is part of classical and lectin pathway once activated splits to C2B and C2A.
2 publications assert a link between gain of function variants in C2 and glomerulopathy/atypical haemolytic uraemic syndrome.

3 unrelated patients were found to have 2 different missense variants (S250C, R249C).

Functional studies supported a gain of function effect increasing C3 on target cells with authors speculating the combined action of CRP and the presence of these variants resulting in elevated complement deposition in kidney microvasculature.

Allele frequencies in gnomAD are relatively high, as such this is likely to be a susceptibility similar to AD variants in other complement genes.; to: This review is for the monoallelic disease assertion - Amber
The recessive C2 deficiency remains green

C2 is part of classical and lectin pathway once activated splits to C2B and C2A.
2 publications assert a link between gain of function variants in C2 and glomerulopathy/atypical haemolytic uraemic syndrome.

3 unrelated patients were found to have 2 different missense variants (S250C, R249C).

Functional studies supported a gain of function effect increasing C3 on target cells with authors speculating the combined action of CRP and the presence of these variants resulting in elevated complement deposition in kidney microvasculature.

Allele frequencies in gnomAD are relatively high, as such this is likely to be a susceptibility similar to AD variants in other complement genes.

Given only a few patients are reported in 2020 and 2021 with relatively high frequency variants this association is marked as amber until further literature is published.
Mendeliome v2.489 C2 Sarah Milton reviewed gene: C2: Rating: AMBER; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: 36591303, 32113979; Phenotypes: complement 3 glomerulopathy, MONDO:0018013, C2-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v2.118 PIGB Zornitza Stark Phenotypes for gene: PIGB were changed from Developmental and epileptic encephalopathy 80, MIM# 618580 to Developmental and epileptic encephalopathy 80, MIM# 618580; Acrofrontofacionasal dysplasia 1, MIM# 201180
Intellectual disability syndromic and non-syndromic v2.117 PIGB Zornitza Stark Publications for gene: PIGB were set to PubMed: 31256876
Intellectual disability syndromic and non-syndromic v2.116 PIGB Zornitza Stark edited their review of gene: PIGB: Added comment: Association with AFFND1, PMID 34400385: two individuals from two Brazilian families reported with the same homozygous intronic variant c.795-19T>G and a distinctive phenotype comprising severe DD/ID, and marked dysmorphic features, including hypertelorism, broad nose with notched nasal tip, cleft lip/palate, and wide and protruding central upper incisors. Vision is impaired due to coloboma and other ocular anomalies, and hearing loss in later life has been reported. Skeletal abnormalities include mesomelic shortening of limbs, distal digital hypoplasia, fibular hypoplasia, and clubfeet.

RED for this association as single, likely founder variant in the Brazilian population.; Changed publications: 34400385; Changed phenotypes: Developmental and epileptic encephalopathy 80, MIM# 618580, Acrofrontofacionasal dysplasia 1, MIM# 201180
Congenital Disorders of Glycosylation v2.2 PIGB Zornitza Stark Phenotypes for gene: PIGB were changed from Developmental and epileptic encephalopathy 80 618580 to Developmental and epileptic encephalopathy 80, MIM# 618580; Acrofrontofacionasal dysplasia 1, MIM# 201180
Congenital Disorders of Glycosylation v2.1 PIGB Zornitza Stark Publications for gene: PIGB were set to 31256876
Congenital Disorders of Glycosylation v2.0 PIGB Zornitza Stark edited their review of gene: PIGB: Added comment: Association with AFFND1, PMID 34400385: two individuals from two Brazilian families reported with the same homozygous intronic variant c.795-19T>G and a distinctive phenotype comprising severe DD/ID, and marked dysmorphic features, including hypertelorism, broad nose with notched nasal tip, cleft lip/palate, and wide and protruding central upper incisors. Vision is impaired due to coloboma and other ocular anomalies, and hearing loss in later life has been reported. Skeletal abnormalities include mesomelic shortening of limbs, distal digital hypoplasia, fibular hypoplasia, and clubfeet.

RED for this association as single, likely founder variant in the Brazilian population.; Changed publications: 31256876, 34400385; Changed phenotypes: Developmental and epileptic encephalopathy 80, MIM# 618580, Acrofrontofacionasal dysplasia 1, MIM# 201180
Frontonasal dysplasia v2.2 PIGB Zornitza Stark Marked gene: PIGB as ready
Frontonasal dysplasia v2.2 PIGB Zornitza Stark Gene: pigb has been classified as Red List (Low Evidence).
Frontonasal dysplasia v2.2 PIGB Zornitza Stark Publications for gene: PIGB were set to
Frontonasal dysplasia v2.1 PIGB Zornitza Stark edited their review of gene: PIGB: Changed publications: 34400385
Frontonasal dysplasia v2.1 PIGB Zornitza Stark gene: PIGB was added
gene: PIGB was added to Frontonasal dysplasia. Sources: Literature
founder tags were added to gene: PIGB.
Mode of inheritance for gene: PIGB was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PIGB were set to Acrofrontofacionasal dysplasia 1, MIM# 201180
Review for gene: PIGB was set to RED
Added comment: PMID 34400385: two individuals from two Brazilian families reported with the same homozygous intronic variant c.795-19T>G and a distinctive phenotype comprising severe DD/ID, and marked dysmorphic features, including hypertelorism, broad nose with notched nasal tip, cleft lip/palate, and wide and protruding central upper incisors. Vision is impaired due to coloboma and other ocular anomalies, and hearing loss in later life has been reported. Skeletal abnormalities include mesomelic shortening of limbs, distal digital hypoplasia, fibular hypoplasia, and clubfeet.

Likely founder variant.
Sources: Literature
Mendeliome v2.489 PIGB Zornitza Stark Phenotypes for gene: PIGB were changed from Developmental and epileptic encephalopathy 80, MIM# 618580 to Developmental and epileptic encephalopathy 80, MIM# 618580; Acrofrontofacionasal dysplasia 1, MIM# 201180
Mendeliome v2.488 PIGB Zornitza Stark Publications for gene: PIGB were set to 31256876
Mendeliome v2.487 PIGB Zornitza Stark edited their review of gene: PIGB: Added comment: Association with AFFND1, PMID 34400385: two individuals from two Brazilian families reported with the same homozygous intronic variant c.795-19T>G and a distinctive phenotype comprising severe DD/ID, and marked dysmorphic features, including hypertelorism, broad nose with notched nasal tip, cleft lip/palate, and wide and protruding central upper incisors. Vision is impaired due to coloboma and other ocular anomalies, and hearing loss in later life has been reported. Skeletal abnormalities include mesomelic shortening of limbs, distal digital hypoplasia, fibular hypoplasia, and clubfeet.

RED for this association as single, likely founder variant in the Brazilian population.; Changed publications: 31256876, 34400385; Changed phenotypes: Developmental and epileptic encephalopathy 80, MIM# 618580, Acrofrontofacionasal dysplasia 1, MIM# 201180
Mendeliome v2.487 10q24 duplication syndrome Split hand foot malformation 3 Sarah Milton Classified Region: 10q24 duplication syndrome Split hand foot malformation 3 as Green List (high evidence)
Mendeliome v2.487 10q24 duplication syndrome Split hand foot malformation 3 Sarah Milton Region: 10q24 duplication syndrome split hand foot malformation 3 has been classified as Green List (High Evidence).
Mendeliome v2.486 10q24 duplication syndrome Split hand foot malformation 3 Sarah Milton Marked Region: 10q24 duplication syndrome Split hand foot malformation 3 as ready
Mendeliome v2.486 10q24 duplication syndrome Split hand foot malformation 3 Sarah Milton Region: 10q24 duplication syndrome split hand foot malformation 3 has been classified as Red List (Low Evidence).
Mendeliome v2.486 10q24 duplication syndrome Split hand foot malformation 3 Sarah Milton Region: 10q24 duplication syndrome Split hand foot malformation 3 was added
Region: 10q24 duplication syndrome Split hand foot malformation 3 was added to Mendeliome. Sources: Literature
Mode of inheritance for Region: 10q24 duplication syndrome Split hand foot malformation 3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for Region: 10q24 duplication syndrome Split hand foot malformation 3 were set to 30622331; 27600068; 38168117; 35908152; 23596994
Phenotypes for Region: 10q24 duplication syndrome Split hand foot malformation 3 were set to Split-hand/foot malformation 3, gene duplication syndrome, MIM#246560
Penetrance for Region: 10q24 duplication syndrome Split hand foot malformation 3 were set to Incomplete
Review for Region: 10q24 duplication syndrome Split hand foot malformation 3 was set to GREEN
Added comment: Tandem genomic duplications at chromosome 10q24 have been reported in at least 50 affected individuals from over 30 families with split hand foot malformation.

Duplications encompassed protein coding genes FBXW4, BTRC and ranged in size from 120kb to 597kb. Interestingly very large duplications did not seem to recapitulate the phenotype.

The critical gene/molecular mechanism remains unclear. Expression analysis showed BTRC and SUFU were overexpressed in patient cells and as such a beta catenin signalling pathway defect was proposed. Regulatory element disruption and positional effect was also noted as a possibility given all causative CNV’s were duplications.

Some reduced penetrance noted.
Sources: Literature
Mendeliome v2.485 KATNA1 Sangavi Sivagnanasundram Classified gene: KATNA1 as Amber List (moderate evidence)
Mendeliome v2.485 KATNA1 Sangavi Sivagnanasundram Gene: katna1 has been classified as Amber List (Moderate Evidence).
Mendeliome v2.484 KATNA1 Sangavi Sivagnanasundram gene: KATNA1 was added
gene: KATNA1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: KATNA1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KATNA1 were set to 42466416
Phenotypes for gene: KATNA1 were set to Macular dystrophy, non-syndromic MONDO:0020242
Review for gene: KATNA1 was set to AMBER
Added comment: This pre-print publication reports >10 unrelated families with rare heterozygous missense variants in KATNA1. Affected individuals presented with non-syndromic macular dystrophy with a range of severity (some early onset and some late onset).
Given this publication is a pre-print and there are no other evidence of reports, GDA to remain AMBER.
Sources: Literature
Speech apraxia v2.2 CHD3 chirag patel Phenotypes for gene: CHD3 were changed from Snijders Blok-Campeau syndrome MIM#618205 to Snijders Blok-Campeau syndrome, MONDO:0032600
Intellectual disability syndromic and non-syndromic v2.116 CHD3 chirag patel Phenotypes for gene: CHD3 were changed from Snijders Blok-Campeau syndrome, MIM#618205 to Snijders Blok-Campeau syndrome, MONDO:0032600
Genetic Epilepsy v2.36 CHD3 chirag patel Phenotypes for gene: CHD3 were changed from Snijders Blok-Campeau syndrome MIM#618205 to Snijders Blok-Campeau syndrome, MONDO:0032600
Craniosynostosis v2.6 CHD3 chirag patel Phenotypes for gene: CHD3 were changed from Snijders Blok-Campeau syndrome, MIM#618205 to Snijders Blok-Campeau syndrome, MONDO:0032600
Mendeliome v2.483 CHD3 chirag patel Phenotypes for gene: CHD3 were changed from Snijders Blok-Campeau syndrome (618205) to Snijders Blok-Campeau syndrome, MONDO:0032600
Macrocephaly_Megalencephaly v1.8 CHD3 chirag patel Marked gene: CHD3 as ready
Macrocephaly_Megalencephaly v1.8 CHD3 chirag patel Gene: chd3 has been classified as Green List (High Evidence).
Macrocephaly_Megalencephaly v1.8 CHD3 chirag patel Mode of inheritance for gene: CHD3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Macrocephaly_Megalencephaly v1.7 CHD3 chirag patel Publications for gene: CHD3 were set to
Macrocephaly_Megalencephaly v1.6 CHD3 chirag patel Phenotypes for gene: CHD3 were changed from to Snijders Blok-Campeau syndrome, MONDO:0032600
Speech apraxia v2.1 chirag patel Added reviews for gene CHD3 from panel Intellectual disability syndromic and non-syndromic
Macrocephaly_Megalencephaly v1.5 chirag patel Added reviews for gene CHD3 from panel Mendeliome
Intellectual disability syndromic and non-syndromic v2.115 chirag patel Added reviews for gene CHD3 from panel Mendeliome
Genetic Epilepsy v2.35 chirag patel Added reviews for gene CHD3 from panel Mendeliome
Craniosynostosis v2.5 chirag patel Added reviews for gene CHD3 from panel Mendeliome
Macrocephaly_Megalencephaly v1.4 chirag patel Added reviews for gene CHD3 from panel Intellectual disability syndromic and non-syndromic
Mendeliome v2.482 CHD3 chirag patel reviewed gene: CHD3: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Snijders Blok-Campeau syndrome, MONDO:0032600; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Severe Combined Immunodeficiency v2.4 Sarah Milton Copied gene GTF3A from panel Mendeliome
Severe Combined Immunodeficiency v2.4 GTF3A Sarah Milton gene: GTF3A was added
gene: GTF3A was added to Severe Combined Immunodeficiency. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: GTF3A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GTF3A were set to 36399538
Phenotypes for gene: GTF3A were set to herpes simplex encephalitis MONDO:0012521
Combined Immunodeficiency v2.8 Sarah Milton Copied gene GTF3A from panel Mendeliome
Combined Immunodeficiency v2.8 GTF3A Sarah Milton gene: GTF3A was added
gene: GTF3A was added to Combined Immunodeficiency. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: GTF3A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GTF3A were set to 36399538
Phenotypes for gene: GTF3A were set to herpes simplex encephalitis MONDO:0012521
Mendeliome v2.482 GTF3A Sarah Milton Classified gene: GTF3A as Green List (high evidence)
Mendeliome v2.482 GTF3A Sarah Milton Gene: gtf3a has been classified as Green List (High Evidence).
Mendeliome v2.481 GTF3A Sarah Milton Classified gene: GTF3A as Green List (high evidence)
Mendeliome v2.481 GTF3A Sarah Milton Gene: gtf3a has been classified as Green List (High Evidence).
Mendeliome v2.480 GTF3A Sarah Milton reviewed gene: GTF3A: Rating: GREEN; Mode of pathogenicity: None; Publications: 42428087, 36399538; Phenotypes: Inborn error of immunity, MONDO:0003778, GTF3A-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v2.480 ATL2 chirag patel Marked gene: ATL2 as ready
Mendeliome v2.480 ATL2 chirag patel Gene: atl2 has been classified as Red List (Low Evidence).
Cerebellar and Pontocerebellar Hypoplasia v2.5 ATL2 chirag patel Marked gene: ATL2 as ready
Cerebellar and Pontocerebellar Hypoplasia v2.5 ATL2 chirag patel Gene: atl2 has been classified as Red List (Low Evidence).
Mendeliome v2.480 chirag patel Copied gene ATL2 from panel Ataxia
Mendeliome v2.480 ATL2 chirag patel gene: ATL2 was added
gene: ATL2 was added to Mendeliome. Sources: Expert Review Red,Other
Mode of inheritance for gene: ATL2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: ATL2 were set to Cerebellar ataxia, MONDO:0000437, ATL2-related
Mode of pathogenicity for gene: ATL2 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Cerebellar and Pontocerebellar Hypoplasia v2.5 chirag patel Copied gene ATL2 from panel Ataxia
Cerebellar and Pontocerebellar Hypoplasia v2.5 ATL2 chirag patel gene: ATL2 was added
gene: ATL2 was added to Cerebellar and Pontocerebellar Hypoplasia. Sources: Expert Review Red,Other
Mode of inheritance for gene: ATL2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: ATL2 were set to Cerebellar ataxia, MONDO:0000437, ATL2-related
Mode of pathogenicity for gene: ATL2 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Ataxia v2.14 ATL2 chirag patel Marked gene: ATL2 as ready
Ataxia v2.14 ATL2 chirag patel Gene: atl2 has been classified as Red List (Low Evidence).
Ataxia v2.14 ATL2 chirag patel gene: ATL2 was added
gene: ATL2 was added to Ataxia. Sources: Other
Mode of inheritance for gene: ATL2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: ATL2 were set to Cerebellar ataxia, MONDO:0000437, ATL2-related
Mode of pathogenicity for gene: ATL2 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: ATL2 was set to RED
Added comment: ESHG 2026

7 living individuals from 1 large multigeneration family presenting with early onset (<20yrs but slowly progressive) ataxia, dysarthria, and cerebellar atrophy. WGS (SR and LR) identified a rare heterozygous 2-bp deletion variant in the ATL2 gene. The variant is deeply intronic in the canonical transcript but leads to a frameshift in an alternate transcript (ATL2-2, NM_001330461.2:c.1208_1209del, p.(Arg403Thrfs*6)), which is predominantly expressed in the brain and cerebellum.

The same variant seen in 2 other unrelated families with dominant cerebellar ataxia.

The variant is positioned in the last exon of this transcript, and it is not expected to cause nonsense-mediated decay but likely leads to a protein with an altered C-terminus. Functional analyses were conducted in ATL2/3 double knockout Cos7 cells with different ATL2 isoforms being reintroduced and subsequent measurements of GTPase activity and confocal imaging. These suggested a gain-of-function effect with increased GTPase activity and altered endoplasmatic reticulum morphology. The proposed disease mechanism is a transcript-specific heterozygous gain-of-function.
Sources: Other
Hereditary Spastic Paraplegia v2.5 GSN chirag patel Marked gene: GSN as ready
Hereditary Spastic Paraplegia v2.5 GSN chirag patel Gene: gsn has been classified as Red List (Low Evidence).
Hereditary Spastic Paraplegia v2.5 GSN chirag patel Publications for gene: GSN were set to 2176164; 28139293
Hereditary Spastic Paraplegia v2.4 GSN chirag patel Phenotypes for gene: GSN were changed from Spastic ataxia, MONDO:0017845, GSN-related to Spastic ataxia, MONDO:0017845, GSN-related
Hereditary Spastic Paraplegia v2.4 GSN chirag patel Mode of inheritance for gene: GSN was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary Spastic Paraplegia v2.4 GSN chirag patel Mode of inheritance for gene: GSN was changed from BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary Spastic Paraplegia v2.3 GSN chirag patel Phenotypes for gene: GSN were changed from Amyloidosis, Finnish type, MIM# 105120; Spastic ataxia, MONDO:0017845, GSN-related to Spastic ataxia, MONDO:0017845, GSN-related
Hereditary Spastic Paraplegia v2.3 GSN chirag patel Classified gene: GSN as Red List (low evidence)
Hereditary Spastic Paraplegia v2.3 GSN chirag patel Gene: gsn has been classified as Red List (Low Evidence).
Ataxia v2.13 GSN chirag patel Marked gene: GSN as ready
Ataxia v2.13 GSN chirag patel Gene: gsn has been classified as Red List (Low Evidence).
Ataxia v2.13 GSN chirag patel Phenotypes for gene: GSN were changed from Spastic ataxia, MONDO:0017845, GSN-related to Spastic ataxia, MONDO:0017845, GSN-related
Ataxia v2.13 GSN chirag patel Phenotypes for gene: GSN were changed from Amyloidosis, Finnish type, MIM# 105120; Spastic ataxia, MONDO:0017845, GSN-related to Spastic ataxia, MONDO:0017845, GSN-related
Ataxia v2.12 GSN chirag patel Publications for gene: GSN were set to 2176164; 28139293
Ataxia v2.11 GSN chirag patel Mode of inheritance for gene: GSN was changed from BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Ataxia v2.10 GSN chirag patel Classified gene: GSN as Red List (low evidence)
Ataxia v2.10 GSN chirag patel Gene: gsn has been classified as Red List (Low Evidence).
Hereditary Spastic Paraplegia v2.2 chirag patel Copied gene GSN from panel Mendeliome
Hereditary Spastic Paraplegia v2.2 GSN chirag patel gene: GSN was added
gene: GSN was added to Hereditary Spastic Paraplegia. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: GSN was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: GSN were set to 2176164; 28139293
Phenotypes for gene: GSN were set to Amyloidosis, Finnish type, MIM# 105120; Spastic ataxia, MONDO:0017845, GSN-related
Ataxia v2.9 chirag patel Copied gene GSN from panel Mendeliome
Ataxia v2.9 GSN chirag patel gene: GSN was added
gene: GSN was added to Ataxia. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: GSN was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: GSN were set to 2176164; 28139293
Phenotypes for gene: GSN were set to Amyloidosis, Finnish type, MIM# 105120; Spastic ataxia, MONDO:0017845, GSN-related
Mendeliome v2.479 GSN chirag patel Phenotypes for gene: GSN were changed from Amyloidosis, Finnish type, MIM# 105120 to Amyloidosis, Finnish type, MIM# 105120; Spastic ataxia, MONDO:0017845, GSN-related
Mendeliome v2.478 GSN chirag patel reviewed gene: GSN: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Spastic ataxia, MONDO:0017845, GSN-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary Neuropathy v2.29 GSN chirag patel Publications for gene: GSN were set to 8684801; 228009; 3513049
Hereditary Neuropathy v2.28 chirag patel Added reviews for gene GSN from panel Amyloidosis
Corneal Dystrophy v2.4 GSN chirag patel Publications for gene: GSN were set to 2176164
Corneal Dystrophy v2.3 GSN chirag patel Mode of inheritance for gene: GSN 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
Corneal Dystrophy v2.2 GSN chirag patel reviewed gene: GSN: Rating: GREEN; Mode of pathogenicity: None; Publications: 2176164, 28139293; Phenotypes: Amyloidosis, Finnish type, MIM# 105120; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Corneal Dystrophy v2.2 chirag patel Added reviews for gene GSN from panel Mendeliome
Amyloidosis v2.2 GSN chirag patel Publications for gene: GSN were set to PubMed: 8395367; 2176164; 8684801; 6975851; 29167514
Amyloidosis v2.1 GSN chirag patel Mode of inheritance for gene: GSN 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
Fetal anomalies v2.59 IRS1 chirag patel Marked gene: IRS1 as ready
Fetal anomalies v2.59 IRS1 chirag patel Gene: irs1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v2.59 chirag patel Copied gene IRS1 from panel Mendeliome
Fetal anomalies v2.59 IRS1 chirag patel gene: IRS1 was added
gene: IRS1 was added to Fetal anomalies. Sources: Expert Review Amber,Victorian Clinical Genetics Services
Mode of inheritance for gene: IRS1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: IRS1 were set to Syndromic disease, MONDO: 0002254, IRS1-related
Growth failure v2.18 IRS1 chirag patel Marked gene: IRS1 as ready
Growth failure v2.18 IRS1 chirag patel Gene: irs1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v2.114 IRS1 chirag patel Marked gene: IRS1 as ready
Intellectual disability syndromic and non-syndromic v2.114 IRS1 chirag patel Gene: irs1 has been classified as Amber List (Moderate Evidence).
Lipodystrophy_Lipoatrophy v2.11 IRS1 chirag patel Marked gene: IRS1 as ready
Lipodystrophy_Lipoatrophy v2.11 IRS1 chirag patel Gene: irs1 has been classified as Amber List (Moderate Evidence).
Lipodystrophy_Lipoatrophy v2.11 chirag patel Copied gene IRS1 from panel Mendeliome
Lipodystrophy_Lipoatrophy v2.11 IRS1 chirag patel gene: IRS1 was added
gene: IRS1 was added to Lipodystrophy_Lipoatrophy. Sources: Expert Review Amber,Victorian Clinical Genetics Services
Mode of inheritance for gene: IRS1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: IRS1 were set to Syndromic disease, MONDO: 0002254, IRS1-related
Intellectual disability syndromic and non-syndromic v2.114 chirag patel Copied gene IRS1 from panel Mendeliome
Intellectual disability syndromic and non-syndromic v2.114 IRS1 chirag patel gene: IRS1 was added
gene: IRS1 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Amber,Victorian Clinical Genetics Services
Mode of inheritance for gene: IRS1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: IRS1 were set to Syndromic disease, MONDO: 0002254, IRS1-related
Growth failure v2.18 chirag patel Copied gene IRS1 from panel Mendeliome
Growth failure v2.18 IRS1 chirag patel gene: IRS1 was added
gene: IRS1 was added to Growth failure. Sources: Expert Review Amber,Victorian Clinical Genetics Services
Mode of inheritance for gene: IRS1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: IRS1 were set to Syndromic disease, MONDO: 0002254, IRS1-related
Mendeliome v2.478 IRS1 chirag patel changed review comment from: ESHG 2026

9 individuals from 4 unrelated families with homozygous variants in the IRS1 gene (p.F222del, p.His598Alafs*13). Segregation data not presented. All individuals presented with severe pre/postnatal growth failure (HT/WT/OFC <-3SD), severe insulin resistance, lipoatrophy, osteopenia, developmental delay, intellectual disability, and triangular facies with bulbous nose. Biochemical analysis showed low leptin levels, elevated adiponectin, mildly increased IGFBP3, low/normal cholesterol.

IRS1 is a key adaptor in insulin and IGF-1 signalling pathways. Patient-derived fibroblast demonstrated preserved IRS1 expression and intracellular localization for the variants, but impaired IRS1-mediated signalling, characterized by reduced ERK phosphorylation and increased FOXO1 expression. Variant-specific IRS1 mouse models exhibited severe growth restriction, insulin resistance, reduced adipocyte volume, and reduced bone strength.; to: ESHG 2026

9 individuals from 4 Turkish families with homozygous variants in the IRS1 gene (p.F222del, p.His598Alafs*13). Segregation data not presented. All individuals presented with severe pre/postnatal growth failure (HT/WT/OFC <-3SD), severe insulin resistance, lipoatrophy, osteopenia, developmental delay, intellectual disability, and triangular facies with bulbous nose. Biochemical analysis showed low leptin levels, elevated adiponectin, mildly increased IGFBP3, low/normal cholesterol.

IRS1 is a key adaptor in insulin and IGF-1 signalling pathways. Patient-derived fibroblast demonstrated preserved IRS1 expression and intracellular localization for the variants, but impaired IRS1-mediated signalling, characterized by reduced ERK phosphorylation and increased FOXO1 expression. Variant-specific IRS1 mouse models exhibited severe growth restriction, insulin resistance, reduced adipocyte volume, and reduced bone strength.
Mendeliome v2.478 IRS1 chirag patel Phenotypes for gene: IRS1 were changed from {Coronary artery disease, susceptibility to}; {Type 2 diabetes mellitus, susceptibility to}, MIM# 125853 to Syndromic disease, MONDO: 0002254, IRS1-related
Mendeliome v2.477 IRS1 chirag patel Mode of inheritance for gene: IRS1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v2.476 IRS1 chirag patel Classified gene: IRS1 as Amber List (moderate evidence)
Mendeliome v2.476 IRS1 chirag patel Gene: irs1 has been classified as Amber List (Moderate Evidence).
Mendeliome v2.475 IRS1 chirag patel reviewed gene: IRS1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Syndromic disease, MONDO: 0002254, IRS1-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.116 Sarah Milton Copied gene HAPLN1 from panel Mendeliome
Skeletal dysplasia v1.116 HAPLN1 Sarah Milton gene: HAPLN1 was added
gene: HAPLN1 was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: HAPLN1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HAPLN1 were set to 42381221
Phenotypes for gene: HAPLN1 were set to Skeletal dysplasia, MONDO:0018230, HAPLN1-related
Mendeliome v2.475 HAPLN1 Sarah Milton gene: HAPLN1 was added
gene: HAPLN1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: HAPLN1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HAPLN1 were set to 42381221
Phenotypes for gene: HAPLN1 were set to Skeletal dysplasia, MONDO:0018230, HAPLN1-related
Review for gene: HAPLN1 was set to RED
Added comment: HAPLN1 encodes hyaluronan and proteoglycan link protein 1 and is a extracellular matrix protein (ECM), required for maintaining tissue architecture and integrity.

PMID 42381221 reports 4 individuals from 1 consanguineous family with a biallelic missense variant presenting with autosomal recessive skeletal dysplasia characterised by rhizomelic‑mesomelic limb shortening, platyspondyly, square iliac wings, short metacarpals. No supportive functional evidence in this paper.

Previous studies cited in above paper have noted skeletal phenotypes in mouse and zebrafish knockout models. Remains a candidate gene.
Sources: Literature
Mendeliome v2.474 LRRFIP1 chirag patel Marked gene: LRRFIP1 as ready
Mendeliome v2.474 LRRFIP1 chirag patel Gene: lrrfip1 has been classified as Red List (Low Evidence).
Mendeliome v2.474 chirag patel Copied gene LRRFIP1 from panel Skeletal dysplasia
Mendeliome v2.474 LRRFIP1 chirag patel gene: LRRFIP1 was added
gene: LRRFIP1 was added to Mendeliome. Sources: Expert Review Red,Other
deep intronic tags were added to gene: LRRFIP1.
Mode of inheritance for gene: LRRFIP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: LRRFIP1 were set to Spondylodysplastic-erosive early-onset scoliosis
Skeletal dysplasia v1.115 LRRFIP1 chirag patel Marked gene: LRRFIP1 as ready
Skeletal dysplasia v1.115 LRRFIP1 chirag patel Gene: lrrfip1 has been classified as Red List (Low Evidence).
Skeletal dysplasia v1.115 LRRFIP1 chirag patel gene: LRRFIP1 was added
gene: LRRFIP1 was added to Skeletal dysplasia. Sources: Other
deep intronic tags were added to gene: LRRFIP1.
Mode of inheritance for gene: LRRFIP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: LRRFIP1 were set to Spondylodysplastic-erosive early-onset scoliosis
Review for gene: LRRFIP1 was set to RED
Added comment: ESHG 2026

Multiple individuals from 1 large multigenerational family with early-onset scoliosis, with a unique pattern of spondylodysplastic elements and progressive endplate erosion. Penetrance was 100% in the family. Linkage analysis and WGS identified a rare noncoding variant in the regulatory element in intron 1 of the LRRFIP1 gene (c.96+34737C>T). The variant segregated with disease in the family.

Short- and long-read RNA sequencing in patient fibroblasts showed altered transcription factor binding and alteration of relative LRRFIP1-isoform expression. Differential gene expression analyses in patient fibroblasts showed alterations in Wnt-signaling during somitogenesis, extracellular matrix organization and TNF-a/NF-kb signaling, partially overlapping with features of common spinal disorders such as Ankylosing Spondylitis. Lrrfip1-knockout mouse had a significantly increased prevalence of kyphoscoliosis.

Rare variant enrichment analysis using genome data from UK Biobank participants showed significant enrichment of LRRFIP1-variants in individuals with idiopathic scoliosis.
Sources: Other
Infertility and Recurrent Pregnancy Loss v2.41 Sarah Milton Copied gene PRRC2A from panel Mendeliome
Infertility and Recurrent Pregnancy Loss v2.41 PRRC2A Sarah Milton gene: PRRC2A was added
gene: PRRC2A was added to Infertility and Recurrent Pregnancy Loss. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: PRRC2A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PRRC2A were set to 42411761
Phenotypes for gene: PRRC2A were set to Spermatogenic failure, MONDO:0004983, PRRC2A-related
Mendeliome v2.473 PRRC2A Sarah Milton Marked gene: PRRC2A as ready
Mendeliome v2.473 PRRC2A Sarah Milton Gene: prrc2a has been classified as Amber List (Moderate Evidence).
Mendeliome v2.473 PRRC2A Sarah Milton Classified gene: PRRC2A as Amber List (moderate evidence)
Mendeliome v2.473 PRRC2A Sarah Milton Gene: prrc2a has been classified as Amber List (Moderate Evidence).
Mendeliome v2.472 PRRC2A Sarah Milton gene: PRRC2A was added
gene: PRRC2A was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PRRC2A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PRRC2A were set to 42411761
Phenotypes for gene: PRRC2A were set to Spermatogenic failure, MONDO:0004983, PRRC2A-related
Review for gene: PRRC2A was set to AMBER
Added comment: PRRC2A encodes proline rich coiled coil protein 2A which is involved in reading modified RNA specifically N6-methyladenosine (m6A). It is thought to have a role in meiotic progression.

PMID 42411761 reports three individuals from two families with biallelic missense PRRC2A variants presenting with severe male factor infertility (non‑obstructive azoospermia or severe oligozoospermia).

Testicular tissue shows markedly reduced PRRC2A protein, meiotic metaphase arrest, and disrupted m6A‑dependent RNA processing.

Presumably loss of function is proposed mechanism, PMID: 30514900 reports a knockout mouse of PRR2CA resulting in significantly hypomyelination and cognitive deficits, as such unclear if a more multisystem phenotype would be expected with biallelic LOF variants in humans.

