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Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.34 POMK Zornitza Stark Publications for gene: POMK were set to
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.33 POMK Zornitza Stark Classified gene: POMK as Amber List (moderate evidence)
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.33 POMK Zornitza Stark Gene: pomk has been classified as Amber List (Moderate Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.32 CAV3 Zornitza Stark Marked gene: CAV3 as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.32 CAV3 Zornitza Stark Added comment: Comment when marking as ready: Phenotypic overlap.
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.32 CAV3 Zornitza Stark Gene: cav3 has been classified as Amber List (Moderate Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.32 CAV3 Zornitza Stark Classified gene: CAV3 as Amber List (moderate evidence)
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.32 CAV3 Zornitza Stark Gene: cav3 has been classified as Amber List (Moderate Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.31 PYGM Zornitza Stark Marked gene: PYGM as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.31 PYGM Zornitza Stark Added comment: Comment when marking as ready: Phenotypic overlap.
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.31 PYGM Zornitza Stark Gene: pygm has been classified as Amber List (Moderate Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.31 PYGM Zornitza Stark Classified gene: PYGM as Amber List (moderate evidence)
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.31 PYGM Zornitza Stark Gene: pygm has been classified as Amber List (Moderate Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.30 CASQ1 Zornitza Stark Marked gene: CASQ1 as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.30 CASQ1 Zornitza Stark Added comment: Comment when marking as ready: Founder variant, but large number of affected individuals reported. Italian, rather than rare, isolated ethnicity.
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.30 CASQ1 Zornitza Stark Gene: casq1 has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.30 CASQ1 Zornitza Stark Classified gene: CASQ1 as Green List (high evidence)
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.30 CASQ1 Zornitza Stark Gene: casq1 has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.29 CASQ1 Zornitza Stark Tag founder tag was added to gene: CASQ1.
Mendeliome v0.3182 CACNB1 Zornitza Stark Marked gene: CACNB1 as ready
Mendeliome v0.3182 CACNB1 Zornitza Stark Gene: cacnb1 has been classified as Red List (Low Evidence).
Mendeliome v0.3182 CACNB1 Zornitza Stark gene: CACNB1 was added
gene: CACNB1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: CACNB1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CACNB1 were set to 27832566; 8943043; 29212769
Phenotypes for gene: CACNB1 were set to Malignant hyperthermia susceptibility
Added comment: A single heterozygous case with a positive IVCT muscle biopsy has been reported with p.Val156Ala. The European non-Finnish allele frequency in gnomAD v2.1 is 0.001146 (148/129,118 alleles), which is higher than the expected population frequency for dominantly inherited malignant hyperthermia (0.1%). Additionally, functional assays of this variant, suggest it would only significantly affect function in the homozygous state (suggesting a recessive condition).
Sources: Expert list
Skeletal Muscle Channelopathies v0.6 CACNB1 Zornitza Stark Marked gene: CACNB1 as ready
Skeletal Muscle Channelopathies v0.6 CACNB1 Zornitza Stark Gene: cacnb1 has been classified as Red List (Low Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.29 PYROXD1 Zornitza Stark Publications for gene: PYROXD1 were set to 30515627
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.28 PYROXD1 Zornitza Stark Marked gene: PYROXD1 as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.28 PYROXD1 Zornitza Stark Added comment: Comment when marking as ready: Mostly myopathy, some families reported with LGMD phenotype.
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.28 PYROXD1 Zornitza Stark Gene: pyroxd1 has been classified as Amber List (Moderate Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.28 PYROXD1 Zornitza Stark Classified gene: PYROXD1 as Amber List (moderate evidence)
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.28 PYROXD1 Zornitza Stark Gene: pyroxd1 has been classified as Amber List (Moderate Evidence).
Arrhythmogenic Cardiomyopathy v0.9 BVES Zornitza Stark Marked gene: BVES as ready
Arrhythmogenic Cardiomyopathy v0.9 BVES Zornitza Stark Gene: bves has been classified as Amber List (Moderate Evidence).
Arrhythmogenic Cardiomyopathy v0.9 BVES Zornitza Stark Publications for gene: BVES were set to PMID: 26642364; 31119192
Arrhythmogenic Cardiomyopathy v0.8 BVES Zornitza Stark Classified gene: BVES as Amber List (moderate evidence)
Arrhythmogenic Cardiomyopathy v0.8 BVES Zornitza Stark Gene: bves has been classified as Amber List (Moderate Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.27 BVES Zornitza Stark Marked gene: BVES as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.27 BVES Zornitza Stark Gene: bves has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.27 BVES Zornitza Stark Publications for gene: BVES were set to PMID: 26642364 32528171 31119192
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.26 BVES Zornitza Stark Classified gene: BVES as Green List (high evidence)
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.26 BVES Zornitza Stark Gene: bves has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.25 BAG3 Zornitza Stark Marked gene: BAG3 as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.25 BAG3 Zornitza Stark Added comment: Comment when marking as ready: Phenotypic overlap.
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.25 BAG3 Zornitza Stark Gene: bag3 has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.25 BAG3 Zornitza Stark Classified gene: BAG3 as Green List (high evidence)
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.25 BAG3 Zornitza Stark Gene: bag3 has been classified as Green List (High Evidence).
Skeletal Muscle Channelopathies v0.6 ATP2A1 Zornitza Stark Marked gene: ATP2A1 as ready
Skeletal Muscle Channelopathies v0.6 ATP2A1 Zornitza Stark Gene: atp2a1 has been classified as Green List (High Evidence).
Skeletal Muscle Channelopathies v0.6 KCNJ5 Zornitza Stark Marked gene: KCNJ5 as ready
Skeletal Muscle Channelopathies v0.6 KCNJ5 Zornitza Stark Gene: kcnj5 has been classified as Red List (Low Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.24 ACTA1 Zornitza Stark Marked gene: ACTA1 as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.24 ACTA1 Zornitza Stark Added comment: Comment when marking as ready: Phenotypic overlap.
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.24 ACTA1 Zornitza Stark Gene: acta1 has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.24 ACTA1 Zornitza Stark Publications for gene: ACTA1 were set to PMID: 28606400; 25938801
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.23 ACTA1 Zornitza Stark Phenotypes for gene: ACTA1 were changed from ?Myopathy, scapulohumeroperoneal 616852 to Myopathy, scapulohumeroperoneal 616852
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.22 ACTA1 Zornitza Stark Classified gene: ACTA1 as Green List (high evidence)
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.22 ACTA1 Zornitza Stark Gene: acta1 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.52 SELENON Zornitza Stark Marked gene: SELENON as ready
Muscular dystrophy and myopathy_Paediatric v0.52 SELENON Zornitza Stark Gene: selenon has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.52 SELENON Zornitza Stark Phenotypes for gene: SELENON were changed from to Muscular dystrophy, rigid spine, 1 (MIM#602771)
Muscular dystrophy and myopathy_Paediatric v0.51 SELENON Zornitza Stark Publications for gene: SELENON were set to
Muscular dystrophy and myopathy_Paediatric v0.50 SELENON Zornitza Stark Mode of inheritance for gene: SELENON was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Muscular dystrophy and myopathy_Paediatric v0.50 SELENON Zornitza Stark Mode of inheritance for gene: SELENON was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Muscular dystrophy and myopathy_Paediatric v0.49 SELENON Zornitza Stark Mode of inheritance for gene: SELENON was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.21 ACADVL Zornitza Stark Marked gene: ACADVL as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.21 ACADVL Zornitza Stark Added comment: Comment when marking as ready: Some phenotypic overlap in view of reports of raised CK, and some individuals having clinical diagnosis of LGMD.
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.21 ACADVL Zornitza Stark Gene: acadvl has been classified as Amber List (Moderate Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.21 ACADVL Zornitza Stark Classified gene: ACADVL as Amber List (moderate evidence)
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.21 ACADVL Zornitza Stark Gene: acadvl has been classified as Amber List (Moderate Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.20 STIM1 Zornitza Stark reviewed gene: STIM1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Myopathy, tubular aggregate, 1 (MIM#160565), Stormorken syndrome (MIM#185070); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.20 STIM1 Zornitza Stark Marked gene: STIM1 as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.20 STIM1 Zornitza Stark Gene: stim1 has been classified as Amber List (Moderate Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.20 STIM1 Zornitza Stark Classified gene: STIM1 as Amber List (moderate evidence)
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.20 STIM1 Zornitza Stark Gene: stim1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3181 GATA6 Zornitza Stark Marked gene: GATA6 as ready
Mendeliome v0.3181 GATA6 Zornitza Stark Gene: gata6 has been classified as Green List (High Evidence).
Mendeliome v0.3181 GATA6 Zornitza Stark Phenotypes for gene: GATA6 were changed from to Pancreatic agenesis and congenital heart defects, 600001; Atrial septal defect 9, 614475; Atrioventricular septal defect 5, 614474; Tetralogy of Fallot, 187500; Persistent truncus arteriosus, 217095
Mendeliome v0.3180 GATA6 Zornitza Stark Publications for gene: GATA6 were set to
Mendeliome v0.3179 GATA6 Zornitza Stark Mode of pathogenicity for gene: GATA6 was changed from to Other
Mendeliome v0.3178 GATA6 Zornitza Stark Mode of inheritance for gene: GATA6 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.19 VMA21 Zornitza Stark Marked gene: VMA21 as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.19 VMA21 Zornitza Stark Added comment: Comment when marking as ready: Phenotypic overlap with LGMD.
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.19 VMA21 Zornitza Stark Gene: vma21 has been classified as Amber List (Moderate Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.19 VMA21 Zornitza Stark Classified gene: VMA21 as Amber List (moderate evidence)
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.19 VMA21 Zornitza Stark Gene: vma21 has been classified as Amber List (Moderate Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.18 VMA21 Zornitza Stark Tag deep intronic tag was added to gene: VMA21.
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.18 PFKM Crystle Lee gene: PFKM was added
gene: PFKM was added to Limb Girdle Muscular Dystrophy. Sources: Expert Review
Mode of inheritance for gene: PFKM was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PFKM were set to 24427140; 27066546; 30792690
Phenotypes for gene: PFKM were set to Glycogen storage disease VII (MIM#232800)
Review for gene: PFKM was set to AMBER
Added comment: Metabolic myopathy gene due to accumulation of glycogen in muscle tissue. Unsure if consisten with LGMD phenotype.

PMID: 24427140: Adult patient reported with lifelong muscle weakness.

PMID: 27066546: 2 siblings reported with glycogen storage disease. Juvenile onset exercise intolerance. Muscle biopsy showed myopathic changes in both siblings.

PMID: 30792690: 1 adult patient reported, onset at 33. Presented with mild proximal muscle weakness, mainly in the lower limbs.
Sources: Expert Review
Glycogen Storage Diseases v0.8 PFKM Crystle Lee reviewed gene: PFKM: Rating: GREEN; Mode of pathogenicity: None; Publications: 24427140, 27066546, 30792690; Phenotypes: Glycogen storage disease VII (MIM#232800); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.18 POMK Crystle Lee reviewed gene: POMK: Rating: AMBER; Mode of pathogenicity: None; Publications: 24556084, 24925318, 29910097; Phenotypes: Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 12 (MIM#616094); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.18 CAV3 Elena Savva gene: CAV3 was added
gene: CAV3 was added to Limb Girdle Muscular Dystrophy. Sources: Expert list
Mode of inheritance for gene: CAV3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CAV3 were set to PMID: 27312022; 26185955; 32090499
Phenotypes for gene: CAV3 were set to Myopathy, distal, Tateyama type 614321; Rippling muscle disease 2 606072
Review for gene: CAV3 was set to AMBER
Added comment: PMID: 27312022 - 8 patients (7 families) with exercise intolerance (7/8), muscle atrophy (2/8) and rhabdomyolysis (2/8). Functional studies show a 50% reduction in protein from patient cells vs controls. Age at onset ranged from 7 years old to 30s, with 3/8 patients presenting <18 years of age.

PMID: 26185955 - 2 patients with muscle hypertrophy
Sources: Expert list
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.18 PYGM Crystle Lee gene: PYGM was added
gene: PYGM was added to Limb Girdle Muscular Dystrophy. Sources: Expert Review
Mode of inheritance for gene: PYGM was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PYGM were set to 29143597; 25914343
Phenotypes for gene: PYGM were set to McArdle disease (MIM#232600)
Review for gene: PYGM was set to AMBER
Added comment: Well established gene disease association. McArdle disease is "one of the most frequent metabolic myopathies". Included in this panel as a differential diagnosis to LGMD (PanelApp Uk)
Sources: Expert Review
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.18 CASQ1 Elena Savva gene: CASQ1 was added
gene: CASQ1 was added to Limb Girdle Muscular Dystrophy. Sources: Expert list
Mode of inheritance for gene: CASQ1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CASQ1 were set to PMID: 26136523; 30258016
Phenotypes for gene: CASQ1 were set to Myopathy, vacuolar, with CASQ1 aggregates 616231
Review for gene: CASQ1 was set to GREEN
Added comment: PMID: 26136523 - 3 unrelated families (10 patients) with a founder missense (p.Asp244Gly) with muscle weaknesses. All patients reported adult onset. 1 proband reported lower limb hypertrophy with normal EMG results. 6 patients had muscle biopsy, with minimal fibre size variation, and a few central nuclei.

PMID: 30258016 - 12 families (22 patients), or which 21 had the recurring p.Asp244Gly mutation. Patients all had adult onset, elevated CK, with slowly progressive proximal weakness with quadriceps atrophy and scapular winging. Pelvic girdle weakness was reported in 4/22 patients.
Sources: Expert list
Skeletal Muscle Channelopathies v0.6 CACNB1 Bryony Thompson Classified gene: CACNB1 as Red List (low evidence)
Skeletal Muscle Channelopathies v0.6 CACNB1 Bryony Thompson Gene: cacnb1 has been classified as Red List (Low Evidence).
Skeletal Muscle Channelopathies v0.5 CACNB1 Bryony Thompson reviewed gene: CACNB1: Rating: RED; Mode of pathogenicity: None; Publications: 27832566, 8943043, 29212769; Phenotypes: Malignant hyperthermia; Mode of inheritance: Unknown
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.18 PYROXD1 Crystle Lee reviewed gene: PYROXD1: Rating: AMBER; Mode of pathogenicity: None; Publications: 30345904, 30515627, 27745833; Phenotypes: Myopathy, myofibrillar, 8 (MIM#617258); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Arrhythmogenic Cardiomyopathy v0.7 BVES Elena Savva gene: BVES was added
gene: BVES was added to Arrhythmogenic Right Ventricular Cardiomyopathy. Sources: Literature
Mode of inheritance for gene: BVES was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BVES were set to PMID: 26642364; 31119192
Phenotypes for gene: BVES were set to Muscular dystrophy, limb-girdle, autosomal recessive 25 616812
Review for gene: BVES was set to AMBER
Added comment: OMIM: aka POPDC1

PMID: 26642364 - 1 family (3 affecteds) with cardiac arrhythmia and limb-girdle muscular dystrophy. Supported by functional studies. The proband showed lower limb girdle weakness at ~40 years old with muscle biopsy proving dystrophic changes. His 2 affected grandchildren had onset in teenage years.

PMID: 31119192 - 3 families (4 affecteds) with limb-girdle muscular weakness and cardiac abnormalities/arrhythmia. All had onset in adulthood, with exercise intolerance or proximal weakness.

Summary: multiple reports of patients with arrhythmias
Sources: Literature
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.18 BVES Elena Savva gene: BVES was added
gene: BVES was added to Limb Girdle Muscular Dystrophy. Sources: Expert list
Mode of inheritance for gene: BVES was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BVES were set to PMID: 26642364 32528171 31119192
Phenotypes for gene: BVES were set to Muscular dystrophy, limb-girdle, autosomal recessive 25 616812
Review for gene: BVES was set to GREEN
Added comment: OMIM: aka POPDC1

PMID: 26642364 - 1 family (3 affecteds) with cardiac arrhythmia and limb-girdle muscular dystrophy. Supported by functional studies. The proband showed lower limb girdle weakness at ~40 years old with muscle biopsy proving dystrophic changes. His 2 affected grandchildren had onset in teenage years.

PMID: 32528171 - 1 patient with limb girdle weakness.

PMID: 31119192 - 3 families (4 affecteds) with limb-girdle muscular weakness and cardiac abnormalities/arrhythmia. All had onset in adulthood, with exercise intolerance or proximal weakness.
Sources: Expert list
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.18 BAG3 Elena Savva gene: BAG3 was added
gene: BAG3 was added to Limb Girdle Muscular Dystrophy. Sources: Expert list
Mode of inheritance for gene: BAG3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: BAG3 were set to PMID: 25208129; 22734908; 30061062
Phenotypes for gene: BAG3 were set to Myopathy, myofibrillar, 6 612954
Review for gene: BAG3 was set to GREEN
Added comment: OMIM notes onset is in late childhood to early teens. Mutation p.Pro209Leu is recurring.

PMID: 25208129 - 1 heterozygous patient with lower limb weakness and onset at 34 years.

PMID: 22734908 - 4 patients with heterozygous mutations.
Patient 1 - onset at 13 years old with lumbar spine rigidity, finger flexion constractures and distal wasting in upper/lower limbs.
Patient 2 - onset 8 years old with muscle stiffness in lower limbs and distal wasting at 12 years old.
Patient 3 - lower limb deformity at 7 years old with declining mobility by 11 years of age.
Patient 4 - Unknown onset but wheelchair bound by 14 years old.

PMID: 30061062 - 1 patient with a de novo mutation, and childhood onset proximal muscle weakness and atrophy, with elevated CK.
Sources: Expert list
Skeletal Muscle Channelopathies v0.5 ATP2A1 Bryony Thompson Publications for gene: ATP2A1 were set to
Skeletal Muscle Channelopathies v0.4 KCNJ5 Bryony Thompson gene: KCNJ5 was added
gene: KCNJ5 was added to Skeletal Muscle Channelopathies. Sources: Expert list
Mode of inheritance for gene: KCNJ5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KCNJ5 were set to 24574546
Phenotypes for gene: KCNJ5 were set to Andersen-Tawil Syndrome; periodic muscle paralysis
Review for gene: KCNJ5 was set to RED
Added comment: Only a single Japanese case with periodic muscle paralysis with no dysmorphic features, reported with the missense variant p.Gly387Arg. In vitro functional expression studies in Xenopus oocytes showed that coexpression of KCNJ2 with mutant KCNJ5 significantly reduced the inwardly rectifying potassium current compared to that observed with coexpression of KCNJ2 with wildtype KCNJ5. However, the East Asian allele frequency for this variant in gnomAD v2.1 is 0.00251 (50/19,924 alleles). Which is higher than would be expected for a dominantly inherited disorder.
Sources: Expert list
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.18 ACTA1 Elena Savva gene: ACTA1 was added
gene: ACTA1 was added to Limb Girdle Muscular Dystrophy. Sources: Expert list
Mode of inheritance for gene: ACTA1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ACTA1 were set to PMID: 28606400; 25938801
Phenotypes for gene: ACTA1 were set to ?Myopathy, scapulohumeroperoneal 616852
Review for gene: ACTA1 was set to GREEN
Added comment: PMID: 28606400 - 1 multigenerational family with dominant ACTA1-scapuloperoneal
myopathy. Proband has progressive limb weakness since childhood, spinal muscular atrophy based on two EMG analyses. Affected carrier children also reported upper limb weakness with onset in chlidhood/teenage years.

PMID: 25938801 - 1 large family (14 affecteds) with dominant ACTA1-scapuloperoneal myopathy. Muscle biopsy specimens demonstrated type I fiber atrophy. Many reported upper and lower body muscle weakness, with age of onset variable between early childhood and adulthood.

PMID: 15832616 - 1 child with a de novo missense mutation, proximal muscle weakness and hypotonia of the shoulder girdle
Sources: Expert list
Muscular dystrophy and myopathy_Paediatric v0.48 SELENON Crystle Lee reviewed gene: SELENON: Rating: GREEN; Mode of pathogenicity: None; Publications: 11528383; Phenotypes: Muscular dystrophy, rigid spine, 1 (MIM#602771); Mode of inheritance: None
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.18 ACADVL Elena Savva gene: ACADVL was added
gene: ACADVL was added to Limb Girdle Muscular Dystrophy. Sources: Expert list
Mode of inheritance for gene: ACADVL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ACADVL were set to PMID: 9546340; 32558070; 22097235; 24305961
Phenotypes for gene: ACADVL were set to VLCAD deficiency 201475
Review for gene: ACADVL was set to AMBER
Added comment: PMID: 9546340 - 4/15 patients developed elevated CK levels and rhabdomyolysis within the first year of life. No mention of myopathy or specific dystrophic features.

PMID: 32558070 - 6 unrelated patients with adult-onset VLCAD deficiency. 4/6 had muscle weakness of the neck flexion, arms abduction and elbow flexion. CK levels varied among the patients, though most were elevated.
Four patients had an EMG showed myopathic changes of the upper and lower limbs, one did not report muscle weakness.
Only 1/6 patients were reported with significant changes on muscle MRI.

PMID: 22097235 - One 18 year old patient with persistent muscle cramps, elevated CK levels. Patient was diagnosed with limb girdle MD, at 21 years old struggled to climb stairs or walk

PMID: 24305961 - 8/12 patients reported either muscle pain and/or exercise intolerance, 9/12 had elevated CK levels. VLCADD patients showed predominantly proximal T1W SI changes.

Summary: dystrophic changes have been reported but does not appear to be a common feature
Sources: Expert list
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.18 STIM1 Crystle Lee gene: STIM1 was added
gene: STIM1 was added to Limb Girdle Muscular Dystrophy. Sources: Expert Review
Mode of inheritance for gene: STIM1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: STIM1 were set to 31448844
Phenotypes for gene: STIM1 were set to Myopathy, tubular aggregate, 1 (MIM#160565); Stormorken syndrome (MIM#185070)
Mode of pathogenicity for gene: STIM1 was set to Other
Review for gene: STIM1 was set to GREEN
Added comment: Dominant STIM1 missense variants via a GOF mechanism cause a spectrum of myopathy covering tubular aggregate myopathy/TAM and Stormorken syndrome/STRMK (slowly progressive muscle weakness with variable multisystemic disease including non-specific dysmorphism, a/hyposplenia, ichthyosis, cytopenias)

PMID: 31448844: Review article. Dominant STIM1 missense variants exert gain of function effect. Variants in EF hand reported in >3 families with childhood and adulthood onset of LGMD.
Sources: Expert Review
Mendeliome v0.3177 GATA6 Elena Savva reviewed gene: GATA6: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID:20581743, 19666519; Phenotypes: Pancreatic agenesis and congenital heart defects, 600001, Atrial septal defect 9, 614475, Atrioventricular septal defect 5, 614474, Tetralogy of Fallot, 187500, Persistent truncus arteriosus, 217095; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.18 VMA21 Crystle Lee gene: VMA21 was added
gene: VMA21 was added to Limb Girdle Muscular Dystrophy. Sources: Expert Review
Mode of inheritance for gene: VMA21 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: VMA21 were set to 27916343; 25809233; 23315026
Phenotypes for gene: VMA21 were set to Myopathy, X-linked, with excessive autophagy (MIM#310440)
Review for gene: VMA21 was set to AMBER
Added comment: Childhood onset muscle disease, primarily affecting proximal muscles and elevated CK. No other muscle group involvement. Characterize by progressive muscle weakness with a limb-girdle pattern (PMID: 25809233). Differential diagnosis with LGMD (PanelApp UK)

Intronic variants in multiple families. Onset in childhood

PMID: 25809233: Different splice site variants reported in 2 families, onset in childhood.

PMID: 23315026: 5 splice region and 1 missense reported in 14 families with multiple affected. Quantitative RT-PCR from patient fibroblasts demonstrated reduction in VMA21 mRNA.
Sources: Expert Review
Sources: Expert Review
Callosome v0.148 CDH2 Zornitza Stark Phenotypes for gene: CDH2 were changed from Intellectual disability; corpus callosum abnormalities; congenital abnormalities to Intellectual disability; corpus callosum abnormalities; congenital abnormalities; Agenesis of corpus callosum, cardiac, ocular, and genital syndrome, MIM# 618929
Callosome v0.147 CDH2 Zornitza Stark edited their review of gene: CDH2: Changed phenotypes: Intellectual disability, corpus callosum abnormalities, congenital abnormalities, Agenesis of corpus callosum, cardiac, ocular, and genital syndrome, MIM# 618929
Mendeliome v0.3177 CDH2 Zornitza Stark Phenotypes for gene: CDH2 were changed from Intellectual disability; corpus callosum abnormalities; congenital abnormalities to Intellectual disability; corpus callosum abnormalities; congenital abnormalities; Agenesis of corpus callosum, cardiac, ocular, and genital syndrome, MIM# 618929
Mendeliome v0.3176 CDH2 Zornitza Stark edited their review of gene: CDH2: Changed phenotypes: Intellectual disability, corpus callosum abnormalities, congenital abnormalities, Agenesis of corpus callosum, cardiac, ocular, and genital syndrome, MIM# 618929
Intellectual disability syndromic and non-syndromic v0.2718 CDH2 Zornitza Stark Phenotypes for gene: CDH2 were changed from Intellectual disability; corpus callosum abnormalities; congenital abnormalities to Intellectual disability; corpus callosum abnormalities; congenital abnormalities; Agenesis of corpus callosum, cardiac, ocular, and genital syndrome, MIM# 618929
Intellectual disability syndromic and non-syndromic v0.2717 CDH2 Zornitza Stark edited their review of gene: CDH2: Changed phenotypes: Intellectual disability, corpus callosum abnormalities, congenital abnormalities, Agenesis of corpus callosum, cardiac, ocular, and genital syndrome, MIM# 618929
Arrhythmia_SuperPanel v0.135 Zornitza Stark Changed child panels to: Long QT Syndrome; Brugada syndrome; Catecholaminergic Polymorphic Ventricular Tachycardia; Arrhythmogenic Right Ventricular Cardiomyopathy; Atrial Fibrillation; Ventricular Fibrillation; Sick sinus syndrome; Short QT syndrome
Intellectual disability syndromic and non-syndromic v0.2717 GRIA2 Zornitza Stark Phenotypes for gene: GRIA2 were changed from no OMIM number yet to Neurodevelopmental disorder with language impairment and behavioral abnormalities, MIM# 618917
Intellectual disability syndromic and non-syndromic v0.2716 GRIA2 Zornitza Stark reviewed gene: GRIA2: Rating: GREEN; Mode of pathogenicity: None; Publications: 31300657; Phenotypes: Neurodevelopmental disorder with language impairment and behavioral abnormalities, MIM# 618917; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.733 GRIA2 Zornitza Stark edited their review of gene: GRIA2: Changed phenotypes: Intellectual disability, autism, Rett-like features, epileptic encephalopathy, Neurodevelopmental disorder with language impairment and behavioral abnormalities, MIM# 618917
Genetic Epilepsy v0.733 GRIA2 Zornitza Stark Phenotypes for gene: GRIA2 were changed from Intellectual disability; autism; Rett-like features; epileptic encephalopathy to Intellectual disability; autism; Rett-like features; epileptic encephalopathy; Neurodevelopmental disorder with language impairment and behavioral abnormalities, MIM# 618917
Mendeliome v0.3176 GRIA2 Zornitza Stark Phenotypes for gene: GRIA2 were changed from Intellectual disability; autism; Rett-like features; epileptic encephalopathy to Intellectual disability; autism; Rett-like features; epileptic encephalopathy; Neurodevelopmental disorder with language impairment and behavioral abnormalities, MIM# 618917
Mendeliome v0.3175 GRIA2 Zornitza Stark edited their review of gene: GRIA2: Changed phenotypes: Intellectual disability, autism, Rett-like features, epileptic encephalopathy, Neurodevelopmental disorder with language impairment and behavioral abnormalities, MIM# 618917
Intellectual disability syndromic and non-syndromic v0.2716 CDK19 Zornitza Stark Phenotypes for gene: CDK19 were changed from Intellectual disability; epileptic encephalopathy to Intellectual disability; epileptic encephalopathy; Epileptic encephalopathy, early infantile, 87, MIM# 618916
Intellectual disability syndromic and non-syndromic v0.2715 CDK19 Zornitza Stark edited their review of gene: CDK19: Changed phenotypes: Intellectual disability, epileptic encephalopathy, Epileptic encephalopathy, early infantile, 87, MIM# 618916
Genetic Epilepsy v0.732 CDK19 Zornitza Stark Phenotypes for gene: CDK19 were changed from Intellectual disability; epileptic encephalopathy to Intellectual disability; epileptic encephalopathy; Epileptic encephalopathy, early infantile, 87, MIM# 618916
Mendeliome v0.3175 CDK19 Zornitza Stark Phenotypes for gene: CDK19 were changed from Intellectual disability; epileptic encephalopathy to Intellectual disability; epileptic encephalopathy; Epileptic encephalopathy, early infantile, 87, MIM# 618916
Mendeliome v0.3174 CDK19 Zornitza Stark edited their review of gene: CDK19: Changed phenotypes: Intellectual disability, epileptic encephalopathy, Epileptic encephalopathy, early infantile, 87, MIM# 618916
Genetic Epilepsy v0.731 CDK19 Zornitza Stark edited their review of gene: CDK19: Changed phenotypes: Intellectual disability, epileptic encephalopathy, Epileptic encephalopathy, early infantile, 87, MIM# 618916
Mendeliome v0.3174 TSHZ1 Zornitza Stark changed review comment from: Two individuals reported with LoF variants, both with a phenotype of congenital aural atresia and hyposmia (PMID: 22152683). Temporal and spatial expression of Tshz1 mRNA during development of the middle ear is consistent with the phenotype (PMID: 17586487). Tsh2 null mouse model showed a middle ear malformation, and neonatal lethality. A conditional nervous system-specific Tshz1 knock out mouse model demonstrated hyposmia (PMIDs: 24487590; 17586487).; to: Two individuals reported with LoF variants, both with a phenotype of congenital aural atresia and hyposmia (PMID: 22152683). Temporal and spatial expression of Tshz1 mRNA during development of the middle ear is consistent with the phenotype (PMID: 17586487). Tsh2 null mouse model showed a middle ear malformation, and neonatal lethality. A conditional nervous system-specific Tshz1 knock out mouse model demonstrated hyposmia (PMIDs: 24487590; 17586487). Also note original report contains four individuals with deletions of this gene, further supporting gene-disease association.
Mendeliome v0.3174 TSHZ1 Zornitza Stark Mode of inheritance for gene: TSHZ1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3173 TSHZ1 Zornitza Stark Marked gene: TSHZ1 as ready
Mendeliome v0.3173 TSHZ1 Zornitza Stark Gene: tshz1 has been classified as Green List (High Evidence).
Mendeliome v0.3173 TSHZ1 Zornitza Stark Phenotypes for gene: TSHZ1 were changed from to Aural atresia, congenital, MIM# 607842; Hyposmia
Mendeliome v0.3172 TSHZ1 Zornitza Stark Publications for gene: TSHZ1 were set to
Mendeliome v0.3171 TSHZ1 Zornitza Stark Mode of inheritance for gene: TSHZ1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3170 TSHZ1 Zornitza Stark reviewed gene: TSHZ1: Rating: GREEN; Mode of pathogenicity: None; Publications: 15834955, 22152683, 17586487, 24487590; Phenotypes: Aural atresia, congenital, MIM# 607842, Hyposmia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3170 ZBTB18 Zornitza Stark Marked gene: ZBTB18 as ready
Mendeliome v0.3170 ZBTB18 Zornitza Stark Gene: zbtb18 has been classified as Green List (High Evidence).
Mendeliome v0.3170 ZBTB18 Zornitza Stark Phenotypes for gene: ZBTB18 were changed from to Mental retardation, autosomal dominant 22, MIM# 612337
Mendeliome v0.3169 ZBTB18 Zornitza Stark Publications for gene: ZBTB18 were set to
Mendeliome v0.3168 ZBTB18 Zornitza Stark Mode of pathogenicity for gene: ZBTB18 was changed from to Other
Mendeliome v0.3167 ZBTB18 Zornitza Stark Mode of inheritance for gene: ZBTB18 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.18 FEZF1 Bryony Thompson Classified gene: FEZF1 as Amber List (moderate evidence)
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.18 FEZF1 Bryony Thompson Gene: fezf1 has been classified as Amber List (Moderate Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.17 FEZF1 Bryony Thompson reviewed gene: FEZF1: Rating: AMBER; Mode of pathogenicity: None; Publications: 25192046, 32400067, 19479999; Phenotypes: Hypogonadotropic hypogonadism 22, with or without anosmia MIM#616030; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.17 FGF17 Bryony Thompson Marked gene: FGF17 as ready
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.17 FGF17 Bryony Thompson Gene: fgf17 has been classified as Amber List (Moderate Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.17 FGF17 Bryony Thompson Classified gene: FGF17 as Amber List (moderate evidence)
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.17 FGF17 Bryony Thompson Gene: fgf17 has been classified as Amber List (Moderate Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.16 FGF17 Bryony Thompson reviewed gene: FGF17: Rating: AMBER; Mode of pathogenicity: None; Publications: 17442747, 23643382; Phenotypes: Hypogonadotropic hypogonadism 20 with or without anosmia MIM#615270; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3166 ESR2 Bryony Thompson Classified gene: ESR2 as Amber List (moderate evidence)
Mendeliome v0.3166 ESR2 Bryony Thompson Gene: esr2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3165 ESR2 Bryony Thompson gene: ESR2 was added
gene: ESR2 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: ESR2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Differences of Sex Development v0.31 ESR2 Bryony Thompson gene: ESR2 was added
gene: ESR2 was added to Disorders of Sex Differentiation. Sources: Literature
Mode of inheritance for gene: ESR2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: ESR2 were set to 29261182; 9861029
Phenotypes for gene: ESR2 were set to 46,XY Disorders of Sex Development
Review for gene: ESR2 was set to AMBER
Added comment: A homozygous indel (Asn181del) was identified in a syndromic case with 46,XY DSD, and 2 heterozygous missense variants were identified in 2 non-syndromic cases with 46,XY DSD. Asn181del and Leu426Arg were found to have significantly increased transcriptional activation in in vitro luciferase assays. Esrb null male mice showed no overt abnormalities and reproduced normally. Older mutant males displayed signs of prostate and bladder hyperplasia.
Sources: Literature
Mendeliome v0.3164 ZBTB18 Elena Savva reviewed gene: ZBTB18: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID 27598823, 29573576; Phenotypes: Mental retardation, autosomal dominant 22 612337; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.16 ESR2 Bryony Thompson Marked gene: ESR2 as ready
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.16 ESR2 Bryony Thompson Gene: esr2 has been classified as Amber List (Moderate Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.16 ESR2 Bryony Thompson Classified gene: ESR2 as Amber List (moderate evidence)
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.16 ESR2 Bryony Thompson Gene: esr2 has been classified as Amber List (Moderate Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.15 ESR2 Bryony Thompson reviewed gene: ESR2: Rating: AMBER; Mode of pathogenicity: None; Publications: 30113650, 9861029; Phenotypes: Ovarian dysgenesis 8 MIM#618187; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.15 ERCC6 Bryony Thompson Marked gene: ERCC6 as ready
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.15 ERCC6 Bryony Thompson Gene: ercc6 has been classified as Amber List (Moderate Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.15 ERCC6 Bryony Thompson Classified gene: ERCC6 as Amber List (moderate evidence)
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.15 ERCC6 Bryony Thompson Added comment: Comment on list classification: Strong segregation in one family and supporting functional assays. POI has not been mentioned in carriers for Cockayne syndrome. More evidence is required to determine whether dominant POI associated variants in this gene are specific to the exon expressed in the alternate transcript.
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.15 ERCC6 Bryony Thompson Gene: ercc6 has been classified as Amber List (Moderate Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.14 ERCC6 Bryony Thompson Deleted their comment
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.14 ERCC6 Bryony Thompson Classified gene: ERCC6 as Amber List (moderate evidence)
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.14 ERCC6 Bryony Thompson Added comment: Comment on list classification: Strong segregation in one family and supporting functional assays.
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.14 ERCC6 Bryony Thompson Gene: ercc6 has been classified as Amber List (Moderate Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.13 ERCC6 Bryony Thompson reviewed gene: ERCC6: Rating: AMBER; Mode of pathogenicity: None; Publications: 26218421; Phenotypes: Premature ovarian failure 11 MIM#616946; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.13 DUSP6 Bryony Thompson Marked gene: DUSP6 as ready
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.13 DUSP6 Bryony Thompson Gene: dusp6 has been classified as Red List (Low Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.13 DUSP6 Bryony Thompson Classified gene: DUSP6 as Red List (low evidence)
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.13 DUSP6 Bryony Thompson Gene: dusp6 has been classified as Red List (Low Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.12 DUSP6 Bryony Thompson reviewed gene: DUSP6: Rating: RED; Mode of pathogenicity: None; Publications: 23643382, 32389901; Phenotypes: Hypogonadotropic hypogonadism 19 with or without anosmia MIM#615269; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3164 MT-TP Bryony Thompson Marked gene: MT-TP as ready
Mendeliome v0.3164 MT-TP Bryony Thompson Gene: mt-tp has been classified as Red List (Low Evidence).
Mendeliome v0.3164 MT-TP Bryony Thompson Classified gene: MT-TP as Red List (low evidence)
Mendeliome v0.3164 MT-TP Bryony Thompson Added comment: Comment on list classification: This is a mitochondrial gene, which is on the Mitochondrial disease gene panel.
Mendeliome v0.3164 MT-TP Bryony Thompson Gene: mt-tp has been classified as Red List (Low Evidence).
Congenital Heart Defect v0.49 ABL1 Zornitza Stark Marked gene: ABL1 as ready
Congenital Heart Defect v0.49 ABL1 Zornitza Stark Gene: abl1 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.49 ABL1 Zornitza Stark Classified gene: ABL1 as Green List (high evidence)
Congenital Heart Defect v0.49 ABL1 Zornitza Stark Gene: abl1 has been classified as Green List (High Evidence).
Macrocephaly_Megalencephaly v0.36 SETD2 Zornitza Stark Marked gene: SETD2 as ready
Macrocephaly_Megalencephaly v0.36 SETD2 Zornitza Stark Gene: setd2 has been classified as Green List (High Evidence).
Macrocephaly_Megalencephaly v0.36 SETD2 Zornitza Stark Phenotypes for gene: SETD2 were changed from to Luscan-Lumish syndrome, MIM#616831
Macrocephaly_Megalencephaly v0.35 SETD2 Zornitza Stark Publications for gene: SETD2 were set to
Macrocephaly_Megalencephaly v0.34 SETD2 Zornitza Stark Mode of inheritance for gene: SETD2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Macrocephaly_Megalencephaly v0.33 SETD2 Zornitza Stark reviewed gene: SETD2: Rating: GREEN; Mode of pathogenicity: None; Publications: 29681085; Phenotypes: Luscan-Lumish syndrome, MIM#616831; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Overgrowth v0.22 SETD2 Zornitza Stark Marked gene: SETD2 as ready
Overgrowth v0.22 SETD2 Zornitza Stark Gene: setd2 has been classified as Green List (High Evidence).
Overgrowth v0.22 SETD2 Zornitza Stark Phenotypes for gene: SETD2 were changed from to Luscan-Lumish syndrome, MIM#616831
Overgrowth v0.21 SETD2 Zornitza Stark Publications for gene: SETD2 were set to
Overgrowth v0.20 SETD2 Zornitza Stark Mode of inheritance for gene: SETD2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Overgrowth v0.19 SETD2 Zornitza Stark reviewed gene: SETD2: Rating: GREEN; Mode of pathogenicity: None; Publications: 29681085; Phenotypes: Luscan-Lumish syndrome, MIM#616831; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v0.34 SETD2 Zornitza Stark Phenotypes for gene: SETD2 were changed from Luscan-Lumish syndrome 616831; Luscan-Lumish syndrome 616831 to Luscan-Lumish syndrome 616831
Intellectual disability syndromic and non-syndromic v0.2715 SETD2 Zornitza Stark Marked gene: SETD2 as ready
Intellectual disability syndromic and non-syndromic v0.2715 SETD2 Zornitza Stark Gene: setd2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2715 SETD2 Zornitza Stark Phenotypes for gene: SETD2 were changed from to Luscan-Lumish syndrome, MIM#616831
Intellectual disability syndromic and non-syndromic v0.2714 SETD2 Zornitza Stark Publications for gene: SETD2 were set to
Intellectual disability syndromic and non-syndromic v0.2713 SETD2 Zornitza Stark Mode of inheritance for gene: SETD2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2712 SETD2 Zornitza Stark reviewed gene: SETD2: Rating: GREEN; Mode of pathogenicity: None; Publications: 29681085; Phenotypes: Luscan-Lumish syndrome, MIM#616831; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3163 SETD2 Zornitza Stark reviewed gene: SETD2: Rating: GREEN; Mode of pathogenicity: None; Publications: 29681085; Phenotypes: Luscan-Lumish syndrome, MIM#616831; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3163 SETD2 Zornitza Stark Marked gene: SETD2 as ready
Mendeliome v0.3163 SETD2 Zornitza Stark Gene: setd2 has been classified as Green List (High Evidence).
Mendeliome v0.3163 SETD2 Zornitza Stark Phenotypes for gene: SETD2 were changed from to Luscan-Lumish syndrome, MIM#616831
Mendeliome v0.3162 SETD2 Zornitza Stark Publications for gene: SETD2 were set to
Mendeliome v0.3161 SETD2 Zornitza Stark Mode of inheritance for gene: SETD2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Haem degradation and bilirubin metabolism defects v0.11 HMBS Zornitza Stark Marked gene: HMBS as ready
Haem degradation and bilirubin metabolism defects v0.11 HMBS Zornitza Stark Gene: hmbs has been classified as Green List (High Evidence).
Haem degradation and bilirubin metabolism defects v0.11 HMBS Zornitza Stark reviewed gene: HMBS: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Porphyria, acute intermittent, MIM# 176000, Porphyria, acute intermittent, nonerythroid variant, MIM# 176000; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Haem degradation and bilirubin metabolism defects v0.11 CPOX Zornitza Stark Marked gene: CPOX as ready
Haem degradation and bilirubin metabolism defects v0.11 CPOX Zornitza Stark Gene: cpox has been classified as Green List (High Evidence).
Haem degradation and bilirubin metabolism defects v0.11 CPOX Zornitza Stark reviewed gene: CPOX: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Coproporphyria, MIM# 121300, Harderoporphyria, MIM# 618892; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Haem degradation and bilirubin metabolism defects v0.11 GATA1 Zornitza Stark Marked gene: GATA1 as ready
Haem degradation and bilirubin metabolism defects v0.11 GATA1 Zornitza Stark Gene: gata1 has been classified as Amber List (Moderate Evidence).
Haem degradation and bilirubin metabolism defects v0.11 UROS Zornitza Stark Marked gene: UROS as ready
Haem degradation and bilirubin metabolism defects v0.11 UROS Zornitza Stark Gene: uros has been classified as Green List (High Evidence).
Haem degradation and bilirubin metabolism defects v0.11 UROS Zornitza Stark Publications for gene: UROS were set to
Haem degradation and bilirubin metabolism defects v0.10 UROD Zornitza Stark Marked gene: UROD as ready
Haem degradation and bilirubin metabolism defects v0.10 UROD Zornitza Stark Gene: urod has been classified as Green List (High Evidence).
Haem degradation and bilirubin metabolism defects v0.10 UROD Zornitza Stark Publications for gene: UROD were set to
Haem degradation and bilirubin metabolism defects v0.9 UROD Zornitza Stark Mode of inheritance for gene: UROD was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Haem degradation and bilirubin metabolism defects v0.8 PPOX Zornitza Stark Marked gene: PPOX as ready
Haem degradation and bilirubin metabolism defects v0.8 PPOX Zornitza Stark Gene: ppox has been classified as Green List (High Evidence).
Haem degradation and bilirubin metabolism defects v0.8 PPOX Zornitza Stark Phenotypes for gene: PPOX were changed from Porphyria variegata 176200 to Porphyria variegata, MIM# 176200
Haem degradation and bilirubin metabolism defects v0.7 PPOX Zornitza Stark Publications for gene: PPOX were set to
Haem degradation and bilirubin metabolism defects v0.6 FECH Zornitza Stark Marked gene: FECH as ready
Haem degradation and bilirubin metabolism defects v0.6 FECH Zornitza Stark Gene: fech has been classified as Green List (High Evidence).
Haem degradation and bilirubin metabolism defects v0.6 FECH Zornitza Stark Publications for gene: FECH were set to
Haem degradation and bilirubin metabolism defects v0.5 ALAS2 Zornitza Stark Marked gene: ALAS2 as ready
Haem degradation and bilirubin metabolism defects v0.5 ALAS2 Zornitza Stark Gene: alas2 has been classified as Green List (High Evidence).
Haem degradation and bilirubin metabolism defects v0.5 ALAS2 Zornitza Stark Mode of inheritance for gene: ALAS2 was changed from X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Haem degradation and bilirubin metabolism defects v0.4 ALAD Zornitza Stark Marked gene: ALAD as ready
Haem degradation and bilirubin metabolism defects v0.4 ALAD Zornitza Stark Gene: alad has been classified as Green List (High Evidence).
Haem degradation and bilirubin metabolism defects v0.4 ALAD Zornitza Stark Publications for gene: ALAD were set to
Haem degradation and bilirubin metabolism defects v0.3 HFE Zornitza Stark Marked gene: HFE as ready
Haem degradation and bilirubin metabolism defects v0.3 HFE Zornitza Stark Gene: hfe has been classified as Red List (Low Evidence).
Haem degradation and bilirubin metabolism defects v0.3 Zornitza Stark Panel types changed to Victorian Clinical Genetics Services; Royal Melbourne Hospital; Rare Disease
Mendeliome v0.3160 UBE2A Zornitza Stark Marked gene: UBE2A as ready
Mendeliome v0.3160 UBE2A Zornitza Stark Gene: ube2a has been classified as Green List (High Evidence).
Mendeliome v0.3160 UBE2A Zornitza Stark Phenotypes for gene: UBE2A were changed from to Mental retardation, X-linked syndromic, Nascimento-type (MIM#300860)
Mendeliome v0.3159 UBE2A Zornitza Stark Publications for gene: UBE2A were set to
Mendeliome v0.3158 UBE2A Zornitza Stark Mode of inheritance for gene: UBE2A was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.3157 UBE2A Zornitza Stark reviewed gene: UBE2A: Rating: GREEN; Mode of pathogenicity: None; Publications: 24053514, 16909393; Phenotypes: Mental retardation, X-linked syndromic, Nascimento-type (MIM#300860); Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.2712 UBE2A Zornitza Stark Marked gene: UBE2A as ready
Intellectual disability syndromic and non-syndromic v0.2712 UBE2A Zornitza Stark Gene: ube2a has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2712 UBE2A Zornitza Stark Phenotypes for gene: UBE2A were changed from to Mental retardation, X-linked syndromic, Nascimento-type (MIM#300860)
Intellectual disability syndromic and non-syndromic v0.2711 UBE2A Zornitza Stark Publications for gene: UBE2A were set to
Intellectual disability syndromic and non-syndromic v0.2710 UBE2A Zornitza Stark Mode of inheritance for gene: UBE2A was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Aortopathy_Connective Tissue Disorders v0.96 COL5A2 Zornitza Stark Marked gene: COL5A2 as ready
Aortopathy_Connective Tissue Disorders v0.96 COL5A2 Zornitza Stark Gene: col5a2 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.96 COL5A2 Zornitza Stark Mode of inheritance for gene: COL5A2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Aortopathy_Connective Tissue Disorders v0.95 COL5A2 Zornitza Stark Classified gene: COL5A2 as Green List (high evidence)
Aortopathy_Connective Tissue Disorders v0.95 COL5A2 Zornitza Stark Gene: col5a2 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.94 C1S Zornitza Stark Marked gene: C1S as ready
Aortopathy_Connective Tissue Disorders v0.94 C1S Zornitza Stark Gene: c1s has been classified as Amber List (Moderate Evidence).
Aortopathy_Connective Tissue Disorders v0.94 C1S Zornitza Stark Phenotypes for gene: C1S were changed from to Ehlers-Danlos syndrome, periodontal type, 1 (MIM# 130080)
Aortopathy_Connective Tissue Disorders v0.93 C1S Zornitza Stark Publications for gene: C1S were set to
Aortopathy_Connective Tissue Disorders v0.92 C1S Zornitza Stark Mode of inheritance for gene: C1S was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Aortopathy_Connective Tissue Disorders v0.91 TGFBR2 Zornitza Stark Marked gene: TGFBR2 as ready
Aortopathy_Connective Tissue Disorders v0.91 TGFBR2 Zornitza Stark Gene: tgfbr2 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.91 TGFBR2 Zornitza Stark Phenotypes for gene: TGFBR2 were changed from to Loeys-Dietz syndrome 2, MIM# 610168
Aortopathy_Connective Tissue Disorders v0.90 TGFBR2 Zornitza Stark Publications for gene: TGFBR2 were set to
Aortopathy_Connective Tissue Disorders v0.89 TGFBR2 Zornitza Stark Mode of inheritance for gene: TGFBR2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Aortopathy_Connective Tissue Disorders v0.88 TGFBR1 Zornitza Stark Marked gene: TGFBR1 as ready
Aortopathy_Connective Tissue Disorders v0.88 TGFBR1 Zornitza Stark Gene: tgfbr1 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.88 TGFBR1 Zornitza Stark Phenotypes for gene: TGFBR1 were changed from to Loeys-Dietz syndrome 1, MIM# 609192
Aortopathy_Connective Tissue Disorders v0.87 TGFBR1 Zornitza Stark Publications for gene: TGFBR1 were set to
Aortopathy_Connective Tissue Disorders v0.86 TGFBR1 Zornitza Stark Mode of inheritance for gene: TGFBR1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Aortopathy_Connective Tissue Disorders v0.85 TGFB3 Zornitza Stark Marked gene: TGFB3 as ready
Aortopathy_Connective Tissue Disorders v0.85 TGFB3 Zornitza Stark Gene: tgfb3 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.85 TGFB3 Zornitza Stark Phenotypes for gene: TGFB3 were changed from to Loeys-Dietz syndrome 5, MI# 615582
Aortopathy_Connective Tissue Disorders v0.84 TGFB3 Zornitza Stark Publications for gene: TGFB3 were set to
Aortopathy_Connective Tissue Disorders v0.83 TGFB3 Zornitza Stark Mode of inheritance for gene: TGFB3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Aortopathy_Connective Tissue Disorders v0.82 TGFB2 Zornitza Stark Marked gene: TGFB2 as ready
Aortopathy_Connective Tissue Disorders v0.82 TGFB2 Zornitza Stark Gene: tgfb2 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.82 TGFB2 Zornitza Stark Phenotypes for gene: TGFB2 were changed from to Loeys-Dietz syndrome 4, MIM# 614816
Aortopathy_Connective Tissue Disorders v0.81 TGFB2 Zornitza Stark Publications for gene: TGFB2 were set to
Aortopathy_Connective Tissue Disorders v0.80 TGFB2 Zornitza Stark Mode of inheritance for gene: TGFB2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Aortopathy_Connective Tissue Disorders v0.79 SLC2A10 Zornitza Stark Marked gene: SLC2A10 as ready
Aortopathy_Connective Tissue Disorders v0.79 SLC2A10 Zornitza Stark Gene: slc2a10 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.79 SLC2A10 Zornitza Stark Phenotypes for gene: SLC2A10 were changed from to Arterial tortuosity syndrome MIM#606145
Aortopathy_Connective Tissue Disorders v0.78 SLC2A10 Zornitza Stark Publications for gene: SLC2A10 were set to
Aortopathy_Connective Tissue Disorders v0.77 SLC2A10 Zornitza Stark Mode of inheritance for gene: SLC2A10 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Aortopathy_Connective Tissue Disorders v0.76 SKI Zornitza Stark Marked gene: SKI as ready
Aortopathy_Connective Tissue Disorders v0.76 SKI Zornitza Stark Added comment: Comment when marking as ready: Syndromic connective tissue disorder.
Aortopathy_Connective Tissue Disorders v0.76 SKI Zornitza Stark Gene: ski has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.76 SKI Zornitza Stark Phenotypes for gene: SKI were changed from to Shprintzen-Goldberg syndrome, MIM#164780
Aortopathy_Connective Tissue Disorders v0.75 SKI Zornitza Stark Publications for gene: SKI were set to
Aortopathy_Connective Tissue Disorders v0.74 SKI Zornitza Stark Mode of inheritance for gene: SKI was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Aortopathy_Connective Tissue Disorders v0.73 PRKG1 Zornitza Stark Marked gene: PRKG1 as ready
Aortopathy_Connective Tissue Disorders v0.73 PRKG1 Zornitza Stark Gene: prkg1 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.73 PRKG1 Zornitza Stark Phenotypes for gene: PRKG1 were changed from to Aortic aneurysm, familial thoracic 8, MIM#176894
Aortopathy_Connective Tissue Disorders v0.72 PRKG1 Zornitza Stark Publications for gene: PRKG1 were set to
Aortopathy_Connective Tissue Disorders v0.71 PRKG1 Zornitza Stark Mode of inheritance for gene: PRKG1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Aortopathy_Connective Tissue Disorders v0.70 PCGF2 Zornitza Stark Marked gene: PCGF2 as ready
Aortopathy_Connective Tissue Disorders v0.70 PCGF2 Zornitza Stark Gene: pcgf2 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.70 PCGF2 Zornitza Stark Phenotypes for gene: PCGF2 were changed from to Turnpenny-Fry syndrome, MIM#600346
Aortopathy_Connective Tissue Disorders v0.69 PCGF2 Zornitza Stark Publications for gene: PCGF2 were set to
Aortopathy_Connective Tissue Disorders v0.68 PCGF2 Zornitza Stark Mode of inheritance for gene: PCGF2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Aortopathy_Connective Tissue Disorders v0.67 MYLK Zornitza Stark Marked gene: MYLK as ready
Aortopathy_Connective Tissue Disorders v0.67 MYLK Zornitza Stark Gene: mylk has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.67 MYLK Zornitza Stark Phenotypes for gene: MYLK were changed from to Aortic aneurysm, familial thoracic 7, MIM#600922
Aortopathy_Connective Tissue Disorders v0.66 MYLK Zornitza Stark Publications for gene: MYLK were set to
Aortopathy_Connective Tissue Disorders v0.65 MYLK Zornitza Stark Mode of inheritance for gene: MYLK was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Aortopathy_Connective Tissue Disorders v0.64 MYH11 Zornitza Stark Marked gene: MYH11 as ready
Aortopathy_Connective Tissue Disorders v0.64 MYH11 Zornitza Stark Gene: myh11 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.64 MYH11 Zornitza Stark Phenotypes for gene: MYH11 were changed from to Aortic aneurysm, familial thoracic 4, MIM#160745
Aortopathy_Connective Tissue Disorders v0.63 MYH11 Zornitza Stark Publications for gene: MYH11 were set to
Aortopathy_Connective Tissue Disorders v0.62 MED12 Zornitza Stark Marked gene: MED12 as ready
Aortopathy_Connective Tissue Disorders v0.62 MED12 Zornitza Stark Gene: med12 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.62 MED12 Zornitza Stark Phenotypes for gene: MED12 were changed from to Lujan-Fryns syndrome, MIM# 309520; Ohdo syndrome, X-linked, MIM# 300895; Opitz-Kaveggia syndrome, MIM# 305450
Aortopathy_Connective Tissue Disorders v0.61 MED12 Zornitza Stark Publications for gene: MED12 were set to
Aortopathy_Connective Tissue Disorders v0.60 MED12 Zornitza Stark Mode of inheritance for gene: MED12 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Aortopathy_Connective Tissue Disorders v0.59 LOX Zornitza Stark Marked gene: LOX as ready
Aortopathy_Connective Tissue Disorders v0.59 LOX Zornitza Stark Gene: lox has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.59 LOX Zornitza Stark Phenotypes for gene: LOX were changed from to Aortic aneurysm, familial thoracic 10, MIM#617168
Aortopathy_Connective Tissue Disorders v0.58 LOX Zornitza Stark Publications for gene: LOX were set to
Aortopathy_Connective Tissue Disorders v0.57 LOX Zornitza Stark Mode of inheritance for gene: LOX was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Aortopathy_Connective Tissue Disorders v0.56 FBN1 Zornitza Stark Marked gene: FBN1 as ready
Aortopathy_Connective Tissue Disorders v0.56 FBN1 Zornitza Stark Gene: fbn1 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.56 FBN1 Zornitza Stark Phenotypes for gene: FBN1 were changed from to Marfan syndrome (154700); MASS syndrome (604308)
Aortopathy_Connective Tissue Disorders v0.55 FBN1 Zornitza Stark Publications for gene: FBN1 were set to
Aortopathy_Connective Tissue Disorders v0.54 FBN1 Zornitza Stark Mode of inheritance for gene: FBN1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Aortopathy_Connective Tissue Disorders v0.53 COL5A1 Zornitza Stark Marked gene: COL5A1 as ready
Aortopathy_Connective Tissue Disorders v0.53 COL5A1 Zornitza Stark Gene: col5a1 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.53 COL5A1 Zornitza Stark Phenotypes for gene: COL5A1 were changed from to Ehlers-Danlos syndrome, classic type, 1, MIM# 130000
Aortopathy_Connective Tissue Disorders v0.52 COL5A1 Zornitza Stark Publications for gene: COL5A1 were set to
Aortopathy_Connective Tissue Disorders v0.51 COL5A1 Zornitza Stark Mode of inheritance for gene: COL5A1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Aortopathy_Connective Tissue Disorders v0.50 COL3A1 Zornitza Stark Marked gene: COL3A1 as ready
Aortopathy_Connective Tissue Disorders v0.50 COL3A1 Zornitza Stark Gene: col3a1 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.50 COL3A1 Zornitza Stark Phenotypes for gene: COL3A1 were changed from to Ehlers-Danlos syndrome, vascular type, MIM# 130050; Polymicrogyria with or without vascular-type EDS, MIM# 618343
Aortopathy_Connective Tissue Disorders v0.49 COL3A1 Zornitza Stark Mode of inheritance for gene: COL3A1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Aortopathy_Connective Tissue Disorders v0.48 COL3A1 Zornitza Stark Publications for gene: COL3A1 were set to
Aortopathy_Connective Tissue Disorders v0.47 COL3A1 Zornitza Stark Mode of inheritance for gene: COL3A1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Aortopathy_Connective Tissue Disorders v0.46 COL1A1 Zornitza Stark Marked gene: COL1A1 as ready
Aortopathy_Connective Tissue Disorders v0.46 COL1A1 Zornitza Stark Gene: col1a1 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.46 COL1A1 Zornitza Stark Phenotypes for gene: COL1A1 were changed from to Ehlers-Danlos syndrome, arthrochalasia type, 1, MIM# 130060
Aortopathy_Connective Tissue Disorders v0.45 COL1A1 Zornitza Stark Publications for gene: COL1A1 were set to
Aortopathy_Connective Tissue Disorders v0.44 COL1A1 Zornitza Stark Mode of inheritance for gene: COL1A1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Aortopathy_Connective Tissue Disorders v0.43 CBS Zornitza Stark Marked gene: CBS as ready
Aortopathy_Connective Tissue Disorders v0.43 CBS Zornitza Stark Gene: cbs has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.43 CBS Zornitza Stark Phenotypes for gene: CBS were changed from to Homocystinuria (MIM# 236200)
Aortopathy_Connective Tissue Disorders v0.42 CBS Zornitza Stark Publications for gene: CBS were set to
Aortopathy_Connective Tissue Disorders v0.41 CBS Zornitza Stark Mode of inheritance for gene: CBS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Aortopathy_Connective Tissue Disorders v0.40 CBS Zornitza Stark reviewed gene: CBS: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Aortopathy_Connective Tissue Disorders v0.40 BGN Zornitza Stark Marked gene: BGN as ready
Aortopathy_Connective Tissue Disorders v0.40 BGN Zornitza Stark Added comment: Comment when marking as ready: Females variably affected.
Aortopathy_Connective Tissue Disorders v0.40 BGN Zornitza Stark Gene: bgn has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.40 BGN Zornitza Stark Marked gene: BGN as ready
Aortopathy_Connective Tissue Disorders v0.40 BGN Zornitza Stark Gene: bgn has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.40 BGN Zornitza Stark Mode of inheritance for gene: BGN was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Aortopathy_Connective Tissue Disorders v0.39 BGN Zornitza Stark Publications for gene: BGN were set to
Aortopathy_Connective Tissue Disorders v0.38 BGN Zornitza Stark Phenotypes for gene: BGN were changed from to Meester-Loeys syndrome, MIM# 300989
Aortopathy_Connective Tissue Disorders v0.37 ACTA2 Zornitza Stark Marked gene: ACTA2 as ready
Aortopathy_Connective Tissue Disorders v0.37 ACTA2 Zornitza Stark Gene: acta2 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.37 ACTA2 Zornitza Stark Phenotypes for gene: ACTA2 were changed from to Aortic aneurysm, familial thoracic 6, MIM# 611788
Aortopathy_Connective Tissue Disorders v0.36 ACTA2 Zornitza Stark Publications for gene: ACTA2 were set to
Aortopathy_Connective Tissue Disorders v0.35 ACTA2 Zornitza Stark Mode of inheritance for gene: ACTA2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Aortopathy_Connective Tissue Disorders v0.34 ABL1 Zornitza Stark Marked gene: ABL1 as ready
Aortopathy_Connective Tissue Disorders v0.34 ABL1 Zornitza Stark Gene: abl1 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.34 ABL1 Zornitza Stark Phenotypes for gene: ABL1 were changed from to Congenital heart defects and skeletal malformations syndrome (MIM# 617602)
Haem degradation and bilirubin metabolism defects v0.2 HFE Bryony Thompson Classified gene: HFE as Red List (low evidence)
Haem degradation and bilirubin metabolism defects v0.2 HFE Bryony Thompson Gene: hfe has been classified as Red List (Low Evidence).
Aortopathy_Connective Tissue Disorders v0.33 ABL1 Zornitza Stark Publications for gene: ABL1 were set to
Aortopathy_Connective Tissue Disorders v0.32 ABL1 Zornitza Stark Mode of inheritance for gene: ABL1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.12 DIAPH2 Bryony Thompson Marked gene: DIAPH2 as ready
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.12 DIAPH2 Bryony Thompson Gene: diaph2 has been classified as Red List (Low Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.12 DIAPH2 Bryony Thompson Tag SV/CNV tag was added to gene: DIAPH2.
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.12 DIAPH2 Bryony Thompson Classified gene: DIAPH2 as Red List (low evidence)
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.12 DIAPH2 Bryony Thompson Gene: diaph2 has been classified as Red List (Low Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.11 DIAPH2 Bryony Thompson reviewed gene: DIAPH2: Rating: RED; Mode of pathogenicity: None; Publications: 9497258, 30689869, 26175800, 11129329; Phenotypes: ?Premature ovarian failure 2A MIM#300511; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Aortopathy_Connective Tissue Disorders v0.30 COL5A2 Paul De Fazio changed review comment from: Well-known association with classic Ehlers-Danlos syndrome e.g. PMID 22696272. Reviewed in PMID 20847697 and GeneReviews (Available from: https://www.ncbi.nlm.nih.gov/books/NBK1244/).
Sources: Literature; to: Well-known association with classic Ehlers-Danlos syndrome e.g. PMID 22696272. Variants in this gene make up ~14% of cases. Reviewed in PMID 20847697 and GeneReviews (Available from: https://www.ncbi.nlm.nih.gov/books/NBK1244/).
Sources: Literature
Aortopathy_Connective Tissue Disorders v0.30 COL5A2 Paul De Fazio gene: COL5A2 was added
gene: COL5A2 was added to Aortopathy_Connective Tissue Disorders. Sources: Literature
Mode of inheritance for gene: COL5A2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: COL5A2 were set to 20847697; 22696272
Phenotypes for gene: COL5A2 were set to Ehlers-Danlos syndrome, classic type, 2, MIM#120190
Penetrance for gene: COL5A2 were set to unknown
Review for gene: COL5A2 was set to GREEN
gene: COL5A2 was marked as current diagnostic
Added comment: Well-known association with classic Ehlers-Danlos syndrome e.g. PMID 22696272. Reviewed in PMID 20847697 and GeneReviews (Available from: https://www.ncbi.nlm.nih.gov/books/NBK1244/).
Sources: Literature
Aortopathy_Connective Tissue Disorders v0.30 MED12 Ain Roesley edited their review of gene: MED12: Changed rating: GREEN
Aortopathy_Connective Tissue Disorders v0.30 SMAD4 Paul De Fazio edited their review of gene: SMAD4: Changed rating: GREEN; Changed publications: 30071989, 25931195, 25931195, 30809044
Aortopathy_Connective Tissue Disorders v0.30 SMAD4 Paul De Fazio changed review comment from: "Limited evidence" for association with aortic dilatation/dissection by ClinGen:

"Eight genes scored as moderate (EFEMP2) or limited (ELN, FBN2, FLNA, NOTCH1,
SLC2A10, SMAD4, and SKI) for association with HTAAD. These genes are a heterogeneous group for which the evidence was often difficult to assess...the evidence, therefore, for their association with a presentation of aortic dilatation and/or dissection is often rather lacking. The other common feature of these conditions is that there is no robust evidence of progression to aortic dissection."

The ClinGen review of SMAD4, viewable in the supplementary material, dates to 22/12/2016 and so does not account for the reported individuals in PMID 30809044.

Green in PanelApp UK although with quite a few Amber reviews.

There is an association between people with with SMAD4 variants and aortic dissection (PMID 25931195).; to: "Limited evidence" for association with aortic dilatation/dissection by ClinGen:

"Eight genes scored as moderate (EFEMP2) or limited (ELN, FBN2, FLNA, NOTCH1,
SLC2A10, SMAD4, and SKI) for association with HTAAD. These genes are a heterogeneous group for which the evidence was often difficult to assess...the evidence, therefore, for their association with a presentation of aortic dilatation and/or dissection is often rather lacking. The other common feature of these conditions is that there is no robust evidence of progression to aortic dissection."


Green in PanelApp UK although with quite a few Amber reviews.

There is an association between people with with SMAD4 variants and aortic dissection (PMID 25931195). The ClinGen review of SMAD4, viewable in the supplementary material, dates to 22/12/2016 and so does not account for the reported individuals in PMID 30809044. Given this more recent data Green is appropriate.
Aortopathy_Connective Tissue Disorders v0.30 C1S Zornitza Stark Classified gene: C1S as Amber List (moderate evidence)
Aortopathy_Connective Tissue Disorders v0.30 C1S Zornitza Stark Gene: c1s has been classified as Amber List (Moderate Evidence).
Aortopathy_Connective Tissue Disorders v0.29 BGN Belinda Chong changed review comment from: 5 unrelated individuals with TAAD (PMID:27632686) plus mouse model (PMID:17502576)

PMID:27632686
Proband associated with syndromic TAAD: c.5G>A, p.Trp2*, 21 kb del: chrX:152767424-152787984 28 kb del: chrX:152768438-152795976, c.908A>C, p.Gln303Pro, c.238G>A, p.Gly80Ser. Some segregation evidence and mutation-carrying females ranged from unaffected upon repeated echocardiographic evaluation over aortic root dilatation to death due to aortic dissection.
PMID:17502576
Biglycan deficiency in male BALB/cA mice has been shown to lead to sudden death due to aortic rupture.

GEL PanelApp: As per evidence above.

ClinGen assessment uncertain due to focuses on isolated TAAD; however support involvement of BGN in syndromic TAAD: "Strong for syndromic , X-linked TAAD and “limited” for isolated TAAD. The curation shows strong assertion with syndromic TAAD. There was 1 reported proband with isolated TAAD harboring variant in this gene. Given this, the association with isolated TAAD should be limited."; to: 5 unrelated individuals with TAAD (PMID:27632686) plus mouse model (PMID:17502576)

PMID:27632686
Proband associated with syndromic TAAD: c.5G>A, p.Trp2*, 21 kb del: chrX:152767424-152787984 28 kb del: chrX:152768438-152795976, c.908A>C, p.Gln303Pro, c.238G>A, p.Gly80Ser. Some segregation evidence and mutation-carrying females ranged from unaffected upon repeated echocardiographic evaluation over aortic root dilatation to death due to aortic dissection.
PMID:17502576
Biglycan deficiency in male BALB/cA mice has been shown to lead to sudden death due to aortic rupture.

GEL PanelApp: As per evidence above.