Requires further literature to establish gene disease assocation.
Sources: Literature
Hand and foot malformations v1.7 S1PR2 chirag patel Marked gene: S1PR2 as ready
Hand and foot malformations v1.7 S1PR2 chirag patel Gene: s1pr2 has been classified as Green List (High Evidence).
Mendeliome v2.471 S1PR2 chirag patel Phenotypes for gene: S1PR2 were changed from Deafness, autosomal recessive 68, MIM# 610419 to Sensorineural hearing loss disorder MONDO:0020678, S1PR2-related; Congenital limb malformation, MONDO:0019054, S1PR2-related
Skeletal dysplasia v1.114 S1PR2 chirag patel Marked gene: S1PR2 as ready
Skeletal dysplasia v1.114 S1PR2 chirag patel Gene: s1pr2 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.114 chirag patel Copied gene S1PR2 from panel Deafness_IsolatedAndComplex
Skeletal dysplasia v1.114 S1PR2 chirag patel gene: S1PR2 was added
gene: S1PR2 was added to Skeletal dysplasia. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: S1PR2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: S1PR2 were set to 26805784; 29776397; 27383011
Phenotypes for gene: S1PR2 were set to Sensorineural hearing loss disorder MONDO:0020678, S1PR2-related; Congenital limb malformation, MONDO:0019054, S1PR2-related
Mendeliome v2.470 chirag patel Added reviews for gene S1PR2 from panel Deafness_IsolatedAndComplex
Hand and foot malformations v1.7 chirag patel Copied gene S1PR2 from panel Deafness_IsolatedAndComplex
Hand and foot malformations v1.7 S1PR2 chirag patel gene: S1PR2 was added
gene: S1PR2 was added to Hand and foot malformations. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: S1PR2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: S1PR2 were set to 26805784; 29776397; 27383011
Phenotypes for gene: S1PR2 were set to Sensorineural hearing loss disorder MONDO:0020678, S1PR2-related; Congenital limb malformation, MONDO:0019054, S1PR2-related
Deafness_IsolatedAndComplex v2.10 S1PR2 chirag patel Phenotypes for gene: S1PR2 were changed from Deafness, autosomal recessive 68, MIM# 610419 to Sensorineural hearing loss disorder MONDO:0020678, S1PR2-related; Congenital limb malformation, MONDO:0019054, S1PR2-related
Deafness_IsolatedAndComplex v2.9 S1PR2 chirag patel reviewed gene: S1PR2: Rating: GREEN; Mode of pathogenicity: None; Publications: 26805784, 29776397; Phenotypes: Sensorineural hearing loss disorder MONDO:0020678, S1PR2-related, Congenital limb malformation, MONDO:0019054, S1PR2-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v2.113 FRY chirag patel Phenotypes for gene: FRY were changed from Intellectual disability; no OMIM number yet to Sensorineural hearing loss disorder, MONDO:0020678; Neurodevelopmental disorder, MONDO:0700092, FRY-related
Intellectual disability syndromic and non-syndromic v2.112 FRY chirag patel Publications for gene: FRY were set to PMID: 31487712; 27457812; 21937992
Intellectual disability syndromic and non-syndromic v2.111 FRY chirag patel edited their review of gene: FRY: Added comment: ESHG 2026

18 individuals with 6 unrelated families with biallelic variants in the FRY gene (3 nonsense, 3 missense, 1 multiexon deletion). All variants segregated with disease. The 6 families include 4 families previously reported (31487712, 27457812, 21937992, 33098347). Individuals had moderate sensorineural hearing loss (13/18), developmental/speech delay (10/18), intellectual disability (18/18), ASD (9/10), and dysmorphism (7/10).

FRY encodes a scaffolding protein involved in kinase signalling and cytoskeletal dynamics in the HIPPO signalling pathway, which regulates YAP (a transcription coactivator). YAP variants are associated with multisystem disease with SNHL. Mouse studies showed robust expression of FRY in the cochlea and brain. The Fry null/null homozygous knockout mouse also displays moderate sensorineural hearing-loss consistent with the human phenotype.; Changed publications: 31487712, 27457812, 21937992, 33098347; Changed phenotypes: Sensorineural hearing loss disorder, MONDO:0020678, Neurodevelopmental disorder, MONDO:0700092, FRY-related
Deafness_IsolatedAndComplex v2.9 FRY chirag patel Marked gene: FRY as ready
Deafness_IsolatedAndComplex v2.9 FRY chirag patel Gene: fry has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v2.111 chirag patel Added reviews for gene FRY from panel Mendeliome
Deafness_IsolatedAndComplex v2.9 chirag patel Copied gene FRY from panel Mendeliome
Deafness_IsolatedAndComplex v2.9 FRY chirag patel gene: FRY was added
gene: FRY was added to Deafness_IsolatedAndComplex. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: FRY was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FRY were set to 31487712, 27457812, 21937992, 33098347
Phenotypes for gene: FRY were set to Sensorineural hearing loss disorder, MONDO:0020678, FRY-related; Neurodevelopmental disorder, MONDO:0700092, FRY-related
Mendeliome v2.469 FRY chirag patel Phenotypes for gene: FRY were changed from Neurodevelopmental disorder MONDO:0700092 to Sensorineural hearing loss disorder, MONDO:0020678, FRY-related; Neurodevelopmental disorder, MONDO:0700092, FRY-related
Mendeliome v2.468 FRY chirag patel Publications for gene: FRY were set to 31487712; 27457812; 21937992
Mendeliome v2.467 FRY chirag patel reviewed gene: FRY: Rating: AMBER; Mode of pathogenicity: None; Publications: 31487712, 27457812, 21937992, 33098347; Phenotypes: Sensorineural hearing loss disorder, MONDO:0020678, Neurodevelopmental disorder, MONDO:0700092, FRY-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia v2.8 DDX41 chirag patel Marked gene: DDX41 as ready
Ataxia v2.8 DDX41 chirag patel Gene: ddx41 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v2.110 DDX41 chirag patel Marked gene: DDX41 as ready
Intellectual disability syndromic and non-syndromic v2.110 DDX41 chirag patel Gene: ddx41 has been classified as Green List (High Evidence).
Cerebellar and Pontocerebellar Hypoplasia v2.4 DDX41 chirag patel Marked gene: DDX41 as ready
Cerebellar and Pontocerebellar Hypoplasia v2.4 DDX41 chirag patel Gene: ddx41 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v2.110 chirag patel Copied gene DDX41 from panel Syndromic Retinopathy
Intellectual disability syndromic and non-syndromic v2.110 DDX41 chirag patel gene: DDX41 was added
gene: DDX41 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Green,Literature
preprint tags were added to gene: DDX41.
Mode of inheritance for gene: DDX41 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DDX41 were set to 41646732
Phenotypes for gene: DDX41 were set to Inherited retinal dystrophy, MONDO:0019118, DDX41-related
Cerebellar and Pontocerebellar Hypoplasia v2.4 chirag patel Copied gene DDX41 from panel Syndromic Retinopathy
Cerebellar and Pontocerebellar Hypoplasia v2.4 DDX41 chirag patel gene: DDX41 was added
gene: DDX41 was added to Cerebellar and Pontocerebellar Hypoplasia. Sources: Expert Review Green,Literature
preprint tags were added to gene: DDX41.
Mode of inheritance for gene: DDX41 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DDX41 were set to 41646732
Phenotypes for gene: DDX41 were set to Inherited retinal dystrophy, MONDO:0019118, DDX41-related
Ataxia v2.8 chirag patel Copied gene DDX41 from panel Syndromic Retinopathy
Ataxia v2.8 DDX41 chirag patel gene: DDX41 was added
gene: DDX41 was added to Ataxia. Sources: Expert Review Green,Literature
preprint tags were added to gene: DDX41.
Mode of inheritance for gene: DDX41 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DDX41 were set to 41646732
Phenotypes for gene: DDX41 were set to Inherited retinal dystrophy, MONDO:0019118, DDX41-related
Syndromic Retinopathy v1.2 DDX41 chirag patel reviewed gene: DDX41: Rating: GREEN; Mode of pathogenicity: None; Publications: 41646732; Phenotypes: Inherited retinal dystrophy, MONDO:0019118, DDX41-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v1.77 DTNA Zornitza Stark changed review comment from: PMID 38551768 reports a sinlge individual with a heterozygous DTNA missense variant (p.Gln201Arg) presenting with hypertrophic cardiomyopathy; PMID 29118297 reports another individual with a heterozygous DTNA missense variant (p.N49S) presenting with left ventricular noncompaction cardiomyopathy; a transgenic mouse model overexpressing p.N49S recapitulates LVNC‑like hyper‑trabeculation and dilated cardiomyopathy.; to: PMID 38551768 reports a sinlge individual with a heterozygous DTNA missense variant (p.Gln201Arg) presenting with hypertrophic cardiomyopathy; PMID 29118297 reports another individual with a heterozygous DTNA missense variant (p.N49S) presenting with left ventricular noncompaction cardiomyopathy; a transgenic mouse model overexpressing p.N49S recapitulates LVNC‑like hyper‑trabeculation and dilated cardiomyopathy.

Note association with CHD is DISPUTED.
Cardiomyopathy_Paediatric v1.77 DTNA Zornitza Stark Marked gene: DTNA as ready
Cardiomyopathy_Paediatric v1.77 DTNA Zornitza Stark Gene: dtna has been classified as Red List (Low Evidence).
Cardiomyopathy_Paediatric v1.77 DTNA Zornitza Stark Phenotypes for gene: DTNA were changed from Left ventricular noncompaction 1, with or without congenital heart defects, to Left ventricular noncompaction 1, with or without congenital heart defects, MIM# 604169
Cardiomyopathy_Paediatric v1.76 DTNA Zornitza Stark Publications for gene: DTNA were set to
Cardiomyopathy_Paediatric v1.75 DTNA Zornitza Stark reviewed gene: DTNA: Rating: RED; Mode of pathogenicity: None; Publications: 38551768, 29118297; Phenotypes: left ventricular noncompaction 1, MONDO:0011403; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cardiomyopathy_Paediatric v1.75 MIB1 Zornitza Stark Publications for gene: MIB1 were set to 30322850; 23314057
Fetal anomalies v2.58 TK1 chirag patel Marked gene: TK1 as ready
Fetal anomalies v2.58 TK1 chirag patel Gene: tk1 has been classified as Amber List (Moderate Evidence).
Mendeliome v2.467 TK1 chirag patel Marked gene: TK1 as ready
Mendeliome v2.467 TK1 chirag patel Gene: tk1 has been classified as Amber List (Moderate Evidence).
Cardiomyopathy_Paediatric v1.74 MIB1 Zornitza Stark edited their review of gene: MIB1: Added comment: PMID 36325906: Two families (R530X nonsense; V943F missense) reported a third novel frameshift family was reported in PMID 34564127 (c.1582_1589delinsGAGCCC). Variant‑specific rescue in patient‑derived cardiomyocytes (V943F) and a Mib1 knockout mouse model recapitulate the LVNC phenotype.

However, R530X has 64 hets in gnomADv4; V943F has 161 hets.; Changed publications: 40334239, 36325906, 34564127; Changed phenotypes: left ventricular noncompaction 7, MONDO:0014042, MIB1-related
Mendeliome v2.467 chirag patel Copied gene TK1 from panel Skeletal dysplasia
Mendeliome v2.467 TK1 chirag patel gene: TK1 was added
gene: TK1 was added to Mendeliome. Sources: Expert Review Amber,Other
Mode of inheritance for gene: TK1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: TK1 were set to Thoracolaryngopelvic dysplasia, MONDO:0008551
Fetal anomalies v2.58 chirag patel Copied gene TK1 from panel Skeletal dysplasia
Fetal anomalies v2.58 TK1 chirag patel gene: TK1 was added
gene: TK1 was added to Fetal anomalies. Sources: Expert Review Amber,Other
Mode of inheritance for gene: TK1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: TK1 were set to Thoracolaryngopelvic dysplasia, MONDO:0008551
Skeletal dysplasia v1.113 TK1 chirag patel Marked gene: TK1 as ready
Skeletal dysplasia v1.113 TK1 chirag patel Gene: tk1 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v1.113 TK1 chirag patel Classified gene: TK1 as Amber List (moderate evidence)
Skeletal dysplasia v1.113 TK1 chirag patel Gene: tk1 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v1.112 TK1 chirag patel gene: TK1 was added
gene: TK1 was added to Skeletal dysplasia. Sources: Other
Mode of inheritance for gene: TK1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: TK1 were set to Thoracolaryngopelvic dysplasia, MONDO:0008551
Review for gene: TK1 was set to AMBER
Added comment: ESHG 2026

Barnes syndrome (thoraco-laryngo-pelvic dysplasia/TLPD) is a very rare autosomal dominant skeletal dysplasia, clinically characterised by thoracic dystrophy, narrow pelvis and laryngeal stenosis.

They report 3 unrelated individuals with TLPD with neonatal hypotonia, thoracic dystrophy with short ribs, subglottic stenosis/tracheal hypoplasia requiring tracheostomy, and narrow pelvis with delayed ossification of pubic rami. Trio WGS identified 2 different rare heterozygous de novo variants (1 x p.Phe29Leu and 2 x p.Lys170del) in TK1 gene.

TK1 gene codes for cytosolic thymidine kinase, which phosphorylates thymidine and plays role in DNA synthesis and cell proliferation. Functional studies in lymphoblastoid cell lines suggest a significant reduction of TK1 activity. Further studies are needed to clarify the role of TK1 in bone morphogenesis.
Sources: Other
Palmoplantar Keratoderma and Erythrokeratoderma v1.4 ERO1A chirag patel Marked gene: ERO1A as ready
Palmoplantar Keratoderma and Erythrokeratoderma v1.4 ERO1A chirag patel Gene: ero1a has been classified as Amber List (Moderate Evidence).
Osteogenesis Imperfecta and Osteoporosis v2.8 ERO1A chirag patel Marked gene: ERO1A as ready
Osteogenesis Imperfecta and Osteoporosis v2.8 ERO1A chirag patel Gene: ero1a has been classified as Amber List (Moderate Evidence).
Mendeliome v2.466 ERO1A chirag patel Marked gene: ERO1A as ready
Mendeliome v2.466 ERO1A chirag patel Gene: ero1a has been classified as Amber List (Moderate Evidence).
Palmoplantar Keratoderma and Erythrokeratoderma v1.4 chirag patel Copied gene ERO1A from panel Ichthyosis and Porokeratosis
Palmoplantar Keratoderma and Erythrokeratoderma v1.4 ERO1A chirag patel gene: ERO1A was added
gene: ERO1A was added to Palmoplantar Keratoderma and Erythrokeratoderma. Sources: Expert Review Amber,Other
Mode of inheritance for gene: ERO1A was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ERO1A were set to Ichthyosis, keratoderma and bone fragility
Osteogenesis Imperfecta and Osteoporosis v2.8 chirag patel Copied gene ERO1A from panel Ichthyosis and Porokeratosis
Osteogenesis Imperfecta and Osteoporosis v2.8 ERO1A chirag patel gene: ERO1A was added
gene: ERO1A was added to Osteogenesis Imperfecta and Osteoporosis. Sources: Expert Review Amber,Other
Mode of inheritance for gene: ERO1A was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ERO1A were set to Ichthyosis, keratoderma and bone fragility
Mendeliome v2.466 chirag patel Copied gene ERO1A from panel Ichthyosis and Porokeratosis
Mendeliome v2.466 ERO1A chirag patel gene: ERO1A was added
gene: ERO1A was added to Mendeliome. Sources: Expert Review Amber,Other
Mode of inheritance for gene: ERO1A was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ERO1A were set to Ichthyosis, keratoderma and bone fragility
Ichthyosis and Porokeratosis v2.4 ERO1A chirag patel Marked gene: ERO1A as ready
Ichthyosis and Porokeratosis v2.4 ERO1A chirag patel Gene: ero1a has been classified as Amber List (Moderate Evidence).
Ichthyosis and Porokeratosis v2.4 ERO1A chirag patel Classified gene: ERO1A as Amber List (moderate evidence)
Ichthyosis and Porokeratosis v2.4 ERO1A chirag patel Gene: ero1a has been classified as Amber List (Moderate Evidence).
Ichthyosis and Porokeratosis v2.3 ERO1A chirag patel gene: ERO1A was added
gene: ERO1A was added to Ichthyosis and Porokeratosis. Sources: Other
Mode of inheritance for gene: ERO1A was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ERO1A were set to Ichthyosis, keratoderma and bone fragility
Review for gene: ERO1A was set to AMBER
Added comment: ESHG 2026

3 individuals from 2 unrelated families (1 consanguineous) with homozygous variants in ERO1A ((p.His22Glnfs19) and p.(Gln154*)). They presented with ichthyosis (3), palmoplantar keratoderma (3), sparse eyebrows (2), fragile nails (2), microcephaly (2), low bone mineral density (1), and recurrent long bone fractures in early childhood (2). The variants segregated in the families.

Endoplasmic reticulum (ER) oxidoreductase 1α (ERO1A) oxidizes the protein disulfide isomerase (PDI) and promotes disulfide bond formation in newly synthesized polypeptides such as collagen I. The 3 patient-derived fibroblasts showed significantly reduced ERO1A mRNA levels, indicating nonsense-mediated mRNA decay. This was accompanied by absence of ERO1A protein and increased PDI levels. In whole-cell lysates from fibroblasts of 2 patients, collagen I was detected as a triple band, whereas only two bands were observed in control cells. They found disordered collagen I aggregates in the extracellular matrix of all patient-derived fibroblasts. As a possible compensatory response, mRNA and protein levels for the collagen-specific ER chaperone HSP47 were increased in patient cells.
Sources: Other
Aortopathy_Connective Tissue Disorders v2.8 chirag patel Added reviews for gene PMEPA1 from panel Mendeliome
Mendeliome v2.465 PMEPA1 chirag patel reviewed gene: PMEPA1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Hereditary disorder of connective tissue, MONDO:0023603, PMEPA1-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cardiomyopathy_Paediatric v1.74 ANK2 Zornitza Stark Publications for gene: ANK2 were set to
Cardiomyopathy_Paediatric v1.73 ANK2 Zornitza Stark Tag disputed tag was added to gene: ANK2.
Cardiomyopathy_Paediatric v1.73 ANK2 Zornitza Stark reviewed gene: ANK2: Rating: RED; Mode of pathogenicity: None; Publications: 39866811, 37123301, 31264976, 28196901; Phenotypes: Cardiac arrhythmia, ankyrin-B-related MIM#600919; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Leukodystrophy v1.9 SUPV3L1 Zornitza Stark Marked gene: SUPV3L1 as ready
Leukodystrophy v1.9 SUPV3L1 Zornitza Stark Gene: supv3l1 has been classified as Green List (High Evidence).
Microcephaly v2.24 SUPV3L1 Zornitza Stark Marked gene: SUPV3L1 as ready
Microcephaly v2.24 SUPV3L1 Zornitza Stark Gene: supv3l1 has been classified as Green List (High Evidence).
Microcephaly v2.24 Zornitza Stark Copied gene SUPV3L1 from panel Regression
Microcephaly v2.24 SUPV3L1 Zornitza Stark gene: SUPV3L1 was added
gene: SUPV3L1 was added to Microcephaly. Sources: Expert Review Green,Literature,Literature
Mode of inheritance for gene: SUPV3L1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SUPV3L1 were set to 39596606; 35023579; 42466401; 10.21203/rs.3.rs-4356120; 36344539; 34946966
Phenotypes for gene: SUPV3L1 were set to Mitochondrial disease, MONDO:0044970, SUPV3L1-related
Leukodystrophy v1.9 Zornitza Stark Copied gene SUPV3L1 from panel Regression
Leukodystrophy v1.9 SUPV3L1 Zornitza Stark gene: SUPV3L1 was added
gene: SUPV3L1 was added to Leukodystrophy. Sources: Expert Review Green,Literature,Literature
Mode of inheritance for gene: SUPV3L1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SUPV3L1 were set to 39596606; 35023579; 42466401; 10.21203/rs.3.rs-4356120; 36344539; 34946966
Phenotypes for gene: SUPV3L1 were set to Mitochondrial disease, MONDO:0044970, SUPV3L1-related
Regression v1.6 SUPV3L1 Zornitza Stark Publications for gene: SUPV3L1 were set to 39596606; 35023579
Regression v1.5 SUPV3L1 Zornitza Stark Phenotypes for gene: SUPV3L1 were changed from Mitochondrial disease, MONDO:0044970 to Mitochondrial disease, MONDO:0044970, SUPV3L1-related
Regression v1.4 SUPV3L1 Zornitza Stark Classified gene: SUPV3L1 as Green List (high evidence)
Regression v1.4 SUPV3L1 Zornitza Stark Gene: supv3l1 has been classified as Green List (High Evidence).
Regression v1.3 SUPV3L1 Zornitza Stark edited their review of gene: SUPV3L1: Added comment: Six studies have now identified over 20 families with biallelic SUPV3L1 variants, expanding the phenotype to a variable neurodevelopmental/mitochondrial disorder characterised by infant‑onset motor delay, intellectual disability, microcephaly, spasticity, leukodystrophy, optic atrophy and skin hypopigmentation. Functional data include variant‑specific dsRNA‑clearance assays for missense alleles, lentiviral rescue of the mitochondrial RNA‑processing defect in patient fibroblasts, and a supv3l1 knockout zebrafish model that recapitulates mitochondrial dysfunction and interferon activation.; Changed rating: GREEN; Changed publications: 39596606, 35023579, 42466401, 10.21203/rs.3.rs-4356120, 36344539, 34946966; Changed phenotypes: Mitochondrial disease, MONDO:0044970, SUPV3L1-related
Mitochondrial disease v2.4 SUPV3L1 Zornitza Stark Phenotypes for gene: SUPV3L1 were changed from Mitochondrial disease, MONDO:0044970 to Mitochondrial disease, MONDO:0044970, SUPV3L1-related
Mitochondrial disease v2.3 SUPV3L1 Zornitza Stark Publications for gene: SUPV3L1 were set to 39596606; 35023579
Mitochondrial disease v2.2 SUPV3L1 Zornitza Stark Classified gene: SUPV3L1 as Green List (high evidence)
Mitochondrial disease v2.2 SUPV3L1 Zornitza Stark Gene: supv3l1 has been classified as Green List (High Evidence).
Mitochondrial disease v2.1 SUPV3L1 Zornitza Stark edited their review of gene: SUPV3L1: Added comment: Six studies have now identified over 20 families with biallelic SUPV3L1 variants, expanding the phenotype to a variable neurodevelopmental/mitochondrial disorder characterised by infant‑onset motor delay, intellectual disability, microcephaly, spasticity, leukodystrophy, optic atrophy and skin hypopigmentation. Functional data include variant‑specific dsRNA‑clearance assays for missense alleles, lentiviral rescue of the mitochondrial RNA‑processing defect in patient fibroblasts, and a supv3l1 knockout zebrafish model that recapitulates mitochondrial dysfunction and interferon activation.; Changed rating: GREEN; Changed publications: 39596606, 35023579, 42466401, 10.21203/rs.3.rs-4356120, 36344539, 34946966; Changed phenotypes: Mitochondrial disease, MONDO:0044970, SUPV3L1-related
Optic Atrophy v2.4 SUPV3L1 Zornitza Stark Phenotypes for gene: SUPV3L1 were changed from Mitochondrial disease, MONDO:0044970 to Mitochondrial disease, MONDO:0044970, SUPV3L1-related
Optic Atrophy v2.3 SUPV3L1 Zornitza Stark Publications for gene: SUPV3L1 were set to 39596606; 35023579
Optic Atrophy v2.2 SUPV3L1 Zornitza Stark Classified gene: SUPV3L1 as Green List (high evidence)
Optic Atrophy v2.2 SUPV3L1 Zornitza Stark Gene: supv3l1 has been classified as Green List (High Evidence).
Optic Atrophy v2.1 SUPV3L1 Zornitza Stark edited their review of gene: SUPV3L1: Added comment: Six studies have now identified over 20 families with biallelic SUPV3L1 variants, expanding the phenotype to a variable neurodevelopmental/mitochondrial disorder characterised by infant‑onset motor delay, intellectual disability, microcephaly, spasticity, leukodystrophy, optic atrophy and skin hypopigmentation. Functional data include variant‑specific dsRNA‑clearance assays for missense alleles, lentiviral rescue of the mitochondrial RNA‑processing defect in patient fibroblasts, and a supv3l1 knockout zebrafish model that recapitulates mitochondrial dysfunction and interferon activation.; Changed rating: GREEN; Changed publications: 39596606, 35023579, 42466401, 10.21203/rs.3.rs-4356120, 36344539, 34946966; Changed phenotypes: Mitochondrial disease, MONDO:0044970, SUPV3L1-related
Mendeliome v2.465 SUPV3L1 Zornitza Stark Phenotypes for gene: SUPV3L1 were changed from Mitochondrial disease, MONDO:0044970 to Mitochondrial disease, MONDO:0044970, SUPV3L1-related
Mendeliome v2.464 SUPV3L1 Zornitza Stark Publications for gene: SUPV3L1 were set to 39596606; 35023579
Mendeliome v2.463 SUPV3L1 Zornitza Stark Classified gene: SUPV3L1 as Green List (high evidence)
Mendeliome v2.463 SUPV3L1 Zornitza Stark Gene: supv3l1 has been classified as Green List (High Evidence).
Mendeliome v2.462 SUPV3L1 Zornitza Stark Tag preprint tag was added to gene: SUPV3L1.
Mendeliome v2.462 SUPV3L1 Zornitza Stark edited their review of gene: SUPV3L1: Added comment: Six studies have now identified over 20 families with biallelic SUPV3L1 variants, expanding the phenotype to a variable neurodevelopmental/mitochondrial disorder characterised by infant‑onset motor delay, intellectual disability, microcephaly, spasticity, leukodystrophy, optic atrophy and skin hypopigmentation. Functional data include variant‑specific dsRNA‑clearance assays for missense alleles, lentiviral rescue of the mitochondrial RNA‑processing defect in patient fibroblasts, and a supv3l1 knockout zebrafish model that recapitulates mitochondrial dysfunction and interferon activation.; Changed rating: GREEN; Changed publications: 42466401, 10.21203/rs.3.rs-4356120, 39596606, 36344539, 35023579, 34946966; Changed phenotypes: Mitochondrial disease, MONDO:0044970, SUPV3L1-related
Intellectual disability syndromic and non-syndromic v2.109 MORF4L1 Zornitza Stark Marked gene: MORF4L1 as ready
Intellectual disability syndromic and non-syndromic v2.109 MORF4L1 Zornitza Stark Gene: morf4l1 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v2.109 Zornitza Stark Copied gene MORF4L1 from panel Mendeliome
Intellectual disability syndromic and non-syndromic v2.109 MORF4L1 Zornitza Stark gene: MORF4L1 was added
gene: MORF4L1 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Red,Literature
Mode of inheritance for gene: MORF4L1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MORF4L1 were set to 42457791
Phenotypes for gene: MORF4L1 were set to Neurodevelopmental disorder, MONDO:0700092, MORF4L1-related
Mendeliome v2.462 MORF4L1 Zornitza Stark Marked gene: MORF4L1 as ready
Mendeliome v2.462 MORF4L1 Zornitza Stark Gene: morf4l1 has been classified as Red List (Low Evidence).
Mendeliome v2.462 MORF4L1 Zornitza Stark gene: MORF4L1 was added
gene: MORF4L1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MORF4L1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MORF4L1 were set to 42457791
Phenotypes for gene: MORF4L1 were set to Neurodevelopmental disorder, MONDO:0700092, MORF4L1-related
Review for gene: MORF4L1 was set to RED
Added comment: PMID 42457791 reports two individuals from a single family with a homozygous missense MORF4L1 variant (c.491T>C, p.Leu164Pro) presenting with a neurodevelopmental disorder characterised by trigonocephaly, dysmorphic facial features, global developmental delay, obesity and multi‑system anomalies. The variant is absent from gnomAD, and causes ~99 % reduction of MORF4L1 protein in patient fibroblasts; zebrafish loss‑of‑function mutants recapitulate growth restriction and skeletal defects, although knock‑in models appear phenotypically normal.
Sources: Literature
Autism v1.17 USP15 Zornitza Stark Marked gene: USP15 as ready
Autism v1.17 USP15 Zornitza Stark Gene: usp15 has been classified as Red List (Low Evidence).
Autism v1.17 Zornitza Stark Copied gene USP15 from panel Mendeliome
Autism v1.17 USP15 Zornitza Stark gene: USP15 was added
gene: USP15 was added to Autism. Sources: Expert Review Red,Literature
Mode of inheritance for gene: USP15 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: USP15 were set to 42526765; 28344757
Phenotypes for gene: USP15 were set to Neurodevelopmental disorder, MONDO:0700092, USP15-related
Mendeliome v2.461 USP15 Zornitza Stark Marked gene: USP15 as ready
Mendeliome v2.461 USP15 Zornitza Stark Gene: usp15 has been classified as Red List (Low Evidence).
Mendeliome v2.461 USP15 Zornitza Stark gene: USP15 was added
gene: USP15 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: USP15 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: USP15 were set to 42526765; 28344757
Phenotypes for gene: USP15 were set to Neurodevelopmental disorder, MONDO:0700092, USP15-related
Review for gene: USP15 was set to RED
Added comment: PMID 42526765 reports a single individual with a de novo start‑codon loss‑of‑function USP15 variant and autism spectrum disorder; PMID 28344757 reports another individual with a de novo loss‑of‑function USP15 variant and autism spectrum disorder but variant details not provided. The PMID 42526765 study demonstrated progenitor‑centric transcriptional dysregulation and neuronal maturation defects in isogenic hiPSC‑derived cortical organoids harbouring the heterozygous variant.
Sources: Literature
Incidentalome v1.10 RRAD Zornitza Stark Marked gene: RRAD as ready
Incidentalome v1.10 RRAD Zornitza Stark Gene: rrad has been classified as Red List (Low Evidence).
Incidentalome v1.10 Zornitza Stark Copied gene RRAD from panel Brugada syndrome
Incidentalome v1.10 RRAD Zornitza Stark gene: RRAD was added
gene: RRAD was added to Incidentalome. Sources: Expert Review Red,Literature
Mode of inheritance for gene: RRAD was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RRAD were set to 34185406; 31114854
Phenotypes for gene: RRAD were set to Brugada syndrome, MONDO:0015263, RRAD-related
Brugada syndrome v1.4 RRAD Zornitza Stark Marked gene: RRAD as ready
Brugada syndrome v1.4 RRAD Zornitza Stark Gene: rrad has been classified as Red List (Low Evidence).
Brugada syndrome v1.4 RRAD Zornitza Stark gene: RRAD was added
gene: RRAD was added to Brugada syndrome. Sources: Literature
Mode of inheritance for gene: RRAD was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RRAD were set to 34185406; 31114854
Phenotypes for gene: RRAD were set to Brugada syndrome, MONDO:0015263, RRAD-related
Review for gene: RRAD was set to RED
Added comment: RRAD encodes the RAD GTPase, a member of the RGK subfamily involved in regulation of cardiac ion channels and cytoskeletal dynamics.

PMID 31114854 reports five affected members of a three‑generation French family carrying a rare missense variant p.R211H in RRAD, present in 3 hets in gnomAD v4. iPSC‑derived cardiomyocytes from two affected relatives, as well as a CRISPR‑edited isogenic line, showed reduced Na⁺ peak current, increased persistent Na⁺ current, prolonged action potentials and cytoskeletal disorganisation, supporting a gain‑of‑function effect of the mutant GTPase. Screening of 186 unrelated BrS patients identified three additional rare RRAD missense variants without functional validation and with much higher gnomAD counts.
Sources: Literature
Mendeliome v2.460 B4GALT5 Rylee Peters Marked gene: B4GALT5 as ready
Mendeliome v2.460 B4GALT5 Rylee Peters Gene: b4galt5 has been classified as Red List (Low Evidence).
Mendeliome v2.460 B4GALT5 Rylee Peters gene: B4GALT5 was added
gene: B4GALT5 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: B4GALT5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: B4GALT5 were set to 42425491
Phenotypes for gene: B4GALT5 were set to Syndromic disease, MONDO:0002254, B4GALT5-related
Review for gene: B4GALT5 was set to RED
Added comment: PMID: 42425491 reports 1 individual from 1 family with biallelic loss-of-function missense variants presenting with a congenital disorder of glycosylation characterised by microcephaly, mild cognitive impairment and bilateral cataracts. Enzymatic activity of the identified B4GALT5 variants were measured in B4GALT5/6 double KO cell model. Cells transfected with each mutant B4GALT5 lacked LacCer synthase activity, whereas WT rescued activity.
Sources: Literature
Infertility and Recurrent Pregnancy Loss v2.40 LRGUK Rylee Peters Marked gene: LRGUK as ready
Infertility and Recurrent Pregnancy Loss v2.40 LRGUK Rylee Peters Gene: lrguk has been classified as Amber List (Moderate Evidence).
Infertility and Recurrent Pregnancy Loss v2.40 Rylee Peters Copied gene LRGUK from panel Mendeliome
Infertility and Recurrent Pregnancy Loss v2.40 LRGUK Rylee Peters gene: LRGUK was added
gene: LRGUK was added to Infertility and Recurrent Pregnancy Loss. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: LRGUK was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LRGUK were set to 42493466; 38884051
Phenotypes for gene: LRGUK were set to Infertility disorder, MONDO:0005047, LRGUK-related
Congenital Heart Defect v1.31 PFKP Rylee Peters Marked gene: PFKP as ready
Congenital Heart Defect v1.31 PFKP Rylee Peters Gene: pfkp has been classified as Amber List (Moderate Evidence).
Mendeliome v2.459 LRGUK Rylee Peters Marked gene: LRGUK as ready
Mendeliome v2.459 LRGUK Rylee Peters Gene: lrguk has been classified as Amber List (Moderate Evidence).
Mendeliome v2.459 LRGUK Rylee Peters Classified gene: LRGUK as Amber List (moderate evidence)
Mendeliome v2.459 LRGUK Rylee Peters Gene: lrguk has been classified as Amber List (Moderate Evidence).
Mendeliome v2.458 LRGUK Rylee Peters gene: LRGUK was added
gene: LRGUK was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: LRGUK was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LRGUK were set to 42493466; 38884051
Phenotypes for gene: LRGUK were set to Infertility disorder, MONDO:0005047, LRGUK-related
Review for gene: LRGUK was set to AMBER
Added comment: PMID: 38884051 and PMID: 42493466 report 3 individuals from 2 families with biallelic loss-of-function LRGUK variants presenting with male infertility (asthenozoospermia and multiple morphological abnormalities of the sperm flagella). Functional studies show loss of LRGUK protein and flagellar ultrastructural defects.
Sources: Literature
Arthrogryposis v2.2 TTN Sarah Milton reviewed gene: TTN: Rating: AMBER; Mode of pathogenicity: None; Publications: 39277846, 37935568; Phenotypes: TTN-related myopathy, dominant-negative TTNsv, MONDO:1060225; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Muscular dystrophy and myopathy_Paediatric v2.7 Sarah Milton Added reviews for gene TTN from panel Limb-Girdle Muscular Dystrophy and Distal Myopathy
Limb-Girdle Muscular Dystrophy and Distal Myopathy v2.0 TTN Sarah Milton reviewed gene: TTN: Rating: GREEN; Mode of pathogenicity: None; Publications: 39277846, 37935568; Phenotypes: TTN-related myopathy, dominant-negative TTNsv, MONDO:1060225; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v2.57 chirag patel Added reviews for gene LDB1 from panel Intellectual disability syndromic and non-syndromic
Fetal anomalies v2.56 LDB1 chirag patel Phenotypes for gene: LDB1 were changed from Congenital hydrocephalus MONDO:0016349 to Congenital hydrocephalus MONDO:0016349; Neurodevelopmental disorder, MONDO:0700092, LDB1-related
Mendeliome v2.457 LDB1 chirag patel Phenotypes for gene: LDB1 were changed from Congenital hydrocephalus MONDO:0016349 to Congenital hydrocephalus MONDO:0016349; Neurodevelopmental disorder, MONDO:0700092, LDB1-related
Hydrocephalus_Ventriculomegaly v1.12 LDB1 chirag patel Phenotypes for gene: LDB1 were changed from Congenital hydrocephalus MONDO:0016349 to Congenital hydrocephalus MONDO:0016349; Neurodevelopmental disorder, MONDO:0700092, LDB1-related
Mendeliome v2.456 chirag patel Added reviews for gene LDB1 from panel Intellectual disability syndromic and non-syndromic
Hydrocephalus_Ventriculomegaly v1.11 chirag patel Added reviews for gene LDB1 from panel Intellectual disability syndromic and non-syndromic
Intellectual disability syndromic and non-syndromic v2.108 LDB1 chirag patel Marked gene: LDB1 as ready
Intellectual disability syndromic and non-syndromic v2.108 LDB1 chirag patel Gene: ldb1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v2.108 LDB1 chirag patel Classified gene: LDB1 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v2.108 LDB1 chirag patel Gene: ldb1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v2.107 LDB1 chirag patel gene: LDB1 was added
gene: LDB1 was added to Intellectual disability syndromic and non-syndromic. Sources: Other
Mode of inheritance for gene: LDB1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: LDB1 were set to Neurodevelopmental disorder, MONDO:0700092, LDB1-related
Review for gene: LDB1 was set to AMBER
Added comment: ESHG 2026

16 unrelated individuals with 16 different rare heterozygous de novo variants (missense, nonsense, frameshift, gene deletions) in the LDB1 gene. Eleven variants affect the whole gene or the N-terminal dimerization domain and 5 variants affect only the C-terminus. All individuals presented with developmental delay and behaviour issues, but individuals with C-terminal variants also presented with ventriculomegaly.