ClinGen assessment uncertain due to focus on isolated TAAD; however support involvement of BGN in syndromic TAAD: "Strong for syndromic , X-linked TAAD and “limited” for isolated TAAD. The curation shows strong assertion with syndromic TAAD. There was 1 reported proband with isolated TAAD harboring variant in this gene. Given this, the association with isolated TAAD should be limited."
Aortopathy_Connective Tissue Disorders v0.29 PCGF2 Zornitza Stark reviewed gene: PCGF2: Rating: GREEN; Mode of pathogenicity: None; Publications: 30343942; Phenotypes: Turnpenny-Fry syndrome, MIM#600346; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2709 UBE2A Crystle Lee reviewed gene: UBE2A: Rating: GREEN; Mode of pathogenicity: None; Publications: 24053514, 16909393; Phenotypes: Mental retardation, X-linked syndromic, Nascimento-type (MIM#300860); Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Aortopathy_Connective Tissue Disorders v0.29 TGFB3 Zornitza Stark reviewed gene: TGFB3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Aortopathy_Connective Tissue Disorders v0.29 TGFB3 Paul De Fazio changed review comment from: "Uncertain" by ClinGen. 43 patients from 11 families reported in PMID 25835445 but this seemed insufficient for the ClinGen working group.; to: "Uncertain" by ClinGen. 43 patients from 11 families with syndromic presentations of aortic aneurysms reported in PMID 25835445 but this seemed insufficient for the ClinGen working group.
Aortopathy_Connective Tissue Disorders v0.29 TGFB3 Paul De Fazio changed review comment from: "Uncertain" by ClinGen. Quite a few individuals in PMID 25835445 but this seemed insufficient for the ClinGen working group.; to: "Uncertain" by ClinGen. 43 patients from 11 families reported in PMID 25835445 but this seemed insufficient for the ClinGen working group.
Aortopathy_Connective Tissue Disorders v0.29 ABL1 Zornitza Stark reviewed gene: ABL1: Rating: GREEN; Mode of pathogenicity: None; Publications: 30071989, 28288113; Phenotypes: Congenital heart defects and skeletal malformations syndrome (MIM# 617602); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Aortopathy_Connective Tissue Disorders v0.29 TGFB3 Paul De Fazio changed review comment from: "Uncertain" by ClinGen. 3 unrelated individuals in PMID 25835445 but this was insufficient for the ClinGen working group.; to: "Uncertain" by ClinGen. Quite a few individuals in PMID 25835445 but this seemed insufficient for the ClinGen working group.
Aortopathy_Connective Tissue Disorders v0.29 FLNA Zornitza Stark Marked gene: FLNA as ready
Aortopathy_Connective Tissue Disorders v0.29 FLNA Zornitza Stark Gene: flna has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.29 FLNA Zornitza Stark Phenotypes for gene: FLNA were changed from to Heterotopia, periventricular, 1 MIM# 300049; Cardiac valvular dysplasia, X-linked MIM# 314400.
Haem degradation and bilirubin metabolism defects v0.1 HFE Belinda Chong edited their review of gene: HFE: Changed publications: 30683557
Aortopathy_Connective Tissue Disorders v0.28 FLNA Zornitza Stark Publications for gene: FLNA were set to
Aortopathy_Connective Tissue Disorders v0.27 FLNA Zornitza Stark Mode of inheritance for gene: FLNA was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Haem degradation and bilirubin metabolism defects v0.1 HFE Zornitza Stark reviewed gene: HFE: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: {Porphyria cutanea tarda, susceptibility to} 176100, {Porphyria variegata, susceptibility to} 176200; Mode of inheritance: None
Mendeliome v0.3157 SETD2 Michelle Torres reviewed gene: SETD2: Rating: GREEN; Mode of pathogenicity: None; Publications: 29681085; Phenotypes: Luscan-Lumish syndrome, 616831 AD; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3157 AXL Bryony Thompson Marked gene: AXL as ready
Mendeliome v0.3157 AXL Bryony Thompson Gene: axl has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3157 AXL Bryony Thompson Classified gene: AXL as Amber List (moderate evidence)
Mendeliome v0.3157 AXL Bryony Thompson Gene: axl has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3156 AXL Bryony Thompson gene: AXL was added
gene: AXL was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: AXL was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: AXL were set to 18787040; 24476074
Phenotypes for gene: AXL were set to Kallman syndrome; normosmic idiopathic hypogonadotropic hypogonadism
Review for gene: AXL was set to AMBER
Added comment: Axl null mice had delayed first oestrus and persistently abnormal oestrous cyclicality compared with wild-type controls. Only a single study reported screening human cases. In a screen of 104 probands with KS or nIHH, four heterozygous AXL mutations were identified in two KS and two nIHH unrelated subjects (two males and two females). Three of the variants appear to be too common in gnomAD v2.1 given the reported prevalence of KS reported in GeneReviews (1:30,000 in males and 1:125,000 in females): c.587-6C>T (normal splicing in RNA studies, NFE AF 0.0001472), p.Q361P (NFE 0.002560), p.L50F (AJ 0.004405). The other variant p.S202C (4 hets, 1 female in gnomAD v2.1) is rare enough in gnomAD for a dominant disorder. In vitro functional assays were conducted and p.S202C had an significant effect on function, but so did the more common variant p.Q361P.
Sources: Literature
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.11 AXL Bryony Thompson Phenotypes for gene: AXL were changed from to Kallman syndrome; normosmic idiopathic hypogonadotropic hypogonadism
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.10 AXL Bryony Thompson Publications for gene: AXL were set to
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.9 AXL Bryony Thompson Marked gene: AXL as ready
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.9 AXL Bryony Thompson Gene: axl has been classified as Amber List (Moderate Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.9 AXL Bryony Thompson Classified gene: AXL as Amber List (moderate evidence)
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.9 AXL Bryony Thompson Gene: axl has been classified as Amber List (Moderate Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.8 AXL Bryony Thompson reviewed gene: AXL: Rating: AMBER; Mode of pathogenicity: None; Publications: 18787040, 24476074; Phenotypes: Kallman syndrome, normosmic idiopathic hypogonadotropic hypogonadism; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Haem degradation and bilirubin metabolism defects v0.1 PPOX Paul De Fazio reviewed gene: PPOX: Rating: GREEN; Mode of pathogenicity: None; Publications: 27982422; Phenotypes: Porphyria variegata, MIM#600923; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Aortopathy_Connective Tissue Disorders v0.26 MED12 Ain Roesley reviewed gene: MED12: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 30071989, 19938245, 17369503; Phenotypes: heritable thoracic aortic aneurysm and dissection, Opitz-Kaveggia syndrome (FS syndrome), X-Linked Ohdo Syndrome (XLOS), Lujan Syndrome (LS); Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Aortopathy_Connective Tissue Disorders v0.26 FLNA Naomi Baker reviewed gene: FLNA: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 30071989, 29334594.; Phenotypes: Heterotopia, periventricular, 1 MIM# 300049, Cardiac valvular dysplasia, X-linked MIM# 314400.; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Haem degradation and bilirubin metabolism defects v0.1 UROD Paul De Fazio reviewed gene: UROD: Rating: GREEN; Mode of pathogenicity: None; Publications: 9792863; Phenotypes: Porphyria cutanea tarda; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Aortopathy_Connective Tissue Disorders v0.26 PCGF2 Paul De Fazio changed review comment from: Not reviewed by ClinGen Aortopathy Working Group.

Not on any relevant PanelApp UK panel although green on others.

11 unrelated individuals and a pair of monozygotic twins were reported all with missense variants at proline 65. 5 individuals had aortic dilatation.; to: Not reviewed by ClinGen Aortopathy Working Group.

Not on any relevant PanelApp UK panel although green on others.

11 unrelated individuals and a pair of monozygotic twins were reported all with missense variants at proline 65 in the context of Turnpenny-Fry Syndrome. 5 individuals had aortic dilatation.
Aortopathy_Connective Tissue Disorders v0.26 BGN Belinda Chong reviewed gene: BGN: Rating: GREEN; Mode of pathogenicity: None; Publications: 30071989, 27632686, 17502576; Phenotypes: Heritable Thoracic Aortic Aneurysm and Dissection; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Aortopathy_Connective Tissue Disorders v0.26 SMAD4 Paul De Fazio edited their review of gene: SMAD4: Changed publications: 30071989, 25931195, 25931195
Aortopathy_Connective Tissue Disorders v0.26 SMAD4 Paul De Fazio changed review comment from: "Limited evidence" for association with aortic dilatation/dissection by ClinGen:

"Eight genes scored as moderate (EFEMP2) or limited (ELN, FBN2, FLNA, NOTCH1,
SLC2A10, SMAD4, and SKI) for association with HTAAD. These genes are a heterogeneous group for which the evidence was often difficult to assess...the evidence, therefore, for their association with a presentation of aortic dilatation and/or dissection is often rather lacking. The other common feature of these conditions is that there is no robust evidence of progression to aortic dissection."

The ClinGen review of SMAD4, viewable in the supplementary material, dates to 22/12/2016 and does not account for the reported individuals cited below.; to: "Limited evidence" for association with aortic dilatation/dissection by ClinGen:

"Eight genes scored as moderate (EFEMP2) or limited (ELN, FBN2, FLNA, NOTCH1,
SLC2A10, SMAD4, and SKI) for association with HTAAD. These genes are a heterogeneous group for which the evidence was often difficult to assess...the evidence, therefore, for their association with a presentation of aortic dilatation and/or dissection is often rather lacking. The other common feature of these conditions is that there is no robust evidence of progression to aortic dissection."

The ClinGen review of SMAD4, viewable in the supplementary material, dates to 22/12/2016 and so does not account for the reported individuals in PMID 30809044.

Green in PanelApp UK although with quite a few Amber reviews.

There is an association between people with with SMAD4 variants and aortic dissection (PMID 25931195).
Aortopathy_Connective Tissue Disorders v0.26 TGFBR1 Paul De Fazio changed review comment from: "Definitive" by ClinGen.

Reviewed in PMID 27879313 (176 cases with variants in TGFBR1).; to: "Definitive" by ClinGen Aortopathy working group.

Reviewed in PMID 27879313 (176 cases with variants in TGFBR1).
Aortopathy_Connective Tissue Disorders v0.26 TGFB2 Paul De Fazio changed review comment from: "Definitive" by ClinGen.

ClinGen cite PMID 22772371 which describes 4 families with variants in this gene.; to: "Definitive" by ClinGen Aortopathy Working Group.

The ClinGen Working Group cite PMID 22772371 which describes 4 families with variants in this gene.
Aortopathy_Connective Tissue Disorders v0.26 TGFB3 Paul De Fazio changed review comment from: "Uncertain" by ClinGen. 3 unrelated individuals in PMID 25835445 but insufficient for the ClinGen working group.; to: "Uncertain" by ClinGen. 3 unrelated individuals in PMID 25835445 but this was insufficient for the ClinGen working group.
Aortopathy_Connective Tissue Disorders v0.26 MYH11 Paul De Fazio edited their review of gene: MYH11: Changed rating: GREEN
Aortopathy_Connective Tissue Disorders v0.26 MYH11 Paul De Fazio reviewed gene: MYH11: Rating: ; Mode of pathogenicity: None; Publications: 30071989, 16444274, 17666408, 27081537; Phenotypes: Aortic aneurysm, familial thoracic 4, MIM#160745; Mode of inheritance: None; Current diagnostic: yes
Aortopathy_Connective Tissue Disorders v0.26 MYLK Paul De Fazio Deleted their comment
Aortopathy_Connective Tissue Disorders v0.26 MYLK Paul De Fazio edited their review of gene: MYLK: Added comment: "Definitive" by Clingen Aortopathy Working Group.

Green on PanelApp UK.

Association between variants in this gene and aortic dissection established in multiple individuals and a 5-generation family (PMID 27586135;21055718;25907466).; Changed rating: GREEN
Aortopathy_Connective Tissue Disorders v0.26 MYLK Paul De Fazio changed review comment from: "Definitive" by Clingen Aortopathy Working Group.

Green on PanelApp UK.

Association between variants in this gene and aortic dissection established in multiple individuals and a 5-generation family (PMID 27586135;21055718;25907466).; to: "Definitive" by Clingen Aortopathy Working Group.

Green on PanelApp UK.

Association between variants in this gene and aortic dissection established in multiple individuals and a 5-generation family (PMID 27586135;21055718;25907466).
Aortopathy_Connective Tissue Disorders v0.26 MYLK Paul De Fazio reviewed gene: MYLK: Rating: ; Mode of pathogenicity: None; Publications: 30071989, 27586135, 21055718, 25907466; Phenotypes: Aortic aneurysm, familial thoracic 7, MIM#600922; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Ataxia v0.221 HARS Bryony Thompson Marked gene: HARS as ready
Ataxia v0.221 HARS Bryony Thompson Gene: hars has been classified as Amber List (Moderate Evidence).
Ataxia v0.221 HARS Bryony Thompson Classified gene: HARS as Amber List (moderate evidence)
Ataxia v0.221 HARS Bryony Thompson Gene: hars has been classified as Amber List (Moderate Evidence).
Aortopathy_Connective Tissue Disorders v0.26 PCGF2 Paul De Fazio changed review comment from: Not reviewed by ClinGen Aortopathy Working Group.

Not on any relevant PanelApp UK panel.

11 unrelated individuals and a pair of monozygotic twins were reported all with missense variants at proline 65. 5 individuals had aortic dilatation.; to: Not reviewed by ClinGen Aortopathy Working Group.

Not on any relevant PanelApp UK panel although green on others.

11 unrelated individuals and a pair of monozygotic twins were reported all with missense variants at proline 65. 5 individuals had aortic dilatation.
Aortopathy_Connective Tissue Disorders v0.26 PCGF2 Paul De Fazio changed review comment from: Not reviewed by ClinGen Aortopathy Working Group.

Not on any relevant PanelApp UK panel.

11 unrelated individuals and a pair of monozygotic twins were reported all with missense variants at proline 65. 5 individuals had aortic dilatation.; to: Not reviewed by ClinGen Aortopathy Working Group.

Not on any relevant PanelApp UK panel.

11 unrelated individuals and a pair of monozygotic twins were reported all with missense variants at proline 65. 5 individuals had aortic dilatation.
Aortopathy_Connective Tissue Disorders v0.26 PCGF2 Paul De Fazio reviewed gene: PCGF2: Rating: AMBER; Mode of pathogenicity: None; Publications: 30343942; Phenotypes: Turnpenny-Fry syndrome, MIM#600346; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Ataxia v0.220 HARS Bryony Thompson gene: HARS was added
gene: HARS was added to Ataxia - paediatric. Sources: Literature
Mode of inheritance for gene: HARS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HARS were set to 32296180
Phenotypes for gene: HARS were set to multisystem ataxic syndrome
Review for gene: HARS was set to AMBER
Added comment: 3 cases from 2 unrelated families with biallelic variants and paediatric onset of progressive ataxic gait as a feature of the condition.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2709 HARS Bryony Thompson Marked gene: HARS as ready
Intellectual disability syndromic and non-syndromic v0.2709 HARS Bryony Thompson Gene: hars has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2709 HARS Bryony Thompson Classified gene: HARS as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2709 HARS Bryony Thompson Gene: hars has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2708 HARS Bryony Thompson gene: HARS was added
gene: HARS was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: HARS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HARS were set to 32296180
Phenotypes for gene: HARS were set to multisystem ataxic syndrome; mild-severe intellectual disability
Review for gene: HARS was set to AMBER
Added comment: 3 cases from 2 unrelated families with biallelic variants and mild to severe intellectual disability as a feature of the condition.
Sources: Literature
Aortopathy_Connective Tissue Disorders v0.26 PRKG1 Paul De Fazio reviewed gene: PRKG1: Rating: GREEN; Mode of pathogenicity: None; Publications: 30071989, 23910461, 30577811; Phenotypes: Aortic aneurysm, familial thoracic 8, MIM#176894; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Aortopathy_Connective Tissue Disorders v0.26 SKI Paul De Fazio changed review comment from: "Limited" evidence by ClinGen Aortopathy Working Group but:

"Diagnosis of Loeys-Dietz syndrome versus Shprintzen-Goldberg syndrome is thus important for correct management and risk stratification, and supports the conclusion that the gene for Shprintzen- Goldberg syndrome, SKI, should be included in diagnostic panels for characteristic syndromic presentations, especially in the pediatric setting."

>20 individuals described in the context of Shprintzen-Goldberg syndrome which can involve aortic dilatations (PMID 23023332, 24736733); to: "Limited" evidence by ClinGen Aortopathy Working Group but:

"Diagnosis of Loeys-Dietz syndrome versus Shprintzen-Goldberg syndrome is thus important for correct management and risk stratification, and supports the conclusion that the gene for Shprintzen- Goldberg syndrome, SKI, should be included in diagnostic panels for characteristic syndromic presentations, especially in the pediatric setting."

>20 individuals described in the context of Shprintzen-Goldberg syndrome which can involve aortic dilatations (PMID 23023332, 24736733)

Also Green on PanelApp UK
Aortopathy_Connective Tissue Disorders v0.26 SKI Paul De Fazio reviewed gene: SKI: Rating: GREEN; Mode of pathogenicity: None; Publications: 30071989, 23023332, 24736733; Phenotypes: Shprintzen-Goldberg syndrome, MIM#164780; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Aortopathy_Connective Tissue Disorders v0.26 SLC2A10 Paul De Fazio reviewed gene: SLC2A10: Rating: GREEN; Mode of pathogenicity: None; Publications: 30071989, 16550171, 17935213; Phenotypes: Arterial tortuosity syndrome MIM#606145; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Aortopathy_Connective Tissue Disorders v0.26 COL5A1 Ain Roesley changed review comment from: PMID: 30071989; Classified as 'No Evidence' by Clingen for heritable thoracic aortic aneurysm and dissection


Gene reviews: 75-78% of classical EDS is caused by pathogenic variants in COL5A1. Haploinsufficiency is the more common disease mechanism whoeever, missense variants in the triple helical domain of the α1(V) or α2(V) chains are likely to have dominant-negative activity.
(https://www.ncbi.nlm.nih.gov/books/NBK1244/); to: PMID: 30071989; Classified as 'No Evidence' by Clingen for heritable thoracic aortic aneurysm and dissection


GeneReviews: 75-78% of classical EDS is caused by pathogenic variants in COL5A1. Haploinsufficiency is the more common disease mechanism whoeever, missense variants in the triple helical domain of the α1(V) or α2(V) chains are likely to have dominant-negative activity.
(https://www.ncbi.nlm.nih.gov/books/NBK1244/)
Aortopathy_Connective Tissue Disorders v0.26 COL5A1 Ain Roesley reviewed gene: COL5A1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 30071989; Phenotypes: Heritable Thoracic Aortic Aneurysm and Dissection, Classic Ehlers-Danlos Syndrome (MIM# 130000); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Aortopathy_Connective Tissue Disorders v0.26 SLC2A10 Paul De Fazio Deleted their review
Aortopathy_Connective Tissue Disorders v0.26 SLC2A10 Paul De Fazio reviewed gene: SLC2A10: Rating: RED; Mode of pathogenicity: None; Publications: 30071989; Phenotypes: Hereditary thoracic aortic aneurysm and dissection; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Aortopathy_Connective Tissue Disorders v0.26 SLC2A10 Paul De Fazio Deleted their review
Aortopathy_Connective Tissue Disorders v0.26 SLC2A10 Paul De Fazio reviewed gene: SLC2A10: Rating: RED; Mode of pathogenicity: None; Publications: 30071989; Phenotypes: Hereditary thoracic aortic aneurysm and dissection; Mode of inheritance: None
Aortopathy_Connective Tissue Disorders v0.26 COL3A1 Ain Roesley reviewed gene: COL3A1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 30071989, 25758994; Phenotypes: Ehlers-Danlos syndrome, vascular type, heritable thoracic aortic aneurysm and dissection; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Aortopathy_Connective Tissue Disorders v0.26 COL1A1 Ain Roesley reviewed gene: COL1A1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 30071989, 28981071; Phenotypes: Classical Ehlers-Danlos Syndrome, arthrochalasia Ehlers-Danlos Syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Aortopathy_Connective Tissue Disorders v0.26 LOX Naomi Baker reviewed gene: LOX: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 30071989, 26838787, 30675029.; Phenotypes: Aortic aneurysm, familial thoracic 10 MIM#617168; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Aortopathy_Connective Tissue Disorders v0.26 SMAD3 Paul De Fazio reviewed gene: SMAD3: Rating: GREEN; Mode of pathogenicity: None; Publications: 30071989; Phenotypes: Loeys-Dietz syndrome 3, MIM# 613795; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Aortopathy_Connective Tissue Disorders v0.26 SMAD4 Paul De Fazio changed review comment from: "Limited evidence" for association with aortic dilatation/dissection by ClinGen:

"Eight genes scored as moderate (EFEMP2) or limited (ELN, FBN2, FLNA, NOTCH1,
SLC2A10, SMAD4, and SKI) for association with HTAAD. These genes are a heterogeneous group for which the evidence was often difficult to assess...the evidence, therefore, for their association with a presentation of aortic dilatation and/or dissection is often rather lacking. The other common feature of these conditions is that there is no robust evidence of progression to aortic dissection."; to: "Limited evidence" for association with aortic dilatation/dissection by ClinGen:

"Eight genes scored as moderate (EFEMP2) or limited (ELN, FBN2, FLNA, NOTCH1,
SLC2A10, SMAD4, and SKI) for association with HTAAD. These genes are a heterogeneous group for which the evidence was often difficult to assess...the evidence, therefore, for their association with a presentation of aortic dilatation and/or dissection is often rather lacking. The other common feature of these conditions is that there is no robust evidence of progression to aortic dissection."

The ClinGen review of SMAD4, viewable in the supplementary material, dates to 22/12/2016 and does not account for the reported individuals cited below.
Aortopathy_Connective Tissue Disorders v0.26 SMAD4 Paul De Fazio reviewed gene: SMAD4: Rating: AMBER; Mode of pathogenicity: None; Publications: 30071989; Phenotypes: Hereditary thoracic aortic aneurysm and dissection; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Aortopathy_Connective Tissue Disorders v0.26 TGFB2 Paul De Fazio reviewed gene: TGFB2: Rating: GREEN; Mode of pathogenicity: None; Publications: 30071989, 22772371; Phenotypes: Loeys-Dietz syndrome 4; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Aortopathy_Connective Tissue Disorders v0.26 TGFB3 Paul De Fazio reviewed gene: TGFB3: Rating: AMBER; Mode of pathogenicity: None; Publications: 30071989, 25835445; Phenotypes: Arrhythmogenic right ventricular dysplasia 1, Loeys-Dietz syndrome 5; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Aortopathy_Connective Tissue Disorders v0.26 TGFBR1 Paul De Fazio reviewed gene: TGFBR1: Rating: GREEN; Mode of pathogenicity: None; Publications: 30071989, 27879313; Phenotypes: Loeys-Dietz syndrome 1; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Aortopathy_Connective Tissue Disorders v0.26 TGFBR2 Paul De Fazio reviewed gene: TGFBR2: Rating: GREEN; Mode of pathogenicity: None; Publications: 30071989, 27879313; Phenotypes: Loeys-Dietz syndrome 2; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Aortopathy_Connective Tissue Disorders v0.26 CBS Ain Roesley reviewed gene: CBS: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 30071989, 1301198, 10408774, 7762555, 12815602, 16307898, 25455305, 26667307, 29508359; Phenotypes: Homocystinuria (MIM# 236200); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Aortopathy_Connective Tissue Disorders v0.26 C1S Ain Roesley reviewed gene: C1S: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 30071989, 27745832, 31921203; Phenotypes: Ehlers-Danlos syndrome, periodontal type, 1 (MIM# 130080); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Aortopathy_Connective Tissue Disorders v0.26 C1R Ain Roesley reviewed gene: C1R: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 30071989, 27745832; Phenotypes: Ehlers-Danlos syndrome, periodontal type, 1 (MIM# 130080); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Aortopathy_Connective Tissue Disorders v0.26 ABL1 Ain Roesley reviewed gene: ABL1: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 30071989, 28288113; Phenotypes: Congenital heart defects and skeletal malformations syndrome (MIM# 617602); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Aortopathy_Connective Tissue Disorders v0.26 LOX Naomi Baker Deleted their review
Aortopathy_Connective Tissue Disorders v0.26 LOX Naomi Baker reviewed gene: LOX: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Aortic aneurysm, familial thoracic 10 MIM#10617168; Mode of inheritance: None
Aortopathy_Connective Tissue Disorders v0.26 ABL1 Ain Roesley Deleted their review
Aortopathy_Connective Tissue Disorders v0.26 ACTA2 Ain Roesley reviewed gene: ACTA2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 30724374; Phenotypes: hereditary thoracic aortic aneurysm and dissection; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital Heart Defect v0.48 ABL1 Ain Roesley gene: ABL1 was added
gene: ABL1 was added to Congenital Heart Defect. Sources: Literature
Mode of inheritance for gene: ABL1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ABL1 were set to PMID: 28288113
Phenotypes for gene: ABL1 were set to Congenital heart defects and skeletal malformations syndrome (MIM# 617602)
Penetrance for gene: ABL1 were set to unknown
Review for gene: ABL1 was set to GREEN
Added comment: PMID: 28288113: six affected individuals from 4 unrelated families who shared similar clinical features including dysmorphic facial features (6/6), congenital heart disease (CHD, 6/6), skeletal abnormalities (6/6), joint problems (5/6), failure to thrive (5/6), gastrointestinal problems (5/6), and male genital/sexual abnormalities (3/4). Missense variants with 3 families sharing the same variant (Tyr245Cys).
Authors also noted similar congenital malformations observed in fetuses exposed to the selective tyrosine kinase inhibitor imatinib, and patients with constitutional ABL1 variants
Sources: Literature
Aortopathy_Connective Tissue Disorders v0.26 ABL1 Ain Roesley reviewed gene: ABL1: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 30071989, 28288113; Phenotypes: Congenital heart defects and skeletal malformations syndrome (MIM# 617602); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Haem degradation and bilirubin metabolism defects v0.1 GATA1 Belinda Chong reviewed gene: GATA1: Rating: AMBER; Mode of pathogenicity: None; Publications: 25251786, 17148589; Phenotypes: Congenital Erythropoietic Porphyria; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Arrhythmogenic Cardiomyopathy v0.7 CHD2 Zornitza Stark Marked gene: CHD2 as ready
Arrhythmogenic Cardiomyopathy v0.7 CHD2 Zornitza Stark Gene: chd2 has been classified as Red List (Low Evidence).
Arrhythmogenic Cardiomyopathy v0.7 CHD2 Zornitza Stark gene: CHD2 was added
gene: CHD2 was added to Arrhythmogenic Right Ventricular Cardiomyopathy. Sources: Expert list
Mode of inheritance for gene: CHD2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: CHD2 were set to Arrhythmogenic right ventricular dysplasia, familial, 14, OMIM#618920
Review for gene: CHD2 was set to RED
Added comment: Several South African families reported, where missense variants segregate with ARVC. Two different variants reported.
Sources: Expert list
Haem degradation and bilirubin metabolism defects v0.1 UROD Paul De Fazio Deleted their review
Haem degradation and bilirubin metabolism defects v0.1 UROD Paul De Fazio reviewed gene: UROD: Rating: GREEN; Mode of pathogenicity: None; Publications: 9792863; Phenotypes: Porphyria cutanea tarda; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Haem degradation and bilirubin metabolism defects v0.1 ALAD Ain Roesley reviewed gene: ALAD: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 16343966, 30724374, 31311713; Phenotypes: Porphyria, acute hepatic (MIM# 612740); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Haem degradation and bilirubin metabolism defects v0.1 UROS Paul De Fazio reviewed gene: UROS: Rating: GREEN; Mode of pathogenicity: None; Publications: 8829650; Phenotypes: Congenital erythropoietic porphyria; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Haem degradation and bilirubin metabolism defects v0.1 HFE Belinda Chong reviewed gene: HFE: Rating: RED; Mode of pathogenicity: None; Publications: 235200; Phenotypes: Hemochromatosis; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hypertrophic cardiomyopathy v0.89 MYOM1 Zornitza Stark Classified gene: MYOM1 as Red List (low evidence)
Hypertrophic cardiomyopathy v0.89 MYOM1 Zornitza Stark Gene: myom1 has been classified as Red List (Low Evidence).
Mendeliome v0.3155 GANAB Zornitza Stark Marked gene: GANAB as ready
Mendeliome v0.3155 GANAB Zornitza Stark Gene: ganab has been classified as Green List (High Evidence).
Mendeliome v0.3155 GANAB Zornitza Stark Phenotypes for gene: GANAB were changed from to Polycystic kidney disease 3, MIM# 600666
Mendeliome v0.3154 GANAB Zornitza Stark Publications for gene: GANAB were set to
Mendeliome v0.3153 GANAB Zornitza Stark Mode of inheritance for gene: GANAB was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3152 GANAB Zornitza Stark reviewed gene: GANAB: Rating: GREEN; Mode of pathogenicity: None; Publications: 27259053; Phenotypes: Polycystic kidney disease 3, MIM# 600666; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Renal Macrocystic Disease v0.37 GANAB Zornitza Stark Marked gene: GANAB as ready
Renal Macrocystic Disease v0.37 GANAB Zornitza Stark Gene: ganab has been classified as Green List (High Evidence).
Renal Macrocystic Disease v0.37 GANAB Zornitza Stark Phenotypes for gene: GANAB were changed from to Polycystic kidney disease 3, MIM# 600666
Renal Macrocystic Disease v0.36 GANAB Zornitza Stark Publications for gene: GANAB were set to
Renal Macrocystic Disease v0.35 GANAB Zornitza Stark Mode of inheritance for gene: GANAB was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Renal Macrocystic Disease v0.34 GANAB Zornitza Stark reviewed gene: GANAB: Rating: GREEN; Mode of pathogenicity: None; Publications: 27259053; Phenotypes: Polycystic kidney disease 3, MIM# 600666; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Renal Macrocystic Disease v0.34 PKHD1 Zornitza Stark Marked gene: PKHD1 as ready
Renal Macrocystic Disease v0.34 PKHD1 Zornitza Stark Gene: pkhd1 has been classified as Green List (High Evidence).
Renal Macrocystic Disease v0.34 PKHD1 Zornitza Stark Phenotypes for gene: PKHD1 were changed from to Polycystic kidney disease 4, with or without hepatic disease, MIM# 263200
Renal Macrocystic Disease v0.33 PKHD1 Zornitza Stark Mode of inheritance for gene: PKHD1 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Renal Macrocystic Disease v0.33 PKHD1 Zornitza Stark Mode of inheritance for gene: PKHD1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Renal Macrocystic Disease v0.32 PKHD1 Zornitza Stark reviewed gene: PKHD1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Polycystic kidney disease 4, with or without hepatic disease, MIM# 263200; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Renal Macrocystic Disease v0.32 LRP5 Zornitza Stark Marked gene: LRP5 as ready
Renal Macrocystic Disease v0.32 LRP5 Zornitza Stark Gene: lrp5 has been classified as Red List (Low Evidence).
Renal Macrocystic Disease v0.32 LRP5 Zornitza Stark gene: LRP5 was added
gene: LRP5 was added to Renal Macrocystic Disease. Sources: Expert list
Mode of inheritance for gene: LRP5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: LRP5 were set to 25920554; 24706814
Phenotypes for gene: LRP5 were set to Polycystic liver disease 4 with or without kidney cysts, MIM# 617875
Review for gene: LRP5 was set to RED
Added comment: 5 families reported. However, some non-penetrance reported in family members in original family. In two of the families reported subsequently, PKD1 LP variants were found and LRP5 variant was postulated to be a modifier. Note that one of the variants p.Arg1036Gln is present in 692 individuals in gnomad, p.Trp560Cys is present in 9, and p.Arg1135Cys is present in 70. Overall limited evidence for association with cystic renal phenotype. Note the gene has a well-established association with eye/bone phenotypes.
Sources: Expert list
Muscular dystrophy and myopathy_Paediatric v0.48 DMD Zornitza Stark Marked gene: DMD as ready
Muscular dystrophy and myopathy_Paediatric v0.48 DMD Zornitza Stark Gene: dmd has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.48 DMD Zornitza Stark Tag SV/CNV tag was added to gene: DMD.
Muscular dystrophy and myopathy_Paediatric v0.48 DMD Zornitza Stark Phenotypes for gene: DMD were changed from to Duchenne muscular dystrophy (MIM#310200); Becker muscular dystrophy (MIM#300376)
Muscular dystrophy and myopathy_Paediatric v0.47 DMD Zornitza Stark Mode of inheritance for gene: DMD was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Muscular dystrophy and myopathy_Paediatric v0.46 Zornitza Stark removed gene:SGCG from the panel
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.18 SGCG Zornitza Stark Marked gene: SGCG as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.18 SGCG Zornitza Stark Gene: sgcg has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.18 SGCG Zornitza Stark Publications for gene: SGCG were set to
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.17 SGCG Zornitza Stark reviewed gene: SGCG: Rating: GREEN; Mode of pathogenicity: None; Publications: 30838351, 25802879; Phenotypes: Muscular dystrophy, limb-girdle, autosomal recessive 5, MIM# 253700; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Muscular dystrophy and myopathy_Paediatric v0.45 CAPN3 Zornitza Stark Marked gene: CAPN3 as ready
Muscular dystrophy and myopathy_Paediatric v0.45 CAPN3 Zornitza Stark Gene: capn3 has been classified as Red List (Low Evidence).
Muscular dystrophy and myopathy_Paediatric v0.45 CAPN3 Zornitza Stark Classified gene: CAPN3 as Red List (low evidence)
Muscular dystrophy and myopathy_Paediatric v0.45 CAPN3 Zornitza Stark Gene: capn3 has been classified as Red List (Low Evidence).
Muscular dystrophy and myopathy_Paediatric v0.44 CAPN3 Zornitza Stark reviewed gene: CAPN3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.17 CAPN3 Zornitza Stark Marked gene: CAPN3 as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.17 CAPN3 Zornitza Stark Gene: capn3 has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.17 CAPN3 Zornitza Stark Phenotypes for gene: CAPN3 were changed from Muscular dystrophy, limb-girdle, type 2A, 253600 to Muscular dystrophy, limb-girdle, autosomal dominant 4, MIM# 618129; Muscular dystrophy, limb-girdle, autosomal recessive 1, MIM# 253600
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.16 CAPN3 Zornitza Stark Publications for gene: CAPN3 were set to
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.15 CAPN3 Zornitza Stark Mode of inheritance for gene: CAPN3 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.14 CAPN3 Zornitza Stark reviewed gene: CAPN3: Rating: GREEN; Mode of pathogenicity: None; Publications: 31937337, 28881388; Phenotypes: Muscular dystrophy, limb-girdle, autosomal dominant 4, MIM# 618129, Muscular dystrophy, limb-girdle, autosomal recessive 1, MIM# 253600; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Muscular dystrophy and myopathy_Paediatric v0.44 CAPN3 Zornitza Stark Classified gene: CAPN3 as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v0.44 CAPN3 Zornitza Stark Gene: capn3 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.43 GOSR2 Zornitza Stark Marked gene: GOSR2 as ready
Muscular dystrophy and myopathy_Paediatric v0.43 GOSR2 Zornitza Stark Gene: gosr2 has been classified as Red List (Low Evidence).
Muscular dystrophy and myopathy_Paediatric v0.43 GOSR2 Zornitza Stark Classified gene: GOSR2 as Red List (low evidence)
Muscular dystrophy and myopathy_Paediatric v0.43 GOSR2 Zornitza Stark Gene: gosr2 has been classified as Red List (Low Evidence).
Muscular dystrophy and myopathy_Paediatric v0.42 MSTO1 Zornitza Stark Marked gene: MSTO1 as ready
Muscular dystrophy and myopathy_Paediatric v0.42 MSTO1 Zornitza Stark Added comment: Comment when marking as ready: Green for bi-allelic disease.
Muscular dystrophy and myopathy_Paediatric v0.42 MSTO1 Zornitza Stark Gene: msto1 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.42 MSTO1 Zornitza Stark Classified gene: MSTO1 as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v0.42 MSTO1 Zornitza Stark Gene: msto1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2707 GOLGA2 Zornitza Stark reviewed gene: GOLGA2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability syndromic and non-syndromic v0.2707 GOLGA2 Zornitza Stark Marked gene: GOLGA2 as ready
Intellectual disability syndromic and non-syndromic v0.2707 GOLGA2 Zornitza Stark Gene: golga2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2707 GOLGA2 Zornitza Stark Classified gene: GOLGA2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2707 GOLGA2 Zornitza Stark Gene: golga2 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.41 GOLGA2 Zornitza Stark reviewed gene: GOLGA2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Muscular dystrophy and myopathy_Paediatric v0.41 GOLGA2 Zornitza Stark Marked gene: GOLGA2 as ready
Muscular dystrophy and myopathy_Paediatric v0.41 GOLGA2 Zornitza Stark Gene: golga2 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.41 GOLGA2 Zornitza Stark Classified gene: GOLGA2 as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v0.41 GOLGA2 Zornitza Stark Gene: golga2 has been classified as Green List (High Evidence).
Microcephaly v0.131 GOLGA2 Zornitza Stark Marked gene: GOLGA2 as ready
Microcephaly v0.131 GOLGA2 Zornitza Stark Gene: golga2 has been classified as Green List (High Evidence).
Microcephaly v0.131 GOLGA2 Zornitza Stark Classified gene: GOLGA2 as Green List (high evidence)
Microcephaly v0.131 GOLGA2 Zornitza Stark Gene: golga2 has been classified as Green List (High Evidence).
Mendeliome v0.3152 GOLGA2 Zornitza Stark Phenotypes for gene: GOLGA2 were changed from Nueromuscular disorder to Neuromuscular disorder
Mendeliome v0.3151 GOLGA2 Zornitza Stark Marked gene: GOLGA2 as ready
Mendeliome v0.3151 GOLGA2 Zornitza Stark Gene: golga2 has been classified as Green List (High Evidence).
Mendeliome v0.3151 GOLGA2 Zornitza Stark Classified gene: GOLGA2 as Green List (high evidence)
Mendeliome v0.3151 GOLGA2 Zornitza Stark Gene: golga2 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.40 FHL1 Zornitza Stark Marked gene: FHL1 as ready
Muscular dystrophy and myopathy_Paediatric v0.40 FHL1 Zornitza Stark Gene: fhl1 has been classified as Amber List (Moderate Evidence).
Muscular dystrophy and myopathy_Paediatric v0.40 FHL1 Zornitza Stark Classified gene: FHL1 as Amber List (moderate evidence)
Muscular dystrophy and myopathy_Paediatric v0.40 FHL1 Zornitza Stark Gene: fhl1 has been classified as Amber List (Moderate Evidence).
Muscular dystrophy and myopathy_Paediatric v0.39 PLEC Zornitza Stark reviewed gene: PLEC: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Muscular dystrophy and myopathy_Paediatric v0.39 PLEC Zornitza Stark Marked gene: PLEC as ready
Muscular dystrophy and myopathy_Paediatric v0.39 PLEC Zornitza Stark Gene: plec has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.39 PLEC Zornitza Stark Classified gene: PLEC as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v0.39 PLEC Zornitza Stark Gene: plec has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.38 EMD Zornitza Stark Marked gene: EMD as ready
Muscular dystrophy and myopathy_Paediatric v0.38 EMD Zornitza Stark Gene: emd has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.38 EMD Zornitza Stark Classified gene: EMD as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v0.38 EMD Zornitza Stark Gene: emd has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.14 POGLUT1 Zornitza Stark Marked gene: POGLUT1 as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.14 POGLUT1 Zornitza Stark Gene: poglut1 has been classified as Amber List (Moderate Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.14 POGLUT1 Zornitza Stark Phenotypes for gene: POGLUT1 were changed from Limb-girdle muscular dystrophy to Muscular dystrophy, limb-girdle, autosomal recessive 21 (MIM#617232)
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.13 POGLUT1 Zornitza Stark Publications for gene: POGLUT1 were set to
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.12 POGLUT1 Zornitza Stark Classified gene: POGLUT1 as Amber List (moderate evidence)
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.12 POGLUT1 Zornitza Stark Gene: poglut1 has been classified as Amber List (Moderate Evidence).
Muscular dystrophy and myopathy_Paediatric v0.37 RYR1 Zornitza Stark Marked gene: RYR1 as ready
Muscular dystrophy and myopathy_Paediatric v0.37 RYR1 Zornitza Stark Gene: ryr1 has been classified as Red List (Low Evidence).
Muscular dystrophy and myopathy_Paediatric v0.37 RYR1 Zornitza Stark Phenotypes for gene: RYR1 were changed from to Central core disease (MIM#117000); Minicore myopathy with external ophthalmoplegia (MIM#255320); Neuromuscular disease, congenital, with uniform type 1 fiber (MIM#117000)
Muscular dystrophy and myopathy_Paediatric v0.36 RYR1 Zornitza Stark Publications for gene: RYR1 were set to
Muscular dystrophy and myopathy_Paediatric v0.35 RYR1 Zornitza Stark Mode of inheritance for gene: RYR1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Muscular dystrophy and myopathy_Paediatric v0.34 RYR1 Zornitza Stark Classified gene: RYR1 as Red List (low evidence)
Muscular dystrophy and myopathy_Paediatric v0.34 RYR1 Zornitza Stark Gene: ryr1 has been classified as Red List (Low Evidence).
Muscular dystrophy and myopathy_Paediatric v0.33 RYR1 Zornitza Stark reviewed gene: RYR1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability syndromic and non-syndromic v0.2706 SIL1 Zornitza Stark Marked gene: SIL1 as ready
Intellectual disability syndromic and non-syndromic v0.2706 SIL1 Zornitza Stark Gene: sil1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2706 SIL1 Zornitza Stark Phenotypes for gene: SIL1 were changed from to Marinesco-Sjogren syndrome (MIM#248800)
Intellectual disability syndromic and non-syndromic v0.2705 SIL1 Zornitza Stark Publications for gene: SIL1 were set to
Intellectual disability syndromic and non-syndromic v0.2704 SIL1 Zornitza Stark Mode of inheritance for gene: SIL1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Cataract v0.149 SIL1 Zornitza Stark Marked gene: SIL1 as ready
Cataract v0.149 SIL1 Zornitza Stark Gene: sil1 has been classified as Green List (High Evidence).
Cataract v0.149 SIL1 Zornitza Stark Phenotypes for gene: SIL1 were changed from to Marinesco-Sjogren syndrome (MIM#248800)
Cataract v0.148 SIL1 Zornitza Stark Publications for gene: SIL1 were set to
Cataract v0.147 SIL1 Zornitza Stark Mode of inheritance for gene: SIL1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Muscular dystrophy and myopathy_Paediatric v0.33 SIL1 Zornitza Stark Marked gene: SIL1 as ready
Muscular dystrophy and myopathy_Paediatric v0.33 SIL1 Zornitza Stark Gene: sil1 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.33 SIL1 Zornitza Stark Classified gene: SIL1 as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v0.33 SIL1 Zornitza Stark Gene: sil1 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.32 SIL1 Zornitza Stark reviewed gene: SIL1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.11 TCAP Zornitza Stark Marked gene: TCAP as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.11 TCAP Zornitza Stark Gene: tcap has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.11 TCAP Zornitza Stark Publications for gene: TCAP were set to
Muscular dystrophy and myopathy_Paediatric v0.32 TCAP Zornitza Stark Marked gene: TCAP as ready
Muscular dystrophy and myopathy_Paediatric v0.32 TCAP Zornitza Stark Gene: tcap has been classified as Red List (Low Evidence).
Muscular dystrophy and myopathy_Paediatric v0.32 TCAP Zornitza Stark Phenotypes for gene: TCAP were changed from to Muscular dystrophy, limb-girdle, autosomal recessive 7 (MIM#601954)
Muscular dystrophy and myopathy_Paediatric v0.31 TCAP Zornitza Stark Publications for gene: TCAP were set to
Muscular dystrophy and myopathy_Paediatric v0.30 TCAP Zornitza Stark Mode of inheritance for gene: TCAP was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Muscular dystrophy and myopathy_Paediatric v0.29 TCAP Zornitza Stark Classified gene: TCAP as Red List (low evidence)
Muscular dystrophy and myopathy_Paediatric v0.29 TCAP Zornitza Stark Gene: tcap has been classified as Red List (Low Evidence).
Microcephaly v0.130 DPM1 Zornitza Stark Marked gene: DPM1 as ready
Microcephaly v0.130 DPM1 Zornitza Stark Gene: dpm1 has been classified as Green List (High Evidence).
Microcephaly v0.130 DPM1 Zornitza Stark Classified gene: DPM1 as Green List (high evidence)
Microcephaly v0.130 DPM1 Zornitza Stark Gene: dpm1 has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.10 TRAPPC11 Zornitza Stark Marked gene: TRAPPC11 as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.10 TRAPPC11 Zornitza Stark Gene: trappc11 has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.10 TRAPPC11 Zornitza Stark Publications for gene: TRAPPC11 were set to
Muscular dystrophy and myopathy_Paediatric v0.28 TRAPPC11 Zornitza Stark Marked gene: TRAPPC11 as ready
Muscular dystrophy and myopathy_Paediatric v0.28 TRAPPC11 Zornitza Stark Gene: trappc11 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.28 TRAPPC11 Zornitza Stark Classified gene: TRAPPC11 as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v0.28 TRAPPC11 Zornitza Stark Gene: trappc11 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.27 SGCG Elena Savva gene: SGCG was added
gene: SGCG was added to Muscular dystrophy. Sources: Literature
Mode of inheritance for gene: SGCG was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SGCG were set to PMID: 30838351; 25802879
Phenotypes for gene: SGCG were set to Muscular dystrophy, limb-girdle, autosomal recessive 5 253700
Review for gene: SGCG was set to AMBER
Added comment: PMID: 30838351 - 7 patients with childhood onset limb girdle MD and biallelic variants. Muscle biopsy supported the diagnosis. Mild proximal muscle weakness and increased serum creatine kinase levels

PMID: 25802879 - 2 unrelated patients with a founder missense variant (p.E263K). Patients had childhood onset, with proximal muscle weakness in pelvic girdle muscles and highly elevated CK levels.

Summary: Childhood onset limb girdle rather than muscular dystrophy
Sources: Literature
Muscular dystrophy and myopathy_Paediatric v0.27 CAPN3 Elena Savva gene: CAPN3 was added
gene: CAPN3 was added to Muscular dystrophy. Sources: Literature
Mode of inheritance for gene: CAPN3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CAPN3 were set to PMID: 31937337
Phenotypes for gene: CAPN3 were set to Muscular dystrophy, limb-girdle, autosomal recessive 1 253600
Review for gene: CAPN3 was set to GREEN
Added comment: PMID: 31937337 - 15 families with limb girdle muscular dystrophy. 13/15 report childhood onset in multiple affected children, where EMG confirmed a myopathic disorder, with mild-severe dystrophic changes.
Sources: Literature
Muscular dystrophy and myopathy_Paediatric v0.27 GOSR2 Elena Savva reviewed gene: GOSR2: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 30363482, 29855340; Phenotypes: Epilepsy, progressive myoclonic 6 614018; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Muscular dystrophy and myopathy_Paediatric v0.27 GOSR2 Elena Savva Deleted their review
Muscular dystrophy and myopathy_Paediatric v0.27 GOSR2 Elena Savva gene: GOSR2 was added
gene: GOSR2 was added to Muscular dystrophy. Sources: Expert list
Mode of inheritance for gene: GOSR2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GOSR2 were set to PMID: 30363482; 29855340
Phenotypes for gene: GOSR2 were set to Epilepsy, progressive myoclonic 6 614018
Added comment: PMID: 30363482 - 1 chet patient, no mention of myopathy or muscular dystrophy. Patient had a missense and inframe deletion of a single amino acid.

PMID: 29855340 - 1 chet family (2 siblings) with neonatal hypotonia, muscle weaknes and elevated CK levels. One sibling died before genotyping, the other was found to be chet for a missense/start loss variant. Patient had dystrophic muscle biopsy with hypoglycosylation of α-dystroglycan
Paper reviews other patients and notes muscle histology and EMG were normal, no specific abnormalities reported (most carried recurring variant p.Gly144Trp).

Summary: single report of muscular dystrophy but only report of a start loss variant. All others are of an inframe deletion or the recurring missense.
Sources: Expert list
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.8 IL17RD Bryony Thompson gene: IL17RD was added
gene: IL17RD was added to Amenorrhoea. Sources: Expert Review Green,Royal Melbourne Hospital
Mode of inheritance for gene: IL17RD was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: IL17RD were set to Hypogonadotropic hypogonadism 18 with or without anosmia 615267
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.8 HS6ST1 Bryony Thompson gene: HS6ST1 was added
gene: HS6ST1 was added to Amenorrhoea. Sources: Expert Review Green,Royal Melbourne Hospital
Mode of inheritance for gene: HS6ST1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: HS6ST1 were set to {Hypogonadotropic hypogonadism 15 with or without anosmia} 614880
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.8 HNF1B Bryony Thompson gene: HNF1B was added
gene: HNF1B was added to Amenorrhoea. Sources: Expert Review Green,Royal Melbourne Hospital
Mode of inheritance for gene: HNF1B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: HNF1B were set to Renal cysts and diabetes syndrome 137920 AD
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.8 HARS2 Bryony Thompson gene: HARS2 was added
gene: HARS2 was added to Amenorrhoea. Sources: Expert Review Green,Royal Melbourne Hospital
Mode of inheritance for gene: HARS2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: HARS2 were set to ?Perrault syndrome 2 614926
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.8 GNRHR Bryony Thompson gene: GNRHR was added
gene: GNRHR was added to Amenorrhoea. Sources: Expert Review Green,Royal Melbourne Hospital
Mode of inheritance for gene: GNRHR was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: GNRHR were set to Hypogonadotropic hypogonadism 7 without anosmia 146110
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.8 GNRH1 Bryony Thompson gene: GNRH1 was added
gene: GNRH1 was added to Amenorrhoea. Sources: Expert Review Green,Royal Melbourne Hospital
Mode of inheritance for gene: GNRH1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: GNRH1 were set to ?Hypogonadotropic hypogonadism 12 with or without anosmia 614841
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.8 FLRT3 Bryony Thompson gene: FLRT3 was added
gene: FLRT3 was added to Amenorrhoea. Sources: Expert Review Green,Royal Melbourne Hospital
Mode of inheritance for gene: FLRT3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: FLRT3 were set to Hypogonadotropic hypogonadism 21 with anosmia 615271
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.8 FGF8 Bryony Thompson gene: FGF8 was added
gene: FGF8 was added to Amenorrhoea. Sources: Expert Review Green,Royal Melbourne Hospital
Mode of inheritance for gene: FGF8 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: FGF8 were set to Hypogonadotropic hypogonadism 6 with or without anosmia 612702
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.8 FGF17 Bryony Thompson gene: FGF17 was added
gene: FGF17 was added to Amenorrhoea. Sources: Expert Review Green,Royal Melbourne Hospital
Mode of inheritance for gene: FGF17 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: FGF17 were set to Hypogonadotropic hypogonadism 20 with or without anosmia 615270
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.8 FEZF1 Bryony Thompson gene: FEZF1 was added
gene: FEZF1 was added to Amenorrhoea. Sources: Expert Review Green,Royal Melbourne Hospital
Mode of inheritance for gene: FEZF1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: FEZF1 were set to Hypogonadotropic hypogonadism 22, with or without anosmia 616030
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.8 ESR2 Bryony Thompson gene: ESR2 was added
gene: ESR2 was added to Amenorrhoea. Sources: Expert Review Green,Royal Melbourne Hospital
Mode of inheritance for gene: ESR2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: ESR2 were set to ?Ovarian dysgenesis 8 618187
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.8 ERCC6 Bryony Thompson gene: ERCC6 was added
gene: ERCC6 was added to Amenorrhoea. Sources: Expert Review Green,Royal Melbourne Hospital
Mode of inheritance for gene: ERCC6 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: ERCC6 were set to Premature ovarian failure 11 616946
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.8 DUSP6 Bryony Thompson gene: DUSP6 was added
gene: DUSP6 was added to Amenorrhoea. Sources: Expert Review Green,Royal Melbourne Hospital
Mode of inheritance for gene: DUSP6 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: DUSP6 were set to Hypogonadotropic hypogonadism 19 with or without anosmia 615269
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.8 DIAPH2 Bryony Thompson gene: DIAPH2 was added
gene: DIAPH2 was added to Amenorrhoea. Sources: Expert Review Green,Royal Melbourne Hospital
Mode of inheritance for gene: DIAPH2 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Phenotypes for gene: DIAPH2 were set to ?Premature ovarian failure 2A 300511
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.8 CHD7 Bryony Thompson gene: CHD7 was added
gene: CHD7 was added to Amenorrhoea. Sources: Expert Review Green,Royal Melbourne Hospital
Mode of inheritance for gene: CHD7 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: CHD7 were set to Hypogonadotropic hypogonadism 5 with or without anosmia 612370; CHARGE syndrome 214800
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.8 AXL Bryony Thompson gene: AXL was added
gene: AXL was added to Amenorrhoea. Sources: Expert Review Green,Royal Melbourne Hospital
Mode of inheritance for gene: AXL was set to
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.8 ANOS1 Bryony Thompson gene: ANOS1 was added
gene: ANOS1 was added to Amenorrhoea. Sources: Expert Review Green,Royal Melbourne Hospital
Mode of inheritance for gene: ANOS1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: ANOS1 were set to Hypogonadotropic hypogonadism 1 with or without anosmia (Kallmann syndrome 1) 308700
Muscular dystrophy and myopathy_Paediatric v0.27 MSTO1 Crystle Lee gene: MSTO1 was added
gene: MSTO1 was added to Muscular dystrophy. Sources: Expert Review
Mode of inheritance for gene: MSTO1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: MSTO1 were set to 28554942; 28544275; 31604776
Phenotypes for gene: MSTO1 were set to Myopathy, mitochondrial, and ataxia (MIM#617675)
Review for gene: MSTO1 was set to GREEN
Added comment: >5 families reported. Early onset, elevated CK levels and myopathic patterns on EMG reported in almost all patients. Primarily a recessive disorder. Limited evidence supporting AD inheritance, which was reported in one family where CK levels were normal and age of onset was later.

PMID: 31604776: One patient reported. Provides review of previously published MSTO1 families.
Sources: Expert Review
Intellectual disability syndromic and non-syndromic v0.2703 GOLGA2 Elena Savva gene: GOLGA2 was added
gene: GOLGA2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: GOLGA2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GOLGA2 were set to PMID: 30237576; 26742501
Phenotypes for gene: GOLGA2 were set to Neuromuscular disorder
Review for gene: GOLGA2 was set to AMBER
Added comment: PMID: 30237576 - One 11 year old patient with a homozygous PTC.
Patient had global dev delay, microcephaly, distal muscle weakness with joint contractures and elevated CK levels. Muscle biopsy showed dystrophin changes. MRI at 2 years old showed brain atrophy with thin corpus callosum and hypomyelination. No seizures or regression.

PMID: 26742501 - One infant with a homozygous PTC.
Patient had dev delay, seizures, microcephaly and muscular dystrophy. Zebrafish null model recapitulates the human phenotype with microcephaly and skeletal muscle disorganization.

Summary: 2 patients
Sources: Literature
Muscular dystrophy and myopathy_Paediatric v0.27 GOLGA2 Elena Savva gene: GOLGA2 was added
gene: GOLGA2 was added to Muscular dystrophy. Sources: Literature
Mode of inheritance for gene: GOLGA2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GOLGA2 were set to PMID: 30237576; 26742501
Phenotypes for gene: GOLGA2 were set to Neuromuscular disorder
Review for gene: GOLGA2 was set to AMBER
Added comment: PMID: 30237576 - One 11 year old patient with a homozygous PTC.
Patient had global dev delay, microcephaly, distal muscle weakness with joint contractures and elevated CK levels. Muscle biopsy showed dystrophin changes. MRI at 2 years old showed brain atrophy with thin corpus callosum and hypomyelination. No seizures or regression.

PMID: 26742501 - One infant with a homozygous PTC.
Patient had dev delay, seizures, microcephaly and muscular dystrophy. Zebrafish null model recapitulates the human phenotype with microcephaly and skeletal muscle disorganization.

Summary: 2 patients + animal model
Sources: Literature
Microcephaly v0.129 GOLGA2 Elena Savva gene: GOLGA2 was added
gene: GOLGA2 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: GOLGA2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GOLGA2 were set to PMID: 30237576; 26742501
Phenotypes for gene: GOLGA2 were set to Neuromuscular disorder
Review for gene: GOLGA2 was set to GREEN
Added comment: PMID: 30237576 - One 11 year old patient with a homozygous PTC.
Patient had global dev delay, microcephaly, distal muscle weakness with joint contractures and elevated CK levels. Muscle biopsy showed dystrophin changes. MRI at 2 years old showed brain atrophy with thin corpus callosum and hypomyelination. No seizures or regression.

PMID: 26742501 - One infant with a homozygous PTC.
Patient had dev delay, seizures, microcephaly and muscular dystrophy. Zebrafish null model recapitulates the human phenotype with microcephaly and skeletal muscle disorganization.

Summary: 2 patients + animal model
Sources: Literature
Mendeliome v0.3150 GOLGA2 Elena Savva gene: GOLGA2 was added
gene: GOLGA2 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: GOLGA2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GOLGA2 were set to PMID: 30237576; 26742501
Phenotypes for gene: GOLGA2 were set to Nueromuscular disorder
Review for gene: GOLGA2 was set to GREEN
Added comment: PMID: 30237576 - One 11 year old patient with a homozygous PTC.
Patient had global dev delay, microcephaly, distal muscle weakness with joint contractures and elevated CK levels. Muscle biopsy showed dystrophin changes. MRI at 2 years old showed brain atrophy with thin corpus callosum and hypomyelination. No seizures or regression.

PMID: 26742501 - One infant with a homozygous PTC.
Patient had dev delay, seizures, microcephaly and muscular dystrophy. Zebrafish null model recapitulates the human phenotype with microcephaly and skeletal muscle disorganization.

Summary: 2 patients + animal model
Sources: Expert list
Muscular dystrophy and myopathy_Paediatric v0.27 FHL1 Elena Savva gene: FHL1 was added
gene: FHL1 was added to Muscular dystrophy. Sources: Expert list
Mode of inheritance for gene: FHL1 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: FHL1 were set to PMID: 19181672; 19171836
Phenotypes for gene: FHL1 were set to Reducing body myopathy, X-linked 1a, severe, infantile or early childhood onset, MIM# 300717
Review for gene: FHL1 was set to AMBER
Added comment: XLD, severe progressive myopathy with onset in infancy.

PMID: 19181672 - 11 patients (9 families) with reducing body myopathy. All patients had progressive muscle weakness with 7/11 having onset <5 years old. Majority had proximal muscle weakness with elevated CK levels. Authors note "we would be hesitant to use the term dystrophic for this myopathy as the mechanisms of cell damage remain to be fully worked out"
p.His123 is a hotspot with recurring de novo missense mutations at this residue.

PMID: 19171836 - 5 patients with reducing body myopathy, 2/5 had fatal infantile forms of disease.

Summary: congenital onset has been found, however unsure if this qualifies as a dystrophy or only myopathy
Sources: Expert list
Muscular dystrophy and myopathy_Paediatric v0.27 PLEC Crystle Lee gene: PLEC was added
gene: PLEC was added to Muscular dystrophy. Sources: Expert Review
Mode of inheritance for gene: PLEC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PLEC were set to 20624679; 21109228; 28824526
Phenotypes for gene: PLEC were set to Muscular dystrophy, limb-girdle, autosomal recessive 17 (MIM#613723)
Added comment: Onset in early childhood (OMIM).

PMID: 20624679: Reported 1 patient with congenital muscular dystrophy, hypotonia and elevated CK.

PMID: 21109228: Same homozygous variant affecting isoform 1f reported in 3 families. 2 affected members of one family reported as having early onset LMGD. Authors note that PLEC is usually associated with late-onset progressive muscle dystrophy.

PMID: 28824526: 1 patient reported with early childhood onset. Variant affects isoform 1f.


Rated GREEN in CMD (PanelApp UK)
Sources: Expert Review
Muscular dystrophy and myopathy_Paediatric v0.27 EMD Elena Savva gene: EMD was added
gene: EMD was added to Muscular dystrophy. Sources: Expert list
Mode of inheritance for gene: EMD was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: EMD were set to PMID: 21697856; 31802929
Phenotypes for gene: EMD were set to Emery-Dreifuss muscular dystrophy 1, X-linked 310300
Review for gene: EMD was set to GREEN
Added comment: PMID: 21697856 - 21 male patients with EM muscular dystrophy. Age of onset not well reported, only age at diagnosis. Youngest patient was 5 days old but asymptomatic, eldest was 55 years.
Of those with age of onset reported, 3 had progressive muscle weakness onset from neonatal-5 years.

PMID: 31802929 - 1 family (9 affected males) with elevated CK levels and mild skeletal muscular dystrophy. Youngest affected was 7 years old

PMID: 31645980 - 1 patient with difficulty moving his limb girdle and cervical vertebrae from 5 years old.

Summary: childhood onset reported
Sources: Expert list
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.9 POGLUT1 Crystle Lee reviewed gene: POGLUT1: Rating: AMBER; Mode of pathogenicity: None; Publications: 27807076, 29034878; Phenotypes: Muscular dystrophy, limb-girdle, autosomal recessive 21 (MIM#617232); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Muscular dystrophy and myopathy_Paediatric v0.27 TCAP Crystle Lee Deleted their comment
Muscular dystrophy and myopathy_Paediatric v0.27 TCAP Crystle Lee edited their review of gene: TCAP: Added comment: >3 variants/families reported. Mean age at onset 12.5 years (OMIM). More suitable for LGMD panel.

PMID: 25055047: 2 different variants reported in 2 Dravidian families with LGMD, with a predominantly proximo - distal form of weakness. Raised CK levels consistent between all patients reported. Age of onset ranged from 4 - 23.

Abstract (https://doi.org/10.1016/j.nmd.2012.06.100): Same frameshift variant reported in (PMID: 25055047) identified in one adult patient who presented with progressive muscle weakness in his late teenage years. Authors notes this is the 9th family reported with variants in this gene.

PMID: 22029105: 1 adult patient with slowly progressive weakness in the upper and lower limbs reported with onset in early twenties. Elevated CK levels.

PMID: 18948002: Reported one patient who presented at the age of 15 with progressive proximal limb weakness.; Changed rating: RED
Muscular dystrophy and myopathy_Paediatric v0.27 RYR1 Crystle Lee reviewed gene: RYR1: Rating: AMBER; Mode of pathogenicity: None; Publications: 23553484; Phenotypes: Central core disease (MIM#117000), Minicore myopathy with external ophthalmoplegia (MIM#255320), Neuromuscular disease, congenital, with uniform type 1 fiber (MIM#117000); Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2703 SIL1 Crystle Lee reviewed gene: SIL1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24176978, 16282977; Phenotypes: Marinesco-Sjogren syndrome (MIM#248800); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cataract v0.146 SIL1 Crystle Lee reviewed gene: SIL1: Rating: GREEN; Mode of pathogenicity: None; Publications: 16282977, 24176978; Phenotypes: Marinesco-Sjogren syndrome (MIM#248800); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Muscular dystrophy and myopathy_Paediatric v0.27 SIL1 Crystle Lee gene: SIL1 was added
gene: SIL1 was added to Muscular dystrophy. Sources: Expert Review
Mode of inheritance for gene: SIL1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SIL1 were set to 16282977; 24176978
Phenotypes for gene: SIL1 were set to Marinesco-Sjogren syndrome (MIM#248800)
Added comment: Well reported in patients with the associated phenotype. Onset in infancy. Muscle weakness and elevated CK are consistent features of this phenotype. Myopathic changes observed in muscle biopsy.
Sources: Expert Review
Muscular dystrophy and myopathy_Paediatric v0.27 SYNE1 Zornitza Stark changed review comment from: Congenital onset described in at least two families.; to: Congenital onset described in at least two families with bi-allelic variants.
Muscular dystrophy and myopathy_Paediatric v0.27 SYNE1 Zornitza Stark edited their review of gene: SYNE1: Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Muscular dystrophy and myopathy_Paediatric v0.27 SYNE1 Zornitza Stark Mode of inheritance for gene: SYNE1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BIALLELIC, autosomal or pseudoautosomal
Muscular dystrophy and myopathy_Paediatric v0.26 SYNE1 Zornitza Stark Marked gene: SYNE1 as ready
Muscular dystrophy and myopathy_Paediatric v0.26 SYNE1 Zornitza Stark Gene: syne1 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.26 SYNE1 Zornitza Stark Phenotypes for gene: SYNE1 were changed from to Emery-Dreifuss muscular dystrophy 4, autosomal dominant 612998
Muscular dystrophy and myopathy_Paediatric v0.25 SYNE1 Zornitza Stark Publications for gene: SYNE1 were set to
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.9 TCAP Crystle Lee reviewed gene: TCAP: Rating: GREEN; Mode of pathogenicity: None; Publications: 25055047, 22029105, 18948002; Phenotypes: Muscular dystrophy, limb-girdle, autosomal recessive 7 (MIM#601954); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Muscular dystrophy and myopathy_Paediatric v0.24 SYNE1 Zornitza Stark Mode of inheritance for gene: SYNE1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Muscular dystrophy and myopathy_Paediatric v0.23 SYNE1 Zornitza Stark reviewed gene: SYNE1: Rating: GREEN; Mode of pathogenicity: None; Publications: 27782104, 19542096; Phenotypes: Emery-Dreifuss muscular dystrophy 4, autosomal dominant 612998; Mode of inheritance: None
Muscular dystrophy and myopathy_Paediatric v0.23 Zornitza Stark removed gene:ANO5 from the panel
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.9 ANO5 Zornitza Stark Marked gene: ANO5 as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.9 ANO5 Zornitza Stark Gene: ano5 has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.9 ANO5 Zornitza Stark Phenotypes for gene: ANO5 were changed from Gnathodiaphyseal dysplasia, 166260; Muscular dystrophy, limb-girdle, type 2L, 611307; Miyoshi muscular dystrophy 3, 613319 to Muscular dystrophy, limb-girdle, type 2L, 611307; Miyoshi muscular dystrophy 3, 613319
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.8 ANO5 Zornitza Stark Publications for gene: ANO5 were set to
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.7 ANO5 Zornitza Stark reviewed gene: ANO5: Rating: GREEN; Mode of pathogenicity: None; Publications: 20096397 32399949; Phenotypes: Muscular dystrophy, limb-girdle, autosomal recessive 12 611307; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Muscular dystrophy and myopathy_Paediatric v0.22 Zornitza Stark Panel types changed to Victorian Clinical Genetics Services; Rare Disease
Muscular dystrophy and myopathy_Paediatric v0.21 TCAP Crystle Lee reviewed gene: TCAP: Rating: GREEN; Mode of pathogenicity: None; Publications: 25055047, 22029105, 18948002; Phenotypes: Muscular dystrophy, limb-girdle, autosomal recessive 7 (MIM#601954); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v0.129 DPM1 Elena Savva gene: DPM1 was added
gene: DPM1 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: DPM1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DPM1 were set to PMID:16641202; 10642602; 10642597
Phenotypes for gene: DPM1 were set to Congenital disorder of glycosylation, type Ie 608799
Added comment: PMID: 16641202 - 2 siblings of consanguineous parents. One patient showed retarded motor skills at 1, 2 and 4 years old, with distal myopathy present at 3 years of age. The younger sister presented at 7 weeks of age with generalized hypotonia. Both had normal CK levels. Both siblings were progressively microcephalic.

PMID: 10642602 - 2 chet siblings with hypotonia within the first year of life. Both had elevated CK. Both siblings were progressively microcephalic

PMID: 10642597 - 2 unrelated patients. One had profound hypotonia at 3 years of age. The other patient was markedly hypotonic in infancy. Both were microcephalic and hd elevated CK levels.
Sources: Literature
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.7 TRAPPC11 Crystle Lee reviewed gene: TRAPPC11: Rating: GREEN; Mode of pathogenicity: None; Publications: 23830518, 26322222, 29855340, 30105108; Phenotypes: Muscular dystrophy, limb-girdle, autosomal recessive 18 (MIM#615356); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Muscular dystrophy and myopathy_Paediatric v0.21 TRAPPC11 Crystle Lee gene: TRAPPC11 was added
gene: TRAPPC11 was added to Muscular dystrophy. Sources: Expert list
Mode of inheritance for gene: TRAPPC11 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRAPPC11 were set to 23830518; 26322222; 29855340; 30105108
Phenotypes for gene: TRAPPC11 were set to Muscular dystrophy, limb-girdle, autosomal recessive 18 (MIM#615356)
Review for gene: TRAPPC11 was set to GREEN
Added comment: >3 patients reported with variable muscle phenotype (primarily LGMD), which is a significant feature of this multisystemic childhood onset condition. Elevated CK consistent feature.