LDB1 encodes transcriptional regulator protein LIM-domain-binding protein 1, which plays an important role in neurogenesis. In vitro assays showed the N-terminal missense variants disrupted homodimerization of LDB1 (likely leading to a loss of function) but the C-terminal variants impaired interaction with the essential partner LHX2 (in a dominant-negative fashion). Toxicity of overexpressed human LDB1 in Drosophila was not seen for N-terminal missense variants but was exacerbated by C-terminal variants. Phenotypes associated with LDB1/chi loss in Drosophila were a) rescued by overexpression of wild-type LDB1, b) not rescued by N-terminal missense variants, and c) worsened by C-terminal variants. This suggests 2 distinct pathomechanisms of LDB1-related NDDs.
Sources: Other
Congenital Heart Defect v1.31 Rylee Peters Copied gene PFKP from panel Mendeliome
Congenital Heart Defect v1.31 PFKP Rylee Peters gene: PFKP was added
gene: PFKP was added to Congenital Heart Defect. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: PFKP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PFKP were set to 42385441
Phenotypes for gene: PFKP were set to Congenital heart disease, MONDO:0005453, PFKP-related
Mendeliome v2.455 PFKP Rylee Peters Marked gene: PFKP as ready
Mendeliome v2.455 PFKP Rylee Peters Gene: pfkp has been classified as Amber List (Moderate Evidence).
Mendeliome v2.455 PFKP Rylee Peters Classified gene: PFKP as Amber List (moderate evidence)
Mendeliome v2.455 PFKP Rylee Peters Gene: pfkp has been classified as Amber List (Moderate Evidence).
Mendeliome v2.454 PFKP Rylee Peters gene: PFKP was added
gene: PFKP was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PFKP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PFKP were set to 42385441
Phenotypes for gene: PFKP were set to Congenital heart disease, MONDO:0005453, PFKP-related
Review for gene: PFKP was set to AMBER
Added comment: PMID: 42385441 reports >10 individuals from 2 families with a heterozygous missense PFKP p.(R755W) variant (gnomAD v4: 3 hets) presenting with a congenital heart malformation syndrome characterised by prenatal ventricular wall thinning and septal defects. Heterozygous mutant (PfkpR754W/+) mice did not show significant structural abnormalities whilst homozygous mutant (PfkpR754W/R754W) mice recapitulated the core phenotypes including significantly thinned ventricular walls.
Sources: Literature
Mendeliome v2.453 MACROH2A1 chirag patel Marked gene: MACROH2A1 as ready
Mendeliome v2.453 MACROH2A1 chirag patel Gene: macroh2a1 has been classified as Amber List (Moderate Evidence).
Mendeliome v2.453 chirag patel Copied gene MACROH2A1 from panel Intellectual disability syndromic and non-syndromic
Mendeliome v2.453 MACROH2A1 chirag patel gene: MACROH2A1 was added
gene: MACROH2A1 was added to Mendeliome. Sources: Expert Review Amber,Other
Mode of inheritance for gene: MACROH2A1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: MACROH2A1 were set to Neurodevelopmental disorder, MONDO:0700092, MACROH2A1-related
Intellectual disability syndromic and non-syndromic v2.106 MACROH2A1 chirag patel Marked gene: MACROH2A1 as ready
Intellectual disability syndromic and non-syndromic v2.106 MACROH2A1 chirag patel Gene: macroh2a1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v2.106 MACROH2A1 chirag patel Classified gene: MACROH2A1 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v2.106 MACROH2A1 chirag patel Gene: macroh2a1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v2.105 MACROH2A1 chirag patel gene: MACROH2A1 was added
gene: MACROH2A1 was added to Intellectual disability syndromic and non-syndromic. Sources: Other
Mode of inheritance for gene: MACROH2A1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: MACROH2A1 were set to Neurodevelopmental disorder, MONDO:0700092, MACROH2A1-related
Review for gene: MACROH2A1 was set to AMBER
Added comment: ESHG 2026

5 unrelated individuals with 3 different rare heterozygous de novo missense variants in H2A-like domain in MACROH2A1 gene. Two missense variants affected the same amino acid in 4 individuals (p.Arg27Gln and p.Arg27Trp). Individuals presented with global developmental delay (5/5), intellectual disability (5/5), hypotonia (4/4), microcephaly (3/5), seizures (2/5), brain abnormalities (3/4), and dysmorphism (5/5).

MACROH2A1 is a distinctive H2A variant involved in transcriptional regulation, chromatin organization, and neuronal differentiation. Structural modeling indicated that variants destabilize the nucleosome and impair MACROH2A1-DNA interactions. Transcriptomic profiling of patient-derived fibroblasts highlighted dysregulation of the actin cytoskeleton organization and cell-matrix interaction dynamics, ER-related trafficking, and neuronal differentiation programs. Patient fibroblasts exhibited disorganized F-actin with defective focal adhesions and ER disorganization with lumen dilation. Patient fibroblasts also showed impaired fibroblast-to-neuronal reprogramming with reduced TuJ1-positive cells, and abnormal neurite morphology. Methylation profiling revealed a distinct episignature discriminating affected individuals from controls, consistent with global epigenetic dysregulation.
Sources: Other
Kabuki syndrome v1.1 RLF chirag patel Marked gene: RLF as ready
Kabuki syndrome v1.1 RLF chirag patel Gene: rlf has been classified as Amber List (Moderate Evidence).
Mendeliome v2.452 RLF chirag patel Marked gene: RLF as ready
Mendeliome v2.452 RLF chirag patel Gene: rlf has been classified as Amber List (Moderate Evidence).
Mendeliome v2.452 chirag patel Copied gene RLF from panel Intellectual disability syndromic and non-syndromic
Mendeliome v2.452 RLF chirag patel gene: RLF was added
gene: RLF was added to Mendeliome. Sources: Expert Review Amber,Other
Mode of inheritance for gene: RLF was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: RLF were set to Neurodevelopmental disorder, MONDO:0700092, RLF-related
Kabuki syndrome v1.1 chirag patel Copied gene RLF from panel Intellectual disability syndromic and non-syndromic
Kabuki syndrome v1.1 RLF chirag patel gene: RLF was added
gene: RLF was added to Kabuki syndrome. Sources: Expert Review Amber,Other
Mode of inheritance for gene: RLF was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: RLF were set to Neurodevelopmental disorder, MONDO:0700092, RLF-related
Intellectual disability syndromic and non-syndromic v2.104 RLF chirag patel Marked gene: RLF as ready
Intellectual disability syndromic and non-syndromic v2.104 RLF chirag patel Gene: rlf has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v2.104 RLF chirag patel Classified gene: RLF as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v2.104 RLF chirag patel Gene: rlf has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v2.103 RLF chirag patel gene: RLF was added
gene: RLF was added to Intellectual disability syndromic and non-syndromic. Sources: Other
Mode of inheritance for gene: RLF was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: RLF were set to Neurodevelopmental disorder, MONDO:0700092, RLF-related
Review for gene: RLF was set to AMBER
Added comment: ESHG 2026

22 unrelated individuals with rare heterozygous de novo variants (14 frameshift, 8 nonsense) located in the last exon of RLF gene. Individuals presented with developmental delay, intellectual disability, autism-type behaviour, and Kabuki syndrome-like facial features.

RLF is a poly-ZNF protein which acts as a transcription factor. In vitro assays showed the variants profoundly altered the epigenome, the transcriptome and the DNA secondary structure. ONT whole genome sequencing in patient IPSCs showed hypermethylation and hypo-5-hydroxymethylation at multiple CpG sites. ATAC-seq demonstrated altered chromatin accessibility at promoters and enhancers in patient IPSCs. RNA-seq unveiled several differentially expressed genes enriched for disease-relevant gene ontology terms. RLP variants upregulated neuronal differentiation genes. RLF-ChIP-seq data showed a marked reduction in G4 access signal in patient iPSCs. Methylation arrays revealed a distinct methylation profile overlapping with Kabuki syndrome.
Sources: Other
Mendeliome v2.451 DHX36 chirag patel Marked gene: DHX36 as ready
Mendeliome v2.451 DHX36 chirag patel Gene: dhx36 has been classified as Amber List (Moderate Evidence).
Mendeliome v2.451 DHX36 chirag patel Classified gene: DHX36 as Amber List (moderate evidence)
Mendeliome v2.451 DHX36 chirag patel Gene: dhx36 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v2.102 DHX36 chirag patel Marked gene: DHX36 as ready
Intellectual disability syndromic and non-syndromic v2.102 DHX36 chirag patel Gene: dhx36 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v2.102 DHX36 chirag patel Classified gene: DHX36 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v2.102 DHX36 chirag patel Gene: dhx36 has been classified as Amber List (Moderate Evidence).
Mendeliome v2.450 chirag patel Copied gene DHX36 from panel Intellectual disability syndromic and non-syndromic
Mendeliome v2.450 DHX36 chirag patel gene: DHX36 was added
gene: DHX36 was added to Mendeliome. Sources: Other
Mode of inheritance for gene: DHX36 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: DHX36 were set to Neurodevelopmental disorder, MONDO:0700092, DHX36-related
Mode of pathogenicity for gene: DHX36 was set to Other
Intellectual disability syndromic and non-syndromic v2.101 DHX36 chirag patel gene: DHX36 was added
gene: DHX36 was added to Intellectual disability syndromic and non-syndromic. Sources: Other
Mode of inheritance for gene: DHX36 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: DHX36 were set to Neurodevelopmental disorder, MONDO:0700092, DHX36-related
Mode of pathogenicity for gene: DHX36 was set to Other
Review for gene: DHX36 was set to AMBER
Added comment: ESHG 2026

3 unrelated individuals with 3 heterozygous de novo variants (2 missense, 1 in-frame deletion) located in the helicase domain of DHX36 gene. Individuals presented with global developmental delay (3), hypotonia (3), microcephaly (2), cleft palate (2), respiratory defects (3), cardiovascular abnormalities (3), and hearing impairment (2).

DHX36 is an ATP-dependent G4 helicase which regulates G-quadruplexes (G4s), which are bulky DNA secondary structures that form naturally in GC-rich regions and can pose threats to genome integrity. Functional studies performed in in vitro, Xenopus egg extract and human cell based assays. DHX36 mutant proteins showed reduced ATPase and G4 unwinding activity, but retained G4 binding affinity. Mutant DHX36 also interfered with wild-type helicase activity, exerting a dominant-negative mechanism.
Sources: Other
Microcephaly v2.23 chirag patel Added reviews for gene CUL1 from panel Mendeliome
Intellectual disability syndromic and non-syndromic v2.100 chirag patel Added reviews for gene CUL1 from panel Mendeliome
Mendeliome v2.449 CUL1 chirag patel reviewed gene: CUL1: Rating: GREEN; Mode of pathogenicity: Other; Publications: ; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, CUL1-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v2.34 THAP12 chirag patel Marked gene: THAP12 as ready
Genetic Epilepsy v2.34 THAP12 chirag patel Gene: thap12 has been classified as Red List (Low Evidence).
Microcephaly v2.22 THAP12 chirag patel Marked gene: THAP12 as ready
Microcephaly v2.22 THAP12 chirag patel Gene: thap12 has been classified as Red List (Low Evidence).
Mendeliome v2.449 THAP12 chirag patel Marked gene: THAP12 as ready
Mendeliome v2.449 THAP12 chirag patel Gene: thap12 has been classified as Red List (Low Evidence).
Microcephaly v2.22 chirag patel Copied gene THAP12 from panel Intellectual disability syndromic and non-syndromic
Microcephaly v2.22 THAP12 chirag patel gene: THAP12 was added
gene: THAP12 was added to Microcephaly. Sources: Expert Review Red,Other
Mode of inheritance for gene: THAP12 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: THAP12 were set to Neurodevelopmental disorder, MONDO:0700092, THAP12-related
Mendeliome v2.449 chirag patel Copied gene THAP12 from panel Intellectual disability syndromic and non-syndromic
Mendeliome v2.449 THAP12 chirag patel gene: THAP12 was added
gene: THAP12 was added to Mendeliome. Sources: Expert Review Red,Other
Mode of inheritance for gene: THAP12 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: THAP12 were set to Neurodevelopmental disorder, MONDO:0700092, THAP12-related
Genetic Epilepsy v2.34 chirag patel Copied gene THAP12 from panel Intellectual disability syndromic and non-syndromic
Genetic Epilepsy v2.34 THAP12 chirag patel gene: THAP12 was added
gene: THAP12 was added to Genetic Epilepsy. Sources: Expert Review Red,Other
Mode of inheritance for gene: THAP12 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: THAP12 were set to Neurodevelopmental disorder, MONDO:0700092, THAP12-related
Intellectual disability syndromic and non-syndromic v2.99 THAP12 chirag patel Marked gene: THAP12 as ready
Intellectual disability syndromic and non-syndromic v2.99 THAP12 chirag patel Gene: thap12 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v2.99 THAP12 chirag patel gene: THAP12 was added
gene: THAP12 was added to Intellectual disability syndromic and non-syndromic. Sources: Other
Mode of inheritance for gene: THAP12 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: THAP12 were set to Neurodevelopmental disorder, MONDO:0700092, THAP12-related
Review for gene: THAP12 was set to RED
Added comment: ESHG 2026

2 siblings from 1 family with compound heterozygous variants in THAP12 (1 missense, 1 frameshift), presenting with refractory early onset epilepsy, severe developmental delay and hypotonia, and microcephaly.

ChIP-seq confirmed the role of THAP12 as a transcriptional activator of genes essential for proliferation, apoptosis, and mitochondrial function in HEK293FT cells. In silico predictions (AlphaFold 3) showed that THAP12 forms homodimers, enabling it to bind DNA. The patient variants were shown to lead to a significant reduction in THAP12 protein level, suggesting a loss-of-function mechanism. Mouse models show embryonic lethality in both Thap12-KO and models harbouring patient specific alleles. Zebrafish models showed THAP12 is primarily expressed in cycling neural progenitors, and loss-of-function models phenocopy the clinical presentation with microcephaly, abnormal neural activity, and seizure like-behaviour.
Sources: Other
Intellectual disability syndromic and non-syndromic v2.98 Richard Lin Copied gene EHMT2 from panel Mendeliome
Intellectual disability syndromic and non-syndromic v2.98 EHMT2 Richard Lin gene: EHMT2 was added
gene: EHMT2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: EHMT2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: EHMT2 were set to 42434347; 42386776; 39674972
Phenotypes for gene: EHMT2 were set to Kleefstra syndrome, MONDO:0012455, EHMT2-related
Congenital Heart Defect v1.30 Richard Lin Copied gene EHMT2 from panel Mendeliome
Congenital Heart Defect v1.30 EHMT2 Richard Lin gene: EHMT2 was added
gene: EHMT2 was added to Congenital Heart Defect. Sources: Literature
Mode of inheritance for gene: EHMT2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: EHMT2 were set to 42434347; 42386776; 39674972
Phenotypes for gene: EHMT2 were set to Kleefstra syndrome, MONDO:0012455, EHMT2-related
Mendeliome v2.448 EHMT2 Richard Lin changed review comment from: EHMT1 and EHMT2 encode histone lysine methyltransferase 1 (GLP) and 2 (G9a) respectively. Together, they form heteromeric GLP/G9a complexes which catalyse H3K9 mono‑ and di‑methylation. EHMT1 is associated with Kleefstra syndrome 1.

PMID 42386776 report 7 unrelated individuals with de novo heterozygous EHMT2 missense and inframe deletion variants causing a Kleefstra‑like neurodevelopmental syndrome, with psychomotor developmental delay, intellectual disability, absent speech, structural brain anomalies, hypotonia, dental anomalies and behavioural and sleep difficulties. Additional features also included recognisable facial dysmorphism (hypertelorism, synophrys, flat face, everted lips and protruding jaw) and cardiac anomalies (septal defects, pulmonic valve stenosis, aortic coarctation). All variants are absent from gnomAD. Episignature partially overlaps with Kleefstra syndrome 1 but was reported to form its own distinct profile. Biochemical assays show severe loss of G9a activity in fibroblast cell culture collected from patient 2 (EHMT2 c.3229G>T). A heterozygous knock‑in mouse model with Ehmt2 +/del_1076-1079 recapitulated the neurobehavioural and craniofacial phenotype. In vitro studies show that patient variants encode for structurally stable G9a proteins which are catalytically incompetent due to aberrant interactions either with histone H3 tail or with S-adenosylmethionine. The proposed mechanism is dominant negative effect on the GLP/G9a complexes.

PMID 3967492 and 42434347 describe two unrelated probands with biallelic loss‑of‑function EHMT2 variants presenting with a Kleefstra‑like neurodevelopmental disorder that includes developmental delay, facial dysmorphism, vertebral anomalies and congenital heart disease. A DNA‑methylation episignature matching Kleefstra syndrome 1 was reported for both patients.
Sources: Literature; to: EHMT1 and EHMT2 encode histone lysine methyltransferase 1 (GLP) and 2 (G9a) respectively. Together, they form heteromeric GLP/G9a complexes which catalyse H3K9 mono‑ and di‑methylation. EHMT1 is associated with Kleefstra syndrome 1.

PMID 42386776 report 7 unrelated individuals with de novo heterozygous EHMT2 missense and inframe deletion variants causing a Kleefstra‑like neurodevelopmental syndrome, with psychomotor developmental delay, intellectual disability, absent speech, structural brain anomalies, hypotonia, dental anomalies and behavioural and sleep difficulties. Additional features also included recognisable facial dysmorphism (hypertelorism, synophrys, flat face, everted lips and protruding jaw) and cardiac anomalies (septal defects, pulmonic valve stenosis, aortic coarctation). All variants are absent from gnomAD. Episignature partially overlaps with Kleefstra syndrome 1 but was reported to form its own distinct profile. Biochemical assays show severe loss of G9a activity in fibroblast cell culture collected from patient 2 (EHMT2 c.3229G>T). A heterozygous knock‑in mouse model with a patient derived variant (Ehmt2 +/del_1076-1079) recapitulated the neurobehavioural and craniofacial phenotype. In vitro studies show that patient variants encode for structurally stable G9a proteins which are catalytically incompetent due to aberrant interactions either with histone H3 tail or with S-adenosylmethionine. The proposed mechanism is dominant negative effect on the GLP/G9a complexes.

PMID 3967492 and 42434347 describe two unrelated probands with biallelic loss‑of‑function EHMT2 variants presenting with a Kleefstra‑like neurodevelopmental disorder that includes developmental delay, facial dysmorphism, vertebral anomalies and congenital heart disease. A DNA‑methylation episignature matching Kleefstra syndrome 1 was reported for both patients.
Sources: Literature
Mendeliome v2.448 EHMT2 Richard Lin changed review comment from: EHMT1 and EHMT2 encode histone lysine methyltransferase 1 (GLP) and 2 (G9a) respectively. Together, they form heteromeric GLP/G9a complexes which catalyse H3K9 mono‑ and di‑methylation. EHMT1 is associated with Kleefstra syndrome 1.

PMID 42386776 report 7 unrelated individuals with de novo heterozygous EHMT2 missense and inframe deletion variants causing a Kleefstra‑like neurodevelopmental syndrome, with psychomotor developmental delay, intellectual disability, absent speech, structural brain anomalies, hypotonia, dental anomalies and behavioural and sleep difficulties. Additional features also included recognisable facial dysmorphism (hypertelorism, synophrys, flat face, everted lips and protruding jaw) and cardiac anomalies (septal defects, pulmonic valve stenosis, aortic coarctation). All variants are absent from gnomAD. Biochemical assays show severe loss of G9a activity in fibroblast cell culture collected from patient 2 (EHMT2 c.3229G>T). A heterozygous knock‑in mouse model with Ehmt2 +/del_1076-1079 recapitulated the neurobehavioural and craniofacial phenotype. In vitro studies show that patient variants encode for structurally stable G9a proteins which are catalytically incompetent due to aberrant interactions either with histone H3 tail or with S-adenosylmethionine. The proposed mechanism is dominant negative effect on the GLP/G9a complexes.

PMID 3967492 and 42434347 describe two unrelated probands with biallelic loss‑of‑function EHMT2 variants presenting with a Kleefstra‑like neurodevelopmental disorder that includes developmental delay, facial dysmorphism, vertebral anomalies and congenital heart disease. A DNA‑methylation episignature matching Kleefstra syndrome 1 was reported for both patients.
Sources: Literature; to: EHMT1 and EHMT2 encode histone lysine methyltransferase 1 (GLP) and 2 (G9a) respectively. Together, they form heteromeric GLP/G9a complexes which catalyse H3K9 mono‑ and di‑methylation. EHMT1 is associated with Kleefstra syndrome 1.

PMID 42386776 report 7 unrelated individuals with de novo heterozygous EHMT2 missense and inframe deletion variants causing a Kleefstra‑like neurodevelopmental syndrome, with psychomotor developmental delay, intellectual disability, absent speech, structural brain anomalies, hypotonia, dental anomalies and behavioural and sleep difficulties. Additional features also included recognisable facial dysmorphism (hypertelorism, synophrys, flat face, everted lips and protruding jaw) and cardiac anomalies (septal defects, pulmonic valve stenosis, aortic coarctation). All variants are absent from gnomAD. Episignature partially overlaps with Kleefstra syndrome 1 but was reported to form its own distinct profile. Biochemical assays show severe loss of G9a activity in fibroblast cell culture collected from patient 2 (EHMT2 c.3229G>T). A heterozygous knock‑in mouse model with Ehmt2 +/del_1076-1079 recapitulated the neurobehavioural and craniofacial phenotype. In vitro studies show that patient variants encode for structurally stable G9a proteins which are catalytically incompetent due to aberrant interactions either with histone H3 tail or with S-adenosylmethionine. The proposed mechanism is dominant negative effect on the GLP/G9a complexes.

PMID 3967492 and 42434347 describe two unrelated probands with biallelic loss‑of‑function EHMT2 variants presenting with a Kleefstra‑like neurodevelopmental disorder that includes developmental delay, facial dysmorphism, vertebral anomalies and congenital heart disease. A DNA‑methylation episignature matching Kleefstra syndrome 1 was reported for both patients.
Sources: Literature
Mendeliome v2.448 DDX1 chirag patel Marked gene: DDX1 as ready
Mendeliome v2.448 DDX1 chirag patel Gene: ddx1 has been classified as Amber List (Moderate Evidence).
Mendeliome v2.448 chirag patel Copied gene DDX1 from panel Intellectual disability syndromic and non-syndromic
Mendeliome v2.448 DDX1 chirag patel gene: DDX1 was added
gene: DDX1 was added to Mendeliome. Sources: Expert Review Amber,Other
Mode of inheritance for gene: DDX1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: DDX1 were set to Neurodevelopmental disorder, MONDO:0700092, DDX1-related
Intellectual disability syndromic and non-syndromic v2.97 DDX1 chirag patel Marked gene: DDX1 as ready
Intellectual disability syndromic and non-syndromic v2.97 DDX1 chirag patel Gene: ddx1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v2.97 DDX1 chirag patel Classified gene: DDX1 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v2.97 DDX1 chirag patel Gene: ddx1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v2.96 DDX1 chirag patel gene: DDX1 was added
gene: DDX1 was added to Intellectual disability syndromic and non-syndromic. Sources: Other
Mode of inheritance for gene: DDX1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: DDX1 were set to Neurodevelopmental disorder, MONDO:0700092, DDX1-related
Review for gene: DDX1 was set to AMBER
Added comment: ESHG 2026

9 unrelated individuals with 7 different rare heterozygous de novo variants (6 missense, 1 splice) involving conserved residues in critical domains of DDX1 gene. Individuals presented with developmental delay, hypotonia (9/9), distinctive facial gestalt (9/9), behavioral dysregulation (8/9), hand/foot skeletal anomalies (7/9), seizures (4/9), spasticity (4/9), and ataxia (3/9).

DEAD/DExH-box RNA (DDX) helicases are key regulators of RNA metabolism and cellular stress responses, and their dysfunction has been associated with distinct neurodevelopmental syndromes. DDX1 regulates RNA metabolism and genome integrity, and is an essential regulator of cellular responses to genotoxic and environmental stress. In silico analysis predicted all variants decrease protein stability. Patient-derived fibroblasts showed impaired radiation-induced DNA double-strand break repair, defective protection of specific target mRNAs under oxidative stress conditions, increased production of reactive oxygen species, and reduced mitochondrial function.
Sources: Other
Mendeliome v2.447 EHMT2 Richard Lin changed review comment from: EHMT1 and EHMT2 encode histone lysine methyltransferase 1 (GLP) and 2 (G9a) respectively. Together, they form heteromeric GLP/G9a complexes which catalyse H3K9 mono‑ and di‑methylation. EHMT1 is associated with Kleefstra syndrome 1.

PMID 42386776 report 7 unrelated individuals with de novo heterozygous EHMT2 variants causing a Kleefstra‑like neurodevelopmental syndrome, with psychomotor developmental delay, intellectual disability, absent speech, strcutural brain anomalies, hypotonia, dental anomalies and behavioural and sleep difficulties. Additional features also included recognisable facial dysmorphism (hypertelorism, synophrys, flat face, everted lips anrd protruding jaw) and cardiac anomalies (septal defects, pulmonic valve stenosis, aortic coarctation). All variants are absent from gnomAD. Biochemical assay show severe loss of G9a activity in fibroblast cell culture collected from patient 2 (EHMT2 c.3229G>T). A heterozygous knock‑in mouse model with Ehmt2 +/del_1076-1079 recapitulated the neurobehavioural and craniofacial phenotype.

PMID 3967492 and 42434347 describe two unrelated probands with biallelic loss‑of‑function EHMT2 variants presenting with a Kleefstra‑like neurodevelopmental disorder that includes developmental delay, facial dysmorphism, vertebral anomalies and congenital heart disease. A DNA‑methylation episignature matching Kleefstra syndrome 1 was reported for both patients.
Sources: Literature; to: EHMT1 and EHMT2 encode histone lysine methyltransferase 1 (GLP) and 2 (G9a) respectively. Together, they form heteromeric GLP/G9a complexes which catalyse H3K9 mono‑ and di‑methylation. EHMT1 is associated with Kleefstra syndrome 1.

PMID 42386776 report 7 unrelated individuals with de novo heterozygous EHMT2 missense and inframe deletion variants causing a Kleefstra‑like neurodevelopmental syndrome, with psychomotor developmental delay, intellectual disability, absent speech, structural brain anomalies, hypotonia, dental anomalies and behavioural and sleep difficulties. Additional features also included recognisable facial dysmorphism (hypertelorism, synophrys, flat face, everted lips and protruding jaw) and cardiac anomalies (septal defects, pulmonic valve stenosis, aortic coarctation). All variants are absent from gnomAD. Biochemical assays show severe loss of G9a activity in fibroblast cell culture collected from patient 2 (EHMT2 c.3229G>T). A heterozygous knock‑in mouse model with Ehmt2 +/del_1076-1079 recapitulated the neurobehavioural and craniofacial phenotype. In vitro studies show that patient variants encode for structurally stable G9a proteins which are catalytically incompetent due to aberrant interactions either with histone H3 tail or with S-adenosylmethionine. The proposed mechanism is dominant negative effect on the GLP/G9a complexes.

PMID 3967492 and 42434347 describe two unrelated probands with biallelic loss‑of‑function EHMT2 variants presenting with a Kleefstra‑like neurodevelopmental disorder that includes developmental delay, facial dysmorphism, vertebral anomalies and congenital heart disease. A DNA‑methylation episignature matching Kleefstra syndrome 1 was reported for both patients.
Sources: Literature
Mendeliome v2.447 EHMT2 Richard Lin gene: EHMT2 was added
gene: EHMT2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: EHMT2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: EHMT2 were set to 42434347; 42386776; 39674972
Phenotypes for gene: EHMT2 were set to Kleefstra syndrome, MONDO:0012455, EHMT2-related
Review for gene: EHMT2 was set to GREEN
Added comment: EHMT1 and EHMT2 encode histone lysine methyltransferase 1 (GLP) and 2 (G9a) respectively. Together, they form heteromeric GLP/G9a complexes which catalyse H3K9 mono‑ and di‑methylation. EHMT1 is associated with Kleefstra syndrome 1.

PMID 42386776 report 7 unrelated individuals with de novo heterozygous EHMT2 variants causing a Kleefstra‑like neurodevelopmental syndrome, with psychomotor developmental delay, intellectual disability, absent speech, strcutural brain anomalies, hypotonia, dental anomalies and behavioural and sleep difficulties. Additional features also included recognisable facial dysmorphism (hypertelorism, synophrys, flat face, everted lips anrd protruding jaw) and cardiac anomalies (septal defects, pulmonic valve stenosis, aortic coarctation). All variants are absent from gnomAD. Biochemical assay show severe loss of G9a activity in fibroblast cell culture collected from patient 2 (EHMT2 c.3229G>T). A heterozygous knock‑in mouse model with Ehmt2 +/del_1076-1079 recapitulated the neurobehavioural and craniofacial phenotype.

PMID 3967492 and 42434347 describe two unrelated probands with biallelic loss‑of‑function EHMT2 variants presenting with a Kleefstra‑like neurodevelopmental disorder that includes developmental delay, facial dysmorphism, vertebral anomalies and congenital heart disease. A DNA‑methylation episignature matching Kleefstra syndrome 1 was reported for both patients.
Sources: Literature
Mendeliome v2.446 XPO7 chirag patel Marked gene: XPO7 as ready
Mendeliome v2.446 XPO7 chirag patel Gene: xpo7 has been classified as Amber List (Moderate Evidence).
Mendeliome v2.446 chirag patel Copied gene XPO7 from panel Intellectual disability syndromic and non-syndromic
Mendeliome v2.446 XPO7 chirag patel gene: XPO7 was added
gene: XPO7 was added to Mendeliome. Sources: Expert Review Amber,Other
Mode of inheritance for gene: XPO7 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: XPO7 were set to Neurodevelopmental disorder, MONDO:0700092, XPO7-related
Intellectual disability syndromic and non-syndromic v2.95 XPO7 chirag patel Marked gene: XPO7 as ready
Intellectual disability syndromic and non-syndromic v2.95 XPO7 chirag patel Gene: xpo7 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v2.95 XPO7 chirag patel Classified gene: XPO7 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v2.95 XPO7 chirag patel Gene: xpo7 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v2.94 XPO7 chirag patel gene: XPO7 was added
gene: XPO7 was added to Intellectual disability syndromic and non-syndromic. Sources: Other
Mode of inheritance for gene: XPO7 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: XPO7 were set to Neurodevelopmental disorder, MONDO:0700092, XPO7-related
Review for gene: XPO7 was set to AMBER
Added comment: ESHG 2026

25 unrelated individuals with 19 different heterozygous variants in XPO7 (10 missense, 3 splice, 6 truncating). The R756W variant occurred in 6 unrelated individuals. Inheritance of variants was de novo (21), inherited (2), or unknown (1). Individuals presented with mild to severe developmental delay/intellectual disability (24/25), behavioural disturbances (17/24), nonspecific brain abnormalities (9/17), epilepsy (4/25), overweight (7/22), and other variable congenital anomalies.

XPO7 encodes a nuclear transport receptor. The R756W knock-in mouse model exhibited reduced XPO7 protein levels, reduced brain volume, decreased dendritic complexity, diminished excitatory synaptic transmission, and altered anxiety-related behaviour.
Sources: Other
Microcephaly v2.21 CENPT chirag patel Marked gene: CENPT as ready
Microcephaly v2.21 CENPT chirag patel Gene: cenpt has been classified as Amber List (Moderate Evidence).
Growth failure v2.17 CENPT chirag patel Marked gene: CENPT as ready
Growth failure v2.17 CENPT chirag patel Gene: cenpt has been classified as Amber List (Moderate Evidence).
Fetal anomalies v2.55 CENPT chirag patel Marked gene: CENPT as ready
Fetal anomalies v2.55 CENPT chirag patel Gene: cenpt has been classified as Amber List (Moderate Evidence).
Eye Anterior Segment Abnormalities v2.1 CENPT chirag patel Marked gene: CENPT as ready
Eye Anterior Segment Abnormalities v2.1 CENPT chirag patel Gene: cenpt has been classified as Amber List (Moderate Evidence).
Microcephaly v2.21 chirag patel Copied gene CENPT from panel Mendeliome
Microcephaly v2.21 CENPT chirag patel gene: CENPT was added
gene: CENPT was added to Microcephaly. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: CENPT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CENPT were set to 29228025
Phenotypes for gene: CENPT were set to Syndromic disease, MONDO: 0002254, CENPT-related
Growth failure v2.17 chirag patel Copied gene CENPT from panel Mendeliome
Growth failure v2.17 CENPT chirag patel gene: CENPT was added
gene: CENPT was added to Growth failure. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: CENPT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CENPT were set to 29228025
Phenotypes for gene: CENPT were set to Syndromic disease, MONDO: 0002254, CENPT-related
Fetal anomalies v2.55 chirag patel Copied gene CENPT from panel Mendeliome
Fetal anomalies v2.55 CENPT chirag patel gene: CENPT was added
gene: CENPT was added to Fetal anomalies. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: CENPT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CENPT were set to 29228025
Phenotypes for gene: CENPT were set to Syndromic disease, MONDO: 0002254, CENPT-related
Eye Anterior Segment Abnormalities v2.1 chirag patel Copied gene CENPT from panel Mendeliome
Eye Anterior Segment Abnormalities v2.1 CENPT chirag patel gene: CENPT was added
gene: CENPT was added to Eye Anterior Segment Abnormalities. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: CENPT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CENPT were set to 29228025
Phenotypes for gene: CENPT were set to Syndromic disease, MONDO: 0002254, CENPT-related
Mendeliome v2.445 CENPT chirag patel Phenotypes for gene: CENPT were changed from short stature and microcephaly with genital anomalies MONDO:0032875 to Syndromic disease, MONDO: 0002254, CENPT-related
Mendeliome v2.444 CENPT chirag patel Classified gene: CENPT as Amber List (moderate evidence)
Mendeliome v2.444 CENPT chirag patel Gene: cenpt has been classified as Amber List (Moderate Evidence).
Mendeliome v2.443 CENPT chirag patel reviewed gene: CENPT: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Syndromic disease, MONDO: 0002254, CENPT-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital ophthalmoplegia v2.1 TUBB3 Zornitza Stark Phenotypes for gene: TUBB3 were changed from Fibrosis of extraocular muscles, congenital, 3A 600638; CFEOM3A to Fibrosis of extraocular muscles, congenital, 3A 600638; CFEOM3A; Congenital fibrosis of extraocular muscles 3A, syndromic 1, with anosmia and developmental delay MIM#621655; Congenital fibrosis of extraocular muscles 3A2, syndromic, with joint contractures, developmental delay, and peripheral neuropathy, MIM#621666
Congenital ophthalmoplegia v2.0 TUBB3 Zornitza Stark edited their review of gene: TUBB3: Changed phenotypes: Fibrosis of extraocular muscles, congenital, 3A, MIM# 600638, Congenital fibrosis of extraocular muscles 3A, syndromic 1, with anosmia and developmental delay MIM#621655, Congenital fibrosis of extraocular muscles 3A2, syndromic, with joint contractures, developmental delay, and peripheral neuropathy, MIM#621666
Hypogonadotropic hypogonadism v1.16 TUBB3 Zornitza Stark Phenotypes for gene: TUBB3 were changed from TUBB3-related tubulinopathy, MONDO:0100154 to TUBB3-related tubulinopathy, MONDO:0100154; Congenital fibrosis of extraocular muscles 3A, syndromic 1, with anosmia and developmental delay, MIM#621655
Hypogonadotropic hypogonadism v1.15 TUBB3 Zornitza Stark reviewed gene: TUBB3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Congenital fibrosis of extraocular muscles 3A, syndromic 1, with anosmia and developmental delay, MIM#621655; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Pituitary hormone deficiency v1.19 TUBB3 Zornitza Stark Phenotypes for gene: TUBB3 were changed from TUBB3-related tubulinopathy, MONDO:0100154 to TUBB3-related tubulinopathy, MONDO:0100154; Congenital fibrosis of extraocular muscles 3A, syndromic 1, with anosmia and developmental delay, MIM#621655
Pituitary hormone deficiency v1.18 TUBB3 Zornitza Stark reviewed gene: TUBB3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Congenital fibrosis of extraocular muscles 3A, syndromic 1, with anosmia and developmental delay, MIM#621655; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v2.93 TUBB3 Zornitza Stark Phenotypes for gene: TUBB3 were changed from complex cortical dysplasia with other brain malformations 1 MONDO:0013541; Congenital fibrosis of extraocular muscles 3A, syndromic 1, with anosmia and developmental delay MIM#621655 Congenital fibrosis of extraocular muscles 3A2, syndromic, with joint contractures, developmental delay, and peripheral neuropathy, MIM#621666 to complex cortical dysplasia with other brain malformations 1 MONDO:0013541; Congenital fibrosis of extraocular muscles 3A, syndromic 1, with anosmia and developmental delay; MIM#621655 Congenital fibrosis of extraocular muscles 3A2, syndromic, with joint contractures, developmental delay, and peripheral neuropathy, MIM#621666
Intellectual disability syndromic and non-syndromic v2.92 TUBB3 Zornitza Stark edited their review of gene: TUBB3: Changed phenotypes: Congenital fibrosis of extraocular muscles 3A, syndromic 1, with anosmia and developmental delay MIM#621655, Congenital fibrosis of extraocular muscles 3A2, syndromic, with joint contractures, developmental delay, and peripheral neuropathy, MIM#621666
Intellectual disability syndromic and non-syndromic v2.92 TUBB3 Zornitza Stark Phenotypes for gene: TUBB3 were changed from complex cortical dysplasia with other brain malformations 1 MONDO:0013541 to complex cortical dysplasia with other brain malformations 1 MONDO:0013541; Congenital fibrosis of extraocular muscles 3A, syndromic 1, with anosmia and developmental delay MIM#621655 Congenital fibrosis of extraocular muscles 3A2, syndromic, with joint contractures, developmental delay, and peripheral neuropathy, MIM#621666
Intellectual disability syndromic and non-syndromic v2.91 TUBB3 Zornitza Stark commented on gene: TUBB3: CFEOM: multiple families reported, some affected individuals show additional features, including developmental delay or learning disabilities associated with dysgenesis of the corpus callosum. Other variable features include facial weakness and peripheral axonal neuropathy, sometimes associated with wrist and finger contractures. OMIM have split into three disorders.

Complex cortical dysplasia with other brain malformations (CDCBM), MIM#614039 is a disorder of aberrant neuronal migration and disturbed axonal guidance. Affected individuals have mild to severe DD/ID, strabismus, axial hypotonia, and spasticity. Brain imaging shows variable malformations of cortical development, including polymicrogyria, gyral disorganization, and fusion of the basal ganglia, as well as thin corpus callosum, hypoplastic brainstem, and dysplastic cerebellar vermis.

Unclear if the four disorders are distinct or part of a spectrum of TUBB3-associated abnormalities.
Intellectual disability syndromic and non-syndromic v2.91 TUBB3 Zornitza Stark reviewed gene: TUBB3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Congenital fibrosis of extraocular muscles 3A, syndromic 1, with anosmia and developmental delay MIM#621655 Congenital fibrosis of extraocular muscles 3A2, syndromic, with joint contractures, developmental delay, and peripheral neuropathy, MIM#621666; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary Neuropathy v2.27 TUBB3 Zornitza Stark Phenotypes for gene: TUBB3 were changed from Fibrosis of extraocular muscles, congenital, 3A (MIM#600638); Neuropathy to Fibrosis of extraocular muscles, congenital, 3A (MIM#600638); Neuropathy; Congenital fibrosis of extraocular muscles 3A2, syndromic, with joint contractures, developmental delay, and peripheral neuropathy, MIM#621666
Hereditary Neuropathy v2.26 TUBB3 Zornitza Stark edited their review of gene: TUBB3: Changed phenotypes: Fibrosis of extraocular muscles, congenital, 3A (MIM#600638), Neuropathy, Congenital fibrosis of extraocular muscles 3A2, syndromic, with joint contractures, developmental delay, and peripheral neuropathy, MIM#621666
Arthrogryposis v2.2 TUBB3 Zornitza Stark Phenotypes for gene: TUBB3 were changed from Fibrosis of extraocular muscles, congenital, 3A (MIM#600638); Neuropathy to Fibrosis of extraocular muscles, congenital, 3A (MIM#600638); Neuropathy; Congenital fibrosis of extraocular muscles 3A2, syndromic, with joint contractures, developmental delay, and peripheral neuropathy, MIM#621666
Arthrogryposis v2.1 TUBB3 Zornitza Stark edited their review of gene: TUBB3: Changed phenotypes: Fibrosis of extraocular muscles, congenital, 3A (MIM#600638), Congenital fibrosis of extraocular muscles 3A2, syndromic, with joint contractures, developmental delay, and peripheral neuropathy, MIM#621666
Mendeliome v2.443 TUBB3 Zornitza Stark Phenotypes for gene: TUBB3 were changed from Cortical dysplasia, complex, with other brain malformations 1, MIM# 614039; Fibrosis of extraocular muscles, congenital, 3A, MIM# 600638 to Cortical dysplasia, complex, with other brain malformations 1, MIM# 614039; Fibrosis of extraocular muscles, congenital, 3A, MIM# 600638; Congenital fibrosis of extraocular muscles 3A, syndromic 1, with anosmia and developmental delay MIM#621655; Congenital fibrosis of extraocular muscles 3A2, syndromic, with joint contractures, developmental delay, and peripheral neuropathy, MIM#621666
Mendeliome v2.442 TUBB3 Zornitza Stark edited their review of gene: TUBB3: Changed phenotypes: Cortical dysplasia, complex, with other brain malformations 1, MIM# 614039, Fibrosis of extraocular muscles, congenital, 3A, MIM# 600638, Congenital fibrosis of extraocular muscles 3A, syndromic 1, with anosmia and developmental delay MIM#621655, Congenital fibrosis of extraocular muscles 3A2, syndromic, with joint contractures, developmental delay, and peripheral neuropathy, MIM#621666
Mendeliome v2.442 CSMD2 chirag patel Phenotypes for gene: CSMD2 were changed from Neurodevelopmental disorder, MONDO:0700092, CSMD2-related to Neurodevelopmental disorder, MONDO:0700092, CSMD2-related
Mendeliome v2.441 CSMD2 chirag patel Phenotypes for gene: CSMD2 were changed from Neurodevelopmental disorder, MONDO:0700092, CSMD2-related to Neurodevelopmental disorder, MONDO:0700092, CSMD2-related
Mendeliome v2.441 CSMD2 chirag patel Phenotypes for gene: CSMD2 were changed from Focal epilepsy - MONDO:0005384, CSMD1-related to Neurodevelopmental disorder, MONDO:0700092, CSMD2-related
Mendeliome v2.440 CSMD2 chirag patel Mode of inheritance for gene: CSMD2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v2.439 CSMD2 chirag patel Mode of inheritance for gene: CSMD2 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v2.438 CSMD2 chirag patel Classified gene: CSMD2 as Amber List (moderate evidence)
Mendeliome v2.438 CSMD2 chirag patel Gene: csmd2 has been classified as Amber List (Moderate Evidence).
Mendeliome v2.437 chirag patel Added reviews for gene CSMD2 from panel Intellectual disability syndromic and non-syndromic
Intellectual disability syndromic and non-syndromic v2.91 CSMD2 chirag patel Phenotypes for gene: CSMD2 were changed from Focal epilepsy - MONDO:0005384, CSMD2-related to Neurodevelopmental disorder, MONDO:0700092, CSMD2-related
Intellectual disability syndromic and non-syndromic v2.90 CSMD2 chirag patel Mode of inheritance for gene: CSMD2 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v2.89 CSMD2 chirag patel Classified gene: CSMD2 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v2.89 CSMD2 chirag patel Gene: csmd2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v2.88 CSMD2 chirag patel reviewed gene: CSMD2: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, CSMD2-related; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v2.88 DLGAP1 chirag patel Marked gene: DLGAP1 as ready
Intellectual disability syndromic and non-syndromic v2.88 DLGAP1 chirag patel Gene: dlgap1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v2.88 chirag patel Copied gene DLGAP1 from panel Mendeliome
Intellectual disability syndromic and non-syndromic v2.88 DLGAP1 chirag patel gene: DLGAP1 was added
gene: DLGAP1 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Amber,Other
Mode of inheritance for gene: DLGAP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: DLGAP1 were set to Neurodevelopmental disorder, MONDO:0700092, DLGAP1-related
Mendeliome v2.436 DLGAP1 chirag patel Marked gene: DLGAP1 as ready
Mendeliome v2.436 DLGAP1 chirag patel Gene: dlgap1 has been classified as Amber List (Moderate Evidence).
Mendeliome v2.436 DLGAP1 chirag patel Classified gene: DLGAP1 as Amber List (moderate evidence)
Mendeliome v2.436 DLGAP1 chirag patel Gene: dlgap1 has been classified as Amber List (Moderate Evidence).
Mendeliome v2.435 DLGAP1 chirag patel gene: DLGAP1 was added
gene: DLGAP1 was added to Mendeliome. Sources: Other
Mode of inheritance for gene: DLGAP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: DLGAP1 were set to Neurodevelopmental disorder, MONDO:0700092, DLGAP1-related
Review for gene: DLGAP1 was set to AMBER
Added comment: ESHG 2026

14 unrelated individuals with 13 different rare heterozygous de novo variants (missense, nonsense, splice, frameshift) throughout DLGAP1 gene. Individuals presented with developmental delay (14), intellectual disability (7), ASD (11), seizures (5) and other non-specific features.

DLGAP1 (GKAP) encodes a postsynaptic scaffold protein bridging DLG4 to SHANK3. Disruption of other synaptic scaffolding proteins (DLG4 and SHANK3) is well known to cause neurodevelopmental disorders. Expression experiments revealed no gross instability of the mutant proteins. However, co-immunoprecipitation assays demonstrated impaired binding between DLGAP1 and DLG4 for the p.(Arg343Gln) variant and complete loss of SHANK interaction for the frameshift mutant, indicating a disruption of postsynaptic scaffold integrity.
Sources: Other
Mendeliome v2.434 UBE2I chirag patel Marked gene: UBE2I as ready
Mendeliome v2.434 UBE2I chirag patel Gene: ube2i has been classified as Amber List (Moderate Evidence).
Mendeliome v2.434 chirag patel Copied gene UBE2I from panel Intellectual disability syndromic and non-syndromic
Mendeliome v2.434 UBE2I chirag patel gene: UBE2I was added
gene: UBE2I was added to Mendeliome. Sources: Expert Review Amber,Other
Mode of inheritance for gene: UBE2I was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: UBE2I were set to Neurodevelopmental disorder, MONDO:0700092, UBE2I-related
Intellectual disability syndromic and non-syndromic v2.87 UBE2I chirag patel Marked gene: UBE2I as ready
Intellectual disability syndromic and non-syndromic v2.87 UBE2I chirag patel Gene: ube2i has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v2.87 UBE2I chirag patel Classified gene: UBE2I as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v2.87 UBE2I chirag patel Gene: ube2i has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v2.86 UBE2I chirag patel gene: UBE2I was added
gene: UBE2I was added to Intellectual disability syndromic and non-syndromic. Sources: Other
Mode of inheritance for gene: UBE2I was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: UBE2I were set to Neurodevelopmental disorder, MONDO:0700092, UBE2I-related
Review for gene: UBE2I was set to AMBER
Added comment: ESHG 2026

10 unrelated individuals with 10 different heterozygous missense variants throughout UBE2I gene (9 confirmed de novo) presenting with developmental delay (10), intellectual disability (4), ASD (5), microcephaly (3), hearing loss (3), and dysmorphism.

UBE2I encodes the only human E2 enzyme UBC9. SUMOylation is a critical post-translational modification regulating protein function, localization, and stability through E1, E2, and E3 enzymes. SUMOylation pathway is key regulator of neurodevelopment processes. Structural modeling for all variants suggested possible protein destabilization, disruption of the catalytic core, and altered SUMO binding. LCLs from patient with 2 variants (p.W53L and p.N124I) showed normal UBE2I mRNA levels, whereas protein levels were markedly reduced, and accompanied by decreased global SUMOylation. Yeast-based assays showed reduced protein stability for the p.W53L variant.
Sources: Other
Growth failure v2.16 SMC6 chirag patel Marked gene: SMC6 as ready
Growth failure v2.16 SMC6 chirag patel Gene: smc6 has been classified as Amber List (Moderate Evidence).
Microcephaly v2.20 SMC6 chirag patel Marked gene: SMC6 as ready
Microcephaly v2.20 SMC6 chirag patel Gene: smc6 has been classified as Amber List (Moderate Evidence).
Mendeliome v2.433 SMC6 chirag patel Marked gene: SMC6 as ready
Mendeliome v2.433 SMC6 chirag patel Gene: smc6 has been classified as Amber List (Moderate Evidence).
Chromosome Breakage Disorders v2.3 SMC6 chirag patel Marked gene: SMC6 as ready
Chromosome Breakage Disorders v2.3 SMC6 chirag patel Gene: smc6 has been classified as Amber List (Moderate Evidence).
Microcephaly v2.20 chirag patel Copied gene SMC6 from panel Intellectual disability syndromic and non-syndromic
Microcephaly v2.20 SMC6 chirag patel gene: SMC6 was added
gene: SMC6 was added to Microcephaly. Sources: Expert Review Amber,Other
Mode of inheritance for gene: SMC6 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SMC6 were set to Neurodevelopmental disorder, MONDO:0700092, SMC6-related
Mendeliome v2.433 chirag patel Copied gene SMC6 from panel Intellectual disability syndromic and non-syndromic
Mendeliome v2.433 SMC6 chirag patel gene: SMC6 was added
gene: SMC6 was added to Mendeliome. Sources: Expert Review Amber,Other
Mode of inheritance for gene: SMC6 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SMC6 were set to Neurodevelopmental disorder, MONDO:0700092, SMC6-related
Growth failure v2.16 chirag patel Copied gene SMC6 from panel Intellectual disability syndromic and non-syndromic
Growth failure v2.16 SMC6 chirag patel gene: SMC6 was added
gene: SMC6 was added to Growth failure. Sources: Expert Review Amber,Other
Mode of inheritance for gene: SMC6 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SMC6 were set to Neurodevelopmental disorder, MONDO:0700092, SMC6-related
Chromosome Breakage Disorders v2.3 chirag patel Copied gene SMC6 from panel Intellectual disability syndromic and non-syndromic
Chromosome Breakage Disorders v2.3 SMC6 chirag patel gene: SMC6 was added
gene: SMC6 was added to Chromosome Breakage Disorders. Sources: Expert Review Amber,Other
Mode of inheritance for gene: SMC6 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SMC6 were set to Neurodevelopmental disorder, MONDO:0700092, SMC6-related
Intellectual disability syndromic and non-syndromic v2.85 SMC6 chirag patel Marked gene: SMC6 as ready
Intellectual disability syndromic and non-syndromic v2.85 SMC6 chirag patel Gene: smc6 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v2.85 SMC6 chirag patel Classified gene: SMC6 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v2.85 SMC6 chirag patel Gene: smc6 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v2.84 SMC6 chirag patel gene: SMC6 was added
gene: SMC6 was added to Intellectual disability syndromic and non-syndromic. Sources: Other
Mode of inheritance for gene: SMC6 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SMC6 were set to Neurodevelopmental disorder, MONDO:0700092, SMC6-related
Review for gene: SMC6 was set to AMBER
Added comment: ESHG 2026

17 affected individuals from 2 families (1 consanguineous family with 16 individuals) with biallelic variants in SMC6 (3 missense) which segregated with disease. Phenotype included microcephaly (1 family), short stature, DD/ID (1 family), dysmorphism (Seckel like), haematological anomalies (1 family), and lung disease (1 family).

SMC5/6 complex is a highly conserved multi-subunit protein complex essential for repairing DNA damage and preventing replication stress. SMC5 has been associated with a developmental disorder. SMC6 patient-derived cell lines display a shared cellular phenotype (to SMC5) typified by chromosome instability with elevated replication stress and genome instability, exacerbated when exposed to genotoxins that stabilise G-quadruplex structures. Zebrafish models showed microcephaly and reduced length.
Sources: Other
Intellectual disability syndromic and non-syndromic v2.83 CMIP Eleanor Ludington Marked gene: CMIP as ready
Intellectual disability syndromic and non-syndromic v2.83 CMIP Eleanor Ludington Gene: cmip has been classified as Green List (High Evidence).
Genetic Epilepsy v2.33 CMIP Eleanor Ludington Marked gene: CMIP as ready
Genetic Epilepsy v2.33 CMIP Eleanor Ludington Gene: cmip has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v2.83 Eleanor Ludington Copied gene CMIP from panel Mendeliome
Intellectual disability syndromic and non-syndromic v2.83 CMIP Eleanor Ludington gene: CMIP was added
gene: CMIP was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Green,Literature
Mode of inheritance for gene: CMIP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CMIP were set to 42386996; 28504353; 22689534
Phenotypes for gene: CMIP were set to Neurodevelopmental disorder, MONDO:0700092
Genetic Epilepsy v2.33 Eleanor Ludington Copied gene CMIP from panel Mendeliome
Genetic Epilepsy v2.33 CMIP Eleanor Ludington gene: CMIP was added
gene: CMIP was added to Genetic Epilepsy. Sources: Expert Review Green,Literature
Mode of inheritance for gene: CMIP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CMIP were set to 42386996; 28504353; 22689534
Phenotypes for gene: CMIP were set to Neurodevelopmental disorder, MONDO:0700092
Mendeliome v2.432 CMIP Eleanor Ludington Marked gene: CMIP as ready
Mendeliome v2.432 CMIP Eleanor Ludington Gene: cmip has been classified as Green List (High Evidence).
Mendeliome v2.432 CMIP Eleanor Ludington Classified gene: CMIP as Green List (high evidence)
Mendeliome v2.432 CMIP Eleanor Ludington Gene: cmip has been classified as Green List (High Evidence).
Mendeliome v2.431 CMIP Eleanor Ludington gene: CMIP was added
gene: CMIP was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CMIP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CMIP were set to 42386996; 28504353; 22689534
Phenotypes for gene: CMIP were set to Neurodevelopmental disorder, MONDO:0700092
Review for gene: CMIP was set to GREEN
Added comment: PMID 42386996 reports 7 individuals from 7 families with de novo heterozygous loss-of-function SNVs in CMIP presenting with developmental delay, intellectual disability, autism spectrum disorder and epilepsy (childhood‑onset). Earlier studies (PMID 28504353; PMID 22689534) described de novo heterozygous deletions of CMIP in individuals with autism spectrum disorder and developmental delay. Functional evidence includes a zebrafish loss‑of-function model showing reduced locomotion and increased spontaneous epileptiform activity.
Sources: Literature
Mendeliome v2.430 GTF3C1 chirag patel Marked gene: GTF3C1 as ready
Mendeliome v2.430 GTF3C1 chirag patel Gene: gtf3c1 has been classified as Amber List (Moderate Evidence).
Callosome v1.23 GTF3C1 chirag patel Marked gene: GTF3C1 as ready
Callosome v1.23 GTF3C1 chirag patel Gene: gtf3c1 has been classified as Amber List (Moderate Evidence).
Microcephaly v2.19 GTF3C1 chirag patel Marked gene: GTF3C1 as ready
Microcephaly v2.19 GTF3C1 chirag patel Gene: gtf3c1 has been classified as Amber List (Moderate Evidence).
Cerebellar and Pontocerebellar Hypoplasia v2.3 GTF3C1 chirag patel Marked gene: GTF3C1 as ready
Cerebellar and Pontocerebellar Hypoplasia v2.3 GTF3C1 chirag patel Gene: gtf3c1 has been classified as Amber List (Moderate Evidence).
Mendeliome v2.430 chirag patel Copied gene GTF3C1 from panel Intellectual disability syndromic and non-syndromic
Mendeliome v2.430 GTF3C1 chirag patel gene: GTF3C1 was added
gene: GTF3C1 was added to Mendeliome. Sources: Expert Review Amber,Other
Mode of inheritance for gene: GTF3C1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: GTF3C1 were set to Neurodevelopmental disorder, MONDO:0700092, GTF3C1-related
Microcephaly v2.19 chirag patel Copied gene GTF3C1 from panel Intellectual disability syndromic and non-syndromic
Microcephaly v2.19 GTF3C1 chirag patel gene: GTF3C1 was added
gene: GTF3C1 was added to Microcephaly. Sources: Expert Review Amber,Other
Mode of inheritance for gene: GTF3C1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: GTF3C1 were set to Neurodevelopmental disorder, MONDO:0700092, GTF3C1-related
Cerebellar and Pontocerebellar Hypoplasia v2.3 chirag patel Copied gene GTF3C1 from panel Intellectual disability syndromic and non-syndromic
Cerebellar and Pontocerebellar Hypoplasia v2.3 GTF3C1 chirag patel gene: GTF3C1 was added
gene: GTF3C1 was added to Cerebellar and Pontocerebellar Hypoplasia. Sources: Expert Review Amber,Other
Mode of inheritance for gene: GTF3C1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: GTF3C1 were set to Neurodevelopmental disorder, MONDO:0700092, GTF3C1-related
Callosome v1.23 chirag patel Copied gene GTF3C1 from panel Intellectual disability syndromic and non-syndromic
Callosome v1.23 GTF3C1 chirag patel gene: GTF3C1 was added
gene: GTF3C1 was added to Callosome. Sources: Expert Review Amber,Other
Mode of inheritance for gene: GTF3C1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: GTF3C1 were set to Neurodevelopmental disorder, MONDO:0700092, GTF3C1-related
Intellectual disability syndromic and non-syndromic v2.82 GTF3C1 chirag patel Marked gene: GTF3C1 as ready
Intellectual disability syndromic and non-syndromic v2.82 GTF3C1 chirag patel Gene: gtf3c1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v2.82 GTF3C1 chirag patel Classified gene: GTF3C1 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v2.82 GTF3C1 chirag patel Gene: gtf3c1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v2.81 GTF3C1 chirag patel Classified gene: GTF3C1 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v2.81 GTF3C1 chirag patel Gene: gtf3c1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v2.80 GTF3C1 chirag patel gene: GTF3C1 was added
gene: GTF3C1 was added to Intellectual disability syndromic and non-syndromic. Sources: Other
Mode of inheritance for gene: GTF3C1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: GTF3C1 were set to Neurodevelopmental disorder, MONDO:0700092, GTF3C1-related
Review for gene: GTF3C1 was set to AMBER
Added comment: ESHG 2026

6 individuals from 6 unrelated families (4 consanguineous) with biallelic variants in GTF3C1 which segregated with disease (6 missense, 1 nonsense). Phenotype included developmental delay, intellectual disability, microcephaly, cerebellar atrophy/hypoplasia, abnormal corpus callosum, arthrogryposis, and variable craniofacial features.

GTF3C1 encodes a subunit within the general Transcription Factor IIIC (TFIIIC), which is involved general transcription factor activity via recruitment of RNA polymerase III for target gene transcription. Two other TFIIIC subunits, GTF3C3 and GTF3C5, have been implicated in neurodevelopmental disorders. Molecular modelling suggested missense variants disrupt intramolecular interactions, causing instability of the TFIIIC complex. Proteomic analysis using patient cell lines revealed significantly reduced GTF3C1 protein. A relative complex abundance assay demonstrated the five other subunits of the TFIIIC complex were also reduced, and suggests a loss-of-function mechanism. Gtf3c1 knockdown in mouse brain revealed impaired neuronal production and cell cycle exit.
Sources: Other
Cerebellar and Pontocerebellar Hypoplasia v2.2 GTF3C5 chirag patel Marked gene: GTF3C5 as ready
Cerebellar and Pontocerebellar Hypoplasia v2.2 GTF3C5 chirag patel Gene: gtf3c5 has been classified as Green List (High Evidence).
Cerebellar and Pontocerebellar Hypoplasia v2.2 chirag patel Copied gene GTF3C5 from panel Intellectual disability syndromic and non-syndromic
Cerebellar and Pontocerebellar Hypoplasia v2.2 GTF3C5 chirag patel gene: GTF3C5 was added
gene: GTF3C5 was added to Cerebellar and Pontocerebellar Hypoplasia. Sources: Expert Review Green,Literature
Mode of inheritance for gene: GTF3C5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GTF3C5 were set to 38520561; 35503477
Phenotypes for gene: GTF3C5 were set to neurodevelopmental disorder MONDO:0700092, GTF3C5-related
Cerebellar and Pontocerebellar Hypoplasia v2.1 GTF3C3 chirag patel Marked gene: GTF3C3 as ready
Cerebellar and Pontocerebellar Hypoplasia v2.1 GTF3C3 chirag patel Gene: gtf3c3 has been classified as Green List (High Evidence).
Callosome v1.22 GTF3C3 chirag patel Marked gene: GTF3C3 as ready
Callosome v1.22 GTF3C3 chirag patel Gene: gtf3c3 has been classified as Green List (High Evidence).
Cerebellar and Pontocerebellar Hypoplasia v2.1 chirag patel Copied gene GTF3C3 from panel Intellectual disability syndromic and non-syndromic
Cerebellar and Pontocerebellar Hypoplasia v2.1 GTF3C3 chirag patel gene: GTF3C3 was added
gene: GTF3C3 was added to Cerebellar and Pontocerebellar Hypoplasia. Sources: Expert Review Green,Genetic Health Queensland
Mode of inheritance for gene: GTF3C3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GTF3C3 were set to 28940097; 28097321; 30552426
Phenotypes for gene: GTF3C3 were set to Neurodevelopmental disorder with dysmorphic facies, brain anomalies, and seizures, MIM# 621201
Callosome v1.22 chirag patel Copied gene GTF3C3 from panel Intellectual disability syndromic and non-syndromic
Callosome v1.22 GTF3C3 chirag patel gene: GTF3C3 was added
gene: GTF3C3 was added to Callosome. Sources: Expert Review Green,Genetic Health Queensland
Mode of inheritance for gene: GTF3C3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GTF3C3 were set to 28940097; 28097321; 30552426
Phenotypes for gene: GTF3C3 were set to Neurodevelopmental disorder with dysmorphic facies, brain anomalies, and seizures, MIM# 621201
Intellectual disability syndromic and non-syndromic v2.79 NUAK1 chirag patel changed review comment from: 7 individuals from 5 unrelated consanguineous families with craniofacial dysmorphism (hypertelorism, DSPF, dental anomalies), neurodevelopmental issues, and omphalocele (2 families with LOF variants). WES identified 5 different homozygous variants (3 missense, 1 nonsense, 1 splice) which segregated with disease.

NUAK1 has a kinase function and all variants were located in the kinase domain. Patient fibroblast assays showed reduced transcript and loss of NUAK1 protein for LOF variants. The missense variants had increased transcript and protein levels but had reduced kinase activity. Mouse models show abdominal wall defects. Xenopus models showed craniofacial defects and ventral body wall defects.
Sources: Other; to: ESHG 2026

7 individuals from 5 unrelated consanguineous families with craniofacial dysmorphism (hypertelorism, DSPF, dental anomalies), neurodevelopmental issues, and omphalocele (2 families with LOF variants). WES identified 5 different homozygous variants (3 missense, 1 nonsense, 1 splice) which segregated with disease.

NUAK1 has a kinase function and all variants were located in the kinase domain. Patient fibroblast assays showed reduced transcript and loss of NUAK1 protein for LOF variants. The missense variants had increased transcript and protein levels but had reduced kinase activity. Mouse models show abdominal wall defects. Xenopus models showed craniofacial defects and ventral body wall defects.
Sources: Other
Fetal anomalies v2.54 NUAK1 chirag patel changed review comment from: 7 individuals from 5 unrelated consanguineous families with craniofacial dysmorphism (hypertelorism, DSPF, dental anomalies), neurodevelopmental issues, and omphalocele (2 families with LOF variants). WES identified 5 different homozygous variants (3 missense, 1 nonsense, 1 splice) which segregated with disease.

NUAK1 has a kinase function and all variants were located in the kinase domain. Patient fibroblast assays showed reduced transcript and loss of NUAK1 protein for LOF variants. The missense variants had increased transcript and protein levels but had reduced kinase activity. Mouse models show abdominal wall defects. Xenopus models showed craniofacial defects and ventral body wall defects.
Sources: Other; to: ESHG 2026

7 individuals from 5 unrelated consanguineous families with craniofacial dysmorphism (hypertelorism, DSPF, dental anomalies), neurodevelopmental issues, and omphalocele (2 families with LOF variants). WES identified 5 different homozygous variants (3 missense, 1 nonsense, 1 splice) which segregated with disease.