PMID: 23830518: 2 different variants reported. Patients from one family presented with early onset proximal muscle weakness and raised CK levels. The second family presented with muscle weakness and elevated CK suggestive of myopathy.

PMID: 26322222: Reported childhood onset muscular dystrophy in one patient

PMID: 29855340: 1 patient with biallelic variants in TRAPPC11

PMID: 30105108: 2 siblings with promixal muscle weakness reported. Childhood onset.
Sources: Expert list
Mendeliome v0.3150 MUC7 Bryony Thompson Classified gene: MUC7 as Red List (low evidence)
Mendeliome v0.3150 MUC7 Bryony Thompson Gene: muc7 has been classified as Red List (Low Evidence).
Mendeliome v0.3149 MUC7 Bryony Thompson reviewed gene: MUC7: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: {Asthma, protection against} MIM#600807; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3149 HTR3D Bryony Thompson Marked gene: HTR3D as ready
Mendeliome v0.3149 HTR3D Bryony Thompson Gene: htr3d has been classified as Red List (Low Evidence).
Mendeliome v0.3149 HTR3D Bryony Thompson Classified gene: HTR3D as Red List (low evidence)
Mendeliome v0.3149 HTR3D Bryony Thompson Gene: htr3d has been classified as Red List (Low Evidence).
Mendeliome v0.3148 HTR3D Bryony Thompson reviewed gene: HTR3D: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: Unknown
Mendeliome v0.3148 ALOX5AP Bryony Thompson Marked gene: ALOX5AP as ready
Mendeliome v0.3148 ALOX5AP Bryony Thompson Gene: alox5ap has been classified as Red List (Low Evidence).
Mendeliome v0.3148 ALOX5AP Bryony Thompson Classified gene: ALOX5AP as Red List (low evidence)
Mendeliome v0.3148 ALOX5AP Bryony Thompson Gene: alox5ap has been classified as Red List (Low Evidence).
Mendeliome v0.3147 ALOX5AP Bryony Thompson reviewed gene: ALOX5AP: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: {Stroke, susceptibility to} MIM#601367; Mode of inheritance: Unknown
Muscular dystrophy and myopathy_Paediatric v0.21 COL4A2 Zornitza Stark Marked gene: COL4A2 as ready
Muscular dystrophy and myopathy_Paediatric v0.21 COL4A2 Zornitza Stark Gene: col4a2 has been classified as Red List (Low Evidence).
Muscular dystrophy and myopathy_Paediatric v0.21 COL4A2 Zornitza Stark Classified gene: COL4A2 as Red List (low evidence)
Muscular dystrophy and myopathy_Paediatric v0.21 COL4A2 Zornitza Stark Gene: col4a2 has been classified as Red List (Low Evidence).
Muscular dystrophy and myopathy_Paediatric v0.20 COL4A1 Zornitza Stark Phenotypes for gene: COL4A1 were changed from ?Retinal arteries, tortuosity of MIM#180000; Angiopathy, hereditary, with nephropathy, aneurysms, and muscle cramps MIM#611773; Brain small vessel disease with or without ocular anomalies MIM#175780; Microangiopathy and leukoencephalopathy, pontine, autosomal dominant MIM#618564 to Angiopathy, hereditary, with nephropathy, aneurysms, and muscle cramps MIM#611773; Brain small vessel disease with or without ocular anomalies MIM#175780; Microangiopathy and leukoencephalopathy, pontine, autosomal dominant MIM#618564
Muscular dystrophy and myopathy_Paediatric v0.19 COL4A1 Zornitza Stark Publications for gene: COL4A1 were set to 23065703; 20818663
Muscular dystrophy and myopathy_Paediatric v0.18 COL4A1 Zornitza Stark Classified gene: COL4A1 as Amber List (moderate evidence)
Muscular dystrophy and myopathy_Paediatric v0.18 COL4A1 Zornitza Stark Gene: col4a1 has been classified as Amber List (Moderate Evidence).
Muscular dystrophy and myopathy_Paediatric v0.17 CAVIN1 Zornitza Stark Publications for gene: CAVIN1 were set to
Muscular dystrophy and myopathy_Paediatric v0.16 CAVIN1 Zornitza Stark edited their review of gene: CAVIN1: Changed publications: 19726876, 12116229
Muscular dystrophy and myopathy_Paediatric v0.16 ANO5 Zornitza Stark Marked gene: ANO5 as ready
Muscular dystrophy and myopathy_Paediatric v0.16 ANO5 Zornitza Stark Gene: ano5 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.16 ANO5 Zornitza Stark Classified gene: ANO5 as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v0.16 ANO5 Zornitza Stark Gene: ano5 has been classified as Green List (High Evidence).
Dystonia and Chorea v0.69 SQSTM1 Zornitza Stark Marked gene: SQSTM1 as ready
Dystonia and Chorea v0.69 SQSTM1 Zornitza Stark Gene: sqstm1 has been classified as Green List (High Evidence).
Dystonia and Chorea v0.69 SQSTM1 Zornitza Stark Classified gene: SQSTM1 as Green List (high evidence)
Dystonia and Chorea v0.69 SQSTM1 Zornitza Stark Gene: sqstm1 has been classified as Green List (High Evidence).
Arrhythmogenic Cardiomyopathy v0.6 JUP Zornitza Stark Marked gene: JUP as ready
Arrhythmogenic Cardiomyopathy v0.6 JUP Zornitza Stark Gene: jup has been classified as Green List (High Evidence).
Arrhythmogenic Cardiomyopathy v0.6 JUP Zornitza Stark Phenotypes for gene: JUP were changed from to Arrhythmogenic right ventricular dysplasia 12 MIM# 611528; Naxos disease MIM# 601214
Arrhythmogenic Cardiomyopathy v0.5 JUP Zornitza Stark Publications for gene: JUP were set to
Arrhythmogenic Cardiomyopathy v0.4 JUP Zornitza Stark Mode of inheritance for gene: JUP was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.7 PNPLA2 Zornitza Stark Marked gene: PNPLA2 as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.7 PNPLA2 Zornitza Stark Gene: pnpla2 has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.7 PNPLA2 Zornitza Stark Classified gene: PNPLA2 as Green List (high evidence)
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.7 PNPLA2 Zornitza Stark Gene: pnpla2 has been classified as Green List (High Evidence).
Mendeliome v0.3147 PHOX2A Zornitza Stark Marked gene: PHOX2A as ready
Mendeliome v0.3147 PHOX2A Zornitza Stark Gene: phox2a has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3147 PHOX2A Zornitza Stark Phenotypes for gene: PHOX2A were changed from to Fibrosis of extraocular muscles, congenital, 2 602078
Mendeliome v0.3146 PHOX2A Zornitza Stark Publications for gene: PHOX2A were set to
Mendeliome v0.3145 PHOX2A Zornitza Stark Mode of inheritance for gene: PHOX2A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3144 PHOX2A Zornitza Stark Classified gene: PHOX2A as Amber List (moderate evidence)
Mendeliome v0.3144 PHOX2A Zornitza Stark Gene: phox2a has been classified as Amber List (Moderate Evidence).
Hereditary Neuropathy v0.64 KLC2 Bryony Thompson edited their review of gene: KLC2: Changed rating: GREEN
Muscular dystrophy and myopathy_Paediatric v0.15 COL4A2 Elena Savva gene: COL4A2 was added
gene: COL4A2 was added to Muscular dystrophy. Sources: Expert list
Mode of inheritance for gene: COL4A2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: COL4A2 were set to PMID: 25719457; 30315939
Phenotypes for gene: COL4A2 were set to Brain small vessel disease 2 614483
Penetrance for gene: COL4A2 were set to Incomplete
Mode of pathogenicity for gene: COL4A2 was set to Other
Review for gene: COL4A2 was set to RED
Added comment: OMIM reports - Variable severity - Incomplete penetrance

PMID: 25719457 - 0/15 heterozygous carriers report any myopathy phenotype. Majority had porencephaly or periventricular leukoencephalopathy.

PMID: 30315939 - two patients with schizencephaly and/or polymicrogyria. Authors specifically noted myopathy was not observed in any patient, one was reported to have normal CK levels.

Both LOF and dominant negative are suggested mechanisms for this gene.
Sources: Expert list
Muscular dystrophy and myopathy_Paediatric v0.15 COL4A1 Elena Savva reviewed gene: COL4A1: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 25719457, 21625620, 23225343; Phenotypes: Microangiopathy and leukoencephalopathy, pontine, autosomal dominant 618564, Angiopathy, hereditary, with nephropathy, aneurysms, and muscle cramps 611773; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Muscular dystrophy and myopathy_Paediatric v0.15 ANO5 Elena Savva gene: ANO5 was added
gene: ANO5 was added to Muscular dystrophy. Sources: Expert list
Mode of inheritance for gene: ANO5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ANO5 were set to PMID: 20096397; 32399949
Phenotypes for gene: ANO5 were set to Muscular dystrophy, limb-girdle, autosomal recessive 12 611307
Penetrance for gene: ANO5 were set to unknown
Review for gene: ANO5 was set to GREEN
Added comment: PMID: 20096397 - 5 families (12 patients) with either proximal limb girdle muscular dystrophy (3/5) or distal miyoshi myopathy (2/5). No obvious genotype-phenotype correlation, homozygous PTCs reported to cause both conditions. Age of onset >30 years old.

PMID: 32399949 - 3 patients with biallelic variants. All are carriers of the common c.191dupA variant with a missense in trans. 1/3 has limb girdle muscular dystrophy, all patients have onset >30 years old
Sources: Expert list
Dystonia and Chorea v0.68 SQSTM1 Elena Savva gene: SQSTM1 was added
gene: SQSTM1 was added to Dystonia - complex. Sources: Literature
Mode of inheritance for gene: SQSTM1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SQSTM1 were set to PMID: 27545679
Phenotypes for gene: SQSTM1 were set to Myopathy, distal, with rimmed vacuoles 617158
Review for gene: SQSTM1 was set to GREEN
Added comment: PMID: 27545679 - 9 patients (4 families) with childhood/adolescent onset neurodegeneration syndrome. 7/9 patients presented with dystonia. None noted to have myopathy.
Sources: Literature
Arrhythmogenic Cardiomyopathy v0.3 JUP Teresa Zhao reviewed gene: JUP: Rating: GREEN; Mode of pathogenicity: None; Publications: 16722579, 17924338; Phenotypes: Arrhythmogenic right ventricular dysplasia 12 MIM# 611528, Naxos disease MIM# 601214; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.6 PNPLA2 Elena Savva gene: PNPLA2 was added
gene: PNPLA2 was added to Limb Girdle Muscular Dystrophy. Sources: Literature
Mode of inheritance for gene: PNPLA2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PNPLA2 were set to PMID: 32269696; 21544567
Phenotypes for gene: PNPLA2 were set to Neutral lipid storage disease with myopathy 610717
Review for gene: PNPLA2 was set to GREEN
Added comment: PMID: 32269696 - 1 patient with both upper and lower limb weakness. She had elevated CK levels, with onset >25 years old.