NUAK1 has a kinase function and all variants were located in the kinase domain. Patient fibroblast assays showed reduced transcript and loss of NUAK1 protein for LOF variants. The missense variants had increased transcript and protein levels but had reduced kinase activity. Mouse models show abdominal wall defects. Xenopus models showed craniofacial defects and ventral body wall defects.
Sources: Other
Fetal anomalies v2.54 NUAK1 chirag patel Marked gene: NUAK1 as ready
Fetal anomalies v2.54 NUAK1 chirag patel Gene: nuak1 has been classified as Amber List (Moderate Evidence).
Mendeliome v2.429 NUAK1 chirag patel Marked gene: NUAK1 as ready
Mendeliome v2.429 NUAK1 chirag patel Gene: nuak1 has been classified as Amber List (Moderate Evidence).
Mendeliome v2.429 NUAK1 chirag patel changed review comment from: 7 individuals from 5 unrelated consanguineous families with craniofacial dysmorphism (hypertelorism, DSPF, dental anomalies), neurodevelopmental issues, and omphalocele (2 families with LOF variants). WES identified 5 different homozygous variants (3 missense, 1 nonsense, 1 splice) which segregated with disease.

NUAK1 has a kinase function and all variants were located in the kinase domain. Patient fibroblast assays showed reduced transcript and loss of NUAK1 protein for LOF variants. The missense variants had increased transcript and protein levels but had reduced kinase activity. Mouse models show abdominal wall defects. Xenopus models showed craniofacial defects and ventral body wall defects.
Sources: Other; to: ESHG 2026

7 individuals from 5 unrelated consanguineous families with craniofacial dysmorphism (hypertelorism, DSPF, dental anomalies), neurodevelopmental issues, and omphalocele (2 families with LOF variants). WES identified 5 different homozygous variants (3 missense, 1 nonsense, 1 splice) which segregated with disease.

NUAK1 has a kinase function and all variants were located in the kinase domain. Patient fibroblast assays showed reduced transcript and loss of NUAK1 protein for LOF variants. The missense variants had increased transcript and protein levels but had reduced kinase activity. Mouse models show abdominal wall defects. Xenopus models showed craniofacial defects and ventral body wall defects.
Sources: Other
Mendeliome v2.429 chirag patel Copied gene NUAK1 from panel Intellectual disability syndromic and non-syndromic
Mendeliome v2.429 NUAK1 chirag patel gene: NUAK1 was added
gene: NUAK1 was added to Mendeliome. Sources: Expert Review Amber,Other
Mode of inheritance for gene: NUAK1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NUAK1 were set to Syndromic disease, MONDO: 0002254
Fetal anomalies v2.54 chirag patel Copied gene NUAK1 from panel Intellectual disability syndromic and non-syndromic
Fetal anomalies v2.54 NUAK1 chirag patel gene: NUAK1 was added
gene: NUAK1 was added to Fetal anomalies. Sources: Expert Review Amber,Other
Mode of inheritance for gene: NUAK1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NUAK1 were set to Syndromic disease, MONDO: 0002254
Intellectual disability syndromic and non-syndromic v2.79 NUAK1 chirag patel Marked gene: NUAK1 as ready
Intellectual disability syndromic and non-syndromic v2.79 NUAK1 chirag patel Gene: nuak1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v2.79 NUAK1 chirag patel Classified gene: NUAK1 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v2.79 NUAK1 chirag patel Gene: nuak1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v2.78 NUAK1 chirag patel gene: NUAK1 was added
gene: NUAK1 was added to Intellectual disability syndromic and non-syndromic. Sources: Other
Mode of inheritance for gene: NUAK1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NUAK1 were set to Syndromic disease, MONDO: 0002254
Review for gene: NUAK1 was set to AMBER
Added comment: 7 individuals from 5 unrelated consanguineous families with craniofacial dysmorphism (hypertelorism, DSPF, dental anomalies), neurodevelopmental issues, and omphalocele (2 families with LOF variants). WES identified 5 different homozygous variants (3 missense, 1 nonsense, 1 splice) which segregated with disease.

NUAK1 has a kinase function and all variants were located in the kinase domain. Patient fibroblast assays showed reduced transcript and loss of NUAK1 protein for LOF variants. The missense variants had increased transcript and protein levels but had reduced kinase activity. Mouse models show abdominal wall defects. Xenopus models showed craniofacial defects and ventral body wall defects.
Sources: Other
Retinitis pigmentosa v1.11 Sangavi Sivagnanasundram Copied gene ATRAID from panel Mendeliome
Retinitis pigmentosa v1.11 ATRAID Sangavi Sivagnanasundram gene: ATRAID was added
gene: ATRAID was added to Retinitis pigmentosa. Sources: Literature
Mode of inheritance for gene: ATRAID was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATRAID were set to 42417592
Phenotypes for gene: ATRAID were set to ATRAID-related retinitis pigmentosa, MONDO:0019200
Mendeliome v2.428 ATRAID Sangavi Sivagnanasundram gene: ATRAID was added
gene: ATRAID was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ATRAID was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATRAID were set to 42417592
Phenotypes for gene: ATRAID were set to ATRAID-related retinitis pigmentosa, MONDO:0019200
Review for gene: ATRAID was set to RED
Added comment: PMID 42417592 reports six individuals from four Norwegian families (one family is consanguineous) with biallelic frameshift variants presenting with late‑onset, non‑syndromic retinitis pigmentosa. Clinical features include mid‑peripheral chorioretinal atrophy, bone‑spicule pigmentation and rod‑cone dysfunction.

LoF is not an established mechanism of disease for this gene yet. gnomAD v4.1 pLI = 0
o/e = 0.9 (0.66 - 1.25) and there are no reported pathogenic LoF variants reported in ClinVar.
Sources: Literature
Mendeliome v2.427 ACTRT3 Zornitza Stark Publications for gene: ACTRT3 were set to 42330090
Mendeliome v2.426 ACTRT3 Zornitza Stark Classified gene: ACTRT3 as Green List (high evidence)
Mendeliome v2.426 ACTRT3 Zornitza Stark Gene: actrt3 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v2.39 ACTRT3 Zornitza Stark Classified gene: ACTRT3 as Green List (high evidence)
Infertility and Recurrent Pregnancy Loss v2.39 ACTRT3 Zornitza Stark Gene: actrt3 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v2.38 ACTRT3 Zornitza Stark edited their review of gene: ACTRT3: Added comment: PMID 42391565 reports another individual with a homozygous nonsense ACTRT3 c.712C>T variant causing male infertility characterised by severe teratozoospermia, acrosomal ultrastructural defects, fertilisation failure and embryonic arrest.; Changed rating: GREEN; Changed publications: 42330090, 42391565
Mendeliome v2.425 ACTRT3 Zornitza Stark edited their review of gene: ACTRT3: Changed rating: GREEN
Mendeliome v2.425 ACTRT3 Zornitza Stark edited their review of gene: ACTRT3: Added comment: PMID 42391565 reports another individual with a homozygous nonsense ACTRT3 c.712C>T variant causing male infertility characterised by severe teratozoospermia, acrosomal ultrastructural defects, fertilisation failure and embryonic arrest.; Changed publications: 42330090, 42391565
Ciliopathies v2.16 DNAJC16 Zornitza Stark Marked gene: DNAJC16 as ready
Ciliopathies v2.16 DNAJC16 Zornitza Stark Gene: dnajc16 has been classified as Red List (Low Evidence).
Ciliopathies v2.16 Zornitza Stark Copied gene DNAJC16 from panel Mendeliome
Ciliopathies v2.16 DNAJC16 Zornitza Stark gene: DNAJC16 was added
gene: DNAJC16 was added to Ciliopathies. Sources: Expert Review Red,Literature
Mode of inheritance for gene: DNAJC16 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DNAJC16 were set to 42434812
Phenotypes for gene: DNAJC16 were set to ciliopathy, MONDO:0005308
Mendeliome v2.425 DNAJC16 Zornitza Stark Marked gene: DNAJC16 as ready
Mendeliome v2.425 DNAJC16 Zornitza Stark Gene: dnajc16 has been classified as Red List (Low Evidence).
Mendeliome v2.425 DNAJC16 Zornitza Stark gene: DNAJC16 was added
gene: DNAJC16 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: DNAJC16 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DNAJC16 were set to 42434812
Phenotypes for gene: DNAJC16 were set to ciliopathy, MONDO:0005308
Review for gene: DNAJC16 was set to RED
Added comment: PMID 42434812 reports ?three families with homozygous loss-of-function DNAJC16 variants causing a ciliopathy phenotype. Minimal phenotypic or genetic detail, part of a large paper putting forward multiple novel gene-disease associations.
Sources: Literature
Mendeliome v2.423 USH1C Michelle Torres reviewed gene: USH1C: Rating: AMBER; Mode of pathogenicity: None; Publications: 31858762, 37973466, 37206537; Phenotypes: Usher syndrome, type 1C, MIM#276904, Deafness, autosomal recessive 18A, MIM#602092; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v2.423 KRT16 Sangavi Sivagnanasundram reviewed gene: KRT16: Rating: AMBER; Mode of pathogenicity: None; Publications: 38170465, 42476612; Phenotypes: palmoplantar keratoderma, nonepidermolytic, focal 1, MONDO:0013073; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Renal Tubulopathies and related disorders v2.7 KCNA1 Lucy Spencer Publications for gene: KCNA1 were set to 32316562; 11026449
Renal Tubulopathies and related disorders v2.6 KCNA1 Lucy Spencer Phenotypes for gene: KCNA1 were changed from Epilepsy, MONDO:0005027, KCNA1-related; Episodic ataxia/myokymia syndrome, MIM# 160120 to Episodic ataxia/myokymia syndrome MIM#160120
Renal Tubulopathies and related disorders v2.5 KCNA1 Lucy Spencer reviewed gene: KCNA1: Rating: GREEN; Mode of pathogenicity: None; Publications: 34784661, 32316562; Phenotypes: Episodic ataxia/myokymia syndrome MIM#160120; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.111 PEX6 chirag patel Marked gene: PEX6 as ready
Skeletal dysplasia v1.111 PEX6 chirag patel Gene: pex6 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.111 PEX6 chirag patel changed review comment from: Variants in this gene account for 14.5% of Zellweger Spectrum Disorder patients according to GeneReviews (https://www.ncbi.nlm.nih.gov/books/NBK1448/) Genetic spectrum of 77 patients reviewed in PMID: 19877282.; to: Variants in this gene account for 14.5% of Zellweger Spectrum Disorder patients according to GeneReviews (https://www.ncbi.nlm.nih.gov/books/NBK1448/) Genetic spectrum of 77 patients reviewed in PMID: 19877282.

Newborns may have bony stippling (chondrodysplasia punctata) of the patella(e) and other long bones.
Skeletal dysplasia v1.111 chirag patel Copied gene PEX6 from panel Peroxisomal Disorders
Skeletal dysplasia v1.111 PEX6 chirag patel gene: PEX6 was added
gene: PEX6 was added to Skeletal dysplasia. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: PEX6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PEX6 were set to 20301621, 19877282
Phenotypes for gene: PEX6 were set to Peroxisome biogenesis disorder 4A (Zellweger), MIM# 614862
Leukodystrophy v1.8 PEX6 chirag patel Marked gene: PEX6 as ready
Leukodystrophy v1.8 PEX6 chirag patel Gene: pex6 has been classified as Green List (High Evidence).
Leukodystrophy v1.8 PEX6 chirag patel Phenotypes for gene: PEX6 were changed from Peroxisome biogenesis disorder 4A (Zellweger), 614862; Peroxisome biogenesis disorder 4B, 614863 to Peroxisome biogenesis disorder 4A (Zellweger), MIM# 614862
Leukodystrophy v1.7 PEX6 chirag patel Publications for gene: PEX6 were set to
Leukodystrophy v1.6 PEX6 chirag patel Mode of inheritance for gene: PEX6 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Leukodystrophy v1.5 PEX6 chirag patel changed review comment from: Variants in this gene account for 14.5% of Zellweger Spectrum Disorder patients according to GeneReviews (https://www.ncbi.nlm.nih.gov/books/NBK1448/) Genetic spectrum of 77 patients reviewed in PMID: 19877282.; to: Variants in this gene account for 14.5% of Zellweger Spectrum Disorder patients according to GeneReviews (https://www.ncbi.nlm.nih.gov/books/NBK1448/) Genetic spectrum of 77 patients reviewed in PMID: 19877282.

Intermediate/milder ZSD is a progressive disorder with hearing and vision worsening with time. Some individuals may develop progressive degeneration of CNS myelin, a leukodystrophy, which may lead to loss of previously acquired skills and ultimately death.
Leukodystrophy v1.5 chirag patel Added reviews for gene PEX6 from panel Peroxisomal Disorders
Peroxisomal Disorders v1.8 PEX6 chirag patel Marked gene: PEX6 as ready
Peroxisomal Disorders v1.8 PEX6 chirag patel Gene: pex6 has been classified as Green List (High Evidence).
Peroxisomal Disorders v1.8 PEX6 chirag patel Phenotypes for gene: PEX6 were changed from to Peroxisome biogenesis disorder 4A (Zellweger), MIM# 614862
Peroxisomal Disorders v1.7 PEX6 chirag patel Publications for gene: PEX6 were set to
Peroxisomal Disorders v1.6 PEX6 chirag patel Mode of inheritance for gene: PEX6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Peroxisomal Disorders v1.5 PEX6 chirag patel reviewed gene: PEX6: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301621, 19877282; Phenotypes: Peroxisome biogenesis disorder 4A (Zellweger), MIM# 614862; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Callosome v1.21 PEX6 chirag patel Marked gene: PEX6 as ready
Callosome v1.21 PEX6 chirag patel Gene: pex6 has been classified as Red List (Low Evidence).
Callosome v1.21 PEX6 chirag patel Mode of inheritance for gene: PEX6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Callosome v1.20 PEX6 chirag patel Phenotypes for gene: PEX6 were changed from to Peroxisome biogenesis disorder 4A (Zellweger), MIM# 614862
Callosome v1.19 PEX6 chirag patel Classified gene: PEX6 as Red List (low evidence)
Callosome v1.19 PEX6 chirag patel Gene: pex6 has been classified as Red List (Low Evidence).
Callosome v1.18 PEX6 chirag patel reviewed gene: PEX6: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Peroxisome biogenesis disorder 4A (Zellweger), MIM# 614862; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hydrops fetalis v1.3 PEX6 chirag patel Marked gene: PEX6 as ready
Hydrops fetalis v1.3 PEX6 chirag patel Gene: pex6 has been classified as Red List (Low Evidence).
Hydrops fetalis v1.3 PEX6 chirag patel Phenotypes for gene: PEX6 were changed from to Peroxisome biogenesis disorder 4A (Zellweger), MIM# 614862
Hydrops fetalis v1.2 PEX6 chirag patel Mode of inheritance for gene: PEX6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Hydrops fetalis v1.1 PEX6 chirag patel Classified gene: PEX6 as Red List (low evidence)
Hydrops fetalis v1.1 PEX6 chirag patel Gene: pex6 has been classified as Red List (Low Evidence).
Hydrops fetalis v1.0 PEX6 chirag patel reviewed gene: PEX6: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Peroxisome biogenesis disorder 4A (Zellweger), MIM# 614862; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.110 PLCB4 chirag patel Marked gene: PLCB4 as ready
Skeletal dysplasia v1.110 PLCB4 chirag patel Gene: plcb4 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.110 chirag patel Copied gene PLCB4 from panel Mandibulofacial Acrofacial dysostosis
Skeletal dysplasia v1.110 PLCB4 chirag patel gene: PLCB4 was added
gene: PLCB4 was added to Skeletal dysplasia. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: PLCB4 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: PLCB4 were set to 22560091; 23315542; 33131036; 32201334; 28328130; 27007857; 23913798
Phenotypes for gene: PLCB4 were set to Auriculocondylar syndrome 2A, MIM# 614669; Auriculocondylar syndrome 2B, MIM# 620458
Mode of pathogenicity for gene: PLCB4 was set to Other
Deafness_IsolatedAndComplex v2.8 PAX1 chirag patel Phenotypes for gene: PAX1 were changed from Otofaciocervical syndrome 2, MIM# 615560 to Otofaciocervical syndrome 2 with T-cell deficiency, MIM #615560
Severe Combined Immunodeficiency v2.3 PAX1 chirag patel Phenotypes for gene: PAX1 were changed from Syndromic SCID; dysmorphism; ear abnormalities; Otofaciocervical syndrome 2, MIM# 615560 to Otofaciocervical syndrome 2 with T-cell deficiency, MIM #615560
Intellectual disability syndromic and non-syndromic v2.77 PAX1 chirag patel Classified gene: PAX1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v2.77 PAX1 chirag patel Gene: pax1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v2.77 PAX1 chirag patel Classified gene: PAX1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v2.77 PAX1 chirag patel Gene: pax1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v2.76 PAX1 chirag patel Phenotypes for gene: PAX1 were changed from Otofaciocervical syndrome 2, 615560 to Otofaciocervical syndrome 2 with T-cell deficiency, MIM #615560
Mendeliome v2.423 PAX1 chirag patel Phenotypes for gene: PAX1 were changed from Otofaciocervical syndrome 2, MIM#615560; Syndromic SCID to Otofaciocervical syndrome 2 with T-cell deficiency, MIM #615560
Intellectual disability syndromic and non-syndromic v2.75 PAX1 chirag patel Publications for gene: PAX1 were set to 29681087; 23851939; 28657137
Severe Combined Immunodeficiency v2.2 PAX1 chirag patel Publications for gene: PAX1 were set to 32111619
Deafness_IsolatedAndComplex v2.7 PAX1 chirag patel Publications for gene: PAX1 were set to 23851939; 29681087
Mendeliome v2.422 PAX1 chirag patel Publications for gene: PAX1 were set to 29681087; 28657137; 23851939; 32111619
Severe Combined Immunodeficiency v2.1 chirag patel Added reviews for gene PAX1 from panel Mendeliome
Intellectual disability syndromic and non-syndromic v2.74 chirag patel Added reviews for gene PAX1 from panel Mendeliome
Deafness_IsolatedAndComplex v2.6 chirag patel Added reviews for gene PAX1 from panel Mendeliome
Mendeliome v2.421 PAX1 chirag patel reviewed gene: PAX1: Rating: GREEN; Mode of pathogenicity: None; Publications: 29681087, 37924468, 37689091, 32111619, 29681087, 28657137, 23851939; Phenotypes: Otofaciocervical syndrome 2 with T-cell deficiency, MIM #615560; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v2.73 PDS5B Zornitza Stark Publications for gene: PDS5B were set to 41810376
Intellectual disability syndromic and non-syndromic v2.72 PDS5B Zornitza Stark Classified gene: PDS5B as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v2.72 PDS5B Zornitza Stark Gene: pds5b has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v2.71 PDS5B Zornitza Stark reviewed gene: PDS5B: Rating: GREEN; Mode of pathogenicity: None; Publications: 42431198; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, PDS5B-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v2.421 PDS5B Zornitza Stark Publications for gene: PDS5B were set to 41810376
Mendeliome v2.420 PDS5B Zornitza Stark Classified gene: PDS5B as Green List (high evidence)
Mendeliome v2.420 PDS5B Zornitza Stark Gene: pds5b has been classified as Green List (High Evidence).
Mendeliome v2.419 PDS5B Zornitza Stark reviewed gene: PDS5B: Rating: GREEN; Mode of pathogenicity: None; Publications: 42431198; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, PDS5B-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v2.71 PDS5A Zornitza Stark Publications for gene: PDS5A were set to 30158690; 41810376
Intellectual disability syndromic and non-syndromic v2.70 PDS5A Zornitza Stark Classified gene: PDS5A as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v2.70 PDS5A Zornitza Stark Gene: pds5a has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v2.69 PDS5A Zornitza Stark reviewed gene: PDS5A: Rating: GREEN; Mode of pathogenicity: None; Publications: 42431198; Phenotypes: Complex neurodevelopmental disorder, MONDO:0100038, PDS5A-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v2.419 PDS5A Zornitza Stark Publications for gene: PDS5A were set to 30158690; 41810376
Mendeliome v2.418 PDS5A Zornitza Stark Classified gene: PDS5A as Green List (high evidence)
Mendeliome v2.418 PDS5A Zornitza Stark Gene: pds5a has been classified as Green List (High Evidence).
Mendeliome v2.417 PDS5A Zornitza Stark reviewed gene: PDS5A: Rating: GREEN; Mode of pathogenicity: None; Publications: 42431198; Phenotypes: Complex neurodevelopmental disorder, MONDO:0100038, PDS5A-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v2.69 WAPL Zornitza Stark Publications for gene: WAPL were set to 10.64898/2026.02.23.26346364; 30158690
Intellectual disability syndromic and non-syndromic v2.68 WAPL Zornitza Stark Tag preprint was removed from gene: WAPL.
Intellectual disability syndromic and non-syndromic v2.68 WAPL Zornitza Stark edited their review of gene: WAPL: Added comment: Now published PMID 42431198: 27 probands reported.; Changed publications: 42431198, 30158690
Mendeliome v2.417 WAPL Zornitza Stark Tag preprint was removed from gene: WAPL.
Mendeliome v2.417 WAPL Zornitza Stark Publications for gene: WAPL were set to 10.64898/2026.02.23.26346364; 30158690
Mendeliome v2.416 WAPL Zornitza Stark edited their review of gene: WAPL: Added comment: Now published PMID 42431198: 27 probands reported.; Changed publications: 42431198, 30158690
Hydrocephalus_Ventriculomegaly v1.10 PPP2R5D chirag patel Marked gene: PPP2R5D as ready
Hydrocephalus_Ventriculomegaly v1.10 PPP2R5D chirag patel Gene: ppp2r5d has been classified as Green List (High Evidence).
Hydrocephalus_Ventriculomegaly v1.10 PPP2R5D chirag patel Phenotypes for gene: PPP2R5D were changed from to Houge-Janssens syndrome 1, MONDO:0014602
Hydrocephalus_Ventriculomegaly v1.9 PPP2R5D chirag patel Mode of inheritance for gene: PPP2R5D was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hydrocephalus_Ventriculomegaly v1.8 PPP2R5D chirag patel Publications for gene: PPP2R5D were set to
Hydrocephalus_Ventriculomegaly v1.7 PPP2R5D chirag patel Classified gene: PPP2R5D as Green List (high evidence)
Hydrocephalus_Ventriculomegaly v1.7 PPP2R5D chirag patel Gene: ppp2r5d has been classified as Green List (High Evidence).
Hydrocephalus_Ventriculomegaly v1.6 PPP2R5D chirag patel reviewed gene: PPP2R5D: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Houge-Janssens syndrome 1, MONDO:0014602; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hydrocephalus_Ventriculomegaly v1.6 chirag patel Added reviews for gene PPP2R5D from panel Intellectual disability syndromic and non-syndromic
Pulmonary Fibrosis_Interstitial Lung Disease v2.5 STAT2 Zornitza Stark Marked gene: STAT2 as ready
Pulmonary Fibrosis_Interstitial Lung Disease v2.5 STAT2 Zornitza Stark Gene: stat2 has been classified as Amber List (Moderate Evidence).
Pulmonary Fibrosis_Interstitial Lung Disease v2.5 STAT2 Zornitza Stark Classified gene: STAT2 as Amber List (moderate evidence)
Pulmonary Fibrosis_Interstitial Lung Disease v2.5 STAT2 Zornitza Stark Gene: stat2 has been classified as Amber List (Moderate Evidence).
Pulmonary Fibrosis_Interstitial Lung Disease v2.4 STAT2 Zornitza Stark gene: STAT2 was added
gene: STAT2 was added to Pulmonary Fibrosis_Interstitial Lung Disease. Sources: Literature
Mode of inheritance for gene: STAT2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: STAT2 were set to 42461263
Phenotypes for gene: STAT2 were set to Inborn error of immunity, MONDO:0003778, STAT2-related
Review for gene: STAT2 was set to AMBER
Added comment: Variants in this gene are associated with immune system disorders, particularly causing auto inflammation.

Report of 3 siblings presenting with early-onset, life-threatening pulmonary alveolar proteinosis (PAP) and autoinflammation; novel homozygous variant (R223Q) in STAT2 identified. R223Q STAT2 preserved signal transduction and viral control in vitro. However, cells homozygous for the R223Q variant failed to terminate IFN-I responses, owing to impaired localization of USP18. GM-CSF signaling remained intact. Instead, persistent IFN-I signaling antagonized monocyte migration toward chemokines essential for lung trafficking. The youngest sibling received JAK inhibitor and anti-IFN-I receptor therapy with marked clinical improvement.
Sources: Literature
Hydrocephalus_Ventriculomegaly v1.5 PPP2R5D chirag patel Deleted their review
Hydrocephalus_Ventriculomegaly v1.5 PPP2R5D chirag patel changed review comment from: Very rare feature of condition; to: Hydrocephalus or mild-moderate ventricular dilation reported in some cases
Hydrocephalus_Ventriculomegaly v1.5 PPP2R5D chirag patel changed review comment from: Not common feature of condition; to: Very rare feature of condition
Autoinflammatory Disorders v3.14 STAT2 Zornitza Stark edited their review of gene: STAT2: Changed phenotypes: Pseudo-TORCH syndrome 3, MIM# 618886
Callosome v1.18 PPP2R5D chirag patel Classified gene: PPP2R5D as Red List (low evidence)
Callosome v1.18 PPP2R5D chirag patel Gene: ppp2r5d has been classified as Red List (Low Evidence).
Callosome v1.17 PPP2R5D chirag patel commented on gene: PPP2R5D: Not feature of condition
Callosome v1.17 PPP2R5D chirag patel reviewed gene: PPP2R5D: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Houge-Janssens syndrome 1, MONDO:0014602; Mode of inheritance: None
Hydrocephalus_Ventriculomegaly v1.5 PPP2R5D chirag patel Classified gene: PPP2R5D as Red List (low evidence)
Hydrocephalus_Ventriculomegaly v1.5 PPP2R5D chirag patel Gene: ppp2r5d has been classified as Red List (Low Evidence).
Autism v1.16 PPP2R5D chirag patel Classified gene: PPP2R5D as Red List (low evidence)
Autism v1.16 PPP2R5D chirag patel Gene: ppp2r5d has been classified as Red List (Low Evidence).
Autism v1.15 PPP2R5D chirag patel reviewed gene: PPP2R5D: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Houge-Janssens syndrome 1, MONDO:0014602; Mode of inheritance: None
Hydrocephalus_Ventriculomegaly v1.4 PPP2R5D chirag patel reviewed gene: PPP2R5D: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Houge-Janssens syndrome 1, MONDO:0014602; Mode of inheritance: None
Intellectual disability syndromic and non-syndromic v2.68 SYTL4 Zornitza Stark Marked gene: SYTL4 as ready
Intellectual disability syndromic and non-syndromic v2.68 SYTL4 Zornitza Stark Gene: sytl4 has been classified as Amber List (Moderate Evidence).
Autism v1.15 SYTL4 Zornitza Stark Marked gene: SYTL4 as ready
Autism v1.15 SYTL4 Zornitza Stark Gene: sytl4 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v2.53 PRIM1 chirag patel Tag deep intronic was removed from gene: PRIM1.
Tag founder was removed from gene: PRIM1.
Intellectual disability syndromic and non-syndromic v2.68 Zornitza Stark Copied gene SYTL4 from panel Mendeliome
Intellectual disability syndromic and non-syndromic v2.68 SYTL4 Zornitza Stark gene: SYTL4 was added
gene: SYTL4 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: SYTL4 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: SYTL4 were set to 42531028
Phenotypes for gene: SYTL4 were set to Neurodevelopmental disorder, MONDO:0700092, SYTL4-related
Growth failure v2.15 PRIM1 chirag patel Tag deep intronic was removed from gene: PRIM1.
Tag founder was removed from gene: PRIM1.
Autism v1.15 Zornitza Stark Copied gene SYTL4 from panel Mendeliome
Autism v1.15 SYTL4 Zornitza Stark gene: SYTL4 was added
gene: SYTL4 was added to Autism. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: SYTL4 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: SYTL4 were set to 42531028
Phenotypes for gene: SYTL4 were set to Neurodevelopmental disorder, MONDO:0700092, SYTL4-related
Microcephaly v2.18 PRIM1 chirag patel Tag deep intronic was removed from gene: PRIM1.
Tag founder was removed from gene: PRIM1.
Mendeliome v2.416 SYTL4 Zornitza Stark Marked gene: SYTL4 as ready
Mendeliome v2.416 SYTL4 Zornitza Stark Gene: sytl4 has been classified as Amber List (Moderate Evidence).
Mendeliome v2.416 SYTL4 Zornitza Stark Classified gene: SYTL4 as Amber List (moderate evidence)
Mendeliome v2.416 SYTL4 Zornitza Stark Gene: sytl4 has been classified as Amber List (Moderate Evidence).
Mendeliome v2.415 SYTL4 Zornitza Stark gene: SYTL4 was added
gene: SYTL4 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SYTL4 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: SYTL4 were set to 42531028
Phenotypes for gene: SYTL4 were set to Neurodevelopmental disorder, MONDO:0700092, SYTL4-related
Review for gene: SYTL4 was set to AMBER
Added comment: Reports a recurrent hemizygous missense variant, R126H, located within the Rab-binding domain of SYTL4 in four unrelated male individuals, consistent with an X-linked recessive mode of ASD. R126H knock-in male mice exhibit ASD-relevant behavioural abnormalities accompanied by synaptic deficits in the medial prefrontal cortex.

Amber rating as all evidence relates to a single variant -- exercise caution in reporting any other variants.
Sources: Literature
Mendeliome v2.414 PRIM1 chirag patel Tag deep intronic was removed from gene: PRIM1.
Tag founder was removed from gene: PRIM1.
Lipodystrophy_Lipoatrophy v2.10 PRIM1 chirag patel Phenotypes for gene: PRIM1 were changed from Primordial dwarfism-immunodeficiency-lipodystrophy syndrome, MIM# 620005 to Primordial dwarfism-immunodeficiency-lipodystrophy syndrome, MONDO:0859276
Microcephaly v2.18 PRIM1 chirag patel Phenotypes for gene: PRIM1 were changed from Primordial dwarfism-immunodeficiency-lipodystrophy syndrome, MIM# 620005 to Primordial dwarfism-immunodeficiency-lipodystrophy syndrome, MONDO:0859276
Combined Immunodeficiency v2.7 PRIM1 chirag patel Phenotypes for gene: PRIM1 were changed from primordial dwarfism-immunodeficiency-lipodystrophy syndrome MONDO:0859276 to Primordial dwarfism-immunodeficiency-lipodystrophy syndrome, MONDO:0859276
Growth failure v2.15 PRIM1 chirag patel Marked gene: PRIM1 as ready
Growth failure v2.15 PRIM1 chirag patel Gene: prim1 has been classified as Green List (High Evidence).
Growth failure v2.15 PRIM1 chirag patel Phenotypes for gene: PRIM1 were changed from Primordial dwarfism-immunodeficiency-lipodystrophy syndrome, MIM# 620005 to Primordial dwarfism-immunodeficiency-lipodystrophy syndrome, MONDO:0859276
Fetal anomalies v2.53 PRIM1 chirag patel Phenotypes for gene: PRIM1 were changed from Primordial dwarfism-immunodeficiency-lipodystrophy syndrome, MIM# 620005 to Primordial dwarfism-immunodeficiency-lipodystrophy syndrome, MONDO:0859276
Mendeliome v2.414 PRIM1 chirag patel Phenotypes for gene: PRIM1 were changed from Primordial dwarfism-immunodeficiency-lipodystrophy syndrome, MIM# 620005 to Primordial dwarfism-immunodeficiency-lipodystrophy syndrome, MONDO:0859276
Fetal anomalies v2.52 PRIM1 chirag patel Publications for gene: PRIM1 were set to 33060134
Fetal anomalies v2.51 PRIM1 chirag patel Classified gene: PRIM1 as Green List (high evidence)
Fetal anomalies v2.51 PRIM1 chirag patel Gene: prim1 has been classified as Green List (High Evidence).
Growth failure v2.14 PRIM1 chirag patel Publications for gene: PRIM1 were set to 33060134
Microcephaly v2.17 PRIM1 chirag patel Publications for gene: PRIM1 were set to 33060134
Microcephaly v2.16 PRIM1 chirag patel Classified gene: PRIM1 as Green List (high evidence)
Microcephaly v2.16 PRIM1 chirag patel Gene: prim1 has been classified as Green List (High Evidence).
Mendeliome v2.413 PRIM1 chirag patel Publications for gene: PRIM1 were set to 33060134
Lipodystrophy_Lipoatrophy v2.9 PRIM1 chirag patel Publications for gene: PRIM1 were set to 33060134
Lipodystrophy_Lipoatrophy v2.8 PRIM1 chirag patel Classified gene: PRIM1 as Green List (high evidence)
Lipodystrophy_Lipoatrophy v2.8 PRIM1 chirag patel Gene: prim1 has been classified as Green List (High Evidence).
Fetal anomalies v2.50 chirag patel Added reviews for gene PRIM1 from panel Mendeliome
Growth failure v2.13 chirag patel Copied gene PRIM1 from panel Mendeliome
Growth failure v2.13 PRIM1 chirag patel gene: PRIM1 was added
gene: PRIM1 was added to Growth failure. Sources: Expert Review Green,Literature
deep intronic, founder tags were added to gene: PRIM1.
Mode of inheritance for gene: PRIM1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PRIM1 were set to 33060134
Phenotypes for gene: PRIM1 were set to Primordial dwarfism-immunodeficiency-lipodystrophy syndrome, MIM# 620005
Combined Immunodeficiency v2.6 chirag patel Added reviews for gene PRIM1 from panel Mendeliome
Microcephaly v2.15 chirag patel Added reviews for gene PRIM1 from panel Mendeliome
Lipodystrophy_Lipoatrophy v2.7 chirag patel Added reviews for gene PRIM1 from panel Mendeliome
Mendeliome v2.412 NOTCH3 chirag patel Marked gene: NOTCH3 as ready
Mendeliome v2.412 NOTCH3 chirag patel Gene: notch3 has been classified as Green List (High Evidence).
Congenital Heart Defect v1.29 NOTCH3 chirag patel Marked gene: NOTCH3 as ready
Congenital Heart Defect v1.29 NOTCH3 chirag patel Gene: notch3 has been classified as Green List (High Evidence).
Mendeliome v2.412 chirag patel Copied gene NOTCH3 from panel Skeletal dysplasia
Mendeliome v2.412 NOTCH3 chirag patel gene: NOTCH3 was added
gene: NOTCH3 was added to Mendeliome. Sources: Expert Review Green,Literature
Mode of inheritance for gene: NOTCH3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NOTCH3 were set to 25394726,40256810; 32141180; 26754023
Phenotypes for gene: NOTCH3 were set to Lateral meningocele syndrome, MONDO:0007537
Congenital Heart Defect v1.29 chirag patel Copied gene NOTCH3 from panel Skeletal dysplasia
Congenital Heart Defect v1.29 NOTCH3 chirag patel gene: NOTCH3 was added
gene: NOTCH3 was added to Congenital Heart Defect. Sources: Expert Review Green,Literature
Mode of inheritance for gene: NOTCH3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NOTCH3 were set to 25394726,40256810; 32141180; 26754023
Phenotypes for gene: NOTCH3 were set to Lateral meningocele syndrome, MONDO:0007537
Skeletal dysplasia v1.109 NOTCH3 chirag patel Marked gene: NOTCH3 as ready
Skeletal dysplasia v1.109 NOTCH3 chirag patel Gene: notch3 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.109 NOTCH3 chirag patel Classified gene: NOTCH3 as Green List (high evidence)
Skeletal dysplasia v1.109 NOTCH3 chirag patel Gene: notch3 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.108 NOTCH3 chirag patel gene: NOTCH3 was added
gene: NOTCH3 was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: NOTCH3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NOTCH3 were set to 25394726,40256810; 32141180; 26754023
Phenotypes for gene: NOTCH3 were set to Lateral meningocele syndrome, MONDO:0007537
Review for gene: NOTCH3 was set to GREEN
Added comment: 9 unrelated individuals with lateral meningocele syndrome and de novo heterozygous truncating variants in exon 33 of NOTCH3. This is a congenital skeletal dysplasia characterised by lateral spinal meningoceles, distinctive facial dysmorphism, joint hypermobility, congenital cardiac anomalies and vertebral anomalies (scoliosis, vertebral scalloping, vertebral fusion). No variant‑specific functional assays.
Sources: Literature
Mendeliome v2.411 STXBP2 Zornitza Stark Publications for gene: STXBP2 were set to 19804848
Mendeliome v2.410 STXBP2 Zornitza Stark edited their review of gene: STXBP2: Added comment: PMID 25564401: four unrelated families (P1‑P4) harbouring heterozygous (monoallelic) or biallelic STXBP2 miss‑sense variants at codon 65 (R65Q or R65W) that cause familial haemophagocytic lymphohistiocytosis (F‑HLH). Functional assays (patient CTL/NK cytotoxicity, degranulation, forced expression in control cells, liposome‑fusion assays) demonstrate that the R65Q/W mutants act in a dominant‑negative manner to inhibit SNARE‑complex assembly and membrane fusion. Two families carry heterozygous variants (monoallelic disease) and two families carry biallelic variants (homozygous R65Q or compound‑heterozygous R65Q + G541S). Insufficient evidence for monoallelic MOI except for variants at this specific codon.; Changed publications: 19804848, 25564401, 32542393
Disorders of immune dysregulation v2.9 STXBP2 Zornitza Stark Publications for gene: STXBP2 were set to 19804848
Disorders of immune dysregulation v2.8 STXBP2 Zornitza Stark edited their review of gene: STXBP2: Changed publications: 19804848, 25564401, 32542393
Disorders of immune dysregulation v2.8 STXBP2 Zornitza Stark edited their review of gene: STXBP2: Added comment: PMID 25564401: four unrelated families (P1‑P4) harbouring heterozygous (monoallelic) or biallelic STXBP2 miss‑sense variants at codon 65 (R65Q or R65W) that cause familial haemophagocytic lymphohistiocytosis (F‑HLH). Functional assays (patient CTL/NK cytotoxicity, degranulation, forced expression in control cells, liposome‑fusion assays) demonstrate that the R65Q/W mutants act in a dominant‑negative manner to inhibit SNARE‑complex assembly and membrane fusion. Two families carry heterozygous variants (monoallelic disease) and two families carry biallelic variants (homozygous R65Q or compound‑heterozygous R65Q + G541S).

Insufficient evidence for monoallelic MOI except for variants at this specific codon.; Changed publications: 19804848, 25564401
Disorders of immune dysregulation v2.8 STXBP2 Zornitza Stark Marked gene: STXBP2 as ready
Disorders of immune dysregulation v2.8 STXBP2 Zornitza Stark Gene: stxbp2 has been classified as Green List (High Evidence).
Disorders of immune dysregulation v2.8 STXBP2 Zornitza Stark Phenotypes for gene: STXBP2 were changed from to Haemophagocytic lymphohistiocytosis, familial, 5, with or without microvillus inclusion disease MIM#613101
Disorders of immune dysregulation v2.7 STXBP2 Zornitza Stark Publications for gene: STXBP2 were set to
Disorders of immune dysregulation v2.6 STXBP2 Zornitza Stark Mode of inheritance for gene: STXBP2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v2.410 PRDM1 chirag patel Marked gene: PRDM1 as ready
Mendeliome v2.410 PRDM1 chirag patel Gene: prdm1 has been classified as Green List (High Evidence).
Mendeliome v2.410 chirag patel Copied gene PRDM1 from panel Skeletal dysplasia
Mendeliome v2.410 PRDM1 chirag patel gene: PRDM1 was added
gene: PRDM1 was added to Mendeliome. Sources: Expert Review Green,Literature
Mode of inheritance for gene: PRDM1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PRDM1 were set to 38456586; 37083955
Phenotypes for gene: PRDM1 were set to Split hand-foot malformation MONDO:0016576, PRDM1-related
Skeletal dysplasia v1.107 PRDM1 chirag patel Classified gene: PRDM1 as Green List (high evidence)
Skeletal dysplasia v1.107 PRDM1 chirag patel Gene: prdm1 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.106 PRDM1 chirag patel Marked gene: PRDM1 as ready
Skeletal dysplasia v1.106 PRDM1 chirag patel Gene: prdm1 has been classified as Red List (Low Evidence).
Skeletal dysplasia v1.106 PRDM1 chirag patel gene: PRDM1 was added
gene: PRDM1 was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: PRDM1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PRDM1 were set to 38456586; 37083955
Phenotypes for gene: PRDM1 were set to Split hand-foot malformation MONDO:0016576, PRDM1-related
Review for gene: PRDM1 was set to GREEN
Added comment: PMID 38456586 (and PMID 37083955) report 3 families with split hand/foot malformation (SHFM) caused by heterozygous PRDM1 variants. The frameshift variant (c.712_713insT) segregated in a multigenerational family (3 affected individuals) with variable penetrance (2 unaffected individuals). The 2 missense variants (p.T524R and p.T819A) were de novo (but the p.T819A variant exceeds population‑frequency thresholds). Zebrafish rescue assays showing loss‑of‑function, as wild‑type human PRDM1 rescues fin defects, whereas each mutant mRNA fails to rescue.
Sources: Literature
Hand and foot malformations v1.6 Sarah Milton Copied Region BMP2 downstream regulatory region from panel Mendeliome
Hand and foot malformations v1.6 BMP2 downstream regulatory region Sarah Milton Region: BMP2 downstream regulatory region was added
Region: BMP2 downstream regulatory region was added to Hand and foot malformations. Sources: Expert Review Green,Literature
regulatory region tags were added to Region: BMP2 downstream regulatory region.
Mode of inheritance for Region: BMP2 downstream regulatory region was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for Region: BMP2 downstream regulatory region were set to 19327734; 24710560; 35227291; 21357617
Phenotypes for Region: BMP2 downstream regulatory region were set to Brachydactyly, type A2 MIM#112600
Clefting disorders v1.22 PIGA chirag patel commented on gene: PIGA
Clefting disorders v1.22 PIGA chirag patel Marked gene: PIGA as ready
Clefting disorders v1.22 PIGA chirag patel Gene: piga has been classified as Red List (Low Evidence).
Clefting disorders v1.22 PIGA chirag patel Publications for gene: PIGA were set to 22305531; 22514539
Mendeliome v2.409 BMP2 downstream regulatory region Sarah Milton Classified Region: BMP2 downstream regulatory region as Green List (high evidence)
Mendeliome v2.409 BMP2 downstream regulatory region Sarah Milton Region: bmp2 downstream regulatory region has been classified as Green List (High Evidence).
Mendeliome v2.409 BMP2 downstream regulatory region Sarah Milton Classified Region: BMP2 downstream regulatory region as Green List (high evidence)
Mendeliome v2.409 BMP2 downstream regulatory region Sarah Milton Region: bmp2 downstream regulatory region has been classified as Green List (High Evidence).
Clefting disorders v1.21 PIGA chirag patel Phenotypes for gene: PIGA were changed from MCAHS2; MULTIPLE CONGENITAL ANOMALIES-HYPOTONIA-SEIZURES SYNDROME 2 to Multiple congenital anomalies-hypotonia-seizures syndrome 2, MIM# 300868, MONDO:0010466
Mendeliome v2.408 BMP2 downstream regulatory region Sarah Milton Region: BMP2 downstream regulatory region was added
Region: BMP2 downstream regulatory region was added to Mendeliome. Sources: Literature
regulatory region tags were added to Region: BMP2 downstream regulatory region.
Mode of inheritance for Region: BMP2 downstream regulatory region was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for Region: BMP2 downstream regulatory region were set to 19327734; 24710560; 35227291; 21357617
Phenotypes for Region: BMP2 downstream regulatory region were set to Brachydactyly, type A2 MIM#112600
Added comment: BMP2 is part of the TGFb family and is a signalling protein primarily involved in promoting bone and cartilage formation.

Duplications in an evolutionary well conserved agenic region downstream of BMP2 have been reported in at least 5 unrelated families, with over 50 affected individuals presenting with brachydactyly type A2 characterised by by hypoplastic or aplastic middle phalanges of the second and fifth finger.

Duplications ranged from 4.6kb to 6.3mb and were generally located 110kb downstream of BMP2.

The molecular mechanism is postulated to be duplication of a cis acting limb specific enhancer resulting in altered equilibrium between GDF5 and BMPR1B and overall reduced BMPR1B signalling.

Note: The minimum duplication coordinates seen in an affected individual have been used for this entry.
Sources: Literature
Skeletal dysplasia v1.105 SF3B2 chirag patel Marked gene: SF3B2 as ready
Skeletal dysplasia v1.105 SF3B2 chirag patel Gene: sf3b2 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.105 chirag patel Copied gene SF3B2 from panel Mandibulofacial Acrofacial dysostosis
Skeletal dysplasia v1.105 SF3B2 chirag patel gene: SF3B2 was added
gene: SF3B2 was added to Skeletal dysplasia. Sources: Expert Review Green,Literature
Mode of inheritance for gene: SF3B2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SF3B2 were set to 34344887
Phenotypes for gene: SF3B2 were set to Craniofacial microsomia, MIM#164210
Fetal anomalies v2.49 SCNM1 chirag patel Publications for gene: SCNM1 were set to 41291844; 36084634
Fetal anomalies v2.49 SCNM1 chirag patel Publications for gene: SCNM1 were set to 36084634
Polydactyly v1.18 SCNM1 chirag patel Publications for gene: SCNM1 were set to 36084634
Fetal anomalies v2.48 SCNM1 chirag patel Phenotypes for gene: SCNM1 were changed from Orofaciodigital syndrome XIX, MIM# 620107 to Orofaciodigital syndrome 19, MONDO:0859310
Polydactyly v1.17 SCNM1 chirag patel Phenotypes for gene: SCNM1 were changed from Orofaciodigital syndrome XIX, MIM# 620107 to Orofaciodigital syndrome 19, MONDO:0859310
Mendeliome v2.407 SCNM1 chirag patel Phenotypes for gene: SCNM1 were changed from Orofaciodigital syndrome 19, MONDO:0859310 to Orofaciodigital syndrome 19, MONDO:0859310
Mendeliome v2.406 SCNM1 chirag patel Phenotypes for gene: SCNM1 were changed from Orofaciodigital syndrome XIX, MIM# 620107 to Orofaciodigital syndrome 19, MONDO:0859310
Mendeliome v2.405 SCNM1 chirag patel Publications for gene: SCNM1 were set to PMID: 36084634
Ciliopathies v2.15 SCNM1 chirag patel Publications for gene: SCNM1 were set to PMID: 36084634
Ciliopathies v2.14 SCNM1 chirag patel Phenotypes for gene: SCNM1 were changed from Orofaciodigital syndrome XIX, MIM# 620107 to Orofaciodigital syndrome 19, MONDO:0859310
Polydactyly v1.16 chirag patel Added reviews for gene SCNM1 from panel Skeletal dysplasia
Mendeliome v2.404 chirag patel Added reviews for gene SCNM1 from panel Skeletal dysplasia
Fetal anomalies v2.47 chirag patel Added reviews for gene SCNM1 from panel Skeletal dysplasia
Ciliopathies v2.13 chirag patel Added reviews for gene SCNM1 from panel Skeletal dysplasia
Skeletal dysplasia v1.104 SCNM1 chirag patel changed review comment from: PMID 36084634 and PMID 41291844 report a total of 9 individuals from 7 independent consanguineous families with biallelic loss‑of‑function SCNM1 variants presenting with orofaciodigital syndrome 19. Clinical features included: bilateral postaxial polydactyly, foot syndactyly, short limbs, tongue hamartomas, micro/retrognathia, arched/cleft palate, hypo/microdontia with missing incisors, talipes equinovarus, delayed speech and brain anomalies. Variants were frameshift, missense, splice, and AluYc1 sequence insertion) with segregation confirmed in all families. Functional studies including a minigene splice assay, SCNM1 knock‑out/knock‑down in RPE‑1 cells and patient‑fibroblast rescue experiments demonstrate reduced SCNM1 protein, defective U12‑type intron splicing, elongated primary cilia and impaired Hedgehog signalling, confirming loss‑of‑function as the disease mechanism.
Sources: Literature; to: PMID 36084634 and PMID 41291844 report a total of 9 individuals from 7 independent consanguineous families with biallelic loss‑of‑function SCNM1 variants presenting with orofaciodigital syndrome 19. Clinical features included: bilateral postaxial polydactyly, foot syndactyly, bifid halluces, short limbs, tongue hamartomas, micro/retrognathia, arched/cleft palate, hypo/microdontia with missing incisors, talipes equinovarus, developmental delay and brain anomalies. Variants were frameshift, missense, splice, and AluYc1 sequence insertion) with segregation confirmed in all families. Functional studies including a minigene splice assay, SCNM1 knock‑out/knock‑down in RPE‑1 cells and patient‑fibroblast rescue experiments demonstrate reduced SCNM1 protein, defective U12‑type intron splicing, elongated primary cilia and impaired Hedgehog signalling, confirming loss‑of‑function as the disease mechanism.
Sources: Literature
Skeletal dysplasia v1.104 SCNM1 chirag patel changed review comment from: PMID 36084634 and PMID 41291844 report a total of 5 individuals from 4 independent consanguineous families with biallelic loss‑of‑function SCNM1 variants presenting with orofaciodigital syndrome 19, a disorder characterised by oral, facial and digital anomalies, limb shortening, polydactyly, tibial hemimelia and neurodevelopmental delay. Variants were frameshift, missense, splice, and AluYc1 sequence insertion) with segregation confirmed in all families. Functional studies including a minigene splice assay, SCNM1 knock‑out/knock‑down in RPE‑1 cells and patient‑fibroblast rescue experiments demonstrate reduced SCNM1 protein, defective U12‑type intron splicing, elongated primary cilia and impaired Hedgehog signalling, confirming loss‑of‑function as the disease mechanism.
Sources: Literature; to: PMID 36084634 and PMID 41291844 report a total of 9 individuals from 7 independent consanguineous families with biallelic loss‑of‑function SCNM1 variants presenting with orofaciodigital syndrome 19. Clinical features included: bilateral postaxial polydactyly, foot syndactyly, short limbs, tongue hamartomas, micro/retrognathia, arched/cleft palate, hypo/microdontia with missing incisors, talipes equinovarus, delayed speech and brain anomalies. Variants were frameshift, missense, splice, and AluYc1 sequence insertion) with segregation confirmed in all families. Functional studies including a minigene splice assay, SCNM1 knock‑out/knock‑down in RPE‑1 cells and patient‑fibroblast rescue experiments demonstrate reduced SCNM1 protein, defective U12‑type intron splicing, elongated primary cilia and impaired Hedgehog signalling, confirming loss‑of‑function as the disease mechanism.
Sources: Literature
Skeletal dysplasia v1.104 SCNM1 chirag patel Classified gene: SCNM1 as Green List (high evidence)
Skeletal dysplasia v1.104 SCNM1 chirag patel Gene: scnm1 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.103 SCNM1 chirag patel Marked gene: SCNM1 as ready
Skeletal dysplasia v1.103 SCNM1 chirag patel Gene: scnm1 has been classified as Red List (Low Evidence).
Skeletal dysplasia v1.103 SCNM1 chirag patel gene: SCNM1 was added
gene: SCNM1 was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: SCNM1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SCNM1 were set to 41291844; 36084634
Phenotypes for gene: SCNM1 were set to Orofaciodigital syndrome 19, MONDO:0859310
Review for gene: SCNM1 was set to GREEN
Added comment: PMID 36084634 and PMID 41291844 report a total of 5 individuals from 4 independent consanguineous families with biallelic loss‑of‑function SCNM1 variants presenting with orofaciodigital syndrome 19, a disorder characterised by oral, facial and digital anomalies, limb shortening, polydactyly, tibial hemimelia and neurodevelopmental delay. Variants were frameshift, missense, splice, and AluYc1 sequence insertion) with segregation confirmed in all families. Functional studies including a minigene splice assay, SCNM1 knock‑out/knock‑down in RPE‑1 cells and patient‑fibroblast rescue experiments demonstrate reduced SCNM1 protein, defective U12‑type intron splicing, elongated primary cilia and impaired Hedgehog signalling, confirming loss‑of‑function as the disease mechanism.
Sources: Literature
Skeletal dysplasia v1.102 TMEM17 chirag patel Marked gene: TMEM17 as ready
Skeletal dysplasia v1.102 TMEM17 chirag patel Gene: tmem17 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.102 chirag patel Copied gene TMEM17 from panel Mendeliome
Skeletal dysplasia v1.102 TMEM17 chirag patel gene: TMEM17 was added
gene: TMEM17 was added to Skeletal dysplasia. Sources: Expert Review Green,Literature
Mode of inheritance for gene: TMEM17 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TMEM17 were set to 41054827, 40841990
Phenotypes for gene: TMEM17 were set to Meckel syndrome MONDO:0018921, TMEM17-related
Fetal anomalies v2.46 TXNDC15 chirag patel Publications for gene: TXNDC15 were set to 41518077; 39679447; 38156946; 38073519; 31411728; 30851085; 27894351
Fetal anomalies v2.46 TXNDC15 chirag patel Publications for gene: TXNDC15 were set to 30851085; 27894351
Renal Ciliopathies and Nephronophthisis v2.2 TXNDC15 chirag patel Publications for gene: TXNDC15 were set to 30851085; 27894351
Mendeliome v2.403 TXNDC15 chirag patel Publications for gene: TXNDC15 were set to 41518077; 39679447; 38156946; 38073519; 31411728; 30851085; 27894351
Mendeliome v2.402 TXNDC15 chirag patel Publications for gene: TXNDC15 were set to 30851085; 27894351
Joubert syndrome and other neurological ciliopathies v2.2 TXNDC15 chirag patel Publications for gene: TXNDC15 were set to 30851085; 27894351
Ciliopathies v2.12 TXNDC15 chirag patel Publications for gene: TXNDC15 were set to 30851085; 27894351
Renal Ciliopathies and Nephronophthisis v2.1 chirag patel Added reviews for gene TXNDC15 from panel Skeletal dysplasia
Mendeliome v2.401 chirag patel Added reviews for gene TXNDC15 from panel Skeletal dysplasia
Joubert syndrome and other neurological ciliopathies v2.1 chirag patel Added reviews for gene TXNDC15 from panel Skeletal dysplasia
Fetal anomalies v2.45 chirag patel Added reviews for gene TXNDC15 from panel Skeletal dysplasia
Ciliopathies v2.11 chirag patel Added reviews for gene TXNDC15 from panel Skeletal dysplasia
Skeletal dysplasia v1.101 TXNDC15 chirag patel Marked gene: TXNDC15 as ready
Skeletal dysplasia v1.101 TXNDC15 chirag patel Gene: txndc15 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.101 TXNDC15 chirag patel Classified gene: TXNDC15 as Green List (high evidence)
Skeletal dysplasia v1.101 TXNDC15 chirag patel Gene: txndc15 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.100 TXNDC15 chirag patel gene: TXNDC15 was added
gene: TXNDC15 was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: TXNDC15 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TXNDC15 were set to 41518077; 39679447; 38156946; 38073519; 31411728; 30851085; 27894351
Phenotypes for gene: TXNDC15 were set to Meckel syndrome 14, MIM# 619879
Review for gene: TXNDC15 was set to GREEN
Added comment: PMID 41518077, PMID 38073519, PMID 38156946, PMID 30851085, PMID 31411728 and PMID 27894351 report 8 families with biallelic loss‑of‑function TXNDC15 variants causing Meckel syndrome, a perinatally lethal autosomal recessive ciliopathy characterised by occipital encephalocele, polycystic kidneys, postaxial polydactyly and omphalocele. Segregation, ultra‑rare population frequencies and functional studies in patient cells and mouse models support the association.
Sources: Literature
Skeletal dysplasia v1.99 TRIM37 chirag patel changed review comment from: long‑bone dysplasia seen in condition; to: fibrous dysplasia of long bones (esp. tibia) seen in condition.
Skeletal dysplasia v1.99 TRIM37 chirag patel Marked gene: TRIM37 as ready
Skeletal dysplasia v1.99 TRIM37 chirag patel Gene: trim37 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.99 TRIM37 chirag patel reviewed gene: TRIM37: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Mulibrey nanism, MIM# 253250; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.99 chirag patel Copied gene TRIM37 from panel Mendeliome
Skeletal dysplasia v1.99 TRIM37 chirag patel gene: TRIM37 was added
gene: TRIM37 was added to Skeletal dysplasia. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: TRIM37 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRIM37 were set to 10888877; 12754710; 15108285; 14757854; 27044324
Phenotypes for gene: TRIM37 were set to Mulibrey nanism, MIM# 253250
Peroxisomal Disorders v1.5 TRIM37 chirag patel Phenotypes for gene: TRIM37 were changed from Mulibrey nanism, MIM# 253250 to Mulibrey nanism, MIM# 253250
Peroxisomal Disorders v1.5 TRIM37 chirag patel Phenotypes for gene: TRIM37 were changed from Mulibrey nanism, MIM# 253250 to Mulibrey nanism, MIM# 253250
Peroxisomal Disorders v1.4 TRIM37 chirag patel Phenotypes for gene: TRIM37 were changed from Mulibrey nanism, MIM# 253250 to Mulibrey nanism, MIM# 253250
Peroxisomal Disorders v1.4 TRIM37 chirag patel Phenotypes for gene: TRIM37 were changed from to Mulibrey nanism, MIM# 253250
Peroxisomal Disorders v1.3 TRIM37 chirag patel Marked gene: TRIM37 as ready
Peroxisomal Disorders v1.3 TRIM37 chirag patel Gene: trim37 has been classified as Green List (High Evidence).
Peroxisomal Disorders v1.3 TRIM37 chirag patel Publications for gene: TRIM37 were set to
Peroxisomal Disorders v1.2 TRIM37 chirag patel Mode of inheritance for gene: TRIM37 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Peroxisomal Disorders v1.1 chirag patel Added reviews for gene TRIM37 from panel Mendeliome
Mandibulofacial Acrofacial dysostosis v2.9 VGLL2 chirag patel Publications for gene: VGLL2 were set to
Skeletal dysplasia v1.98 VGLL2 chirag patel Publications for gene: VGLL2 were set to
Mendeliome v2.400 VGLL2 chirag patel Publications for gene: VGLL2 were set to 37666660
Mendeliome v2.400 VGLL2 chirag patel Publications for gene: VGLL2 were set to
Mendeliome v2.399 VGLL2 chirag patel edited their review of gene: VGLL2: Added comment: PMID 37666660 reports the ESHG cases: 6 individuals from 4 families with biallelic VGLL2 variants presenting with isolated congenital bony syngnathia (jaw bone fusion, sometimes with cleft palate). The variants (p.Gln151Ter p.Glu67Ter) and segregated in all families, with founder effect in Turkish families. Zebrafish vgll2a and vgll4l knockouts and Vgll2‑/‑ mouse models showed no craniofacial defects, suggesting species‑specific compensation.; Changed publications: 37666660; Changed phenotypes: Syngnathia, MONDO:0015409, VGLL2-related
Skeletal dysplasia v1.97 VGLL2 chirag patel Marked gene: VGLL2 as ready
Skeletal dysplasia v1.97 VGLL2 chirag patel Gene: vgll2 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.97 chirag patel Copied gene VGLL2 from panel Mandibulofacial Acrofacial dysostosis
Skeletal dysplasia v1.97 VGLL2 chirag patel gene: VGLL2 was added
gene: VGLL2 was added to Skeletal dysplasia. Sources: Expert Review Green,Other
Mode of inheritance for gene: VGLL2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: VGLL2 were set to Syngnathia, MONDO:0015409, VGLL2-related
Mendeliome v2.399 chirag patel Added reviews for gene VGLL2 from panel Mandibulofacial Acrofacial dysostosis
Mandibulofacial Acrofacial dysostosis v2.8 VGLL2 chirag patel edited their review of gene: VGLL2: Added comment: PMID 37666660 reports the ESHG cases: 6 individuals from 4 families with biallelic VGLL2 variants presenting with isolated congenital bony syngnathia (jaw bone fusion, sometimes with cleft palate). The variants (p.Gln151Ter p.Glu67Ter) and segregated in all families, with founder effect in Turkish families. Zebrafish vgll2a and vgll4l knockouts and Vgll2‑/‑ mouse models showed no craniofacial defects, suggesting species‑specific compensation.; Changed publications: 37666660; Changed phenotypes: Syngnathia, MONDO:0015409, VGLL2-related
Mandibulofacial Acrofacial dysostosis v2.8 VGLL2 chirag patel changed review comment from: ESHG 2023:
4 families/7 affected individuals with isolated unilateral/bilateral syngnathia
biallelic truncating variants in VGLL2
But not phenotype in KO mouse or zebrafish models
Sources: Other; to: ESHG 2023:
4 families/7 affected individuals with isolated unilateral/bilateral syngnathia
biallelic truncating variants in VGLL2
But not phenotype in KO mouse or zebrafish models
Sources: Other
Skeletal dysplasia v1.96 VPS16 chirag patel Classified gene: VPS16 as Green List (high evidence)
Skeletal dysplasia v1.96 VPS16 chirag patel Gene: vps16 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.95 VPS16 chirag patel Marked gene: VPS16 as ready
Skeletal dysplasia v1.95 VPS16 chirag patel Gene: vps16 has been classified as Red List (Low Evidence).
Skeletal dysplasia v1.95 VPS16 chirag patel gene: VPS16 was added
gene: VPS16 was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: VPS16 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: VPS16 were set to 34013567; 33938619
Phenotypes for gene: VPS16 were set to Mucopolysaccharidosis or mucopolysaccharidosis-like disorder, MONDO:0100365
Review for gene: VPS16 was set to GREEN
Added comment: PMID 34013567 reports a consanguineous Turkish‑Arab family with two siblings homozygous for a missense VPS16 p.Trp180Cys variant presenting with a mucopolysaccharidosis‑like multisystem disorder that includes short stature, coarse facies, spondylar dysplasia and severe neutropenia. PMID 33938619 identifies two unrelated families harbouring a homozygous intronic splice‑site c.2272-18C>A variant that causes a similar early‑onset mucopolysaccharidosis‑like disease with dysostosis multiplex, neurodevelopmental regression and hematological abnormalities. Functional studies show ~85 % loss of VPS16 protein in patient fibroblasts rescued by wild‑type VPS16 expression and a vps16‑deficient zebrafish recapitulating the neuro‑developmental and lysosomal phenotypes.
Sources: Literature
Callosome v1.17 WDR4 chirag patel reviewed gene: WDR4: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Galloway-Mowat syndrome 1 MIM#251300; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Proteinuria v1.2 WDR4 chirag patel Marked gene: WDR4 as ready
Proteinuria v1.2 WDR4 chirag patel Gene: wdr4 has been classified as Green List (High Evidence).
Proteinuria v1.2 WDR4 chirag patel Classified gene: WDR4 as Green List (high evidence)
Proteinuria v1.2 WDR4 chirag patel Gene: wdr4 has been classified as Green List (High Evidence).
Proteinuria v1.1 WDR4 chirag patel gene: WDR4 was added
gene: WDR4 was added to Proteinuria. Sources: Literature
Mode of inheritance for gene: WDR4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WDR4 were set to 30079490, 29597095, 28617965
Phenotypes for gene: WDR4 were set to Galloway-Mowat syndrome 6, OMIM #618347
Review for gene: WDR4 was set to GREEN
Added comment: Galloway-Mowat syndrome (GAMOS) is characterised by neurodevelopmental defects combined with nephrotic syndrome and proteinuria. Most patients with GAMOS6 also have growth deficiency with variable microcephaly, and the renal disease may be age-dependent.

1 family with 2 sibs with GMS and compound heterozygous mutations in the WDR4 gene, segregated with the disorder in the family. Functional studies of the variants and studies of patient cells were not performed.

1 family with 1 child with GMS and compound heterozygous mutations in the WDR4 gene, segregated with the disorder in the family. Functional studies of the variants and studies of patient cells were not performed.