PMID: 21544567 - 6 patients with distal muscle weakness, shoulder girdle weakness and elevated CK levels. Severe dystrophic features of the shoulder girdle noted in 3/3 patients analysed by whole body MRI. Proximal muscle weakness was generalised first, with lower limbs affected in the 3rd/4th decade of life. Earliest age of onset 29 years old, 5/6 patients had homozygous PTCs.
Sources: Literature
Mendeliome v0.3143 PHOX2A Elena Savva reviewed gene: PHOX2A: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 11600883, 18323871; Phenotypes: Fibrosis of extraocular muscles, congenital, 2 602078; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hypertrophic cardiomyopathy v0.88 TCAP Zornitza Stark Marked gene: TCAP as ready
Hypertrophic cardiomyopathy v0.88 TCAP Zornitza Stark Gene: tcap has been classified as Red List (Low Evidence).
Hypertrophic cardiomyopathy v0.88 TCAP Zornitza Stark Publications for gene: TCAP were set to
Hypertrophic cardiomyopathy v0.87 TCAP Zornitza Stark reviewed gene: TCAP: Rating: RED; Mode of pathogenicity: None; Publications: 16352453, 15582318; Phenotypes: Cardiomyopathy, hypertrophic, 25, MIM# 607487; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy v0.87 TCAP Zornitza Stark Phenotypes for gene: TCAP were changed from to Cardiomyopathy, hypertrophic, 25, MIM# 607487
Hypertrophic cardiomyopathy v0.86 TCAP Zornitza Stark Mode of inheritance for gene: TCAP was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy v0.85 TCAP Zornitza Stark Classified gene: TCAP as Red List (low evidence)
Hypertrophic cardiomyopathy v0.85 TCAP Zornitza Stark Gene: tcap has been classified as Red List (Low Evidence).
Hypertrophic cardiomyopathy v0.84 VCL Zornitza Stark Marked gene: VCL as ready
Hypertrophic cardiomyopathy v0.84 VCL Zornitza Stark Gene: vcl has been classified as Red List (Low Evidence).
Hypertrophic cardiomyopathy v0.84 VCL Zornitza Stark Phenotypes for gene: VCL were changed from to Cardiomyopathy, hypertrophic, 15, MIM# 613255
Hypertrophic cardiomyopathy v0.83 VCL Zornitza Stark Publications for gene: VCL were set to
Hypertrophic cardiomyopathy v0.82 VCL Zornitza Stark Mode of inheritance for gene: VCL was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy v0.81 VCL Zornitza Stark Classified gene: VCL as Red List (low evidence)
Hypertrophic cardiomyopathy v0.81 VCL Zornitza Stark Gene: vcl has been classified as Red List (Low Evidence).
Hypertrophic cardiomyopathy v0.80 VCL Zornitza Stark reviewed gene: VCL: Rating: RED; Mode of pathogenicity: None; Publications: 17097056; Phenotypes: Cardiomyopathy, hypertrophic, 15, MIM# 613255; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy v0.80 NEXN Zornitza Stark Marked gene: NEXN as ready
Hypertrophic cardiomyopathy v0.80 NEXN Zornitza Stark Gene: nexn has been classified as Red List (Low Evidence).
Hypertrophic cardiomyopathy v0.80 NEXN Zornitza Stark Phenotypes for gene: NEXN were changed from to Cardiomyopathy, hypertrophic, 20, MIM# 613876
Hypertrophic cardiomyopathy v0.79 NEXN Zornitza Stark Publications for gene: NEXN were set to
Hypertrophic cardiomyopathy v0.78 NEXN Zornitza Stark Mode of inheritance for gene: NEXN was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy v0.77 NEXN Zornitza Stark reviewed gene: NEXN: Rating: RED; Mode of pathogenicity: None; Publications: 20970104; Phenotypes: Cardiomyopathy, hypertrophic, 20, MIM# 613876; Mode of inheritance: None
Hypertrophic cardiomyopathy v0.77 NEXN Zornitza Stark Classified gene: NEXN as Red List (low evidence)
Hypertrophic cardiomyopathy v0.77 NEXN Zornitza Stark Gene: nexn has been classified as Red List (Low Evidence).
Hypertrophic cardiomyopathy v0.76 MYLK2 Zornitza Stark Publications for gene: MYLK2 were set to 11733062; 24082139; 25825456; 20301725
Hypertrophic cardiomyopathy v0.75 MYL3 Zornitza Stark Marked gene: MYL3 as ready
Hypertrophic cardiomyopathy v0.75 MYL3 Zornitza Stark Gene: myl3 has been classified as Green List (High Evidence).
Hypertrophic cardiomyopathy v0.75 MYL3 Zornitza Stark Phenotypes for gene: MYL3 were changed from to Cardiomyopathy, hypertrophic, 8, MIM# 608751
Hypertrophic cardiomyopathy v0.74 MYL3 Zornitza Stark Publications for gene: MYL3 were set to
Hypertrophic cardiomyopathy v0.73 MYL3 Zornitza Stark Mode of inheritance for gene: MYL3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy v0.72 TNNI3 Zornitza Stark Marked gene: TNNI3 as ready
Hypertrophic cardiomyopathy v0.72 TNNI3 Zornitza Stark Gene: tnni3 has been classified as Green List (High Evidence).
Hypertrophic cardiomyopathy v0.72 TNNI3 Zornitza Stark Phenotypes for gene: TNNI3 were changed from to Cardiomyopathy, hypertrophic, 7, MIM# 613690
Hypertrophic cardiomyopathy v0.71 TNNI3 Zornitza Stark Publications for gene: TNNI3 were set to 30681346
Hypertrophic cardiomyopathy v0.71 TNNI3 Zornitza Stark Publications for gene: TNNI3 were set to
Hypertrophic cardiomyopathy v0.70 TNNI3 Zornitza Stark Mode of inheritance for gene: TNNI3 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hypertrophic cardiomyopathy v0.69 TPM1 Zornitza Stark Publications for gene: TPM1 were set to 31270709
Hypertrophic cardiomyopathy v0.68 MYBPC3 Zornitza Stark Publications for gene: MYBPC3 were set to 20378854
Mendeliome v0.3143 TANC2 Zornitza Stark Phenotypes for gene: TANC2 were changed from Intellectual disability; autism; epilepsy; dysmorphism to Intellectual disability; autism; epilepsy; dysmorphism; Intellectual developmental disorder with autistic features and language delay, with or without seizures, MIM# 618906
Mendeliome v0.3142 TANC2 Zornitza Stark edited their review of gene: TANC2: Changed phenotypes: Intellectual disability, autism, epilepsy, dysmorphism, Intellectual developmental disorder with autistic features and language delay, with or without seizures, MIM# 618906
Intellectual disability syndromic and non-syndromic v0.2703 TANC2 Zornitza Stark Phenotypes for gene: TANC2 were changed from no OMIM number yet; Intellectual disability; autism; epilepsy; dysmorphism to Intellectual disability; autism; epilepsy; dysmorphism; Intellectual developmental disorder with autistic features and language delay, with or without seizures, MIM# 618906
Intellectual disability syndromic and non-syndromic v0.2702 TANC2 Zornitza Stark reviewed gene: TANC2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Intellectual developmental disorder with autistic features and language delay, with or without seizures, MIM# 618906; Mode of inheritance: None
Mendeliome v0.3142 ABCC1 Zornitza Stark Phenotypes for gene: ABCC1 were changed from Nonsyndromic hearing loss to Deafness-77, autosomal dominant (DFNA77), MIM#618915
Mendeliome v0.3141 ABCC1 Zornitza Stark edited their review of gene: ABCC1: Changed phenotypes: Deafness-77, autosomal dominant (DFNA77), MIM#618915
Deafness_IsolatedAndComplex v0.352 ABCC1 Zornitza Stark Phenotypes for gene: ABCC1 were changed from Nonsyndromic hearing loss; Deafness-77, autosomal dominant (DFNA77), MIM#618915 to Nonsyndromic hearing loss; Deafness-77, autosomal dominant (DFNA77), MIM#618915
Deafness_IsolatedAndComplex v0.352 ABCC1 Zornitza Stark Phenotypes for gene: ABCC1 were changed from Nonsyndromic hearing loss (PMID: 31273342) to Nonsyndromic hearing loss; Deafness-77, autosomal dominant (DFNA77), MIM#618915
Deafness_IsolatedAndComplex v0.351 ABCC1 Zornitza Stark edited their review of gene: ABCC1: Changed rating: AMBER; Changed phenotypes: Deafness-77, autosomal dominant (DFNA77), MIM#618915
Mendeliome v0.3141 SORD Zornitza Stark Phenotypes for gene: SORD were changed from isolated hereditary neuropathy to isolated hereditary neuropathy; Sorbitol dehydrogenase deficiency with peripheral neuropathy (SORDDPN), MIM#618912
Mendeliome v0.3140 SORD Zornitza Stark reviewed gene: SORD: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Sorbitol dehydrogenase deficiency with peripheral neuropathy (SORDDPN), MIM#618912; Mode of inheritance: None
Hypertrophic cardiomyopathy v0.67 MYBPC3 Ivan Macciocca reviewed gene: MYBPC3: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 30681346; Phenotypes: HCM; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Hypertrophic cardiomyopathy v0.67 TPM1 Ivan Macciocca reviewed gene: TPM1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 30681346; Phenotypes: HCM; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy v0.67 TNNI3 Ivan Macciocca reviewed gene: TNNI3: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 30681346; Phenotypes: HCM; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hypertrophic cardiomyopathy v0.67 MYL3 Ivan Macciocca reviewed gene: MYL3: Rating: GREEN; Mode of pathogenicity: None; Publications: 30681346; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy v0.67 MYLK2 Ivan Macciocca reviewed gene: MYLK2: Rating: RED; Mode of pathogenicity: None; Publications: 30681346; Phenotypes: HCM; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy v0.67 NEXN Ivan Macciocca reviewed gene: NEXN: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 30681346; Phenotypes: HCM; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy v0.67 VCL Ivan Macciocca reviewed gene: VCL: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 30681346; Phenotypes: HCM; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy v0.67 TCAP Ivan Macciocca reviewed gene: TCAP: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 30681346; Phenotypes: HCM; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy v0.67 MYOM1 Ivan Macciocca reviewed gene: MYOM1: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 30681346; Phenotypes: HCM; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy v0.67 MYH6 Ivan Macciocca reviewed gene: MYH6: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 30681346; Phenotypes: hypertrophic cardiomyopathy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Leukodystrophy v0.165 Zornitza Stark Panel types changed to Victorian Clinical Genetics Services; Royal Melbourne Hospital; Rare Disease
Leukodystrophy v0.164 RNASEH2A Zornitza Stark Marked gene: RNASEH2A as ready
Leukodystrophy v0.164 RNASEH2A Zornitza Stark Gene: rnaseh2a has been classified as Green List (High Evidence).
Leukodystrophy v0.164 RNASEH2A Zornitza Stark Classified gene: RNASEH2A as Green List (high evidence)
Leukodystrophy v0.164 RNASEH2A Zornitza Stark Gene: rnaseh2a has been classified as Green List (High Evidence).
Leukodystrophy v0.163 RNASEH2A Zornitza Stark gene: RNASEH2A was added
gene: RNASEH2A was added to Leukodystrophy - paediatric. Sources: Expert list
Mode of inheritance for gene: RNASEH2A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RNASEH2A were set to 16845400; 23592335; 17846997
Phenotypes for gene: RNASEH2A were set to Aicardi-Goutieres syndrome 4, MIM# 610333
Review for gene: RNASEH2A was set to GREEN
Added comment: Leukodystrophy is a common feature, onset is typically in infancy.
Sources: Expert list
Leukodystrophy v0.162 RNASEH2B Zornitza Stark Marked gene: RNASEH2B as ready
Leukodystrophy v0.162 RNASEH2B Zornitza Stark Gene: rnaseh2b has been classified as Green List (High Evidence).
Leukodystrophy v0.162 RNASEH2B Zornitza Stark Classified gene: RNASEH2B as Green List (high evidence)
Leukodystrophy v0.162 RNASEH2B Zornitza Stark Gene: rnaseh2b has been classified as Green List (High Evidence).
Leukodystrophy v0.161 RNASEH2B Zornitza Stark gene: RNASEH2B was added
gene: RNASEH2B was added to Leukodystrophy - paediatric. Sources: Expert list
Mode of inheritance for gene: RNASEH2B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RNASEH2B were set to 16845400
Phenotypes for gene: RNASEH2B were set to Aicardi-Goutieres syndrome 2, MIM# 610181
Review for gene: RNASEH2B was set to GREEN
Added comment: Leukodystrophy is common in AGS in general, though basal ganglia calcification seems to predominate here.
Sources: Expert list
Leukodystrophy v0.160 RNASEH2C Zornitza Stark Marked gene: RNASEH2C as ready
Leukodystrophy v0.160 RNASEH2C Zornitza Stark Gene: rnaseh2c has been classified as Green List (High Evidence).
Leukodystrophy v0.160 RNASEH2C Zornitza Stark Classified gene: RNASEH2C as Green List (high evidence)
Leukodystrophy v0.160 RNASEH2C Zornitza Stark Gene: rnaseh2c has been classified as Green List (High Evidence).
Leukodystrophy v0.159 RNASEH2C Zornitza Stark gene: RNASEH2C was added
gene: RNASEH2C was added to Leukodystrophy - paediatric. Sources: Expert list
Mode of inheritance for gene: RNASEH2C was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RNASEH2C were set to 16845400; 23322642
Phenotypes for gene: RNASEH2C were set to Aicardi-Goutieres syndrome 3, MIM# 610329
Review for gene: RNASEH2C was set to GREEN
Added comment: Leukodystrophy is a prominent feature, onset is typically in infancy.
Sources: Expert list
Leukodystrophy v0.158 RNASET2 Zornitza Stark changed review comment from: 5 unrelated families in the original publication.
Sources: Expert list; to: 5 unrelated families in the original publication, onset in infancy.
Sources: Expert list
Leukodystrophy v0.158 RNASET2 Zornitza Stark Marked gene: RNASET2 as ready
Leukodystrophy v0.158 RNASET2 Zornitza Stark Gene: rnaset2 has been classified as Green List (High Evidence).
Leukodystrophy v0.158 RNASET2 Zornitza Stark Classified gene: RNASET2 as Green List (high evidence)
Leukodystrophy v0.158 RNASET2 Zornitza Stark Gene: rnaset2 has been classified as Green List (High Evidence).
Leukodystrophy v0.157 RNASET2 Zornitza Stark gene: RNASET2 was added
gene: RNASET2 was added to Leukodystrophy - paediatric. Sources: Expert list
Mode of inheritance for gene: RNASET2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RNASET2 were set to 19525954
Phenotypes for gene: RNASET2 were set to Leukoencephalopathy, cystic, without megalencephaly, MIM# 612951
Review for gene: RNASET2 was set to GREEN
Added comment: 5 unrelated families in the original publication.
Sources: Expert list
Leukodystrophy v0.156 SAMHD1 Zornitza Stark Marked gene: SAMHD1 as ready
Leukodystrophy v0.156 SAMHD1 Zornitza Stark Gene: samhd1 has been classified as Green List (High Evidence).
Leukodystrophy v0.156 SAMHD1 Zornitza Stark Publications for gene: SAMHD1 were set to
Leukodystrophy v0.155 SAMHD1 Zornitza Stark Classified gene: SAMHD1 as Green List (high evidence)
Leukodystrophy v0.155 SAMHD1 Zornitza Stark Gene: samhd1 has been classified as Green List (High Evidence).
Leukodystrophy v0.154 SAMHD1 Zornitza Stark edited their review of gene: SAMHD1: Changed publications: 19525956; Changed phenotypes: Aicardi-Goutieres syndrome 5, MIM# 612952
Leukodystrophy v0.154 SAMHD1 Zornitza Stark gene: SAMHD1 was added
gene: SAMHD1 was added to Leukodystrophy - paediatric. Sources: Expert list
Mode of inheritance for gene: SAMHD1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SAMHD1 were set to Aicardi-Goutieres syndrome 5, MIM# 612952
Review for gene: SAMHD1 was set to GREEN
Added comment: Leukodystrophy is a prominent feature, onset is variable but typically in infancy/childhood.
Sources: Expert list
Leukodystrophy v0.153 SLC17A5 Zornitza Stark Marked gene: SLC17A5 as ready
Leukodystrophy v0.153 SLC17A5 Zornitza Stark Gene: slc17a5 has been classified as Green List (High Evidence).
Leukodystrophy v0.153 SLC17A5 Zornitza Stark Classified gene: SLC17A5 as Green List (high evidence)
Leukodystrophy v0.153 SLC17A5 Zornitza Stark Gene: slc17a5 has been classified as Green List (High Evidence).
Leukodystrophy v0.152 SLC17A5 Zornitza Stark gene: SLC17A5 was added
gene: SLC17A5 was added to Leukodystrophy - paediatric. Sources: Expert list
Mode of inheritance for gene: SLC17A5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC17A5 were set to 16417876
Phenotypes for gene: SLC17A5 were set to Salla disease 604369; Sialic acid storage disorder, infantile 269920
Review for gene: SLC17A5 was set to GREEN
Added comment: White matter abnormalities described in this metabolic disorder.
Sources: Expert list
Leukodystrophy v0.151 SPG11 Zornitza Stark Publications for gene: SPG11 were set to
Leukodystrophy v0.150 SPG11 Zornitza Stark changed review comment from: Complex SPG with central involvement, including white matter changes.
Sources: Expert list; to: Complex SPG with central involvement, including white matter changes. Variable age of onset, including in childhood.
Sources: Expert list
Leukodystrophy v0.150 SPG11 Zornitza Stark edited their review of gene: SPG11: Changed publications: 18067136; Changed phenotypes: Spastic paraplegia 11, autosomal recessive, MIM# 604360
Leukodystrophy v0.150 SPG11 Zornitza Stark Marked gene: SPG11 as ready
Leukodystrophy v0.150 SPG11 Zornitza Stark Gene: spg11 has been classified as Green List (High Evidence).
Leukodystrophy v0.150 SPG11 Zornitza Stark Classified gene: SPG11 as Green List (high evidence)
Leukodystrophy v0.150 SPG11 Zornitza Stark Gene: spg11 has been classified as Green List (High Evidence).
Leukodystrophy v0.149 SPG11 Zornitza Stark gene: SPG11 was added
gene: SPG11 was added to Leukodystrophy - paediatric. Sources: Expert list
Mode of inheritance for gene: SPG11 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SPG11 were set to Spastic paraplegia 11, autosomal recessive, MIM# 604360
Review for gene: SPG11 was set to GREEN
Added comment: Complex SPG with central involvement, including white matter changes.
Sources: Expert list
Leukodystrophy v0.148 TREX1 Zornitza Stark Marked gene: TREX1 as ready
Leukodystrophy v0.148 TREX1 Zornitza Stark Gene: trex1 has been classified as Green List (High Evidence).
Leukodystrophy v0.148 TREX1 Zornitza Stark Classified gene: TREX1 as Green List (high evidence)
Leukodystrophy v0.148 TREX1 Zornitza Stark Gene: trex1 has been classified as Green List (High Evidence).
Leukodystrophy v0.147 TREX1 Zornitza Stark gene: TREX1 was added
gene: TREX1 was added to Leukodystrophy - paediatric. Sources: Expert list
Mode of inheritance for gene: TREX1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
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: White matter changes are part of the phenotype. Onset is typically in infancy/childhood but can be variable.
Sources: Expert list
Leukodystrophy v0.146 TUBB4A Zornitza Stark Marked gene: TUBB4A as ready
Leukodystrophy v0.146 TUBB4A Zornitza Stark Gene: tubb4a has been classified as Green List (High Evidence).
Leukodystrophy v0.146 TUBB4A Zornitza Stark Classified gene: TUBB4A as Green List (high evidence)
Leukodystrophy v0.146 TUBB4A Zornitza Stark Gene: tubb4a has been classified as Green List (High Evidence).
Leukodystrophy v0.145 TUBB4A Zornitza Stark gene: TUBB4A was added
gene: TUBB4A was added to Leukodystrophy - paediatric. Sources: Expert list
Mode of inheritance for gene: TUBB4A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TUBB4A were set to 24850488; 23582646
Phenotypes for gene: TUBB4A were set to Leukodystrophy, hypomyelinating, 6, MIM# 612438
Review for gene: TUBB4A was set to GREEN
Added comment: Multiple individuals reported, onset of symptoms is typically in infancy and early childhood.
Sources: Expert list
Leukodystrophy v0.144 ZFYVE26 Zornitza Stark Marked gene: ZFYVE26 as ready
Leukodystrophy v0.144 ZFYVE26 Zornitza Stark Gene: zfyve26 has been classified as Green List (High Evidence).
Leukodystrophy v0.144 ZFYVE26 Zornitza Stark Classified gene: ZFYVE26 as Green List (high evidence)
Leukodystrophy v0.144 ZFYVE26 Zornitza Stark Gene: zfyve26 has been classified as Green List (High Evidence).
Leukodystrophy v0.143 ZFYVE26 Zornitza Stark gene: ZFYVE26 was added
gene: ZFYVE26 was added to Leukodystrophy - paediatric. Sources: Expert list
Mode of inheritance for gene: ZFYVE26 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ZFYVE26 were set to Spastic paraplegia 15, autosomal recessive, MIM# 270700
Review for gene: ZFYVE26 was set to GREEN
Added comment: Complex spastic paraplegia, including white matter changes. Variable age of onset ranging from paediatric to adult.
Sources: Expert list
Leukodystrophy v0.142 PSAP Zornitza Stark Marked gene: PSAP as ready
Leukodystrophy v0.142 PSAP Zornitza Stark Gene: psap has been classified as Green List (High Evidence).
Leukodystrophy v0.142 PSAP Zornitza Stark Classified gene: PSAP as Green List (high evidence)
Leukodystrophy v0.142 PSAP Zornitza Stark Gene: psap has been classified as Green List (High Evidence).
Leukodystrophy v0.141 PSAP Zornitza Stark gene: PSAP was added
gene: PSAP was added to Leukodystrophy - paediatric. Sources: Expert list
Mode of inheritance for gene: PSAP was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PSAP were set to Metachromatic leukodystrophy due to SAP-b deficiency, MIM# 249900
Review for gene: PSAP was set to GREEN
Added comment: Childhood onset.
Sources: Expert list
Leukodystrophy v0.140 POLR3B Zornitza Stark Marked gene: POLR3B as ready
Leukodystrophy v0.140 POLR3B Zornitza Stark Gene: polr3b has been classified as Green List (High Evidence).
Leukodystrophy v0.140 POLR3B Zornitza Stark Classified gene: POLR3B as Green List (high evidence)
Leukodystrophy v0.140 POLR3B Zornitza Stark Gene: polr3b has been classified as Green List (High Evidence).
Leukodystrophy v0.139 POLR3B Zornitza Stark gene: POLR3B was added
gene: POLR3B was added to Leukodystrophy - paediatric. Sources: Expert list
Mode of inheritance for gene: POLR3B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POLR3B were set to 27512013; 22036171; 22036172
Phenotypes for gene: POLR3B were set to Leukodystrophy, hypomyelinating, 8, with or without oligodontia and/or hypogonadotropic hypogonadism, MIM# 614381
Review for gene: POLR3B was set to GREEN
Added comment: More than 10 families reported. Early childhood onset of cerebellar ataxia and mild intellectual disabilities associated with diffuse hypomyelination apparent on brain MRI. Variable features include oligodontia and/or hypogonadotropic hypogonadism.
Sources: Expert list
Leukodystrophy v0.138 POLR3A Zornitza Stark Marked gene: POLR3A as ready
Leukodystrophy v0.138 POLR3A Zornitza Stark Gene: polr3a has been classified as Green List (High Evidence).
Leukodystrophy v0.138 POLR3A Zornitza Stark Classified gene: POLR3A as Green List (high evidence)
Leukodystrophy v0.138 POLR3A Zornitza Stark Gene: polr3a has been classified as Green List (High Evidence).
Leukodystrophy v0.137 POLR3A Zornitza Stark gene: POLR3A was added
gene: POLR3A was added to Leukodystrophy - paediatric. Sources: Expert list
Mode of inheritance for gene: POLR3A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POLR3A were set to 21855841
Phenotypes for gene: POLR3A were set to Leukodystrophy, hypomyelinating, 7, with or without oligodontia and/or hypogonadotropic hypogonadism, MIM# 607694
Review for gene: POLR3A was set to GREEN
Added comment: More than 10 families reported. Neurodegenerative disorder characterised by childhood onset of progressive motor decline manifest as spasticity, ataxia, tremor, and cerebellar signs, as well as mild cognitive regression. Other features may include hypodontia or oligodontia and hypogonadotropic hypogonadism.
Sources: Expert list
Leukodystrophy v0.136 POLR1C Zornitza Stark Publications for gene: POLR1C were set to 26151409
Leukodystrophy v0.135 POLR1C Zornitza Stark edited their review of gene: POLR1C: Changed publications: 26151409, 32042905; Changed phenotypes: Leukodystrophy, hypomyelinating, 11, MIM# 616494
Leukodystrophy v0.135 POLR1C Zornitza Stark Marked gene: POLR1C as ready
Leukodystrophy v0.135 POLR1C Zornitza Stark Gene: polr1c has been classified as Green List (High Evidence).
Leukodystrophy v0.135 POLR1C Zornitza Stark Classified gene: POLR1C as Green List (high evidence)
Leukodystrophy v0.135 POLR1C Zornitza Stark Gene: polr1c has been classified as Green List (High Evidence).
Leukodystrophy v0.134 POLR1C Zornitza Stark gene: POLR1C was added
gene: POLR1C was added to Leukodystrophy - paediatric. Sources: Expert list
Mode of inheritance for gene: POLR1C was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POLR1C were set to 26151409
Phenotypes for gene: POLR1C were set to Leukodystrophy, hypomyelinating, 11, MIM# 616494
Review for gene: POLR1C was set to GREEN
Added comment: Over 20 individuals reported.
Sources: Expert list
Mendeliome v0.3140 ANKRD1 Zornitza Stark Marked gene: ANKRD1 as ready
Mendeliome v0.3140 ANKRD1 Zornitza Stark Gene: ankrd1 has been classified as Red List (Low Evidence).
Mendeliome v0.3140 ANKRD1 Zornitza Stark Phenotypes for gene: ANKRD1 were changed from to Hypertrophic cardiomyopathy; Dilated cardiomyopathy
Mendeliome v0.3139 ANKRD1 Zornitza Stark Publications for gene: ANKRD1 were set to
Mendeliome v0.3138 ANKRD1 Zornitza Stark Mode of inheritance for gene: ANKRD1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3137 ANKRD1 Zornitza Stark Classified gene: ANKRD1 as Red List (low evidence)
Mendeliome v0.3137 ANKRD1 Zornitza Stark Gene: ankrd1 has been classified as Red List (Low Evidence).
Mendeliome v0.3136 ANKRD1 Zornitza Stark reviewed gene: ANKRD1: Rating: RED; Mode of pathogenicity: None; Publications: 19608030, 19525294, 30681346; Phenotypes: Hypertrophic cardiomyopathy, Dilated cardiomyopathy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Dilated Cardiomyopathy v0.43 ANKRD1 Zornitza Stark Phenotypes for gene: ANKRD1 were changed from to Dilated cardiomyopathy
Dilated Cardiomyopathy v0.42 ANKRD1 Zornitza Stark Publications for gene: ANKRD1 were set to
Dilated Cardiomyopathy v0.41 ANKRD1 Zornitza Stark Mode of inheritance for gene: ANKRD1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Dilated Cardiomyopathy v0.40 ANKRD1 Zornitza Stark changed review comment from: Three missense variants, P105S, V107L, and M184I reported in 4 individuals in PMID: 19608030. However, note that P105S is present in 45 individuals in gnomad, and V107L in >200. Another 5 missense variants reported in PMID: 19525294. Of these, p.Thr116Met is present in 41 individuals in gnomad, p.Ala276Val in 745 individuals (and 6 homozygotes), p.Glu57Gln is present once, p.Arg66Gln is absent but an alternative change at same residue is present in >300, and p.Leu199Arg is absent. Overall, the population frequency of most of these variants is out of keeping for a Mendelian disorder.; to: DCM: Three missense variants, P105S, V107L, and M184I reported in 4 individuals in PMID: 19608030. However, note that P105S is present in 45 individuals in gnomad, and V107L in >200. Another 5 missense variants reported in PMID: 19525294. Of these, p.Thr116Met is present in 41 individuals in gnomad, p.Ala276Val in 745 individuals (and 6 homozygotes), p.Glu57Gln is present once, p.Arg66Gln is absent but an alternative change at same residue is present in >300, and p.Leu199Arg is absent. Overall, the population frequency of most of these variants is out of keeping for a Mendelian disorder.
Dilated Cardiomyopathy v0.40 ANKRD1 Zornitza Stark edited their review of gene: ANKRD1: Added comment: Three missense variants, P105S, V107L, and M184I reported in 4 individuals in PMID: 19608030. However, note that P105S is present in 45 individuals in gnomad, and V107L in >200. Another 5 missense variants reported in PMID: 19525294. Of these, p.Thr116Met is present in 41 individuals in gnomad, p.Ala276Val in 745 individuals (and 6 homozygotes), p.Glu57Gln is present once, p.Arg66Gln is absent but an alternative change at same residue is present in >300, and p.Leu199Arg is absent. Overall, the population frequency of most of these variants is out of keeping for a Mendelian disorder.; Changed publications: 19608030, 19525294; Changed phenotypes: Dilated cardiomyopathy; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Dilated Cardiomyopathy v0.40 ANKRD1 Zornitza Stark Marked gene: ANKRD1 as ready
Dilated Cardiomyopathy v0.40 ANKRD1 Zornitza Stark Gene: ankrd1 has been classified as Red List (Low Evidence).
Dilated Cardiomyopathy v0.40 ANKRD1 Zornitza Stark Classified gene: ANKRD1 as Red List (low evidence)
Dilated Cardiomyopathy v0.40 ANKRD1 Zornitza Stark Gene: ankrd1 has been classified as Red List (Low Evidence).
Dilated Cardiomyopathy v0.39 ANKRD1 Zornitza Stark reviewed gene: ANKRD1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Hypertrophic cardiomyopathy v0.67 TNNT2 Zornitza Stark Marked gene: TNNT2 as ready
Hypertrophic cardiomyopathy v0.67 TNNT2 Zornitza Stark Gene: tnnt2 has been classified as Green List (High Evidence).
Hypertrophic cardiomyopathy v0.67 TNNT2 Zornitza Stark Publications for gene: TNNT2 were set to
Hypertrophic cardiomyopathy v0.66 TNNT2 Zornitza Stark Phenotypes for gene: TNNT2 were changed from to Cardiomyopathy, hypertrophic, 2, MIM# 115195
Hypertrophic cardiomyopathy v0.65 TNNT2 Zornitza Stark Mode of inheritance for gene: TNNT2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy v0.64 MYL2 Zornitza Stark Marked gene: MYL2 as ready
Hypertrophic cardiomyopathy v0.64 MYL2 Zornitza Stark Gene: myl2 has been classified as Green List (High Evidence).
Hypertrophic cardiomyopathy v0.64 MYL2 Zornitza Stark Publications for gene: MYL2 were set to
Hypertrophic cardiomyopathy v0.63 MYL2 Zornitza Stark Phenotypes for gene: MYL2 were changed from to Cardiomyopathy, hypertrophic, 10, MIM# 608758
Hypertrophic cardiomyopathy v0.62 MYL2 Zornitza Stark Mode of inheritance for gene: MYL2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy v0.61 MYH7 Zornitza Stark Marked gene: MYH7 as ready
Hypertrophic cardiomyopathy v0.61 MYH7 Zornitza Stark Gene: myh7 has been classified as Green List (High Evidence).
Hypertrophic cardiomyopathy v0.61 MYH7 Zornitza Stark Phenotypes for gene: MYH7 were changed from to Cardiomyopathy, hypertrophic, 1, MIM# 192600
Hypertrophic cardiomyopathy v0.60 MYH7 Zornitza Stark Publications for gene: MYH7 were set to
Hypertrophic cardiomyopathy v0.59 MYH7 Zornitza Stark Mode of inheritance for gene: MYH7 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy v0.58 KLHL24 Zornitza Stark Marked gene: KLHL24 as ready
Hypertrophic cardiomyopathy v0.58 KLHL24 Zornitza Stark Gene: klhl24 has been classified as Green List (High Evidence).
Hypertrophic cardiomyopathy v0.58 FLNC Zornitza Stark Publications for gene: FLNC were set to 31924696; 28356264
Hypertrophic cardiomyopathy v0.57 DES Zornitza Stark Marked gene: DES as ready
Hypertrophic cardiomyopathy v0.57 DES Zornitza Stark Gene: des has been classified as Red List (Low Evidence).
Hypertrophic cardiomyopathy v0.57 DES Zornitza Stark Phenotypes for gene: DES were changed from to Hypertrophic cardiomyopathy; Dilated cardiomyopathy; Myofibrillar myopathy; ARVC
Hypertrophic cardiomyopathy v0.56 DES Zornitza Stark Mode of inheritance for gene: DES was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Hypertrophic cardiomyopathy v0.55 DES Zornitza Stark Mode of inheritance for gene: DES was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Hypertrophic cardiomyopathy v0.55 DES Zornitza Stark Mode of inheritance for gene: DES was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hypertrophic cardiomyopathy v0.54 DES Zornitza Stark Classified gene: DES as Red List (low evidence)
Hypertrophic cardiomyopathy v0.54 DES Zornitza Stark Gene: des has been classified as Red List (Low Evidence).
Hypertrophic cardiomyopathy v0.53 CSRP3 Zornitza Stark Marked gene: CSRP3 as ready
Hypertrophic cardiomyopathy v0.53 CSRP3 Zornitza Stark Added comment: Comment when marking as ready: Sufficient number of families reported with good segregation data but agree caution needed in light of some of these variants being present at low frequency in the population.
Hypertrophic cardiomyopathy v0.53 CSRP3 Zornitza Stark Gene: csrp3 has been classified as Green List (High Evidence).
Hypertrophic cardiomyopathy v0.53 CSRP3 Zornitza Stark Phenotypes for gene: CSRP3 were changed from to Cardiomyopathy, hypertrophic, 12, MIM# 612124
Hypertrophic cardiomyopathy v0.52 CSRP3 Zornitza Stark Publications for gene: CSRP3 were set to
Hypertrophic cardiomyopathy v0.51 CSRP3 Zornitza Stark Mode of inheritance for gene: CSRP3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy v0.50 CAV3 Zornitza Stark Marked gene: CAV3 as ready
Hypertrophic cardiomyopathy v0.50 CAV3 Zornitza Stark Gene: cav3 has been classified as Red List (Low Evidence).
Hypertrophic cardiomyopathy v0.50 CAV3 Zornitza Stark Phenotypes for gene: CAV3 were changed from to Cardiomyopathy, familial hypertrophic, MIM# 192600
Hypertrophic cardiomyopathy v0.49 CAV3 Zornitza Stark Publications for gene: CAV3 were set to
Hypertrophic cardiomyopathy v0.48 CAV3 Zornitza Stark Mode of inheritance for gene: CAV3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy v0.47 CAV3 Zornitza Stark Classified gene: CAV3 as Red List (low evidence)
Hypertrophic cardiomyopathy v0.47 CAV3 Zornitza Stark Gene: cav3 has been classified as Red List (Low Evidence).
Hypertrophic cardiomyopathy v0.46 CALR3 Zornitza Stark Marked gene: CALR3 as ready
Hypertrophic cardiomyopathy v0.46 CALR3 Zornitza Stark Gene: calr3 has been classified as Red List (Low Evidence).
Hypertrophic cardiomyopathy v0.46 CALR3 Zornitza Stark Tag refuted tag was added to gene: CALR3.
Mendeliome v0.3136 CALR3 Zornitza Stark Marked gene: CALR3 as ready
Mendeliome v0.3136 CALR3 Zornitza Stark Gene: calr3 has been classified as Red List (Low Evidence).
Mendeliome v0.3136 CALR3 Zornitza Stark Phenotypes for gene: CALR3 were changed from to Hypertrophic cardiomyopathy
Mendeliome v0.3135 CALR3 Zornitza Stark Publications for gene: CALR3 were set to
Mendeliome v0.3134 CALR3 Zornitza Stark Mode of inheritance for gene: CALR3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3133 CALR3 Zornitza Stark Classified gene: CALR3 as Red List (low evidence)
Mendeliome v0.3133 CALR3 Zornitza Stark Gene: calr3 has been classified as Red List (Low Evidence).
Mendeliome v0.3132 CALR3 Zornitza Stark Tag refuted tag was added to gene: CALR3.
Mendeliome v0.3132 CALR3 Zornitza Stark reviewed gene: CALR3: Rating: RED; Mode of pathogenicity: None; Publications: 29988065; Phenotypes: Hypertrophic cardiomyopathy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy v0.46 CALR3 Zornitza Stark Phenotypes for gene: CALR3 were changed from to Hypertrophic cardiomyopathy
Hypertrophic cardiomyopathy v0.45 CALR3 Zornitza Stark Publications for gene: CALR3 were set to
Hypertrophic cardiomyopathy v0.44 CALR3 Zornitza Stark Mode of inheritance for gene: CALR3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy v0.43 CALR3 Zornitza Stark Classified gene: CALR3 as Red List (low evidence)
Hypertrophic cardiomyopathy v0.43 CALR3 Zornitza Stark Gene: calr3 has been classified as Red List (Low Evidence).
Hypertrophic cardiomyopathy v0.42 ANKRD1 Zornitza Stark Marked gene: ANKRD1 as ready
Hypertrophic cardiomyopathy v0.42 ANKRD1 Zornitza Stark Gene: ankrd1 has been classified as Red List (Low Evidence).
Hypertrophic cardiomyopathy v0.42 ANKRD1 Zornitza Stark Phenotypes for gene: ANKRD1 were changed from to hypertrophic cardiomyopathy
Hypertrophic cardiomyopathy v0.41 ANKRD1 Zornitza Stark Publications for gene: ANKRD1 were set to
Hypertrophic cardiomyopathy v0.40 ANKRD1 Zornitza Stark Mode of inheritance for gene: ANKRD1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy v0.39 ANKRD1 Zornitza Stark Classified gene: ANKRD1 as Red List (low evidence)
Hypertrophic cardiomyopathy v0.39 ANKRD1 Zornitza Stark Gene: ankrd1 has been classified as Red List (Low Evidence).
Dilated Cardiomyopathy v0.39 ALPK3 Zornitza Stark Marked gene: ALPK3 as ready
Dilated Cardiomyopathy v0.39 ALPK3 Zornitza Stark Gene: alpk3 has been classified as Green List (High Evidence).
Dilated Cardiomyopathy v0.39 ALPK3 Zornitza Stark Mode of inheritance for gene: ALPK3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Dilated Cardiomyopathy v0.38 ALPK3 Zornitza Stark Phenotypes for gene: ALPK3 were changed from to Cardiomyopathy, familial hypertrophic 27, MIM# 618052
Dilated Cardiomyopathy v0.37 ALPK3 Zornitza Stark Publications for gene: ALPK3 were set to
Dilated Cardiomyopathy v0.36 ALPK3 Zornitza Stark reviewed gene: ALPK3: Rating: GREEN; Mode of pathogenicity: None; Publications: 26846950, 27106955, 32480058; Phenotypes: Cardiomyopathy, familial hypertrophic 27, MIM# 618052; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3132 ALPK3 Zornitza Stark Marked gene: ALPK3 as ready
Mendeliome v0.3132 ALPK3 Zornitza Stark Gene: alpk3 has been classified as Green List (High Evidence).
Mendeliome v0.3132 ALPK3 Zornitza Stark Phenotypes for gene: ALPK3 were changed from to Cardiomyopathy, familial hypertrophic 27, MIM# 618052
Mendeliome v0.3131 ALPK3 Zornitza Stark Publications for gene: ALPK3 were set to
Mendeliome v0.3130 ALPK3 Zornitza Stark Mode of inheritance for gene: ALPK3 was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.3129 ALPK3 Zornitza Stark reviewed gene: ALPK3: Rating: GREEN; Mode of pathogenicity: None; Publications: 26846950, 27106955, 32480058; Phenotypes: Cardiomyopathy, familial hypertrophic 27, MIM# 618052; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Hypertrophic cardiomyopathy v0.38 ALPK3 Zornitza Stark Marked gene: ALPK3 as ready
Hypertrophic cardiomyopathy v0.38 ALPK3 Zornitza Stark Gene: alpk3 has been classified as Green List (High Evidence).
Hypertrophic cardiomyopathy v0.38 ALPK3 Zornitza Stark Phenotypes for gene: ALPK3 were changed from to Cardiomyopathy, familial hypertrophic 27, MIM# 618052
Hypertrophic cardiomyopathy v0.37 ALPK3 Zornitza Stark Publications for gene: ALPK3 were set to
Hypertrophic cardiomyopathy v0.36 ALPK3 Zornitza Stark Mode of inheritance for gene: ALPK3 was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Hypertrophic cardiomyopathy v0.35 ACTN2 Zornitza Stark Marked gene: ACTN2 as ready
Hypertrophic cardiomyopathy v0.35 ACTN2 Zornitza Stark Gene: actn2 has been classified as Amber List (Moderate Evidence).
Hypertrophic cardiomyopathy v0.35 ACTN2 Zornitza Stark Phenotypes for gene: ACTN2 were changed from to Cardiomyopathy, hypertrophic, 23, with or without LVNC, MIM# 612158
Hypertrophic cardiomyopathy v0.34 ACTN2 Zornitza Stark Publications for gene: ACTN2 were set to
Hypertrophic cardiomyopathy v0.33 ACTN2 Zornitza Stark Mode of inheritance for gene: ACTN2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy v0.32 ACTN2 Zornitza Stark Classified gene: ACTN2 as Amber List (moderate evidence)
Hypertrophic cardiomyopathy v0.32 ACTN2 Zornitza Stark Gene: actn2 has been classified as Amber List (Moderate Evidence).
Hypertrophic cardiomyopathy v0.31 ACTC1 Zornitza Stark Marked gene: ACTC1 as ready
Hypertrophic cardiomyopathy v0.31 ACTC1 Zornitza Stark Gene: actc1 has been classified as Green List (High Evidence).
Hypertrophic cardiomyopathy v0.31 ACTC1 Zornitza Stark Mode of inheritance for gene: ACTC1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy v0.30 ACTC1 Zornitza Stark Phenotypes for gene: ACTC1 were changed from to Cardiomyopathy, hypertrophic, 11 612098
Hypertrophic cardiomyopathy v0.29 ACTC1 Zornitza Stark Mode of inheritance for gene: ACTC1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy v0.29 ACTC1 Zornitza Stark Mode of inheritance for gene: ACTC1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy v0.28 MYL2 Ivan Macciocca reviewed gene: MYL2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 30681346; Phenotypes: HCM; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy v0.28 TNNT2 Ivan Macciocca reviewed gene: TNNT2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 30681346; Phenotypes: HCM, LVNC, RCM, DCM; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy v0.28 MYH7 Ivan Macciocca reviewed gene: MYH7: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 30681346; Phenotypes: hypertrophic cardiomyopathy, LVNC, DCM; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy v0.28 FLNC Ivan Macciocca reviewed gene: FLNC: Rating: GREEN; Mode of pathogenicity: None; Publications: 30411535; Phenotypes: hypertrophic cardiomyopathy, distal myopathy, restrictive cardiomyopathy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy v0.28 DES Ivan Macciocca reviewed gene: DES: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: arrhythmogenic right ventricular cardiomyopathy, myofibrillar myopathy 1, dilated cardiomyopathy; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hypertrophic cardiomyopathy v0.28 CSRP3 Ivan Macciocca changed review comment from: Assessed as MODERATE by ClinGen HCM working group PMID: 30681346
Associated with HCM in 4 families reported by a German group with some functional evidence and including 2 large multi-generational families with 6 and 8 affected relatives segregating the variants.
3 of the 4 variants reported in these families have a low frequency (up to 4 alleles) in Gnomad.; to: Assessed as MODERATE by ClinGen HCM working group PMID: 30681346
Associated with HCM in 4 families reported by a German group with some functional evidence and including 2 large multi-generational families with 6 and 8 affected relatives segregating the variants.
3 of the 4 variants reported in these families have a low frequency (up to 4 alleles) in Gnomad.
Assess variants in this gene with caution due to the limited number of families currently reported with pathogenic/likely[pathogenic variants in this gene.