1 family with 4 sibs with GMS and homozygous splice site mutation in the WDR4 gene. Functional studies of the variant and studies of patient cells were not performed.
Sources: Literature
Skeletal dysplasia v1.94 WDR4 chirag patel Classified gene: WDR4 as Green List (high evidence)
Skeletal dysplasia v1.94 WDR4 chirag patel Gene: wdr4 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.93 WDR4 chirag patel Marked gene: WDR4 as ready
Skeletal dysplasia v1.93 WDR4 chirag patel Gene: wdr4 has been classified as Red List (Low Evidence).
Skeletal dysplasia v1.93 WDR4 chirag patel gene: WDR4 was added
gene: WDR4 was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: WDR4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WDR4 were set to 28617965; 26429597; 26416026
Phenotypes for gene: WDR4 were set to Microcephaly, growth deficiency, seizures, and brain malformations, MONDO:0032690
Review for gene: WDR4 was set to GREEN
Added comment: 6 individuals from 5 families with biallelic WDR4 variants causing microcephalic primordial dwarfism characterised by severe growth deficiency, microcephaly, brain malformations, seizures and facial dysmorphism. Skeletal features include: unossified pubic bones, short long bones, and broad metaphyses. Patient lymphoblastoid cells show reduced tRNA m7G46 methylation. Yeast models with orthologous WDR4 mutations display temperature‑sensitive growth defects.
Sources: Literature
Microcephaly v2.14 WDR4 chirag patel Phenotypes for gene: WDR4 were changed from Microcephaly, growth deficiency, seizures, and brain malformations, OMIM #618346; Microcephaly, growth deficiency, seizures, and brain malformations, OMIM #618346 to Galloway-Mowat syndrome 6 MIM#618347; Microcephaly, growth deficiency, seizures, and brain malformations, OMIM #618346
Microcephaly v2.13 WDR4 chirag patel Phenotypes for gene: WDR4 were changed from Microcephaly, growth deficiency, seizures, and brain malformations, OMIM #618346 to Microcephaly, growth deficiency, seizures, and brain malformations, OMIM #618346; Microcephaly, growth deficiency, seizures, and brain malformations, OMIM #618346
Microcephaly v2.12 chirag patel Added reviews for gene WDR4 from panel Mendeliome
Microcephaly v2.11 WDR4 chirag patel Phenotypes for gene: WDR4 were changed from Galloway-Mowat syndrome 6 MIM#618347 to Microcephaly, growth deficiency, seizures, and brain malformations, OMIM #618346
Mendeliome v2.398 YY1AP1 chirag patel Phenotypes for gene: YY1AP1 were changed from Grange syndrome, MIM# 602531 to Grange syndrome, MIM# 602531
Mendeliome v2.397 YY1AP1 chirag patel Phenotypes for gene: YY1AP1 were changed from Grange syndrome, MIM# 602531; stenosis/occlusion of multiple arteries to Grange syndrome, MIM# 602531
Skeletal dysplasia v1.92 YY1AP1 chirag patel Phenotypes for gene: YY1AP1 were changed from Grange syndrome, MIM# 602531; stenosis/occlusion of multiple arteries to Grange syndrome, MIM# 602531
Skeletal dysplasia v1.91 YY1AP1 chirag patel Marked gene: YY1AP1 as ready
Skeletal dysplasia v1.91 YY1AP1 chirag patel Gene: yy1ap1 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.91 YY1AP1 chirag patel reviewed gene: YY1AP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Grange syndrome, MIM# 602531; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.91 chirag patel Copied gene YY1AP1 from panel Mendeliome
Skeletal dysplasia v1.91 YY1AP1 chirag patel gene: YY1AP1 was added
gene: YY1AP1 was added to Skeletal dysplasia. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: YY1AP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: YY1AP1 were set to 31633303; 30356112; 31270375; 22987684; 16691574; 27939641; 30556293
Phenotypes for gene: YY1AP1 were set to Grange syndrome, MIM# 602531; stenosis/occlusion of multiple arteries
Skeletal dysplasia v1.90 ZRSR2 chirag patel Marked gene: ZRSR2 as ready
Skeletal dysplasia v1.90 ZRSR2 chirag patel Gene: zrsr2 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.90 ZRSR2 chirag patel reviewed gene: ZRSR2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Orofaciodigital syndrome XXI, MIM# 301132; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Skeletal dysplasia v1.90 chirag patel Copied gene ZRSR2 from panel Mendeliome
Skeletal dysplasia v1.90 ZRSR2 chirag patel gene: ZRSR2 was added
gene: ZRSR2 was added to Skeletal dysplasia. Sources: Expert Review Green,Expert Review
Mode of inheritance for gene: ZRSR2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: ZRSR2 were set to 38158857
Phenotypes for gene: ZRSR2 were set to Orofaciodigital syndrome XXI, MIM# 301132
Skeletal dysplasia v1.89 SATB2 chirag patel Publications for gene: SATB2 were set to 29023086; 28151491; 32446642
Skeletal dysplasia v1.88 SATB2 chirag patel Marked gene: SATB2 as ready
Skeletal dysplasia v1.88 SATB2 chirag patel Gene: satb2 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.88 SATB2 chirag patel reviewed gene: SATB2: Rating: GREEN; Mode of pathogenicity: None; Publications: 35241104; Phenotypes: Glass syndrome, MONDO:0100147; Mode of inheritance: None
Skeletal dysplasia v1.88 chirag patel Copied gene SATB2 from panel Mendeliome
Skeletal dysplasia v1.88 SATB2 chirag patel gene: SATB2 was added
gene: SATB2 was added to Skeletal dysplasia. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: SATB2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SATB2 were set to 29023086; 28151491; 32446642
Phenotypes for gene: SATB2 were set to Glass syndrome, MIM# 612313; MONDO:0100147
Cardiomyopathy_Paediatric v1.73 MT-ND6 Lucy Spencer Classified gene: MT-ND6 as Amber List (moderate evidence)
Cardiomyopathy_Paediatric v1.73 MT-ND6 Lucy Spencer Gene: mt-nd6 has been classified as Amber List (Moderate Evidence).
Cardiomyopathy_Paediatric v1.72 MT-ND6 Lucy Spencer gene: MT-ND6 was added
gene: MT-ND6 was added to Cardiomyopathy_Paediatric. Sources: Literature
Mode of inheritance for gene gene: MT-ND6 was set to MITOCHONDRIAL
Publications for gene: MT-ND6 were set to 34933128
Phenotypes for gene: MT-ND6 were set to Mitochondrial disease (MONDO:0044970), MT-ND6-related
Review for gene: MT-ND6 was set to AMBER
Added comment: PMID 34933128 reports 4 new patients and reviews the literature for individuals with Leigh syndrome and m.14453G>A in MT-ND6. 2 of the individuals were noted to have childhood/infantile onset HCM.
Sources: Literature
Additional findings_Paediatric v1.1 FBN2 Zornitza Stark Mode of inheritance for gene: FBN2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Additional findings_Paediatric v1.0 FBN2 Zornitza Stark edited their review of gene: FBN2: Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genomic newborn screening: BabyScreen+ v2.1 FBN2 Zornitza Stark Mode of inheritance for gene: FBN2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genomic newborn screening: BabyScreen+ v2.0 FBN2 Zornitza Stark edited their review of gene: FBN2: Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v2.44 FBN2 Zornitza Stark Mode of inheritance for gene: FBN2 was changed from BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.87 FBN2 Zornitza Stark Mode of inheritance for gene: FBN2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.86 FBN2 Zornitza Stark edited their review of gene: FBN2: Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Arthrogryposis v2.1 FBN2 Zornitza Stark Mode of inheritance for gene: FBN2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Aortopathy_Connective Tissue Disorders v2.7 FBN2 Zornitza Stark Mode of inheritance for gene: FBN2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Aortopathy_Connective Tissue Disorders v2.6 FBN2 Zornitza Stark edited their review of gene: FBN2: Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v2.396 FBN2 Zornitza Stark Mode of inheritance for gene: FBN2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v2.395 FBN2 Zornitza Stark edited their review of gene: FBN2: Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.86 COL9A1 Zornitza Stark Marked gene: COL9A1 as ready
Skeletal dysplasia v1.86 COL9A1 Zornitza Stark Gene: col9a1 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.86 COL9A1 Zornitza Stark Publications for gene: COL9A1 were set to
Skeletal dysplasia v1.85 COL9A1 Zornitza Stark Mode of inheritance for gene: COL9A1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v2.395 VMA21 Sangavi Sivagnanasundram reviewed gene: VMA21: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: congenital disorder of glycosylation MONDO:0015286; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v2.395 SPNS2 Sangavi Sivagnanasundram reviewed gene: SPNS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 36494063; Phenotypes: hearing loss, autosomal recessive 115 MONDO:0032762; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Complement Deficiencies v2.7 C2 Zornitza Stark Marked gene: C2 as ready
Complement Deficiencies v2.7 C2 Zornitza Stark Gene: c2 has been classified as Green List (High Evidence).
Complement Deficiencies v2.7 C2 Zornitza Stark Phenotypes for gene: C2 were changed from to C2 deficiency MIM#217000
Complement Deficiencies v2.6 C2 Zornitza Stark Publications for gene: C2 were set to
Complement Deficiencies v2.5 C2 Zornitza Stark Mode of inheritance for gene: C2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v2.395 CIDEC Sangavi Sivagnanasundram Phenotypes for gene: CIDEC were changed from Lipodystrophy, familial partial, type 5, MIM# 615238 to CIDEC-related familial partial lipodystrophy MONDO:0014098
Mendeliome v2.394 CIDEC Sangavi Sivagnanasundram Classified gene: CIDEC as Amber List (moderate evidence)
Mendeliome v2.394 CIDEC Sangavi Sivagnanasundram Gene: cidec has been classified as Amber List (Moderate Evidence).
Mendeliome v2.393 CIDEC Sangavi Sivagnanasundram reviewed gene: CIDEC: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: CIDEC-related familial partial lipodystrophy MONDO:0014098; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v2.32 SYNCRIP Rylee Peters Classified gene: SYNCRIP as Green List (high evidence)
Genetic Epilepsy v2.32 SYNCRIP Rylee Peters Gene: syncrip has been classified as Green List (High Evidence).
Genetic Epilepsy v2.31 SYNCRIP Rylee Peters changed review comment from: Two additional reports of individuals with SYNCRIP-related neurodevelopmental disorder with seizures (https://doi.org/10.1016/j.rare.2024.100052).; to: Two additional reports of individuals with SYNCRIP-related neurodevelopmental disorder including seizures (https://doi.org/10.1016/j.rare.2024.100052).
Genetic Epilepsy v2.31 SYNCRIP Rylee Peters reviewed gene: SYNCRIP: Rating: GREEN; Mode of pathogenicity: None; Publications: https://doi.org/10.1016/j.rare.2024.100052; Phenotypes: SYNCRIP-related neurodevelopmental disorder, MONDO:0800456; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Periventricular Grey Matter Heterotopia v2.2 SYNCRIP Rylee Peters Publications for gene: SYNCRIP were set to 34157790
Periventricular Grey Matter Heterotopia v2.1 SYNCRIP Rylee Peters Classified gene: SYNCRIP as Amber List (moderate evidence)
Periventricular Grey Matter Heterotopia v2.1 SYNCRIP Rylee Peters Gene: syncrip has been classified as Amber List (Moderate Evidence).
Periventricular Grey Matter Heterotopia v2.0 SYNCRIP Rylee Peters reviewed gene: SYNCRIP: Rating: AMBER; Mode of pathogenicity: None; Publications: 39487702; Phenotypes: SYNCRIP-related neurodevelopmental disorder, MONDO:0800456; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v2.43 SYNCRIP Rylee Peters Publications for gene: SYNCRIP were set to 34157790
Fetal anomalies v2.42 SYNCRIP Rylee Peters Classified gene: SYNCRIP as Green List (high evidence)
Fetal anomalies v2.42 SYNCRIP Rylee Peters Gene: syncrip has been classified as Green List (High Evidence).
Fetal anomalies v2.41 SYNCRIP Rylee Peters reviewed gene: SYNCRIP: Rating: GREEN; Mode of pathogenicity: None; Publications: 39487702, https://doi.org/10.1016/j.rare.2024.100052; Phenotypes: SYNCRIP-related neurodevelopmental disorder, MONDO:0800456; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.84 Sarah Milton Copied Region HOXD cluster regulatory region from panel Mendeliome
Skeletal dysplasia v1.84 HOXD cluster regulatory region Sarah Milton Region: HOXD cluster regulatory region was added
Region: HOXD cluster regulatory region was added to Skeletal dysplasia. Sources: Expert Review Green,Literature
regulatory region tags were added to Region: HOXD cluster regulatory region.
Mode of inheritance for Region: HOXD cluster regulatory region was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for Region: HOXD cluster regulatory region were set to 20648051; 36990510; 34408147; 31591517; 20577005; 29517766
Phenotypes for Region: HOXD cluster regulatory region were set to Mesomelic dysplasia, Kantaputra type, MIM#156232
Mendeliome v2.393 HOXD cluster regulatory region Sarah Milton Marked Region: HOXD cluster regulatory region as ready
Mendeliome v2.393 HOXD cluster regulatory region Sarah Milton Region: hoxd cluster regulatory region has been classified as Green List (High Evidence).
Mendeliome v2.393 HOXD cluster regulatory region Sarah Milton Classified Region: HOXD cluster regulatory region as Green List (high evidence)
Mendeliome v2.393 HOXD cluster regulatory region Sarah Milton Region: hoxd cluster regulatory region has been classified as Green List (High Evidence).
Mendeliome v2.392 HOXD cluster regulatory region Sarah Milton changed review comment from: The HOXD cluster of genes including HOXD1, HOXD3, HOXD4, HOXD8, HOXD9, HOXD10, HOXD11, HOXD12, HOXD13 are involved in embryonic patterning in developing limb buds.

Multiple publications report copy number changes in the 2q31 region involving the HOXD cluster resulting in Mesomelic dysplasia, Kantaputra type characterised by marked shortening of the upper and lower limbs and progressive flexion contractures of PIP joints.

Copy number changes in affected individuals included deletions, duplications and inversions ranging from 93kb to 1mb, many individuals had more than one structural variant within the region.

The proposed molecular mechanism is repositioning of the HOX genes in relation to up and downstream enhancers resulting in misexpression.

It should be noted deletions of the HOX gene cluster don't recapitulate the phenotype as it is thought there is compensation from HOXA genes.

Functional studies in a mouse model showed inappropriate expression of HOXD13 in the middle segment of limb (ulnar/radius/tibia/fibula) and loss of normal expression in hand/foot, as well as loss of normal HOXD11 expression in the middle segment of the limb.
This is thought to occur as each enhancer region normally acts on different precursor cells in normal physiology thus rearranging the region results in misexpression.

Note: coordinates used for the above entry were the minimum seen in an affected individual (duplication).
Authors of above publications did note if the copy number variant is too large it did not recapitulate the phenotype.
Sources: Literature; to: The HOXD cluster of genes including HOXD1, HOXD3, HOXD4, HOXD8, HOXD9, HOXD10, HOXD11, HOXD12, HOXD13 are involved in embryonic patterning in developing limb buds.

Multiple publications report copy number changes in the 2q31 region involving the HOXD cluster resulting in Mesomelic dysplasia, Kantaputra type characterised by marked shortening of the upper and lower limbs and progressive flexion contractures of PIP joints.

Copy number changes in affected individuals included deletions, duplications and inversions ranging from 93kb to 1mb, many individuals had more than one structural variant within the region.

The proposed molecular mechanism is repositioning of the HOX genes in relation to up and downstream enhancers resulting in misexpression.

It should be noted deletions of the HOX gene cluster don't recapitulate the phenotype as it is thought there is compensation from HOXA genes.

Functional studies in a mouse model showed inappropriate expression of HOXD13 in the middle segment of limb (ulnar/radius/tibia/fibula) and loss of normal expression in hand/foot, as well as loss of normal HOXD11 expression in the middle segment of the limb.
This is thought to occur as each enhancer region acts on different precursor cells in normal physiology thus rearranging the region results in misexpression.

Note: coordinates used for the above entry were the minimum seen in an affected individual (duplication).
Authors of above publications did note if the copy number variant is too large it did not recapitulate the phenotype.
Sources: Literature
Mendeliome v2.392 HOXD cluster regulatory region Sarah Milton changed review comment from: The HOXD cluster of genes including HOXD1, HOXD3, HOXD4, HOXD8, HOXD9, HOXD10, HOXD11, HOXD12, HOXD13 are involved in embryonic patterning in developing limb buds.

Multiple publications report copy number changes in the 2q31 region involving the HOXD cluster resulting in Mesomelic dysplasia, Kantaputra type characterised by marked shortening of the upper and lower limbs and progressive flexion contractures of PIP joints.

Copy number changes in affected individuals included deletions, duplications and inversions ranging from 93kb to 1mb, many individuals had more than one structural variant within the region.

The proposed molecular mechanism is repositioning of the HOX genes in relation to up and downstream enhancers resulting in misexpression.

It should be noted deletions of the HOX gene cluster don't recapitulate the phenotype as it is thought there is compensation from HOXA genes.

Functional studies in a mouse model showed inappropriate expression of HOXD13 in the middle segment of limb (ulnar/radius/tibia/fibula) and loss of normal expression in hand/foot, as well as loss of normal HOXD11 expression in the middle segment of the limb.
This is thought to occur as each enhancer region normally acts on different precursor cells but repositioning of genes in the region results in misexpression.

Note: coordinates used for the above entry were the minimum seen in an affected individual (duplication).
Authors of above publications did note if the copy number variant is too large it did not recapitulate the phenotype.
Sources: Literature; to: The HOXD cluster of genes including HOXD1, HOXD3, HOXD4, HOXD8, HOXD9, HOXD10, HOXD11, HOXD12, HOXD13 are involved in embryonic patterning in developing limb buds.

Multiple publications report copy number changes in the 2q31 region involving the HOXD cluster resulting in Mesomelic dysplasia, Kantaputra type characterised by marked shortening of the upper and lower limbs and progressive flexion contractures of PIP joints.

Copy number changes in affected individuals included deletions, duplications and inversions ranging from 93kb to 1mb, many individuals had more than one structural variant within the region.

The proposed molecular mechanism is repositioning of the HOX genes in relation to up and downstream enhancers resulting in misexpression.

It should be noted deletions of the HOX gene cluster don't recapitulate the phenotype as it is thought there is compensation from HOXA genes.

Functional studies in a mouse model showed inappropriate expression of HOXD13 in the middle segment of limb (ulnar/radius/tibia/fibula) and loss of normal expression in hand/foot, as well as loss of normal HOXD11 expression in the middle segment of the limb.
This is thought to occur as each enhancer region normally acts on different precursor cells in normal physiology thus rearranging the region results in misexpression.

Note: coordinates used for the above entry were the minimum seen in an affected individual (duplication).
Authors of above publications did note if the copy number variant is too large it did not recapitulate the phenotype.
Sources: Literature
Mendeliome v2.392 HOXD cluster regulatory region Sarah Milton Region: HOXD cluster regulatory region was added
Region: HOXD cluster regulatory region was added to Mendeliome. Sources: Literature
regulatory region tags were added to Region: HOXD cluster regulatory region.
Mode of inheritance for Region: HOXD cluster regulatory region was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for Region: HOXD cluster regulatory region were set to 20648051; 36990510; 34408147; 31591517; 20577005; 29517766
Phenotypes for Region: HOXD cluster regulatory region were set to Mesomelic dysplasia, Kantaputra type, MIM#156232
Review for Region: HOXD cluster regulatory region was set to GREEN
Added comment: The HOXD cluster of genes including HOXD1, HOXD3, HOXD4, HOXD8, HOXD9, HOXD10, HOXD11, HOXD12, HOXD13 are involved in embryonic patterning in developing limb buds.

Multiple publications report copy number changes in the 2q31 region involving the HOXD cluster resulting in Mesomelic dysplasia, Kantaputra type characterised by marked shortening of the upper and lower limbs and progressive flexion contractures of PIP joints.

Copy number changes in affected individuals included deletions, duplications and inversions ranging from 93kb to 1mb, many individuals had more than one structural variant within the region.

The proposed molecular mechanism is repositioning of the HOX genes in relation to up and downstream enhancers resulting in misexpression.

It should be noted deletions of the HOX gene cluster don't recapitulate the phenotype as it is thought there is compensation from HOXA genes.

Functional studies in a mouse model showed inappropriate expression of HOXD13 in the middle segment of limb (ulnar/radius/tibia/fibula) and loss of normal expression in hand/foot, as well as loss of normal HOXD11 expression in the middle segment of the limb.
This is thought to occur as each enhancer region normally acts on different precursor cells but repositioning of genes in the region results in misexpression.

Note: coordinates used for the above entry were the minimum seen in an affected individual (duplication).
Authors of above publications did note if the copy number variant is too large it did not recapitulate the phenotype.
Sources: Literature
Mendeliome v2.391 OTOF Sangavi Sivagnanasundram reviewed gene: OTOF: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: nonsyndromic genetic hearing loss MONDO:0019497; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Neuropathy v2.26 FBXO38 Sangavi Sivagnanasundram reviewed gene: FBXO38: Rating: AMBER; Mode of pathogenicity: None; Publications: 34103343; Phenotypes: distal hereditary motor neuropathy MONDO:0018894; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cardiomyopathy_Paediatric v1.71 TANGO2 Lucy Spencer Classified gene: TANGO2 as Green List (high evidence)
Cardiomyopathy_Paediatric v1.71 TANGO2 Lucy Spencer Gene: tango2 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.70 TANGO2 Lucy Spencer gene: TANGO2 was added
gene: TANGO2 was added to Cardiomyopathy_Paediatric. Sources: Literature
Mode of inheritance for gene: TANGO2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TANGO2 were set to 40156300; 35568137
Phenotypes for gene: TANGO2 were set to Metabolic encephalomyopathic crises, recurrent, with rhabdomyolysis, cardiac arrhythmias, and neurodegeneration MIM#616878
Review for gene: TANGO2 was set to GREEN
Added comment: PMID: 40156300 reports 2 probands with biallelic TANGO2 variants with cardiomyopathy as part of a broader TANGO2-associated phenotype.

PMID: 35568137 Cohort of 27 children with TANGO2 deficiency disorder, 19 developed cardiomyopathy
Sources: Literature
Cardiomyopathy_Paediatric v1.69 TREX1 Lucy Spencer Classified gene: TREX1 as Green List (high evidence)
Cardiomyopathy_Paediatric v1.69 TREX1 Lucy Spencer Gene: trex1 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.68 TREX1 Lucy Spencer gene: TREX1 was added
gene: TREX1 was added to Cardiomyopathy_Paediatric. Sources: Literature
Mode of inheritance for gene: TREX1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: TREX1 were set to 25604658; 36581356
Phenotypes for gene: TREX1 were set to Aicardi-Goutieres syndrome 1, dominant and recessive MIM#225750
Review for gene: TREX1 was set to GREEN
Added comment: PMID: 25604658 infantile onset hypertrophic cardiomyopathy reported in 9/79 individuals with TREX1 related Aicardi-Goutieres syndrome. This paper includes both recessive and dominant TREX1 patients, it is unclear which have HCM.

PMID 36581356 reports one proband with Aicardi-Goutieres syndrome diagnosed with cardiomyopathy in utero. The proband was homozygous for a TREX1 frameshift variant.
Sources: Literature
Microcephaly v2.10 ATP6V0C Vivek Kumar reviewed gene: ATP6V0C: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, maternally imprinted (paternal allele expressed)
Mendeliome v2.391 TKFC Rylee Peters Publications for gene: TKFC were set to 32004446
Mendeliome v2.390 TKFC Rylee Peters reviewed gene: TKFC: Rating: AMBER; Mode of pathogenicity: None; Publications: 39251934; Phenotypes: Triokinase and FMN cyclase deficiency syndrome, MIM#618805; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v1.67 TKFC Rylee Peters Marked gene: TKFC as ready
Cardiomyopathy_Paediatric v1.67 TKFC Rylee Peters Gene: tkfc has been classified as Amber List (Moderate Evidence).
Cardiomyopathy_Paediatric v1.67 TKFC Rylee Peters Classified gene: TKFC as Amber List (moderate evidence)
Cardiomyopathy_Paediatric v1.67 TKFC Rylee Peters Gene: tkfc has been classified as Amber List (Moderate Evidence).
Cardiomyopathy_Paediatric v1.66 TKFC Rylee Peters gene: TKFC was added
gene: TKFC was added to Cardiomyopathy_Paediatric. Sources: Literature
Mode of inheritance for gene: TKFC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TKFC were set to 39251934; 32004446
Phenotypes for gene: TKFC were set to Triokinase and FMN cyclase deficiency syndrome, MIM#618805
Review for gene: TKFC was set to AMBER
Added comment: PMID: 32004446 reports 4 individuals from 2 consanguineous families with homozygous variants in TKFC. The first family had 2 children with phenotypes including cataract, lactic acidosis, cardiomyopathy. The second family had one child with cataracts and poor weight gain and one child with isolated delayed speech and learning difficulties.

PMID: 39251934 reports 2 individuals from 1 consanguineous family with a homozygous TKFC missense variant presenting with severe skeletal abnormalities, fetal cerebral hypoplasia,
fetal reduced movements, liver dysfunction, and fatal hypertrophic cardiomyopathy. They were also homozygous for a TYR LoF variant.
Sources: Literature
Cardiomyopathy_Paediatric v1.65 NAA10 Rylee Peters Marked gene: NAA10 as ready
Cardiomyopathy_Paediatric v1.65 NAA10 Rylee Peters Gene: naa10 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.65 NAA10 Rylee Peters Classified gene: NAA10 as Green List (high evidence)
Cardiomyopathy_Paediatric v1.65 NAA10 Rylee Peters Gene: naa10 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v1.64 NAA10 Rylee Peters gene: NAA10 was added
gene: NAA10 was added to Cardiomyopathy_Paediatric. Sources: Literature
Mode of inheritance for gene: NAA10 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: NAA10 were set to 40304357; 40234403; 38335407; 37441566; 37130971; 33335012; 32864149
Phenotypes for gene: NAA10 were set to NAA10-related syndrome, MONDO:0100124
Review for gene: NAA10 was set to GREEN
Added comment: NAA10-related neurodevelopmental syndrome phenotypic spectrum includes variable levels of intellectual disability, delayed milestones, autism spectrum disorder, craniofacial dysmorphology, cardiac anomalies, seizures, and visual abnormalities. Multiple families also reported with early‑onset cardiomyopathy, predominantly hypertrophic cardiopmyopathy phenotype.
Sources: Literature
Congenital Heart Defect v1.28 NAA10 Rylee Peters Marked gene: NAA10 as ready
Congenital Heart Defect v1.28 NAA10 Rylee Peters Gene: naa10 has been classified as Green List (High Evidence).
Congenital Heart Defect v1.28 NAA10 Rylee Peters Classified gene: NAA10 as Green List (high evidence)
Congenital Heart Defect v1.28 NAA10 Rylee Peters Gene: naa10 has been classified as Green List (High Evidence).
Congenital Heart Defect v1.27 NAA10 Rylee Peters gene: NAA10 was added
gene: NAA10 was added to Congenital Heart Defect. Sources: Literature
Mode of inheritance for gene: NAA10 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: NAA10 were set to 37130971
Phenotypes for gene: NAA10 were set to NAA10-related syndrome MONDO:0100124
Review for gene: NAA10 was set to GREEN
Added comment: PMID: 37130971 – Cohort of individuals with NAA10-related neurodevelopmental syndrome. Phenotypic spectrum includes variable levels of intellectual disability, delayed milestones, autism spectrum disorder, craniofacial dysmorphology, cardiac anomalies, seizures, and visual abnormalities. Congenital heart defects including (ASD, VSD) occur in >10 individuals.
Sources: Literature
Cardiomyopathy_Paediatric v1.63 POPDC2 Rylee Peters Marked gene: POPDC2 as ready
Cardiomyopathy_Paediatric v1.63 POPDC2 Rylee Peters Gene: popdc2 has been classified as Amber List (Moderate Evidence).
Cardiomyopathy_Paediatric v1.63 POPDC2 Rylee Peters Classified gene: POPDC2 as Amber List (moderate evidence)
Cardiomyopathy_Paediatric v1.63 POPDC2 Rylee Peters Gene: popdc2 has been classified as Amber List (Moderate Evidence).
Cardiomyopathy_Paediatric v1.62 POPDC2 Rylee Peters gene: POPDC2 was added
gene: POPDC2 was added to Cardiomyopathy_Paediatric. Sources: Literature
Mode of inheritance for gene: POPDC2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POPDC2 were set to 41456958; 40409267
Phenotypes for gene: POPDC2 were set to Cardiac conduction disease with or without cardiomyopathy 2, MIM# 621367
Review for gene: POPDC2 was set to AMBER
Added comment: Multiple families reported with cardiac conduction and hypertrophic cardiomyopathy (rated GREEN).
AMBER rating given to this panel as there are only 2 reports of paediatric onset of HCM and cardiac conduction disorder (PMIDs: 41456958, 40409267).
Sources: Literature
Fetal anomalies v2.41 CDK20 Zornitza Stark Marked gene: CDK20 as ready
Fetal anomalies v2.41 CDK20 Zornitza Stark Gene: cdk20 has been classified as Green List (High Evidence).
Clefting disorders v1.20 CDK20 Zornitza Stark Marked gene: CDK20 as ready
Clefting disorders v1.20 CDK20 Zornitza Stark Gene: cdk20 has been classified as Green List (High Evidence).
Polydactyly v1.15 CDK20 Zornitza Stark Marked gene: CDK20 as ready
Polydactyly v1.15 CDK20 Zornitza Stark Gene: cdk20 has been classified as Green List (High Evidence).
Hydrocephalus_Ventriculomegaly v1.4 CDK20 Zornitza Stark Marked gene: CDK20 as ready
Hydrocephalus_Ventriculomegaly v1.4 CDK20 Zornitza Stark Gene: cdk20 has been classified as Green List (High Evidence).
Ciliopathies v2.10 CDK20 Zornitza Stark Marked gene: CDK20 as ready
Ciliopathies v2.10 CDK20 Zornitza Stark Gene: cdk20 has been classified as Green List (High Evidence).
Anophthalmia_Microphthalmia_Coloboma v2.4 CDK20 Zornitza Stark Marked gene: CDK20 as ready
Anophthalmia_Microphthalmia_Coloboma v2.4 CDK20 Zornitza Stark Gene: cdk20 has been classified as Green List (High Evidence).
Polydactyly v1.15 Zornitza Stark Copied gene CDK20 from panel Mendeliome
Polydactyly v1.15 CDK20 Zornitza Stark gene: CDK20 was added
gene: CDK20 was added to Polydactyly. Sources: Expert Review Green,Literature
Mode of inheritance for gene: CDK20 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CDK20 were set to 42409022
Phenotypes for gene: CDK20 were set to Ciliopathy, MONDO:0005308, CDK20-related
Hydrocephalus_Ventriculomegaly v1.4 Zornitza Stark Copied gene CDK20 from panel Mendeliome
Hydrocephalus_Ventriculomegaly v1.4 CDK20 Zornitza Stark gene: CDK20 was added
gene: CDK20 was added to Hydrocephalus_Ventriculomegaly. Sources: Expert Review Green,Literature
Mode of inheritance for gene: CDK20 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CDK20 were set to 42409022
Phenotypes for gene: CDK20 were set to Ciliopathy, MONDO:0005308, CDK20-related
Fetal anomalies v2.41 Zornitza Stark Copied gene CDK20 from panel Mendeliome
Fetal anomalies v2.41 CDK20 Zornitza Stark gene: CDK20 was added
gene: CDK20 was added to Fetal anomalies. Sources: Expert Review Green,Literature
Mode of inheritance for gene: CDK20 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CDK20 were set to 42409022
Phenotypes for gene: CDK20 were set to Ciliopathy, MONDO:0005308, CDK20-related
Clefting disorders v1.20 Zornitza Stark Copied gene CDK20 from panel Mendeliome
Clefting disorders v1.20 CDK20 Zornitza Stark gene: CDK20 was added
gene: CDK20 was added to Clefting disorders. Sources: Expert Review Green,Literature
Mode of inheritance for gene: CDK20 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CDK20 were set to 42409022
Phenotypes for gene: CDK20 were set to Ciliopathy, MONDO:0005308, CDK20-related
Ciliopathies v2.10 Zornitza Stark Copied gene CDK20 from panel Mendeliome
Ciliopathies v2.10 CDK20 Zornitza Stark gene: CDK20 was added
gene: CDK20 was added to Ciliopathies. Sources: Expert Review Green,Literature
Mode of inheritance for gene: CDK20 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CDK20 were set to 42409022
Phenotypes for gene: CDK20 were set to Ciliopathy, MONDO:0005308, CDK20-related
Anophthalmia_Microphthalmia_Coloboma v2.4 Zornitza Stark Copied gene CDK20 from panel Mendeliome
Anophthalmia_Microphthalmia_Coloboma v2.4 CDK20 Zornitza Stark gene: CDK20 was added
gene: CDK20 was added to Anophthalmia_Microphthalmia_Coloboma. Sources: Expert Review Green,Literature
Mode of inheritance for gene: CDK20 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CDK20 were set to 42409022
Phenotypes for gene: CDK20 were set to Ciliopathy, MONDO:0005308, CDK20-related
Mendeliome v2.390 CDK20 Zornitza Stark Marked gene: CDK20 as ready
Mendeliome v2.390 CDK20 Zornitza Stark Gene: cdk20 has been classified as Green List (High Evidence).
Mendeliome v2.390 CDK20 Zornitza Stark Classified gene: CDK20 as Green List (high evidence)
Mendeliome v2.390 CDK20 Zornitza Stark Gene: cdk20 has been classified as Green List (High Evidence).
Mendeliome v2.389 CDK20 Zornitza Stark gene: CDK20 was added
gene: CDK20 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CDK20 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CDK20 were set to 42409022
Phenotypes for gene: CDK20 were set to Ciliopathy, MONDO:0005308, CDK20-related
Review for gene: CDK20 was set to GREEN
Added comment: Seven individuals from five unrelated families with bi-allelic variants in CDK20 and an overlapping phenotype of ventriculomegaly or hydrocephalus, midline brain anomalies, abnormal nose, midline cleft lip and/or palate, cryptophthalmos or anophthalmia, postaxial polydactyly, and a sandal toe gap. Immunoblot analysis of fibroblasts derived from two affected fetuses with a homozygous CDK20 c.687+6T>C (p.?) variant demonstrated reduced CDK20 levels. Fibroblasts derived from these affected fetuses were also significantly deficient in cilium formation and function, with abnormal cilium morphology and significantly decreased Hedgehog responsiveness.
Sources: Literature
Fetal anomalies v2.40 DMRTA2 Zornitza Stark Marked gene: DMRTA2 as ready
Fetal anomalies v2.40 DMRTA2 Zornitza Stark Gene: dmrta2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v2.67 DMRTA2 Zornitza Stark Marked gene: DMRTA2 as ready
Intellectual disability syndromic and non-syndromic v2.67 DMRTA2 Zornitza Stark Gene: dmrta2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v2.67 Zornitza Stark Copied gene DMRTA2 from panel Mendeliome
Intellectual disability syndromic and non-syndromic v2.67 DMRTA2 Zornitza Stark gene: DMRTA2 was added
gene: DMRTA2 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: DMRTA2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DMRTA2 were set to 40541527; 26757254
Phenotypes for gene: DMRTA2 were set to Microcephaly, MONDO:0001149, DMRTA2-related
Fetal anomalies v2.40 Zornitza Stark Copied gene DMRTA2 from panel Mendeliome
Fetal anomalies v2.40 DMRTA2 Zornitza Stark gene: DMRTA2 was added
gene: DMRTA2 was added to Fetal anomalies. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: DMRTA2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DMRTA2 were set to 40541527; 26757254
Phenotypes for gene: DMRTA2 were set to Microcephaly, MONDO:0001149, DMRTA2-related
Mendeliome v2.388 DMRTA2 Zornitza Stark Classified gene: DMRTA2 as Amber List (moderate evidence)
Mendeliome v2.388 DMRTA2 Zornitza Stark Gene: dmrta2 has been classified as Amber List (Moderate Evidence).
Mendeliome v2.387 DMRTA2 Zornitza Stark changed review comment from: Single family reported with three affected siblings and bi-allelic LoF variant. Newly published functional data but no further reports.
Sources: Literature; to: Two families reported: PMID 26757254: two siblings from a Bedouin family, with hmz variant 1197delG. Both presented antenatally with abnormal imaging. Third sibling also likely affected in utero but not tested.
PMID 40541527: reports 3 members of a consanguineous Pakistani family, born in different sibships. Hmz missense variant R116P identified. Clinical features included: global developmental delay, dysarthria, muscle atrophy, aggressive behavior, and peripheral neuropathy as well as microcephaly.
Sources: Literature
Mendeliome v2.387 DMRTA2 Zornitza Stark edited their review of gene: DMRTA2: Changed rating: AMBER
Microcephaly v2.10 DMRTA2 Zornitza Stark Classified gene: DMRTA2 as Amber List (moderate evidence)
Microcephaly v2.10 DMRTA2 Zornitza Stark Gene: dmrta2 has been classified as Amber List (Moderate Evidence).
Microcephaly v2.9 DMRTA2 Zornitza Stark edited their review of gene: DMRTA2: Changed rating: AMBER
Microcephaly v2.9 DMRTA2 Zornitza Stark changed review comment from: Single family reported with three affected siblings and bi-allelic LoF variant. Newly published functional data but no further reports.
Sources: Literature; to: Two families reported:
PMID 26757254: two siblings from a Bedouin family, with hmz variant 1197delG. Both presented antenatally with abnormal imaging. Third sibling also likely affected in utero but not tested.
PMID 40541527: reports 3 members of a consanguineous Pakistani family, born in different sibships. Hmz missense variant R116P identified. Clinical features included: global developmental delay, dysarthria, muscle atrophy, aggressive behavior, and peripheral neuropathy as well as microcephaly.

Sources: Literature
Intellectual disability syndromic and non-syndromic v2.66 ELAVL2 Zornitza Stark Marked gene: ELAVL2 as ready
Intellectual disability syndromic and non-syndromic v2.66 ELAVL2 Zornitza Stark Gene: elavl2 has been classified as Green List (High Evidence).
Genetic Epilepsy v2.31 ELAVL2 Zornitza Stark Marked gene: ELAVL2 as ready
Genetic Epilepsy v2.31 ELAVL2 Zornitza Stark Gene: elavl2 has been classified as Green List (High Evidence).
Autism v1.14 ELAVL2 Zornitza Stark Marked gene: ELAVL2 as ready
Autism v1.14 ELAVL2 Zornitza Stark Gene: elavl2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v2.66 Zornitza Stark Copied gene ELAVL2 from panel Mendeliome
Intellectual disability syndromic and non-syndromic v2.66 ELAVL2 Zornitza Stark gene: ELAVL2 was added
gene: ELAVL2 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review Green,Literature
Mode of inheritance for gene: ELAVL2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ELAVL2 were set to 42556336
Phenotypes for gene: ELAVL2 were set to Neurodevelopmental disorder, MONDO:0700092, ELAVL2-related
Genetic Epilepsy v2.31 Zornitza Stark Copied gene ELAVL2 from panel Mendeliome
Genetic Epilepsy v2.31 ELAVL2 Zornitza Stark gene: ELAVL2 was added
gene: ELAVL2 was added to Genetic Epilepsy. Sources: Expert Review Green,Literature
Mode of inheritance for gene: ELAVL2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ELAVL2 were set to 42556336
Phenotypes for gene: ELAVL2 were set to Neurodevelopmental disorder, MONDO:0700092, ELAVL2-related
Autism v1.14 Zornitza Stark Copied gene ELAVL2 from panel Mendeliome
Autism v1.14 ELAVL2 Zornitza Stark gene: ELAVL2 was added
gene: ELAVL2 was added to Autism. Sources: Expert Review Green,Literature
Mode of inheritance for gene: ELAVL2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ELAVL2 were set to 42556336
Phenotypes for gene: ELAVL2 were set to Neurodevelopmental disorder, MONDO:0700092, ELAVL2-related
Mendeliome v2.387 ELAVL2 Zornitza Stark Marked gene: ELAVL2 as ready
Mendeliome v2.387 ELAVL2 Zornitza Stark Gene: elavl2 has been classified as Green List (High Evidence).
Mendeliome v2.387 ELAVL2 Zornitza Stark Classified gene: ELAVL2 as Green List (high evidence)
Mendeliome v2.387 ELAVL2 Zornitza Stark Gene: elavl2 has been classified as Green List (High Evidence).
Mendeliome v2.386 ELAVL2 Zornitza Stark gene: ELAVL2 was added
gene: ELAVL2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ELAVL2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ELAVL2 were set to 42556336
Phenotypes for gene: ELAVL2 were set to Neurodevelopmental disorder, MONDO:0700092, ELAVL2-related
Review for gene: ELAVL2 was set to GREEN
Added comment: 16 individuals with a neurodevelopmental disorder and de novo heterozygous variants in ELAVL2 reported. ELAVL2 encodes an RNA-binding protein. The cohort presented with developmental delay, intellectual disability, autism spectrum disorder, seizures, sleep problems, sensory processing issues, emotional instability, and difficulty with socialization. Over half of the variants reported are LoF, supporting haploinsufficiency as the mechanism of disease. Drosophila loss-of-function models provide further independent evidence for a conserved role in the regulation of seizure-like behavior, sensory processing, and sleep. Some of the missense variants are also shown to be deleterious, leading to decreased protein levels.
Sources: Literature
Disorders of immune dysregulation v2.5 ISCA-37433-Loss Krithika Murali Marked Region: ISCA-37433-Loss as ready
Disorders of immune dysregulation v2.5 ISCA-37433-Loss Krithika Murali Region: isca-37433-loss has been classified as Green List (High Evidence).
Disorders of immune dysregulation v2.5 Krithika Murali Copied Region ISCA-37433-Loss from panel Common deletion and duplication syndromes
Disorders of immune dysregulation v2.5 ISCA-37433-Loss Krithika Murali Region: ISCA-37433-Loss was added
Region: ISCA-37433-Loss was added to Disorders of immune dysregulation. Sources: Expert Review Green,Expert list
Mode of inheritance for Region: ISCA-37433-Loss was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for Region: ISCA-37433-Loss were set to DiGeorge syndrome MIM#188400
Deafness_IsolatedAndComplex v2.5 ISCA-37392-Loss Krithika Murali Marked Region: ISCA-37392-Loss as ready
Deafness_IsolatedAndComplex v2.5 ISCA-37392-Loss Krithika Murali Region: isca-37392-loss has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v2.5 Krithika Murali Copied Region ISCA-37392-Loss from panel Common deletion and duplication syndromes
Deafness_IsolatedAndComplex v2.5 ISCA-37392-Loss Krithika Murali Region: ISCA-37392-Loss was added
Region: ISCA-37392-Loss was added to Deafness_IsolatedAndComplex. Sources: Expert Review Green,Expert Review
SV/CNV tags were added to Region: ISCA-37392-Loss.
Mode of inheritance for Region: ISCA-37392-Loss was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for Region: ISCA-37392-Loss were set to 20301427
Phenotypes for Region: ISCA-37392-Loss were set to Williams-Beuren syndrome, MIM# 194050; intellectual disability; growth retardation; cardiovascular disease
Skeletal dysplasia v1.83 FAR1 chirag patel Marked gene: FAR1 as ready
Skeletal dysplasia v1.83 FAR1 chirag patel Gene: far1 has been classified as Red List (Low Evidence).
Skeletal dysplasia v1.83 FAR1 chirag patel Mode of inheritance for gene: FAR1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.82 FAR1 chirag patel Publications for gene: FAR1 were set to 25439727; 33239752
Skeletal dysplasia v1.81 FAR1 chirag patel Phenotypes for gene: FAR1 were changed from Peroxisomal fatty acyl-CoA reductase 1 disorder, MIM#616154; Cataracts, spastic paraparesis, and speech delay, MIM#619338 to Fatty acyl-CoA reductase 1 deficiency MONDO:0014510
Skeletal dysplasia v1.80 FAR1 chirag patel Classified gene: FAR1 as Red List (low evidence)
Skeletal dysplasia v1.80 FAR1 chirag patel Gene: far1 has been classified as Red List (Low Evidence).
Skeletal dysplasia v1.79 FAR1 chirag patel reviewed gene: FAR1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Fatty acyl-CoA reductase 1 deficiency MONDO:0014510; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.79 chirag patel Copied gene FAR1 from panel Mendeliome
Skeletal dysplasia v1.79 FAR1 chirag patel gene: FAR1 was added
gene: FAR1 was added to Skeletal dysplasia. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: FAR1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: FAR1 were set to 25439727; 33239752
Phenotypes for gene: FAR1 were set to Peroxisomal fatty acyl-CoA reductase 1 disorder, MIM#616154; Cataracts, spastic paraparesis, and speech delay, MIM#619338
Hand and foot malformations v1.5 CCNQ chirag patel Marked gene: CCNQ as ready
Hand and foot malformations v1.5 CCNQ chirag patel Gene: ccnq has been classified as Green List (High Evidence).
Hand and foot malformations v1.5 CCNQ chirag patel Phenotypes for gene: CCNQ were changed from STAR syndrome 300707 to syndactyly-telecanthus-anogenital and renal malformations syndrome MONDO:0010408
Hand and foot malformations v1.4 CCNQ chirag patel Publications for gene: CCNQ were set to
Congenital anomalies of the kidney and urinary tract (CAKUT) v1.13 CCNQ chirag patel Phenotypes for gene: CCNQ were changed from STAR syndrome, MIM# 300707 to syndactyly-telecanthus-anogenital and renal malformations syndrome MONDO:0010408
Congenital anomalies of the kidney and urinary tract (CAKUT) v1.12 CCNQ chirag patel Publications for gene: CCNQ were set to 28225384; 18297069
Congenital anomalies of the kidney and urinary tract (CAKUT) v1.11 CCNQ chirag patel Mode of inheritance for gene: CCNQ was changed from Other to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Hand and foot malformations v1.3 chirag patel Added reviews for gene CCNQ from panel Skeletal dysplasia
Congenital anomalies of the kidney and urinary tract (CAKUT) v1.10 chirag patel Added reviews for gene CCNQ from panel Skeletal dysplasia
Skeletal dysplasia v1.78 CCNQ chirag patel Publications for gene: CCNQ were set to
Skeletal dysplasia v1.77 CCNQ chirag patel Marked gene: CCNQ as ready
Skeletal dysplasia v1.77 CCNQ chirag patel Gene: ccnq has been classified as Green List (High Evidence).
Skeletal dysplasia v1.77 CCNQ chirag patel Phenotypes for gene: CCNQ were changed from STAR syndrome 300707; STAR syndrome 300707 to syndactyly-telecanthus-anogenital and renal malformations syndrome MONDO:0010408
Skeletal dysplasia v1.76 B9D2 chirag patel Marked gene: B9D2 as ready
Skeletal dysplasia v1.76 B9D2 chirag patel Gene: b9d2 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.76 B9D2 chirag patel Publications for gene: B9D2 were set to
Skeletal dysplasia v1.75 B9D2 chirag patel Phenotypes for gene: B9D2 were changed from Meckel syndrome 10 614175 to Joubert syndrome 34, MIM#614175; Meckel syndrome 10, MIM#614175
Skeletal dysplasia v1.74 B9D2 chirag patel Classified gene: B9D2 as Green List (high evidence)
Skeletal dysplasia v1.74 B9D2 chirag patel Gene: b9d2 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.73 chirag patel Added reviews for gene B9D2 from panel Polydactyly
Skeletal dysplasia v1.72 AKT3 chirag patel Marked gene: AKT3 as ready
Skeletal dysplasia v1.72 AKT3 chirag patel Gene: akt3 has been classified as Green List (High Evidence).
Skeletal dysplasia v1.72 chirag patel Copied gene AKT3 from panel Mendeliome
Skeletal dysplasia v1.72 AKT3 chirag patel gene: AKT3 was added
gene: AKT3 was added to Skeletal dysplasia. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: AKT3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: AKT3 were set to PMID: 22729224
Phenotypes for gene: AKT3 were set to Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 2 MIM#615937
Mode of pathogenicity for gene: AKT3 was set to Other
Polydactyly v1.14 AKT3 chirag patel Mode of pathogenicity for gene: AKT3 was changed from to Other
Polydactyly v1.13 AKT3 chirag patel Publications for gene: AKT3 were set to
Polydactyly v1.12 chirag patel Added reviews for gene AKT3 from panel Mendeliome
Polydactyly v1.11 AHI1 chirag patel Classified gene: AHI1 as Red List (low evidence)
Polydactyly v1.11 AHI1 chirag patel Gene: ahi1 has been classified as Red List (Low Evidence).
Polydactyly v1.10 AHI1 chirag patel reviewed gene: AHI1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Joubert syndrome 3, MIM# 608629; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v1.71 AHI1 chirag patel reviewed gene: AHI1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Skeletal dysplasia v1.71 CENPE chirag patel Marked gene: CENPE as ready
Skeletal dysplasia v1.71 CENPE chirag patel Gene: cenpe has been classified as Red List (Low Evidence).
Skeletal dysplasia v1.71 CENPE chirag patel changed review comment from: skeletal findings were not characteristic of a specific bone dysplasia; to: skeletal findings are not characteristic of a specific bone dysplasia
Skeletal dysplasia v1.71 CENPE chirag patel reviewed gene: CENPE: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Skeletal dysplasia v1.71 chirag patel Copied gene CENPE from panel Mendeliome
Skeletal dysplasia v1.71 CENPE chirag patel gene: CENPE was added
gene: CENPE was added to Skeletal dysplasia. Sources: Expert Review Red,Victorian Clinical Genetics Services
Mode of inheritance for gene: CENPE was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CENPE were set to 24748105; 30086807
Phenotypes for gene: CENPE were set to Microcephaly 13, primary, autosomal recessive (MIM#616051)
Fetal anomalies v2.39 ZIC1 chirag patel changed review comment from: 5 families with heterozygous mutations located in the final (third) exon of ZIC1 who have a distinct phenotype in which severe craniosynostosis, specifically involving the coronal sutures, and variable learning disability are the most characteristic features. The location of the nonsense mutations predicts escape of mutant ZIC1 transcripts from nonsense-mediated decay, which was confirmed in a cell line from an affected individual. Both nonsense and missense mutations are associated with altered and/or enhanced expression of a target gene, engrailed-2, in a Xenopus embryo assay. Analysis of mouse embryos revealed a localized domain of Zic1 expression at embryonic days 11.5-12.5 in a region overlapping the supraorbital regulatory center, which patterns the coronal suture.

2 sibs with BAIDCS, Vandervore et al. (2018) identified heterozygosity for a frameshift mutation in the ZIC1 gene. Neither parent had evidence of the mutation by whole-exome sequencing, suggesting that gonadal mosaicism for the mutation was present in one of the parents. Expression of the mutated allele was detected in patient fibroblasts by RT-PCR, evidence that the mutant mRNA did not undergo nonsense-mediated decay and probably generates an abnormal protein.


Also heterozygous deletions of ZIC1 on chromosome 3q25.1 are associated with Dandy-Walker malformation of the cerebellum. Loss of the orthologous Zic1 gene in the mouse causes cerebellar hypoplasia and vertebral defects.
Sources: Expert list; to: Individuals with BAIDCS have microcephaly, brain anomalies (esp corpus callosum), intellectual disability (moderate to severe), and bicoronal synostosis.

5 families with heterozygous mutations located in the final (third) exon of ZIC1 who have a distinct phenotype in which severe craniosynostosis, specifically involving the coronal sutures, and variable learning disability are the most characteristic features. The location of the nonsense mutations predicts escape of mutant ZIC1 transcripts from nonsense-mediated decay, which was confirmed in a cell line from an affected individual. Both nonsense and missense mutations are associated with altered and/or enhanced expression of a target gene, engrailed-2, in a Xenopus embryo assay. Analysis of mouse embryos revealed a localized domain of Zic1 expression at embryonic days 11.5-12.5 in a region overlapping the supraorbital regulatory center, which patterns the coronal suture.

2 sibs with BAIDCS, Vandervore et al. (2018) identified heterozygosity for a frameshift mutation in the ZIC1 gene. Neither parent had evidence of the mutation by whole-exome sequencing, suggesting that gonadal mosaicism for the mutation was present in one of the parents. Expression of the mutated allele was detected in patient fibroblasts by RT-PCR, evidence that the mutant mRNA did not undergo nonsense-mediated decay and probably generates an abnormal protein.


Also heterozygous deletions of ZIC1 on chromosome 3q25.1 are associated with Dandy-Walker malformation of the cerebellum. Loss of the orthologous Zic1 gene in the mouse causes cerebellar hypoplasia and vertebral defects.
Sources: Expert list
Callosome v1.17 ZIC1 chirag patel Marked gene: ZIC1 as ready
Callosome v1.17 ZIC1 chirag patel Gene: zic1 has been classified as Green List (High Evidence).
Callosome v1.17 ZIC1 chirag patel Phenotypes for gene: ZIC1 were changed from to Structural brain anomalies with impaired intellectual development and craniosynostosis; OMIM #618736
Callosome v1.16 ZIC1 chirag patel Publications for gene: ZIC1 were set to
Callosome v1.15 ZIC1 chirag patel Mode of inheritance for gene: ZIC1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Microcephaly v2.9 ZIC1 chirag patel Marked gene: ZIC1 as ready
Microcephaly v2.9 ZIC1 chirag patel Gene: zic1 has been classified as Green List (High Evidence).
Microcephaly v2.9 chirag patel Copied gene ZIC1 from panel Intellectual disability syndromic and non-syndromic
Microcephaly v2.9 ZIC1 chirag patel gene: ZIC1 was added
gene: ZIC1 was added to Microcephaly. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: ZIC1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ZIC1 were set to PMID: 26340333, 30391508
Phenotypes for gene: ZIC1 were set to Structural brain anomalies with impaired intellectual development and craniosynostosis; OMIM #618736 
Fetal anomalies v2.39 chirag patel Added reviews for gene ZIC1 from panel Intellectual disability syndromic and non-syndromic
Craniosynostosis v2.4 chirag patel Added reviews for gene ZIC1 from panel Intellectual disability syndromic and non-syndromic
Callosome v1.14 chirag patel Added reviews for gene ZIC1 from panel Intellectual disability syndromic and non-syndromic
Intellectual disability syndromic and non-syndromic v2.65 ZIC1 chirag patel changed review comment from: 5 families with heterozygous mutations located in the final (third) exon of ZIC1 who have a distinct phenotype in which severe craniosynostosis, specifically involving the coronal sutures, and variable learning disability are the most characteristic features. The location of the nonsense mutations predicts escape of mutant ZIC1 transcripts from nonsense-mediated decay, which was confirmed in a cell line from an affected individual. Both nonsense and missense mutations are associated with altered and/or enhanced expression of a target gene, engrailed-2, in a Xenopus embryo assay. Analysis of mouse embryos revealed a localized domain of Zic1 expression at embryonic days 11.5-12.5 in a region overlapping the supraorbital regulatory center, which patterns the coronal suture.

2 sibs with BAIDCS, Vandervore et al. (2018) identified heterozygosity for a frameshift mutation in the ZIC1 gene. Neither parent had evidence of the mutation by whole-exome sequencing, suggesting that gonadal mosaicism for the mutation was present in one of the parents. Expression of the mutated allele was detected in patient fibroblasts by RT-PCR, evidence that the mutant mRNA did not undergo nonsense-mediated decay and probably generates an abnormal protein.


Also heterozygous deletions of ZIC1 on chromosome 3q25.1 are associated with Dandy-Walker malformation of the cerebellum. Loss of the orthologous Zic1 gene in the mouse causes cerebellar hypoplasia and vertebral defects.
Sources: Expert list; to: Individuals with BAIDCS have microcephaly, brain anomalies (esp corpus callosum), intellectual disability (moderate to severe), and bicoronal synostosis.

5 families with heterozygous mutations located in the final (third) exon of ZIC1 who have a distinct phenotype in which severe craniosynostosis, specifically involving the coronal sutures, and variable learning disability are the most characteristic features. The location of the nonsense mutations predicts escape of mutant ZIC1 transcripts from nonsense-mediated decay, which was confirmed in a cell line from an affected individual. Both nonsense and missense mutations are associated with altered and/or enhanced expression of a target gene, engrailed-2, in a Xenopus embryo assay. Analysis of mouse embryos revealed a localized domain of Zic1 expression at embryonic days 11.5-12.5 in a region overlapping the supraorbital regulatory center, which patterns the coronal suture.

2 sibs with BAIDCS, Vandervore et al. (2018) identified heterozygosity for a frameshift mutation in the ZIC1 gene. Neither parent had evidence of the mutation by whole-exome sequencing, suggesting that gonadal mosaicism for the mutation was present in one of the parents. Expression of the mutated allele was detected in patient fibroblasts by RT-PCR, evidence that the mutant mRNA did not undergo nonsense-mediated decay and probably generates an abnormal protein.


Also heterozygous deletions of ZIC1 on chromosome 3q25.1 are associated with Dandy-Walker malformation of the cerebellum. Loss of the orthologous Zic1 gene in the mouse causes cerebellar hypoplasia and vertebral defects.
Sources: Expert list
Fetal anomalies v2.38 VCP chirag patel Marked gene: VCP as ready
Fetal anomalies v2.38 VCP chirag patel Gene: vcp has been classified as Green List (High Evidence).
Hand and foot malformations v1.2 VCP chirag patel Marked gene: VCP as ready
Hand and foot malformations v1.2 VCP chirag patel Gene: vcp has been classified as Green List (High Evidence).
Pulmonary Arterial Hypertension v2.3 VCP chirag patel Marked gene: VCP as ready
Pulmonary Arterial Hypertension v2.3 VCP chirag patel Gene: vcp has been classified as Green List (High Evidence).
Congenital Heart Defect v1.26 VCP chirag patel Marked gene: VCP as ready
Congenital Heart Defect v1.26 VCP chirag patel Gene: vcp has been classified as Green List (High Evidence).
Mendeliome v2.385 VCP chirag patel Marked gene: VCP as ready
Mendeliome v2.385 VCP chirag patel Gene: vcp has been classified as Green List (High Evidence).
Mendeliome v2.385 VCP chirag patel Phenotypes for gene: VCP were changed from Neurodevelopmental disorder (MONDO: 0700092), VCP-related to Neurodevelopmental disorder (MONDO: 0700092), VCP-related; Adams-Oliver syndrome MONDO:0007034, VCP-related
Mendeliome v2.384 VCP chirag patel Publications for gene: VCP were set to PMID: 37883978, 41979051
Mendeliome v2.383 VCP chirag patel Publications for gene: VCP were set to PMID: 37883978
Pulmonary Arterial Hypertension v2.3 chirag patel Copied gene VCP from panel Skeletal dysplasia
Pulmonary Arterial Hypertension v2.3 VCP chirag patel gene: VCP was added
gene: VCP was added to Pulmonary Arterial Hypertension. Sources: Expert Review Green,Literature
Mode of inheritance for gene: VCP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: VCP were set to 41979051
Phenotypes for gene: VCP were set to Adams-Oliver syndrome MONDO:0007034, VCP-related
Mendeliome v2.382 chirag patel Added reviews for gene VCP from panel Skeletal dysplasia
Hand and foot malformations v1.2 chirag patel Copied gene VCP from panel Skeletal dysplasia
Hand and foot malformations v1.2 VCP chirag patel gene: VCP was added
gene: VCP was added to Hand and foot malformations. Sources: Expert Review Green,Literature
Mode of inheritance for gene: VCP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: VCP were set to 41979051
Phenotypes for gene: VCP were set to Adams-Oliver syndrome MONDO:0007034, VCP-related
Fetal anomalies v2.38 chirag patel Copied gene VCP from panel Skeletal dysplasia
Fetal anomalies v2.38 VCP chirag patel gene: VCP was added
gene: VCP was added to Fetal anomalies. Sources: Expert Review Green,Literature
Mode of inheritance for gene: VCP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: VCP were set to 41979051
Phenotypes for gene: VCP were set to Adams-Oliver syndrome MONDO:0007034, VCP-related
Congenital Heart Defect v1.26 chirag patel Copied gene VCP from panel Skeletal dysplasia
Congenital Heart Defect v1.26 VCP chirag patel gene: VCP was added
gene: VCP was added to Congenital Heart Defect. Sources: Expert Review Green,Literature
Mode of inheritance for gene: VCP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: VCP were set to 41979051
Phenotypes for gene: VCP were set to Adams-Oliver syndrome MONDO:0007034, VCP-related
Skeletal dysplasia v1.70 VCP chirag patel changed review comment from: Adams-Oliver syndrome (AOS) is a rare developmental disorder defined by the combination of aplasia cutis congenita of the scalp vertex and terminal transverse limb defects (e.g., amputations, syndactyly, brachydactyly, or oligodactyly).

PMID 41979051 reports 7 families with Adams-Oliver syndrome and rare heterozygous missense VCP variants (4 de novo, 2 inherited from affected parent, 1 presumed inherited). Variant‑specific functional assays support pathogenicity as they were hypermorphic for ATPase activity. Pulmonary hypertension seen in 5/7 families. 3 families had features of multisystem proteinopathy 1 (MSP1) - progressive myopathy (2 families), neuropathy (1 family), lytic bone lesions (1 family), and frontotemporal dementia (1 family) - and had offspring with AOS and severe or fatal PH, suggesting these conditions form a spectrum of VCP-related disease.
Sources: Literature; to: Adams-Oliver syndrome (AOS) is a rare developmental disorder defined by the combination of aplasia cutis congenita of the scalp vertex and terminal transverse limb defects (e.g., amputations, syndactyly, brachydactyly, or oligodactyly).

PMID 41979051 reports 7 families with Adams-Oliver syndrome and rare heterozygous missense VCP variants (4 de novo, 2 inherited from affected parent, 1 presumed inherited). Variant‑specific functional assays support pathogenicity as they were hypermorphic for ATPase activity. Congenital heart defects seen in 6/7 and pulmonary hypertension seen in 5/7 families. 3 families had features of multisystem proteinopathy 1 (MSP1) - progressive myopathy (2 families), neuropathy (1 family), lytic bone lesions (1 family), and frontotemporal dementia (1 family) - and had offspring with AOS and severe or fatal PH, suggesting these conditions form a spectrum of VCP-related disease.
Sources: Literature
Skeletal dysplasia v1.70 VCP chirag patel Marked gene: VCP as ready
Skeletal dysplasia v1.70 VCP chirag patel Gene: vcp has been classified as Green List (High Evidence).
Skeletal dysplasia v1.70 VCP chirag patel Classified gene: VCP as Green List (high evidence)
Skeletal dysplasia v1.70 VCP chirag patel Gene: vcp has been classified as Green List (High Evidence).
Skeletal dysplasia v1.69 VCP chirag patel gene: VCP was added
gene: VCP was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: VCP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: VCP were set to 41979051
Phenotypes for gene: VCP were set to Adams-Oliver syndrome MONDO:0007034, VCP-related
Review for gene: VCP was set to GREEN
Added comment: Adams-Oliver syndrome (AOS) is a rare developmental disorder defined by the combination of aplasia cutis congenita of the scalp vertex and terminal transverse limb defects (e.g., amputations, syndactyly, brachydactyly, or oligodactyly).

PMID 41979051 reports 7 families with Adams-Oliver syndrome and rare heterozygous missense VCP variants (4 de novo, 2 inherited from affected parent, 1 presumed inherited). Variant‑specific functional assays support pathogenicity as they were hypermorphic for ATPase activity. Pulmonary hypertension seen in 5/7 families. 3 families had features of multisystem proteinopathy 1 (MSP1) - progressive myopathy (2 families), neuropathy (1 family), lytic bone lesions (1 family), and frontotemporal dementia (1 family) - and had offspring with AOS and severe or fatal PH, suggesting these conditions form a spectrum of VCP-related disease.
Sources: Literature
Pulmonary Arterial Hypertension v2.2 ARHGAP31 chirag patel Marked gene: ARHGAP31 as ready
Pulmonary Arterial Hypertension v2.2 ARHGAP31 chirag patel Gene: arhgap31 has been classified as Green List (High Evidence).
Pulmonary Arterial Hypertension v2.2 chirag patel Copied gene ARHGAP31 from panel Mendeliome
Pulmonary Arterial Hypertension v2.2 ARHGAP31 chirag patel gene: ARHGAP31 was added
gene: ARHGAP31 was added to Pulmonary Arterial Hypertension. Sources: Expert Review Green,Genetic Health Queensland,Victorian Clinical Genetics Services,Victorian Clinical Genetics Services
Mode of inheritance for gene: ARHGAP31 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ARHGAP31 were set to PMID: 33655927; 29924900
Phenotypes for gene: ARHGAP31 were set to Adams-Oliver syndrome 1, MIM#100300
Mendeliome v2.381 ARHGAP31 chirag patel reviewed gene: ARHGAP31: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Adams-Oliver syndrome 1, MIM#100300; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital Heart Defect v1.25 ARHGAP31 chirag patel Marked gene: ARHGAP31 as ready
Congenital Heart Defect v1.25 ARHGAP31 chirag patel Gene: arhgap31 has been classified as Green List (High Evidence).
Congenital Heart Defect v1.25 ARHGAP31 chirag patel Classified gene: ARHGAP31 as Green List (high evidence)
Congenital Heart Defect v1.25 ARHGAP31 chirag patel Gene: arhgap31 has been classified as Green List (High Evidence).
Congenital Heart Defect v1.24 ARHGAP31 chirag patel Source Expert Review was added to ARHGAP31.
Rating Changed from No List (delete) to Red List (low evidence)
Congenital Heart Defect v1.23 ARHGAP31 chirag patel All sources for gene: ARHGAP31 were removed
Congenital Heart Defect v1.22 ARHGAP31 chirag patel reviewed gene: ARHGAP31: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Congenital Heart Defect v1.22 chirag patel Copied gene ARHGAP31 from panel Skeletal dysplasia
Congenital Heart Defect v1.22 ARHGAP31 chirag patel gene: ARHGAP31 was added
gene: ARHGAP31 was added to Congenital Heart Defect. Sources: Expert Review Green,Illumina TruGenome Clinical Sequencing Services,UKGTN,Radboud University Medical Center, Nijmegen,Expert Review Green,NHS GMS,Expert list,Emory Genetics Laboratory,Genetic Health Queensland,Victorian Clinical Genetics Services,Victorian Clinical Genetics Services
Mode of inheritance for gene: ARHGAP31 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ARHGAP31 were set to 21565291; 29924900
Phenotypes for gene: ARHGAP31 were set to Adams-Oliver syndrome 1 100300
Mendeliome v2.381 chirag patel Copied gene VCP from panel Macrocephaly_Megalencephaly
Mendeliome v2.381 VCP chirag patel gene: VCP was added
gene: VCP was added to Mendeliome. Sources: Expert Review Green,Literature
Mode of inheritance for gene: VCP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: VCP were set to PMID: 37883978
Phenotypes for gene: VCP were set to Neurodevelopmental disorder (MONDO: 0700092), VCP-related
Macrocephaly_Megalencephaly v1.3 VCP chirag patel Phenotypes for gene: VCP were changed from Neurodevelopmental disorder (MONDO: 0700092) to Neurodevelopmental disorder (MONDO: 0700092), VCP-related
Intellectual disability syndromic and non-syndromic v2.65 VCP chirag patel Phenotypes for gene: VCP were changed from Neurodevelopmental disorder (MONDO: 0700092) to Neurodevelopmental disorder (MONDO: 0700092), VCP-related
Skeletal dysplasia v1.68 SMS chirag patel Marked gene: SMS as ready
Skeletal dysplasia v1.68 SMS chirag patel Gene: sms has been classified as Green List (High Evidence).
Osteogenesis Imperfecta and Osteoporosis v2.7 SMS chirag patel Marked gene: SMS as ready
Osteogenesis Imperfecta and Osteoporosis v2.7 SMS chirag patel Gene: sms has been classified as Green List (High Evidence).
Skeletal dysplasia v1.68 chirag patel Copied gene SMS from panel Mendeliome
Skeletal dysplasia v1.68 SMS chirag patel gene: SMS was added
gene: SMS was added to Skeletal dysplasia. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: SMS was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: SMS were set to 30237987; 34177437; 32838743; 23805436
Phenotypes for gene: SMS were set to Intellectual developmental disorder, X-linked syndromic, Snyder-Robinson type, MIM# 309583; Syndromic X-linked intellectual disability Snyder type, MONDO:0010664
Osteogenesis Imperfecta and Osteoporosis v2.7 chirag patel Copied gene SMS from panel Mendeliome
Osteogenesis Imperfecta and Osteoporosis v2.7 SMS chirag patel gene: SMS was added
gene: SMS was added to Osteogenesis Imperfecta and Osteoporosis. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: SMS was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: SMS were set to 30237987; 34177437; 32838743; 23805436
Phenotypes for gene: SMS were set to Intellectual developmental disorder, X-linked syndromic, Snyder-Robinson type, MIM# 309583; Syndromic X-linked intellectual disability Snyder type, MONDO:0010664
Skeletal dysplasia v1.67 SMO chirag patel Marked gene: SMO as ready
Skeletal dysplasia v1.67 SMO chirag patel Gene: smo has been classified as Green List (High Evidence).
Skeletal dysplasia v1.67 chirag patel Copied gene SMO from panel Congenital Heart Defect
Skeletal dysplasia v1.67 SMO chirag patel gene: SMO was added
gene: SMO was added to Skeletal dysplasia. Sources: Expert Review Green,Literature
Mode of inheritance for gene: SMO was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SMO were set to 32413283
Phenotypes for gene: SMO were set to Microcephaly, congenital heart disease, polydactyly, aganglionosis; Pallister-Hall-like syndrome , MIM#241800
Fetal anomalies v2.37 SMO chirag patel Publications for gene: SMO were set to 27236920; 24859340
Fetal anomalies v2.36 SMO chirag patel Phenotypes for gene: SMO were changed from Curry-Jones syndrome, somatic mosaic, MIM#601707 to Curry-Jones syndrome, somatic mosaic, MIM#601707; Pallister-Hall-like syndrome, MIM# 241800
Callosome v1.13 SMO chirag patel Mode of pathogenicity for gene: SMO was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Callosome v1.12 SMO chirag patel Mode of inheritance for gene: SMO was changed from Other to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Polydactyly v1.10 chirag patel Added reviews for gene SMO from panel Anophthalmia_Microphthalmia_Coloboma
Craniosynostosis v2.3 chirag patel Added reviews for gene SMO from panel Anophthalmia_Microphthalmia_Coloboma