Hypertrophic cardiomyopathy v0.28 CSRP3 Ivan Macciocca reviewed gene: CSRP3: Rating: GREEN; Mode of pathogenicity: None; Publications: 18505755, 30681346; Phenotypes: hypertrophic cardiomyopathy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy v0.28 CAV3 Ivan Macciocca reviewed gene: CAV3: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 14672715,27483260,12138167; Phenotypes: hypertrophic cardiomyopathy, long QT syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy v0.28 C1QBP Ivan Macciocca reviewed gene: C1QBP: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID:28942965; Phenotypes: COMBINED OXIDATIVE PHOSPHORYLATION DEFICIENCY 33, hypertrophic cardiomyopathy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hypertrophic cardiomyopathy v0.28 ANKRD1 Ivan Macciocca reviewed gene: ANKRD1: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 30681346; Phenotypes: hypertrophic cardiomyopathy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy v0.28 ALPK3 Ivan Macciocca reviewed gene: ALPK3: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 26846950, 27106955, 32480058; Phenotypes: hypertrophic cardiomyopathy, dilated cardiomyopathy; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Hypertrophic cardiomyopathy v0.28 ACTN2 Ivan Macciocca reviewed gene: ACTN2: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 30681346; Phenotypes: hypertrophic cardiomyopathy, left ventricular non compaction, dilated cardiomyopathy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy v0.28 ACTC1 Ivan Macciocca reviewed gene: ACTC1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: hypertrophic cardiomyopathy, left ventricular non compaction, dilated cardiomyopathy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Motor Neurone Disease v0.48 SPG7 Bryony Thompson Marked gene: SPG7 as ready
Motor Neurone Disease v0.48 SPG7 Bryony Thompson Gene: spg7 has been classified as Green List (High Evidence).
Motor Neurone Disease v0.48 SPG7 Bryony Thompson Classified gene: SPG7 as Green List (high evidence)
Motor Neurone Disease v0.48 SPG7 Bryony Thompson Gene: spg7 has been classified as Green List (High Evidence).
Motor Neurone Disease v0.47 SPG7 Bryony Thompson gene: SPG7 was added
gene: SPG7 was added to Motor Neuron Disease. Sources: Literature
Mode of inheritance for gene: SPG7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SPG7 were set to 16765570; 19364936
Phenotypes for gene: SPG7 were set to Spastic paraplegia 7, autosomal recessive MIM#607259
Review for gene: SPG7 was set to GREEN
Added comment: The HSP caused by this gene can be classified as a non-ALS MND, affecting the upper motor neurons. There are multiple reports of the condition mimicking MND.
Sources: Literature
Motor Neurone Disease v0.46 SPAST Bryony Thompson Marked gene: SPAST as ready
Motor Neurone Disease v0.46 SPAST Bryony Thompson Gene: spast has been classified as Green List (High Evidence).
Motor Neurone Disease v0.46 SPAST Bryony Thompson Classified gene: SPAST as Green List (high evidence)
Motor Neurone Disease v0.46 SPAST Bryony Thompson Gene: spast has been classified as Green List (High Evidence).
Motor Neurone Disease v0.45 SPAST Bryony Thompson gene: SPAST was added
gene: SPAST was added to Motor Neuron Disease. Sources: Expert list
Mode of inheritance for gene: SPAST was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SPAST were set to 16765570; 19364936
Review for gene: SPAST was set to GREEN
Added comment: The HSP caused by this gene can be classified as a non-ALS MND, affecting the upper motor neurons. There are multiple reports of the condition mimicking MND.
Sources: Expert list
Motor Neurone Disease v0.44 REEP1 Bryony Thompson Marked gene: REEP1 as ready
Motor Neurone Disease v0.44 REEP1 Bryony Thompson Gene: reep1 has been classified as Green List (High Evidence).
Motor Neurone Disease v0.44 REEP1 Bryony Thompson Classified gene: REEP1 as Green List (high evidence)
Motor Neurone Disease v0.44 REEP1 Bryony Thompson Gene: reep1 has been classified as Green List (High Evidence).
Motor Neurone Disease v0.43 REEP1 Bryony Thompson gene: REEP1 was added
gene: REEP1 was added to Motor Neuron Disease. Sources: Expert list
Mode of inheritance for gene: REEP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: REEP1 were set to 23108492; 22703882
Phenotypes for gene: REEP1 were set to Spastic paraplegia 31, autosomal dominant MIM#610250
Review for gene: REEP1 was set to GREEN
Added comment: The HSP caused by this gene can be classified as a non-ALS MND, affecting the upper and lower motor neurons.
Sources: Expert list
Motor Neurone Disease v0.42 GBE1 Bryony Thompson Classified gene: GBE1 as Green List (high evidence)
Motor Neurone Disease v0.42 GBE1 Bryony Thompson Gene: gbe1 has been classified as Green List (High Evidence).
Motor Neurone Disease v0.41 GBE1 Bryony Thompson gene: GBE1 was added
gene: GBE1 was added to Motor Neuron Disease. Sources: Expert list
Mode of inheritance for gene: GBE1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GBE1 were set to 20301758; 26194201
Phenotypes for gene: GBE1 were set to Polyglucosan body disease, adult form MIM#263570
Review for gene: GBE1 was set to GREEN
Added comment: APBD can have upper and lower motor neuron involvement, and at least 5 cases in a cohort of 30 were misdiagnosed with ALS.
Sources: Expert list
Mendeliome v0.3129 HSF4 Zornitza Stark Marked gene: HSF4 as ready
Mendeliome v0.3129 HSF4 Zornitza Stark Gene: hsf4 has been classified as Green List (High Evidence).
Mendeliome v0.3129 HSF4 Zornitza Stark Phenotypes for gene: HSF4 were changed from to Cataract 5, multiple types, 116800
Mendeliome v0.3128 HSF4 Zornitza Stark Publications for gene: HSF4 were set to
Mendeliome v0.3127 HSF4 Zornitza Stark Mode of inheritance for gene: HSF4 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.3126 HSF4 Zornitza Stark reviewed gene: HSF4: Rating: GREEN; Mode of pathogenicity: None; Publications: 31815953, 29243736, 26490182; Phenotypes: Cataract 5, multiple types, 116800; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Cataract v0.146 HSF4 Zornitza Stark Marked gene: HSF4 as ready
Cataract v0.146 HSF4 Zornitza Stark Gene: hsf4 has been classified as Green List (High Evidence).
Cataract v0.146 HSF4 Zornitza Stark Phenotypes for gene: HSF4 were changed from to Cataract 5, multiple types, 116800
Cataract v0.145 HSF4 Zornitza Stark Publications for gene: HSF4 were set to
Cataract v0.144 HSF4 Zornitza Stark Mode of inheritance for gene: HSF4 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Motor Neurone Disease v0.40 BSCL2 Bryony Thompson Classified gene: BSCL2 as Green List (high evidence)
Motor Neurone Disease v0.40 BSCL2 Bryony Thompson Gene: bscl2 has been classified as Green List (High Evidence).
Motor Neurone Disease v0.39 BSCL2 Bryony Thompson gene: BSCL2 was added
gene: BSCL2 was added to Motor Neuron Disease. Sources: Expert list
Mode of inheritance for gene: BSCL2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: BSCL2 were set to 16765570
Phenotypes for gene: BSCL2 were set to Silver spastic paraplegia syndrome MIM#270685; Neuropathy, distal hereditary motor, type VA MIM#600794
Review for gene: BSCL2 was set to GREEN
Added comment: The HSP and distal HMN caused by this gene can be classified as a non-ALS MND, affecting both upper and lower motor neurons.
Sources: Expert list
Motor Neurone Disease v0.38 ATL1 Bryony Thompson Classified gene: ATL1 as Green List (high evidence)
Motor Neurone Disease v0.38 ATL1 Bryony Thompson Gene: atl1 has been classified as Green List (High Evidence).
Motor Neurone Disease v0.37 ATL1 Bryony Thompson gene: ATL1 was added
gene: ATL1 was added to Motor Neuron Disease. Sources: Expert list
Mode of inheritance for gene: ATL1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ATL1 were set to 16765570
Phenotypes for gene: ATL1 were set to Spastic paraplegia 3A, autosomal dominant MIM#182600
Review for gene: ATL1 was set to GREEN
Added comment: The HSP caused by this gene can be classified as a non-ALS MND, affecting the upper motor neurons.
Sources: Expert list
Dystonia and Chorea v0.68 UBTF Bryony Thompson Marked gene: UBTF as ready
Dystonia and Chorea v0.68 UBTF Bryony Thompson Gene: ubtf has been classified as Green List (High Evidence).
Dystonia and Chorea v0.68 UBTF Bryony Thompson Classified gene: UBTF as Green List (high evidence)
Dystonia and Chorea v0.68 UBTF Bryony Thompson Gene: ubtf has been classified as Green List (High Evidence).
Dystonia and Chorea v0.67 UBTF Bryony Thompson gene: UBTF was added
gene: UBTF was added to Dystonia - complex. Sources: Expert list
Mode of inheritance for gene: UBTF was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: UBTF were set to 28777933; 29300972
Phenotypes for gene: UBTF were set to Neurodegeneration, childhood-onset, with brain atrophy MIM#617672
Mode of pathogenicity for gene: UBTF 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: UBTF was set to GREEN
Added comment: 7 out of 11 unrelated cases with a recurrent de novo gain of function missense variant (p.Glu210Lys) have dystonia as a feature of the condition.
Sources: Expert list
Mendeliome v0.3126 FITM2 Bryony Thompson Marked gene: FITM2 as ready
Mendeliome v0.3126 FITM2 Bryony Thompson Gene: fitm2 has been classified as Green List (High Evidence).
Mendeliome v0.3126 FITM2 Bryony Thompson Classified gene: FITM2 as Green List (high evidence)
Mendeliome v0.3126 FITM2 Bryony Thompson Gene: fitm2 has been classified as Green List (High Evidence).
Mendeliome v0.3125 FITM2 Bryony Thompson gene: FITM2 was added
gene: FITM2 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: FITM2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FITM2 were set to 28067622; 30214770; 30288795
Phenotypes for gene: FITM2 were set to Siddiqi syndrome MIM#618635; dystonia; deafness
Review for gene: FITM2 was set to GREEN
Added comment: 7 cases from 3 unrelated families (2 consanguineous) with a dystonia-deafness syndrome and a supporting Drosophila model.
Sources: Expert list
Deafness_IsolatedAndComplex v0.351 FITM2 Bryony Thompson Marked gene: FITM2 as ready
Deafness_IsolatedAndComplex v0.351 FITM2 Bryony Thompson Gene: fitm2 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v0.351 FITM2 Bryony Thompson Classified gene: FITM2 as Green List (high evidence)
Deafness_IsolatedAndComplex v0.351 FITM2 Bryony Thompson Gene: fitm2 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v0.350 FITM2 Bryony Thompson gene: FITM2 was added
gene: FITM2 was added to Deafness. Sources: Literature
Mode of inheritance for gene: FITM2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FITM2 were set to 28067622; 30214770; 30288795
Phenotypes for gene: FITM2 were set to Siddiqi syndrome MIM#618635; dystonia; deafness
Review for gene: FITM2 was set to GREEN
Added comment: 7 cases from 3 unrelated families (2 consanguineous) with a dystonia-deafness syndrome and a supporting Drosophila model.
Sources: Literature
Dystonia and Chorea v0.66 FITM2 Bryony Thompson changed review comment from: Three unrelated cases with a dystonia-deafness syndrome and a supporting Drosophila model.
Sources: Expert list; to: 7 cases from 3 unrelated families (2 consanguineous) with a dystonia-deafness syndrome and a supporting Drosophila model.
Sources: Expert list
Dystonia and Chorea v0.66 FITM2 Bryony Thompson Marked gene: FITM2 as ready
Dystonia and Chorea v0.66 FITM2 Bryony Thompson Gene: fitm2 has been classified as Green List (High Evidence).
Dystonia and Chorea v0.66 FITM2 Bryony Thompson Classified gene: FITM2 as Green List (high evidence)
Dystonia and Chorea v0.66 FITM2 Bryony Thompson Gene: fitm2 has been classified as Green List (High Evidence).
Dystonia and Chorea v0.65 FITM2 Bryony Thompson gene: FITM2 was added
gene: FITM2 was added to Dystonia - complex. Sources: Expert list
Mode of inheritance for gene: FITM2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FITM2 were set to 28067622; 30214770; 30288795
Phenotypes for gene: FITM2 were set to Siddiqi syndrome MIM#618635; dystonia; deafness
Review for gene: FITM2 was set to GREEN
Added comment: Three unrelated cases with a dystonia-deafness syndrome and a supporting Drosophila model.
Sources: Expert list
Cataract v0.143 HSF4 Chern Lim reviewed gene: HSF4: Rating: GREEN; Mode of pathogenicity: None; Publications: 31815953, 29243736, 26490182; Phenotypes: Cataract 5, multiple types, 116800.; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.3124 DALRD3 Zornitza Stark Phenotypes for gene: DALRD3 were changed from Epileptic encephalopathy to Epileptic encephalopathy; Epileptic encephalopathy, early infantile, 86 618910
Mendeliome v0.3123 DALRD3 Zornitza Stark edited their review of gene: DALRD3: Changed phenotypes: Epileptic encephalopathy, Epileptic encephalopathy, early infantile, 86 618910
Genetic Epilepsy v0.731 DALRD3 Zornitza Stark Phenotypes for gene: DALRD3 were changed from Epileptic encephalopathy to Epileptic encephalopathy; Epileptic encephalopathy, early infantile, 86 618910
Genetic Epilepsy v0.730 DALRD3 Zornitza Stark edited their review of gene: DALRD3: Changed phenotypes: Epileptic encephalopathy, Epileptic encephalopathy, early infantile, 86 618910
Mendeliome v0.3123 CHD1L Zornitza Stark Marked gene: CHD1L as ready
Mendeliome v0.3123 CHD1L Zornitza Stark Gene: chd1l has been classified as Red List (Low Evidence).
Mendeliome v0.3123 CHD1L Zornitza Stark Phenotypes for gene: CHD1L were changed from to CAKUT
Mendeliome v0.3122 CHD1L Zornitza Stark Publications for gene: CHD1L were set to
Mendeliome v0.3121 CHD1L Zornitza Stark Mode of inheritance for gene: CHD1L was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3120 CHD1L Zornitza Stark Classified gene: CHD1L as Red List (low evidence)
Mendeliome v0.3120 CHD1L Zornitza Stark Gene: chd1l has been classified as Red List (Low Evidence).
Mendeliome v0.3119 CHD1L Zornitza Stark Tag disputed tag was added to gene: CHD1L.
Mendeliome v0.3119 CHD1L Zornitza Stark reviewed gene: CHD1L: Rating: RED; Mode of pathogenicity: None; Publications: 22146311, 24429398; Phenotypes: CAKUT; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.730 NEXMIF Zornitza Stark Marked gene: NEXMIF as ready
Genetic Epilepsy v0.730 NEXMIF Zornitza Stark Gene: nexmif has been classified as Green List (High Evidence).
Genetic Epilepsy v0.730 NEXMIF Zornitza Stark Phenotypes for gene: NEXMIF were changed from to Mental retardation, X-linked 98, MIM# 300912
Genetic Epilepsy v0.729 NEXMIF Zornitza Stark Publications for gene: NEXMIF were set to
Genetic Epilepsy v0.728 NEXMIF Zornitza Stark Mode of inheritance for gene: NEXMIF was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Genetic Epilepsy v0.727 NEXMIF Zornitza Stark reviewed gene: NEXMIF: Rating: GREEN; Mode of pathogenicity: None; Publications: 27358180; Phenotypes: Mental retardation, X-linked 98, MIM# 300912; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability syndromic and non-syndromic v0.2702 NEXMIF Zornitza Stark Marked gene: NEXMIF as ready
Intellectual disability syndromic and non-syndromic v0.2702 NEXMIF Zornitza Stark Gene: nexmif has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2702 NEXMIF Zornitza Stark Phenotypes for gene: NEXMIF were changed from to Mental retardation, X-linked 98, MIM# 300912
Intellectual disability syndromic and non-syndromic v0.2701 NEXMIF Zornitza Stark Publications for gene: NEXMIF were set to
Intellectual disability syndromic and non-syndromic v0.2700 NEXMIF Zornitza Stark Mode of inheritance for gene: NEXMIF was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability syndromic and non-syndromic v0.2699 NEXMIF Zornitza Stark reviewed gene: NEXMIF: Rating: GREEN; Mode of pathogenicity: None; Publications: 27358180; Phenotypes: Mental retardation, X-linked 98 300912; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Mendeliome v0.3119 NEXMIF Zornitza Stark Marked gene: NEXMIF as ready
Mendeliome v0.3119 NEXMIF Zornitza Stark Gene: nexmif has been classified as Green List (High Evidence).
Mendeliome v0.3119 NEXMIF Zornitza Stark Phenotypes for gene: NEXMIF were changed from to Mental retardation, X-linked 98 300912
Mendeliome v0.3118 NEXMIF Zornitza Stark Publications for gene: NEXMIF were set to
Mendeliome v0.3117 NEXMIF Zornitza Stark Mode of inheritance for gene: NEXMIF was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Mendeliome v0.3116 MEF2C Zornitza Stark Marked gene: MEF2C as ready
Mendeliome v0.3116 MEF2C Zornitza Stark Gene: mef2c has been classified as Green List (High Evidence).
Mendeliome v0.3116 MEF2C Zornitza Stark Phenotypes for gene: MEF2C were changed from to Chromosome 5q14.3 deletion syndrome, 613443; Mental retardation, stereotypic movements, epilepsy, and/or cerebral malformations, 613443
Mendeliome v0.3115 MEF2C Zornitza Stark Mode of inheritance for gene: MEF2C was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3114 KDM6A Zornitza Stark Marked gene: KDM6A as ready
Mendeliome v0.3114 KDM6A Zornitza Stark Gene: kdm6a has been classified as Green List (High Evidence).
Mendeliome v0.3114 KDM6A Zornitza Stark Phenotypes for gene: KDM6A were changed from to Kabuki syndrome 2, 300867
Mendeliome v0.3113 KDM6A Zornitza Stark Publications for gene: KDM6A were set to
Mendeliome v0.3112 KDM6A Zornitza Stark Mode of inheritance for gene: KDM6A was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Craniosynostosis v0.81 SPECC1L Bryony Thompson Marked gene: SPECC1L as ready
Craniosynostosis v0.81 SPECC1L Bryony Thompson Gene: specc1l has been classified as Amber List (Moderate Evidence).
Craniosynostosis v0.81 SPECC1L Bryony Thompson Classified gene: SPECC1L as Amber List (moderate evidence)
Craniosynostosis v0.81 SPECC1L Bryony Thompson Gene: specc1l has been classified as Amber List (Moderate Evidence).
Craniosynostosis v0.80 SPECC1L Bryony Thompson gene: SPECC1L was added
gene: SPECC1L was added to Craniosynostosis. Sources: Expert list
Mode of inheritance for gene: SPECC1L was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SPECC1L were set to 26111080; 30472488
Phenotypes for gene: SPECC1L were set to Hypertelorism, Teebi type MIM#145420
Review for gene: SPECC1L was set to AMBER
Added comment: Three unrelated cases reported with craniosynostosis as a feature of the condition.
Sources: Expert list
Craniosynostosis v0.79 IFT122 Bryony Thompson Marked gene: IFT122 as ready
Craniosynostosis v0.79 IFT122 Bryony Thompson Gene: ift122 has been classified as Green List (High Evidence).
Craniosynostosis v0.79 IFT122 Bryony Thompson Classified gene: IFT122 as Green List (high evidence)
Craniosynostosis v0.79 IFT122 Bryony Thompson Gene: ift122 has been classified as Green List (High Evidence).
Craniosynostosis v0.78 IFT122 Bryony Thompson gene: IFT122 was added
gene: IFT122 was added to Craniosynostosis. Sources: Expert list
Mode of inheritance for gene: IFT122 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IFT122 were set to 26792575; 28370949; 29037998
Phenotypes for gene: IFT122 were set to Cranioectodermal dysplasia 1 MIM#218330
Review for gene: IFT122 was set to GREEN
Added comment: Craniosynostosis has been reported as a prominent feature of the condition in greater than 10 cases.
Sources: Expert list
Craniosynostosis v0.77 GLI3 Bryony Thompson Marked gene: GLI3 as ready
Craniosynostosis v0.77 GLI3 Bryony Thompson Gene: gli3 has been classified as Green List (High Evidence).
Craniosynostosis v0.77 GLI3 Bryony Thompson Classified gene: GLI3 as Green List (high evidence)
Craniosynostosis v0.77 GLI3 Bryony Thompson Gene: gli3 has been classified as Green List (High Evidence).
Craniosynostosis v0.76 GLI3 Bryony Thompson gene: GLI3 was added
gene: GLI3 was added to Craniosynostosis. Sources: Expert list
Mode of inheritance for gene: GLI3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GLI3 were set to 20583172; 20570969; 21326280
Phenotypes for gene: GLI3 were set to Metopic craniosynostosis; Greig cephalopolysyndactyly syndrome MIM#175700
Review for gene: GLI3 was set to GREEN
Added comment: Metopic or sagittal synostosis has been reported as a feature of Greig cephalopolysyndactyly syndrome in at least 7 unrelated cases, and there is a supporting mouse model with craniosynostosis.
Sources: Expert list
Craniosynostosis v0.75 Bryony Thompson Panel types changed to Victorian Clinical Genetics Services; Royal Melbourne Hospital; Rare Disease
Mendeliome v0.3111 KDM6A Elena Savva reviewed gene: KDM6A: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID:27302555, 24664873; Phenotypes: Kabuki syndrome 2, 300867; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males); Current diagnostic: yes
Mendeliome v0.3111 MEF2C Elena Savva reviewed gene: MEF2C: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Chromosome 5q14.3 deletion syndrome, 613443, Mental retardation, stereotypic movements, epilepsy, and/or cerebral malformations, 613443; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.3111 NEXMIF Elena Savva reviewed gene: NEXMIF: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 27358180; Phenotypes: Mental retardation, X-linked 98 300912; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Mendeliome v0.3111 STAG3 Bryony Thompson Marked gene: STAG3 as ready
Mendeliome v0.3111 STAG3 Bryony Thompson Gene: stag3 has been classified as Green List (High Evidence).
Mendeliome v0.3111 STAG3 Bryony Thompson Classified gene: STAG3 as Green List (high evidence)
Mendeliome v0.3111 STAG3 Bryony Thompson Gene: stag3 has been classified as Green List (High Evidence).
Mendeliome v0.3110 STAG3 Bryony Thompson gene: STAG3 was added
gene: STAG3 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: STAG3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: STAG3 were set to 24597867; 26059840; 31803224; 31363903
Phenotypes for gene: STAG3 were set to Premature ovarian failure 8 MIM#615723
Review for gene: STAG3 was set to GREEN
Added comment: At least four unrelated families with ovarian failure and a supporting null mouse model.
Sources: Expert list
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.6 STAG3 Bryony Thompson Marked gene: STAG3 as ready
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.6 STAG3 Bryony Thompson Gene: stag3 has been classified as Green List (High Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.6 STAG3 Bryony Thompson Phenotypes for gene: STAG3 were changed from to Premature ovarian failure 8 MIM#615723
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.5 STAG3 Bryony Thompson Publications for gene: STAG3 were set to
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.4 STAG3 Bryony Thompson reviewed gene: STAG3: Rating: GREEN; Mode of pathogenicity: None; Publications: 24597867, 26059840, 31803224, 31363903; Phenotypes: Premature ovarian failure 8 MIM#615723; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3109 SOHLH1 Bryony Thompson Marked gene: SOHLH1 as ready
Mendeliome v0.3109 SOHLH1 Bryony Thompson Gene: sohlh1 has been classified as Green List (High Evidence).
Mendeliome v0.3109 SOHLH1 Bryony Thompson Classified gene: SOHLH1 as Green List (high evidence)
Mendeliome v0.3109 SOHLH1 Bryony Thompson Gene: sohlh1 has been classified as Green List (High Evidence).
Mendeliome v0.3108 SOHLH1 Bryony Thompson gene: SOHLH1 was added
gene: SOHLH1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: SOHLH1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: SOHLH1 were set to 25774885; 16690745; 31042289; 20506135; 28718531
Phenotypes for gene: SOHLH1 were set to Ovarian dysgenesis 5 MIM#617690; Spermatogenic failure 32 MIM#618115
Review for gene: SOHLH1 was set to GREEN
Added comment: Women in 3 unrelated families with ovarian dysgenesis and homozygous variants, and a supporting null mouse model.
At least 4 males with heterozygous variants and spermatogenic failure.
Sources: Expert list
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.4 SOHLH1 Bryony Thompson Marked gene: SOHLH1 as ready
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.4 SOHLH1 Bryony Thompson Gene: sohlh1 has been classified as Green List (High Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.4 SOHLH1 Bryony Thompson Phenotypes for gene: SOHLH1 were changed from to Ovarian dysgenesis 5 MIM#617690
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.3 SOHLH1 Bryony Thompson Publications for gene: SOHLH1 were set to
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.2 SOHLH1 Bryony Thompson reviewed gene: SOHLH1: Rating: GREEN; Mode of pathogenicity: None; Publications: 25774885, 16690745, 31042289; Phenotypes: Ovarian dysgenesis 5 MIM#617690; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3107 HFM1 Bryony Thompson Marked gene: HFM1 as ready
Mendeliome v0.3107 HFM1 Bryony Thompson Gene: hfm1 has been classified as Green List (High Evidence).
Mendeliome v0.3107 HFM1 Bryony Thompson Classified gene: HFM1 as Green List (high evidence)
Mendeliome v0.3107 HFM1 Bryony Thompson Gene: hfm1 has been classified as Green List (High Evidence).
Mendeliome v0.3106 HFM1 Bryony Thompson gene: HFM1 was added
gene: HFM1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: HFM1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: HFM1 were set to 23555294; 24597873; 31279343
Phenotypes for gene: HFM1 were set to Premature ovarian failure 9 MIM#615724
Review for gene: HFM1 was set to GREEN
Added comment: Three cases from 2 unrelated families with compound heterozygous variants, and a single family with a heterozygous variant have been reported with ovarian failure. There is also a supporting null mouse model.
Sources: Expert list
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.2 HFM1 Bryony Thompson reviewed gene: HFM1: Rating: GREEN; Mode of pathogenicity: None; Publications: 23555294, 24597873, 31279343; Phenotypes: Premature ovarian failure 9 MIM#615724; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.2 GDF9 Bryony Thompson Classified gene: GDF9 as Amber List (moderate evidence)
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.2 GDF9 Bryony Thompson Gene: gdf9 has been classified as Amber List (Moderate Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.1 GDF9 Bryony Thompson reviewed gene: GDF9: Rating: AMBER; Mode of pathogenicity: None; Publications: 29044499, 8849725; Phenotypes: Premature ovarian failure 14 MIM#618014; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.1 FMR1 Bryony Thompson Tag STR tag was added to gene: FMR1.
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.1 Bryony Thompson Panel status changed from internal to public
Panel types changed to Royal Melbourne Hospital; Rare Disease
Craniosynostosis v0.74 ZNF462 Tiong Tan Marked gene: ZNF462 as ready
Craniosynostosis v0.74 ZNF462 Tiong Tan Gene: znf462 has been classified as Green List (High Evidence).
Craniosynostosis v0.74 ZNF462 Tiong Tan Classified gene: ZNF462 as Green List (high evidence)
Craniosynostosis v0.74 ZNF462 Tiong Tan Gene: znf462 has been classified as Green List (High Evidence).
Craniosynostosis v0.73 ZNF462 Tiong Tan gene: ZNF462 was added
gene: ZNF462 was added to Craniosynostosis. Sources: Literature
Mode of inheritance for gene: ZNF462 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ZNF462 were set to 28513610
Phenotypes for gene: ZNF462 were set to WEISS-KRUSZKA SYNDROME
Penetrance for gene: ZNF462 were set to Complete
Review for gene: ZNF462 was set to GREEN
Added comment: Craniosynostosis observed in 38% of affected individuals
Sources: Literature
Craniosynostosis v0.72 WDR35 Tiong Tan Marked gene: WDR35 as ready
Craniosynostosis v0.72 WDR35 Tiong Tan Gene: wdr35 has been classified as Green List (High Evidence).
Craniosynostosis v0.72 WDR35 Tiong Tan Classified gene: WDR35 as Green List (high evidence)
Craniosynostosis v0.72 WDR35 Tiong Tan Gene: wdr35 has been classified as Green List (High Evidence).
Craniosynostosis v0.71 WDR35 Tiong Tan gene: WDR35 was added
gene: WDR35 was added to Craniosynostosis. Sources: Literature
Mode of inheritance for gene: WDR35 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WDR35 were set to 20817137; 24123776
Phenotypes for gene: WDR35 were set to CRANIOECTODERMAL DYSPLASIA
Penetrance for gene: WDR35 were set to Complete
Review for gene: WDR35 was set to GREEN
Added comment: Craniosynostosis is a well-established feature of Sensenbrenner/Cranioectodermal dysplasia
Sources: Literature
Craniosynostosis v0.70 SMAD3 Tiong Tan Marked gene: SMAD3 as ready
Craniosynostosis v0.70 SMAD3 Tiong Tan Gene: smad3 has been classified as Green List (High Evidence).
Craniosynostosis v0.70 SMAD3 Tiong Tan Classified gene: SMAD3 as Green List (high evidence)
Craniosynostosis v0.70 SMAD3 Tiong Tan Gene: smad3 has been classified as Green List (High Evidence).
Craniosynostosis v0.69 SMAD3 Tiong Tan gene: SMAD3 was added
gene: SMAD3 was added to Craniosynostosis. Sources: Literature
Mode of inheritance for gene: SMAD3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SMAD3 were set to 20301312
Phenotypes for gene: SMAD3 were set to LOEYS-DIETZ SYNDROME
Penetrance for gene: SMAD3 were set to Complete
Added comment: Craniosynostosis is a well-established feature of LDS - TGFBR1, TGFBR2 and SMAD3
Sources: Literature
Craniosynostosis v0.68 TGFBR2 Tiong Tan Classified gene: TGFBR2 as Green List (high evidence)
Craniosynostosis v0.68 TGFBR2 Tiong Tan Gene: tgfbr2 has been classified as Green List (High Evidence).
Craniosynostosis v0.67 TGFBR2 Tiong Tan Classified gene: TGFBR2 as Green List (high evidence)
Craniosynostosis v0.67 TGFBR2 Tiong Tan Gene: tgfbr2 has been classified as Green List (High Evidence).
Craniosynostosis v0.66 TGFBR2 Tiong Tan Marked gene: TGFBR2 as ready
Craniosynostosis v0.66 TGFBR2 Tiong Tan Gene: tgfbr2 has been classified as Red List (Low Evidence).
Craniosynostosis v0.66 TGFBR2 Tiong Tan gene: TGFBR2 was added
gene: TGFBR2 was added to Craniosynostosis. Sources: Literature
Mode of inheritance for gene: TGFBR2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TGFBR2 were set to 15731757
Phenotypes for gene: TGFBR2 were set to LOEYS-DIETZ SYNDROME
Penetrance for gene: TGFBR2 were set to Complete
Review for gene: TGFBR2 was set to GREEN
Added comment: Craniosynostosis is a well-established feature of LDS - TGFBR1, TGFBR2 and SMAD3
Sources: Literature
Craniosynostosis v0.65 TGFBR1 Tiong Tan Marked gene: TGFBR1 as ready
Craniosynostosis v0.65 TGFBR1 Tiong Tan Gene: tgfbr1 has been classified as Green List (High Evidence).
Craniosynostosis v0.65 TGFBR1 Tiong Tan Classified gene: TGFBR1 as Green List (high evidence)
Craniosynostosis v0.65 TGFBR1 Tiong Tan Gene: tgfbr1 has been classified as Green List (High Evidence).
Craniosynostosis v0.64 TGFBR1 Tiong Tan gene: TGFBR1 was added
gene: TGFBR1 was added to Craniosynostosis. Sources: Literature
Mode of inheritance for gene: TGFBR1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TGFBR1 were set to 15731757
Phenotypes for gene: TGFBR1 were set to Loeys-Dietz syndrome
Penetrance for gene: TGFBR1 were set to Complete
Review for gene: TGFBR1 was set to GREEN
Added comment: Craniosynostosis is a well-established feature of LDS - TGFBR1, TGFBR2 and SMAD3
Sources: Literature
Craniosynostosis v0.63 SMO Tiong Tan Marked gene: SMO as ready
Craniosynostosis v0.63 SMO Tiong Tan Gene: smo has been classified as Green List (High Evidence).
Craniosynostosis v0.63 SMO Tiong Tan Classified gene: SMO as Green List (high evidence)
Craniosynostosis v0.63 SMO Tiong Tan Gene: smo has been classified as Green List (High Evidence).
Craniosynostosis v0.62 SMO Tiong Tan gene: SMO was added
gene: SMO was added to Craniosynostosis. Sources: Literature
Mode of inheritance for gene: SMO was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SMO were set to 27236920
Phenotypes for gene: SMO were set to Curry-Jones syndrome
Penetrance for gene: SMO were set to Complete
Mode of pathogenicity for gene: SMO 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: SMO was set to GREEN
Added comment: Mosaic activating variants in SMO associated with Curry-Jones syndrome - craniosynostosis is a key feature.
Sources: Literature
Craniosynostosis v0.61 SMAD6 Tiong Tan Marked gene: SMAD6 as ready
Craniosynostosis v0.61 SMAD6 Tiong Tan Gene: smad6 has been classified as Green List (High Evidence).
Craniosynostosis v0.61 SMAD6 Tiong Tan Classified gene: SMAD6 as Green List (high evidence)
Craniosynostosis v0.61 SMAD6 Tiong Tan Gene: smad6 has been classified as Green List (High Evidence).
Craniosynostosis v0.60 SMAD6 Tiong Tan gene: SMAD6 was added
gene: SMAD6 was added to Craniosynostosis. Sources: Literature
Mode of inheritance for gene: SMAD6 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SMAD6 were set to 32499606; 27606499
Phenotypes for gene: SMAD6 were set to non-syndromic craniosynostosis
Penetrance for gene: SMAD6 were set to Incomplete
Review for gene: SMAD6 was set to GREEN
Added comment: Penetrance is 57%. A common polymorphism near BMP2 (rs1884302) was initially proposed to influence penetrance, but follow-up study did not corroborate this. In vitro luciferase assays suggest loss of SMAD6 inhibitory function.
Sources: Literature
Craniosynostosis v0.59 SKI Tiong Tan Classified gene: SKI as Green List (high evidence)
Craniosynostosis v0.59 SKI Tiong Tan Gene: ski has been classified as Green List (High Evidence).
Craniosynostosis v0.58 SKI Tiong Tan gene: SKI was added
gene: SKI was added to Craniosynostosis. Sources: Literature
Mode of inheritance for gene: SKI was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SKI were set to 23023332; 23103230; 24736733
Phenotypes for gene: SKI were set to SHPRINTZEN-GOLDBERG CRANIOSYNOSTOSIS SYNDROME
Penetrance for gene: SKI were set to Complete
Mode of pathogenicity for gene: SKI was set to Other
Review for gene: SKI was set to GREEN
Added comment: Mutational hotspot suggests a mechanism that is not LOF
Sources: Literature
Craniosynostosis v0.57 SHOC2 Tiong Tan Marked gene: SHOC2 as ready
Craniosynostosis v0.57 SHOC2 Tiong Tan Gene: shoc2 has been classified as Amber List (Moderate Evidence).
Craniosynostosis v0.57 SHOC2 Tiong Tan Classified gene: SHOC2 as Amber List (moderate evidence)
Craniosynostosis v0.57 SHOC2 Tiong Tan Gene: shoc2 has been classified as Amber List (Moderate Evidence).
Craniosynostosis v0.56 SHOC2 Tiong Tan gene: SHOC2 was added
gene: SHOC2 was added to Craniosynostosis. Sources: Literature
Mode of inheritance for gene: SHOC2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SHOC2 were set to 28650561; 25123707
Phenotypes for gene: SHOC2 were set to Noonan syndrome with loose anagen hair
Penetrance for gene: SHOC2 were set to Complete
Mode of pathogenicity for gene: SHOC2 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: SHOC2 was set to AMBER
Added comment: Two unrelated individuals with SHOC2-related Noonan syndrome and craniosynostosis; other Noonan syndrome genotypes have higher incidence of craniosynostosis.
Sources: Literature
Craniosynostosis v0.55 MEGF8 Tiong Tan Marked gene: MEGF8 as ready
Craniosynostosis v0.55 MEGF8 Tiong Tan Gene: megf8 has been classified as Green List (High Evidence).
Craniosynostosis v0.55 MEGF8 Tiong Tan Classified gene: MEGF8 as Green List (high evidence)
Craniosynostosis v0.55 MEGF8 Tiong Tan Gene: megf8 has been classified as Green List (High Evidence).
Craniosynostosis v0.54 MEGF8 Tiong Tan gene: MEGF8 was added
gene: MEGF8 was added to Craniosynostosis. Sources: Literature
Mode of inheritance for gene: MEGF8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MEGF8 were set to 23063620
Phenotypes for gene: MEGF8 were set to Carpenter syndrome
Penetrance for gene: MEGF8 were set to Complete
Review for gene: MEGF8 was set to GREEN
Added comment: Craniosynostosis is a key feature of Carpenter syndrome - identified in 4/4 unrelated individuals with MEGF8 biallelic variants
Sources: Literature
Craniosynostosis v0.53 MASP1 Tiong Tan Classified gene: MASP1 as Green List (high evidence)
Craniosynostosis v0.53 MASP1 Tiong Tan Gene: masp1 has been classified as Green List (High Evidence).
Craniosynostosis v0.52 MASP1 Tiong Tan gene: MASP1 was added
gene: MASP1 was added to Craniosynostosis. Sources: Literature
Mode of inheritance for gene: MASP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MASP1 were set to 7677137; 21258343
Phenotypes for gene: MASP1 were set to 3MC syndrome
Penetrance for gene: MASP1 were set to Complete
Review for gene: MASP1 was set to GREEN
Added comment: Craniosynostosis occurs in 20-30% of individuals with 3MC syndrome
Sources: Literature
Mendeliome v0.3105 NEK9 Zornitza Stark Marked gene: NEK9 as ready
Mendeliome v0.3105 NEK9 Zornitza Stark Gene: nek9 has been classified as Red List (Low Evidence).
Mendeliome v0.3105 NEK9 Zornitza Stark Phenotypes for gene: NEK9 were changed from to Lethal congenital contracture syndrome 10, MIM# 617022; Skeletal dysplasia
Mendeliome v0.3104 NEK9 Zornitza Stark Publications for gene: NEK9 were set to
Mendeliome v0.3103 NEK9 Zornitza Stark Mode of inheritance for gene: NEK9 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3102 NEK9 Zornitza Stark Classified gene: NEK9 as Red List (low evidence)
Mendeliome v0.3102 NEK9 Zornitza Stark Gene: nek9 has been classified as Red List (Low Evidence).
Mendeliome v0.3101 NEK9 Zornitza Stark reviewed gene: NEK9: Rating: RED; Mode of pathogenicity: None; Publications: 26908619; Phenotypes: Lethal congenital contracture syndrome 10, MIM# 617022, Skeletal dysplasia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal Dysplasia_Fetal v0.22 NEK9 Zornitza Stark Marked gene: NEK9 as ready
Skeletal Dysplasia_Fetal v0.22 NEK9 Zornitza Stark Gene: nek9 has been classified as Red List (Low Evidence).
Skeletal Dysplasia_Fetal v0.22 NEK9 Zornitza Stark Tag founder tag was added to gene: NEK9.
Skeletal Dysplasia_Fetal v0.22 NEK9 Zornitza Stark gene: NEK9 was added
gene: NEK9 was added to Skeletal Dysplasia_Fetal. Sources: Expert list
Mode of inheritance for gene: NEK9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NEK9 were set to 26908619
Phenotypes for gene: NEK9 were set to Lethal congenital contracture syndrome 10, MIM# 617022; Skeletal dysplasia
Review for gene: NEK9 was set to RED
Added comment: Two Irish traveller families, 5 affected individuals, same homozygous variant identified (founder effect). Limited functional data.
Sources: Expert list
Skeletal dysplasia v0.33 NEK9 Zornitza Stark Tag founder tag was added to gene: NEK9.
Skeletal dysplasia v0.33 NEK9 Zornitza Stark Marked gene: NEK9 as ready
Skeletal dysplasia v0.33 NEK9 Zornitza Stark Gene: nek9 has been classified as Red List (Low Evidence).
Skeletal dysplasia v0.33 NEK9 Zornitza Stark gene: NEK9 was added
gene: NEK9 was added to Skeletal dysplasia. Sources: Expert list
Mode of inheritance for gene: NEK9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NEK9 were set to 26908619
Phenotypes for gene: NEK9 were set to Lethal congenital contracture syndrome 10, MIM# 617022; Skeletal dysplasia
Review for gene: NEK9 was set to RED
Added comment: Two Irish traveller families, 5 affected individuals, same homozygous variant identified (founder effect). Limited functional data.
Sources: Expert list
Mendeliome v0.3101 MSTN Zornitza Stark Marked gene: MSTN as ready
Mendeliome v0.3101 MSTN Zornitza Stark Gene: mstn has been classified as Red List (Low Evidence).
Mendeliome v0.3101 MSTN Zornitza Stark Phenotypes for gene: MSTN were changed from to Muscle hypertrophy, MIM# 614160
Mendeliome v0.3100 MSTN Zornitza Stark Publications for gene: MSTN were set to
Mendeliome v0.3099 MSTN Zornitza Stark Mode of inheritance for gene: MSTN was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3098 MSTN Zornitza Stark Classified gene: MSTN as Red List (low evidence)
Mendeliome v0.3098 MSTN Zornitza Stark Gene: mstn has been classified as Red List (Low Evidence).
Mendeliome v0.3097 MSTN Zornitza Stark reviewed gene: MSTN: Rating: RED; Mode of pathogenicity: None; Publications: 15215484; Phenotypes: Muscle hypertrophy, MIM# 614160; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3097 HSPB8 Zornitza Stark Marked gene: HSPB8 as ready
Mendeliome v0.3097 HSPB8 Zornitza Stark Gene: hspb8 has been classified as Green List (High Evidence).
Mendeliome v0.3097 HSPB8 Zornitza Stark Phenotypes for gene: HSPB8 were changed from to Distal myopathy; Vacuolar myopathy; Neuropathy, distal hereditary motor type IIA, 158590; Charcot-Marie-Tooth disease, axonal, type 2L, MIM# 608673
Mendeliome v0.3096 HSPB8 Zornitza Stark Publications for gene: HSPB8 were set to
Mendeliome v0.3095 HSPB8 Zornitza Stark Mode of inheritance for gene: HSPB8 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3094 HSPB8 Zornitza Stark reviewed gene: HSPB8: Rating: GREEN; Mode of pathogenicity: None; Publications: 32165108, 31403083, 28780615, 15122253, 26718575; Phenotypes: Distal myopathy, Vacuolar myopathy, Neuropathy, distal hereditary motor type IIA, 158590, Charcot-Marie-Tooth disease, axonal, type 2L, MIM# 608673; Mode of inheritance: None
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.6 DYSF Zornitza Stark Marked gene: DYSF as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.6 DYSF Zornitza Stark Gene: dysf has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.6 DYSF Zornitza Stark Publications for gene: DYSF were set to
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.5 DNAJB6 Zornitza Stark Marked gene: DNAJB6 as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.5 DNAJB6 Zornitza Stark Gene: dnajb6 has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.5 DNAJB6 Zornitza Stark Publications for gene: DNAJB6 were set to
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.0 STAG3 Bryony Thompson gene: STAG3 was added
gene: STAG3 was added to Amenorrhoea. Sources: NHS GMS,Expert Review Green
Mode of inheritance for gene: STAG3 was set to BIALLELIC, autosomal or pseudoautosomal
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.0 SOHLH1 Bryony Thompson gene: SOHLH1 was added
gene: SOHLH1 was added to Amenorrhoea. Sources: NHS GMS,Expert Review Green
Mode of inheritance for gene: SOHLH1 was set to BIALLELIC, autosomal or pseudoautosomal
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.0 PMM2 Bryony Thompson gene: PMM2 was added
gene: PMM2 was added to Amenorrhoea. Sources: NHS GMS,Expert Review Green
Mode of inheritance for gene: PMM2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PMM2 were set to Congenital disorder of glycosylation, type Ia 212065
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.0 HFM1 Bryony Thompson gene: HFM1 was added
gene: HFM1 was added to Amenorrhoea. Sources: NHS GMS,Expert Review Green
Mode of inheritance for gene: HFM1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: HFM1 were set to Premature ovarian failure 9,615724
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.0 FSHB Bryony Thompson gene: FSHB was added
gene: FSHB was added to Amenorrhoea. Sources: NHS GMS,Expert Review Green
Mode of inheritance for gene: FSHB was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: FSHB were set to Hypogonadotropic hypogonadism 24 without anosmia 229070
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.0 AARS2 Bryony Thompson gene: AARS2 was added
gene: AARS2 was added to Amenorrhoea. Sources: NHS GMS,Expert Review Green
Mode of inheritance for gene: AARS2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: AARS2 were set to Leukoencephalopathy, progressive, with ovarian failure 615889
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.0 WT1 Bryony Thompson gene: WT1 was added
gene: WT1 was added to Amenorrhoea. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: WT1 was set to
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.0 WDR11 Bryony Thompson gene: WDR11 was added
gene: WDR11 was added to Amenorrhoea. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: WDR11 was set to
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.0 TACR3 Bryony Thompson gene: TACR3 was added
gene: TACR3 was added to Amenorrhoea. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: TACR3 was set to
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.0 TAC3 Bryony Thompson gene: TAC3 was added
gene: TAC3 was added to Amenorrhoea. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: TAC3 was set to
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.0 STAR Bryony Thompson gene: STAR was added
gene: STAR was added to Amenorrhoea. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: STAR was set to
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.0 SEMA3A Bryony Thompson gene: SEMA3A was added
gene: SEMA3A was added to Amenorrhoea. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: SEMA3A was set to
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.0 PSMC3IP Bryony Thompson gene: PSMC3IP was added
gene: PSMC3IP was added to Amenorrhoea. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: PSMC3IP was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PSMC3IP were set to Ovarian dysgenesis 3,614324
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.0 PROKR2 Bryony Thompson gene: PROKR2 was added
gene: PROKR2 was added to Amenorrhoea. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: PROKR2 was set to
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.0 PROK2 Bryony Thompson gene: PROK2 was added
gene: PROK2 was added to Amenorrhoea. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: PROK2 was set to
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.0 POR Bryony Thompson gene: POR was added
gene: POR was added to Amenorrhoea. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: POR was set to
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.0 POLG Bryony Thompson gene: POLG was added
gene: POLG was added to Amenorrhoea. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: POLG was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: POLG were set to Progressive external ophthalmoplegia, autosomal recessive 1 258450; Progressive external ophthalmoplegia, autosomal dominant 1 157640
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.0 NUP107 Bryony Thompson gene: NUP107 was added
gene: NUP107 was added to Amenorrhoea. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: NUP107 was set to BIALLELIC, autosomal or pseudoautosomal
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.0 NR5A1 Bryony Thompson gene: NR5A1 was added
gene: NR5A1 was added to Amenorrhoea. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: NR5A1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: NR5A1 were set to Spermatogenic failure 8,613957; 46XY sex reversal 3,612965; Premature ovarian failure 7,612964
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.0 NOBOX Bryony Thompson gene: NOBOX was added
gene: NOBOX was added to Amenorrhoea. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: NOBOX was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: NOBOX were set to Premature ovarian failure 5,611548
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.0 MCM9 Bryony Thompson gene: MCM9 was added
gene: MCM9 was added to Amenorrhoea. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: MCM9 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: MCM9 were set to Ovarian dysgenesis 4, 616185
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.0 MCM8 Bryony Thompson gene: MCM8 was added
gene: MCM8 was added to Amenorrhoea. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: MCM8 was set to BIALLELIC, autosomal or pseudoautosomal
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.0 LMNA Bryony Thompson gene: LMNA was added
gene: LMNA was added to Amenorrhoea. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: LMNA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.0 LHCGR Bryony Thompson gene: LHCGR was added
gene: LHCGR was added to Amenorrhoea. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: LHCGR was set to
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.0 LHB Bryony Thompson gene: LHB was added
gene: LHB was added to Amenorrhoea. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: LHB was set to
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.0 LARS2 Bryony Thompson gene: LARS2 was added
gene: LARS2 was added to Amenorrhoea. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: LARS2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: LARS2 were set to Perrault syndrome 4 615300
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.0 KISS1R Bryony Thompson gene: KISS1R was added
gene: KISS1R was added to Amenorrhoea. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: KISS1R was set to
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.0 KISS1 Bryony Thompson gene: KISS1 was added
gene: KISS1 was added to Amenorrhoea. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: KISS1 was set to
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.0 HSD17B4 Bryony Thompson gene: HSD17B4 was added
gene: HSD17B4 was added to Amenorrhoea. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: HSD17B4 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: HSD17B4 were set to Perrault syndrome 1 233400
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.0 GNAS Bryony Thompson gene: GNAS was added
gene: GNAS was added to Amenorrhoea. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: GNAS was set to
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.0 GDF9 Bryony Thompson gene: GDF9 was added
gene: GDF9 was added to Amenorrhoea. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: GDF9 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.0 GALT Bryony Thompson gene: GALT was added
gene: GALT was added to Amenorrhoea. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: GALT was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: GALT were set to Galactosemia, 230400
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.0 FSHR Bryony Thompson gene: FSHR was added
gene: FSHR was added to Amenorrhoea. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: FSHR was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: FSHR were set to Ovarian dysgenesis 1 233300; Ovarian response to FSH stimulation 276400
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.0 FOXL2 Bryony Thompson gene: FOXL2 was added
gene: FOXL2 was added to Amenorrhoea. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: FOXL2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: FOXL2 were set to Blepharophimosis,epicanthus inversus and ptosis,type 1 and 2,110100; Premature ovarian failure 3,608996
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.0 FMR1 Bryony Thompson gene: FMR1 was added
gene: FMR1 was added to Amenorrhoea. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: FMR1 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Phenotypes for gene: FMR1 were set to Fragile X tremor ataxia syndrome, 300623; Fragile X syndrome, 300624; Premature ovarian failure 1, 311360
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.0 FIGLA Bryony Thompson gene: FIGLA was added
gene: FIGLA was added to Amenorrhoea. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: FIGLA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: FIGLA were set to Premature ovarian failure,612310
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.0 FGFR1 Bryony Thompson gene: FGFR1 was added
gene: FGFR1 was added to Amenorrhoea. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: FGFR1 was set to
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.0 ESR1 Bryony Thompson gene: ESR1 was added
gene: ESR1 was added to Amenorrhoea. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: ESR1 was set to
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.0 EIF2B5 Bryony Thompson gene: EIF2B5 was added
gene: EIF2B5 was added to Amenorrhoea. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: EIF2B5 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: EIF2B5 were set to Ovarioleukodystrophy 603896
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.0 EIF2B4 Bryony Thompson gene: EIF2B4 was added
gene: EIF2B4 was added to Amenorrhoea. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: EIF2B4 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: EIF2B4 were set to Ovarioleukodystrophy 603896
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.0 EIF2B2 Bryony Thompson gene: EIF2B2 was added
gene: EIF2B2 was added to Amenorrhoea. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: EIF2B2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: EIF2B2 were set to Ovarioleukodystrophy 603896
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.0 CYP19A1 Bryony Thompson gene: CYP19A1 was added
gene: CYP19A1 was added to Amenorrhoea. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: CYP19A1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CYP19A1 were set to Aromatase deficiency 613546
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.0 CYP17A1 Bryony Thompson gene: CYP17A1 was added
gene: CYP17A1 was added to Amenorrhoea. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: CYP17A1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CYP17A1 were set to 17-alpha-hydroxylase, 17,20-lyase deficiency 202110
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.0 CLPP Bryony Thompson gene: CLPP was added
gene: CLPP was added to Amenorrhoea. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: CLPP was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CLPP were set to Perrault syndrome 3 614129
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.0 TWNK Bryony Thompson gene: TWNK was added
gene: TWNK was added to Amenorrhoea. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: TWNK was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TWNK were set to Perrault syndrome 5, 616138
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.0 BMP15 Bryony Thompson gene: BMP15 was added
gene: BMP15 was added to Amenorrhoea. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: BMP15 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Phenotypes for gene: BMP15 were set to Ovarian dysgenesis 2,300510; Premature ovarian failure 4300510
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.0 AMHR2 Bryony Thompson gene: AMHR2 was added
gene: AMHR2 was added to Amenorrhoea. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: AMHR2 was set to
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.0 AMH Bryony Thompson gene: AMH was added
gene: AMH was added to Amenorrhoea. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: AMH was set to
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.0 AIRE Bryony Thompson gene: AIRE was added
gene: AIRE was added to Amenorrhoea. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: AIRE was set to
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.0 Bryony Thompson Added panel Amenorrhoea
Glycogen Storage Diseases v0.8 GAA Crystle Lee reviewed gene: GAA: Rating: GREEN; Mode of pathogenicity: None; Publications: 25103075, 27365701; Phenotypes: Glycogen storage disease II (MIM#232300); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.65 CHST14 Zornitza Stark Marked gene: CHST14 as ready
Arthrogryposis v0.65 CHST14 Zornitza Stark Gene: chst14 has been classified as Green List (High Evidence).
Arthrogryposis v0.65 CHST14 Zornitza Stark Phenotypes for gene: CHST14 were changed from to Ehlers-Danlos syndrome, musculocontractural type 1 (MIM#601776)
Arthrogryposis v0.64 CHST14 Zornitza Stark Publications for gene: CHST14 were set to
Arthrogryposis v0.63 CHST14 Zornitza Stark Mode of inheritance for gene: CHST14 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Muscular dystrophy and myopathy_Paediatric v0.15 CAVIN1 Zornitza Stark Marked gene: CAVIN1 as ready
Muscular dystrophy and myopathy_Paediatric v0.15 CAVIN1 Zornitza Stark Gene: cavin1 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.15 CAVIN1 Zornitza Stark Classified gene: CAVIN1 as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v0.15 CAVIN1 Zornitza Stark Gene: cavin1 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.14 CAVIN1 Zornitza Stark gene: CAVIN1 was added
gene: CAVIN1 was added to Muscular dystrophy. Sources: Expert list
Mode of inheritance for gene: CAVIN1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CAVIN1 were set to Lipodystrophy, congenital generalized, type 4 (MIM#613327)
Review for gene: CAVIN1 was set to GREEN
Added comment: Gene also known as PTRF. Multiple families reported with onset of disease in childhood, muscular dystrophy is a feature.
Sources: Expert list
Rhabdomyolysis and Metabolic Myopathy v0.56 AMPD1 Zornitza Stark Marked gene: AMPD1 as ready
Rhabdomyolysis and Metabolic Myopathy v0.56 AMPD1 Zornitza Stark Gene: ampd1 has been classified as Red List (Low Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.56 AMPD1 Zornitza Stark Classified gene: AMPD1 as Red List (low evidence)
Rhabdomyolysis and Metabolic Myopathy v0.56 AMPD1 Zornitza Stark Gene: ampd1 has been classified as Red List (Low Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.55 AMPD1 Zornitza Stark Tag disputed tag was added to gene: AMPD1.
Rhabdomyolysis and Metabolic Myopathy v0.55 AMPD1 Zornitza Stark reviewed gene: AMPD1: Rating: RED; Mode of pathogenicity: None; Publications: 21343608, 27296017; Phenotypes: Myopathy due to myoadenylate deaminase deficiency (MIM#615511); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3094 AMPD1 Zornitza Stark Marked gene: AMPD1 as ready
Mendeliome v0.3094 AMPD1 Zornitza Stark Gene: ampd1 has been classified as Red List (Low Evidence).
Mendeliome v0.3094 AMPD1 Zornitza Stark Phenotypes for gene: AMPD1 were changed from to Myopathy due to myoadenylate deaminase deficiency (MIM#615511)
Mendeliome v0.3093 AMPD1 Zornitza Stark Publications for gene: AMPD1 were set to
Mendeliome v0.3092 AMPD1 Zornitza Stark Mode of inheritance for gene: AMPD1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3091 AMPD1 Zornitza Stark Classified gene: AMPD1 as Red List (low evidence)
Mendeliome v0.3091 AMPD1 Zornitza Stark Gene: ampd1 has been classified as Red List (Low Evidence).
Mendeliome v0.3090 AMPD1 Zornitza Stark Tag disputed tag was added to gene: AMPD1.
Mendeliome v0.3090 AMPD1 Zornitza Stark reviewed gene: AMPD1: Rating: RED; Mode of pathogenicity: None; Publications: 21343608, 27296017; Phenotypes: Myopathy due to myoadenylate deaminase deficiency (MIM#615511); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.4 DYSF Crystle Lee reviewed gene: DYSF: Rating: GREEN; Mode of pathogenicity: None; Publications: 23243261; Phenotypes: Muscular dystrophy, limb-girdle, autosomal recessive 2 (MIM#253601); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Spastic Paraplegia v0.105 GPT2 Bryony Thompson Marked gene: GPT2 as ready
Hereditary Spastic Paraplegia v0.105 GPT2 Bryony Thompson Gene: gpt2 has been classified as Green List (High Evidence).
Hereditary Spastic Paraplegia v0.105 GPT2 Bryony Thompson Classified gene: GPT2 as Green List (high evidence)
Hereditary Spastic Paraplegia v0.105 GPT2 Bryony Thompson Gene: gpt2 has been classified as Green List (High Evidence).
Hereditary Spastic Paraplegia v0.104 GPT2 Bryony Thompson gene: GPT2 was added
gene: GPT2 was added to Hereditary Spastic Paraplegia - paediatric. Sources: Expert list
Mode of inheritance for gene: GPT2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GPT2 were set to 29882329; 31471722; 27601654
Phenotypes for gene: GPT2 were set to Mental retardation, autosomal recessive 49 MIM#616281
Review for gene: GPT2 was set to GREEN
Added comment: Paediatric onset spastic paraglegia is a prominent feature of the condition, >3 unrelated families reported.
Sources: Expert list
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.4 DNAJB6 Crystle Lee reviewed gene: DNAJB6: Rating: GREEN; Mode of pathogenicity: None; Publications: 26847086, 26338452, 24170373; Phenotypes: Muscular dystrophy, limb-girdle, autosomal dominant 1 (MIM#603511); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Arthrogryposis v0.62 CHST14 Crystle Lee reviewed gene: CHST14: Rating: GREEN; Mode of pathogenicity: None; Publications: 26373698; Phenotypes: Ehlers-Danlos syndrome, musculocontractural type 1 (MIM#601776); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia v0.219 UBTF Bryony Thompson changed review comment from: Ataxia reported as a feature of the condition in 4 unrelated cases with de novo missense variants.
Sources: Expert list; to: Paediatric ataxia reported as a feature of the condition in 4 unrelated cases with de novo missense variants.
Sources: Expert list
Ataxia v0.219 UBTF Bryony Thompson Marked gene: UBTF as ready
Ataxia v0.219 UBTF Bryony Thompson Gene: ubtf has been classified as Green List (High Evidence).
Ataxia v0.219 UBTF Bryony Thompson Classified gene: UBTF as Green List (high evidence)
Ataxia v0.219 UBTF Bryony Thompson Gene: ubtf has been classified as Green List (High Evidence).
Ataxia v0.218 UBTF Bryony Thompson gene: UBTF was added
gene: UBTF was added to Ataxia - paediatric. Sources: Expert list
Mode of inheritance for gene: UBTF was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: UBTF were set to 29300972
Phenotypes for gene: UBTF were set to Neurodegeneration, childhood-onset, with brain atrophy MIM#617672
Review for gene: UBTF was set to GREEN
Added comment: Ataxia reported as a feature of the condition in 4 unrelated cases with de novo missense variants.
Sources: Expert list
Mendeliome v0.3090 FBXW11 Zornitza Stark Phenotypes for gene: FBXW11 were changed from Intellectual disability; developmental eye anomalies; digital anomalies to Neurodevelopmental, eye, jaw, and digital syndrome (NDEJD), MIM#618914; Intellectual disability; developmental eye anomalies; digital anomalies
Mendeliome v0.3089 FBXW11 Zornitza Stark reviewed gene: FBXW11: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental, eye, jaw, and digital syndrome (NDEJD), MIM#618914; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Anophthalmia_Microphthalmia_Coloboma v0.59 FBXW11 Zornitza Stark Phenotypes for gene: FBXW11 were changed from Intellectual disability; developmental eye anomalies; digital anomalies to Neurodevelopmental, eye, jaw, and digital syndrome (NDEJD), MIM#618914; Intellectual disability; developmental eye anomalies; digital anomalies
Anophthalmia_Microphthalmia_Coloboma v0.58 FBXW11 Zornitza Stark reviewed gene: FBXW11: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental, eye, jaw, and digital syndrome (NDEJD), MIM#618914; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2699 FBXW11 Zornitza Stark Phenotypes for gene: FBXW11 were changed from Neurodevelopmental, eye, jaw, and digital syndrome (NDEJD), MIM#618914; Intellectual disability; developmental eye anomalies; digital anomalies to Neurodevelopmental, eye, jaw, and digital syndrome (NDEJD), MIM#618914; Intellectual disability; developmental eye anomalies; digital anomalies
Intellectual disability syndromic and non-syndromic v0.2699 FBXW11 Zornitza Stark Phenotypes for gene: FBXW11 were changed from Intellectual disability; developmental eye anomalies; digital anomalies to Neurodevelopmental, eye, jaw, and digital syndrome (NDEJD), MIM#618914; Intellectual disability; developmental eye anomalies; digital anomalies
Intellectual disability syndromic and non-syndromic v0.2698 FBXW11 Zornitza Stark reviewed gene: FBXW11: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental, eye, jaw, and digital syndrome (NDEJD), MIM#618914; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Ataxia v0.217 MTFMT Bryony Thompson Marked gene: MTFMT as ready
Ataxia v0.217 MTFMT Bryony Thompson Gene: mtfmt has been classified as Green List (High Evidence).
Ataxia v0.217 MTFMT Bryony Thompson Classified gene: MTFMT as Green List (high evidence)
Ataxia v0.217 MTFMT Bryony Thompson Gene: mtfmt has been classified as Green List (High Evidence).
Ataxia v0.216 MTFMT Bryony Thompson gene: MTFMT was added
gene: MTFMT was added to Ataxia - paediatric. Sources: Expert list
Mode of inheritance for gene: MTFMT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MTFMT were set to 26060307; 24461907
Phenotypes for gene: MTFMT were set to Combined oxidative phosphorylation deficiency 15 MIM#614947; Mitochondrial complex I deficiency, nuclear type 27 MIM#618248
Review for gene: MTFMT was set to GREEN
Added comment: Five unrelated cases reported with paediatric onset ataxia as a prominent feature of the condition.
Sources: Expert list
Ataxia v0.215 FA2H Bryony Thompson Marked gene: FA2H as ready
Ataxia v0.215 FA2H Bryony Thompson Gene: fa2h has been classified as Green List (High Evidence).
Ataxia v0.215 FA2H Bryony Thompson Classified gene: FA2H as Green List (high evidence)
Ataxia v0.215 FA2H Bryony Thompson Gene: fa2h has been classified as Green List (High Evidence).
Ataxia v0.214 FA2H Bryony Thompson gene: FA2H was added
gene: FA2H was added to Ataxia - paediatric. Sources: Expert list
Mode of inheritance for gene: FA2H was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FA2H were set to 31135052
Phenotypes for gene: FA2H were set to Spastic paraplegia 35, autosomal recessive MIM#612319
Review for gene: FA2H was set to GREEN
Added comment: Limb ataxia is reported as a feature of the condition in at least 13 cases with mainly paediatric onset.
Sources: Expert list
Leukodystrophy v0.133 FDX2 Bryony Thompson Marked gene: FDX2 as ready
Leukodystrophy v0.133 FDX2 Bryony Thompson Gene: fdx2 has been classified as Amber List (Moderate Evidence).
Leukodystrophy v0.133 FDX2 Bryony Thompson Classified gene: FDX2 as Amber List (moderate evidence)
Leukodystrophy v0.133 FDX2 Bryony Thompson Gene: fdx2 has been classified as Amber List (Moderate Evidence).
Leukodystrophy v0.132 FDX2 Bryony Thompson gene: FDX2 was added
gene: FDX2 was added to Leukodystrophy - paediatric. Sources: Expert list
Mode of inheritance for gene: FDX2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FDX2 were set to 30010796
Phenotypes for gene: FDX2 were set to Mitochondrial myopathy, episodic, with optic atrophy and reversible leukoencephalopathy MIM#251900
Review for gene: FDX2 was set to AMBER
Added comment: Two apparently unrelated consanguineous Brazilian families reported with reversible leukoencephalopathy with a paediatric onset as a feature of the condition.
Sources: Expert list
Leukodystrophy v0.131 COA7 Bryony Thompson Marked gene: COA7 as ready
Leukodystrophy v0.131 COA7 Bryony Thompson Gene: coa7 has been classified as Green List (High Evidence).
Leukodystrophy v0.131 COA7 Bryony Thompson Classified gene: COA7 as Green List (high evidence)
Leukodystrophy v0.131 COA7 Bryony Thompson Gene: coa7 has been classified as Green List (High Evidence).
Leukodystrophy v0.130 COA7 Bryony Thompson changed review comment from: At least 3 unrelated cases reported with leukoencephalopathy as a feature of the condition.
Sources: Expert list; to: At least 3 unrelated cases reported with leukoencephalopathy as a feature of the condition. Paediatric age of onset.
Sources: Expert list
Leukodystrophy v0.130 COA7 Bryony Thompson gene: COA7 was added
gene: COA7 was added to Leukodystrophy - paediatric. Sources: Expert list
Mode of inheritance for gene: COA7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COA7 were set to 27683825; 29718187
Phenotypes for gene: COA7 were set to Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 3 MIM#618387
Review for gene: COA7 was set to GREEN
Added comment: At least 3 unrelated cases reported with leukoencephalopathy as a feature of the condition.
Sources: Expert list
Leukodystrophy v0.129 AP4B1 Bryony Thompson Marked gene: AP4B1 as ready
Leukodystrophy v0.129 AP4B1 Bryony Thompson Gene: ap4b1 has been classified as Green List (High Evidence).
Leukodystrophy v0.129 AP4B1 Bryony Thompson Classified gene: AP4B1 as Green List (high evidence)
Leukodystrophy v0.129 AP4B1 Bryony Thompson Gene: ap4b1 has been classified as Green List (High Evidence).
Leukodystrophy v0.128 AP4B1 Bryony Thompson gene: AP4B1 was added
gene: AP4B1 was added to Leukodystrophy - paediatric. Sources: Expert list
Mode of inheritance for gene: AP4B1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AP4B1 were set to 29193663
Phenotypes for gene: AP4B1 were set to Spastic paraplegia 47, autosomal recessive MIM#614066
Review for gene: AP4B1 was set to GREEN
Added comment: White matter changes have been reported as a feature of the condition in at least ten unrelated cases with biallelic variants. The onset of the condition is paediatric.
Sources: Expert list
Craniosynostosis v0.51 PTPN11 Tiong Tan Marked gene: PTPN11 as ready
Craniosynostosis v0.51 PTPN11 Tiong Tan Gene: ptpn11 has been classified as Green List (High Evidence).
Craniosynostosis v0.51 PTPN11 Tiong Tan Classified gene: PTPN11 as Green List (high evidence)
Craniosynostosis v0.51 PTPN11 Tiong Tan Gene: ptpn11 has been classified as Green List (High Evidence).
Craniosynostosis v0.50 PTPN11 Tiong Tan gene: PTPN11 was added
gene: PTPN11 was added to Craniosynostosis. Sources: Literature
Mode of inheritance for gene: PTPN11 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PTPN11 were set to 28650561
Phenotypes for gene: PTPN11 were set to Noonan syndrome
Penetrance for gene: PTPN11 were set to Complete
Mode of pathogenicity for gene: PTPN11 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: PTPN11 was set to GREEN
Added comment: Three unrelated individuals with PTPN11-related Noonan syndrome and craniosynostosis
Sources: Literature
Craniosynostosis v0.49 BRAF Tiong Tan Marked gene: BRAF as ready
Craniosynostosis v0.49 BRAF Tiong Tan Gene: braf has been classified as Green List (High Evidence).
Craniosynostosis v0.49 BRAF Tiong Tan Classified gene: BRAF as Green List (high evidence)
Craniosynostosis v0.49 BRAF Tiong Tan Gene: braf has been classified as Green List (High Evidence).
Craniosynostosis v0.48 BRAF Tiong Tan gene: BRAF was added
gene: BRAF was added to Craniosynostosis. Sources: Literature
Mode of inheritance for gene: BRAF was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: BRAF were set to 28650561
Phenotypes for gene: BRAF were set to CFC
Penetrance for gene: BRAF were set to Complete
Mode of pathogenicity for gene: BRAF 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: BRAF was set to GREEN
Added comment: Four unrelated individuals with CFC and craniosynostosis
Sources: Literature
Craniosynostosis v0.47 KRAS Tiong Tan Marked gene: KRAS as ready
Craniosynostosis v0.47 KRAS Tiong Tan Gene: kras has been classified as Green List (High Evidence).
Craniosynostosis v0.47 KRAS Tiong Tan Classified gene: KRAS as Green List (high evidence)
Craniosynostosis v0.47 KRAS Tiong Tan Gene: kras has been classified as Green List (High Evidence).
Craniosynostosis v0.46 KRAS Tiong Tan gene: KRAS was added
gene: KRAS was added to Craniosynostosis. Sources: Literature
Mode of inheritance for gene: KRAS was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KRAS were set to 26249544; 28650561
Phenotypes for gene: KRAS were set to Noonan syndrome
Penetrance for gene: KRAS were set to Complete
Mode of pathogenicity for gene: KRAS 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: KRAS was set to GREEN
Added comment: 10% of all individuals with KRAS-related Noonan syndrome have craniosynostosis
Sources: Literature
Craniosynostosis v0.45 KAT6A Tiong Tan Classified gene: KAT6A as Green List (high evidence)
Craniosynostosis v0.45 KAT6A Tiong Tan Gene: kat6a has been classified as Green List (High Evidence).
Craniosynostosis v0.44 KAT6A Tiong Tan Classified gene: KAT6A as Green List (high evidence)
Craniosynostosis v0.44 KAT6A Tiong Tan Gene: kat6a has been classified as Green List (High Evidence).
Craniosynostosis v0.43 KAT6A Tiong Tan Marked gene: KAT6A as ready
Craniosynostosis v0.43 KAT6A Tiong Tan Gene: kat6a has been classified as Red List (Low Evidence).
Craniosynostosis v0.43 Zornitza Stark Panel types changed to Victorian Clinical Genetics Services; Rare Disease
Craniosynostosis v0.42 KAT6A Tiong Tan gene: KAT6A was added
gene: KAT6A was added to Craniosynostosis. Sources: Literature
Mode of inheritance for gene: KAT6A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KAT6A were set to 30245513; 25728777
Phenotypes for gene: KAT6A were set to Arboleda-Tham syndrome
Penetrance for gene: KAT6A were set to Complete
Review for gene: KAT6A was set to GREEN
Added comment: Low frequency association of craniosynostosis in Arboleda-Tham syndrome. Six individuals reported in two publications.
Sources: Literature
Craniosynostosis v0.41 FLNA Tiong Tan Marked gene: FLNA as ready
Craniosynostosis v0.41 FLNA Tiong Tan Gene: flna has been classified as Green List (High Evidence).
Craniosynostosis v0.41 FLNA Tiong Tan Classified gene: FLNA as Green List (high evidence)
Craniosynostosis v0.41 FLNA Tiong Tan Gene: flna has been classified as Green List (High Evidence).
Craniosynostosis v0.40 FLNA Tiong Tan gene: FLNA was added
gene: FLNA was added to Craniosynostosis. Sources: Literature
Mode of inheritance for gene: FLNA was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: FLNA were set to 25873011; 16835913; 21031081
Phenotypes for gene: FLNA were set to otopalatodigital spectrum
Penetrance for gene: FLNA were set to Complete
Mode of pathogenicity for gene: FLNA 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: FLNA was set to GREEN
Added comment: LOF variants cause PVNH; GOF variants cause OPD spectrum. Craniosynostosis is a low frequency association with FLNA-related OPD spectrum. Six unrelated probands reported in three publications.
Sources: Literature
Hereditary Spastic Paraplegia v0.103 ARL6IP1 Zornitza Stark Publications for gene: ARL6IP1 were set to 30980493; 24482476; 28471035
Hereditary Spastic Paraplegia v0.102 ARL6IP1 Zornitza Stark Phenotypes for gene: ARL6IP1 were changed from ?Spastic paraplegia 61, autosomal recessive, MIM#615685 to Spastic paraplegia 61, autosomal recessive, MIM#615685
Hereditary Spastic Paraplegia v0.101 ARL6IP1 Zornitza Stark Marked gene: ARL6IP1 as ready
Hereditary Spastic Paraplegia v0.101 ARL6IP1 Zornitza Stark Gene: arl6ip1 has been classified as Green List (High Evidence).
Alternating Hemiplegia and Hemiplegic Migraine v0.10 NOTCH3 Bryony Thompson Classified gene: NOTCH3 as Amber List (moderate evidence)
Alternating Hemiplegia and Hemiplegic Migraine v0.10 NOTCH3 Bryony Thompson Gene: notch3 has been classified as Amber List (Moderate Evidence).
Alternating Hemiplegia and Hemiplegic Migraine v0.9 NOTCH3 Bryony Thompson gene: NOTCH3 was added
gene: NOTCH3 was added to Alternating Hemiplegia and Hemiplegic Migraine. Sources: Expert list
Mode of inheritance for gene: NOTCH3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NOTCH3 were set to 22250206; 10356105; 27881154; 28271496
Phenotypes for gene: NOTCH3 were set to Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy 1 MIM#125310
Review for gene: NOTCH3 was set to AMBER
Added comment: Migraine with aura is a common feature of CADASIL and the condition can be misdiagnosed as familial hemiplegic migraine. However, can only find one family reported with a confirmed NOTCH3 variant and a diagnosis of hemiplegic migraine (PMID: 22250206).
Sources: Expert list
Alternating Hemiplegia and Hemiplegic Migraine v0.8 Bryony Thompson Panel types changed to Victorian Clinical Genetics Services; Royal Melbourne Hospital; Rare Disease
Mendeliome v0.3089 DCAF8 Bryony Thompson Classified gene: DCAF8 as Amber List (moderate evidence)
Mendeliome v0.3089 DCAF8 Bryony Thompson Gene: dcaf8 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3088 DCAF8 Bryony Thompson gene: DCAF8 was added
gene: DCAF8 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: DCAF8 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DCAF8 were set to 24500646
Phenotypes for gene: DCAF8 were set to Giant axonal neuropathy 2, autosomal dominant MIM#610100
Review for gene: DCAF8 was set to AMBER
Added comment: A single large family segregating a missense variant and in vitro functional assays demonstrating the variant reduces the association of DCAF8 and DDB1, which is important in Cul4-ubiquitin E3 function
Sources: Expert list
Hereditary Neuropathy v0.64 DCAF8 Bryony Thompson Classified gene: DCAF8 as Amber List (moderate evidence)
Hereditary Neuropathy v0.64 DCAF8 Bryony Thompson Gene: dcaf8 has been classified as Amber List (Moderate Evidence).
Hereditary Neuropathy v0.63 DCAF8 Bryony Thompson edited their review of gene: DCAF8: Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary Neuropathy v0.63 DCAF8 Bryony Thompson reviewed gene: DCAF8: Rating: AMBER; Mode of pathogenicity: None; Publications: 24500646; Phenotypes: Giant axonal neuropathy 2, autosomal dominant MIM#610100; Mode of inheritance: None
Mendeliome v0.3087 ARL6IP1 Bryony Thompson Marked gene: ARL6IP1 as ready
Mendeliome v0.3087 ARL6IP1 Bryony Thompson Gene: arl6ip1 has been classified as Green List (High Evidence).
Mendeliome v0.3087 ARL6IP1 Bryony Thompson Classified gene: ARL6IP1 as Green List (high evidence)
Mendeliome v0.3087 ARL6IP1 Bryony Thompson Gene: arl6ip1 has been classified as Green List (High Evidence).
Mendeliome v0.3086 ARL6IP1 Bryony Thompson gene: ARL6IP1 was added
gene: ARL6IP1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: ARL6IP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ARL6IP1 were set to 24482476; 31272422; 30980493; 28471035
Phenotypes for gene: ARL6IP1 were set to Spastic paraplegia 61, autosomal recessive MIM#615685
Review for gene: ARL6IP1 was set to GREEN
gene: ARL6IP1 was marked as current diagnostic
Added comment: At least 4 families reported with paediatric onset complicated spastic paraplegia and neuropathy. Supporting zebrafish model.
Sources: Expert list
Hereditary Neuropathy v0.63 ARL6IP1 Bryony Thompson Marked gene: ARL6IP1 as ready
Hereditary Neuropathy v0.63 ARL6IP1 Bryony Thompson Gene: arl6ip1 has been classified as Green List (High Evidence).
Hereditary Neuropathy v0.63 ARL6IP1 Bryony Thompson reviewed gene: ARL6IP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24482476, 31272422, 30980493, 28471035; Phenotypes: Spastic paraplegia 61, autosomal recessive MIM#615685; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3085 RFC1 Bryony Thompson Tag STR tag was added to gene: RFC1.
Mendeliome v0.3085 PMP2 Bryony Thompson Marked gene: PMP2 as ready
Mendeliome v0.3085 PMP2 Bryony Thompson Gene: pmp2 has been classified as Green List (High Evidence).
Mendeliome v0.3085 PMP2 Bryony Thompson Classified gene: PMP2 as Green List (high evidence)
Mendeliome v0.3085 PMP2 Bryony Thompson Gene: pmp2 has been classified as Green List (High Evidence).
Mendeliome v0.3084 PMP2 Bryony Thompson gene: PMP2 was added
gene: PMP2 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: PMP2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PMP2 were set to 26257172; 26828946; 27009151
Phenotypes for gene: PMP2 were set to Charcot-Marie-Tooth disease, demyelinating, type 1G MIM#618279
Review for gene: PMP2 was set to GREEN
Added comment: 4 unrelated families reported with missense variants, with supporting transgenic mouse and null zebrafish models.
Sources: Expert list
Mendeliome v0.3083 HPRT1 Zornitza Stark Publications for gene: HPRT1 were set to
Mendeliome v0.3082 HPRT1 Zornitza Stark Mode of inheritance for gene: HPRT1 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.3081 HPRT1 Ain Roesley reviewed gene: HPRT1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 20176575; Phenotypes: HPRT-related gout (MIM# 300323), Lesch-Nyhan syndrome (MIM# 300322); Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.3081 ASTN2 Zornitza Stark Phenotypes for gene: ASTN2 were changed from to Intellectual disability
Mendeliome v0.3080 ASTN2 Zornitza Stark Publications for gene: ASTN2 were set to
Mendeliome v0.3079 ASTN2 Zornitza Stark Mode of inheritance for gene: ASTN2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3078 ASTN2 Zornitza Stark edited their review of gene: ASTN2: Changed phenotypes: Intellectual disability
Mendeliome v0.3078 ASTN2 Zornitza Stark edited their review of gene: ASTN2: Changed phenotypes: Intellectual disability, microcephaly
Arthrogryposis v0.62 ASCC1 Zornitza Stark Marked gene: ASCC1 as ready
Arthrogryposis v0.62 ASCC1 Zornitza Stark Gene: ascc1 has been classified as Green List (High Evidence).
Arthrogryposis v0.62 ASCC1 Zornitza Stark Classified gene: ASCC1 as Green List (high evidence)
Arthrogryposis v0.62 ASCC1 Zornitza Stark Gene: ascc1 has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.55 ATP2A1 Zornitza Stark Marked gene: ATP2A1 as ready
Rhabdomyolysis and Metabolic Myopathy v0.55 ATP2A1 Zornitza Stark Gene: atp2a1 has been classified as Amber List (Moderate Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.55 ATP2A1 Zornitza Stark Classified gene: ATP2A1 as Amber List (moderate evidence)
Rhabdomyolysis and Metabolic Myopathy v0.55 ATP2A1 Zornitza Stark Gene: atp2a1 has been classified as Amber List (Moderate Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.54 ATP2A1 Zornitza Stark gene: ATP2A1 was added
gene: ATP2A1 was added to Rhabdomyolysis RMH. Sources: Expert list
Mode of inheritance for gene: ATP2A1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATP2A1 were set to 32040565
Phenotypes for gene: ATP2A1 were set to Brody myopathy, MIM# 601003
Review for gene: ATP2A1 was set to AMBER
Added comment: Two patients reported with rhabdomyolysis
Sources: Expert list
Mendeliome v0.3078 SI Zornitza Stark Marked gene: SI as ready
Mendeliome v0.3078 SI Zornitza Stark Gene: si has been classified as Green List (High Evidence).
Mendeliome v0.3078 SI Zornitza Stark Phenotypes for gene: SI were changed from to Sucrase-isomaltase deficiency, congenital #222900
Mendeliome v0.3077 SI Zornitza Stark Publications for gene: SI were set to
Mendeliome v0.3076 SI Zornitza Stark Mode of inheritance for gene: SI was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Hydrocephalus_Ventriculomegaly v0.18 B4GAT1 Zornitza Stark Marked gene: B4GAT1 as ready
Hydrocephalus_Ventriculomegaly v0.18 B4GAT1 Zornitza Stark Gene: b4gat1 has been classified as Amber List (Moderate Evidence).
Hydrocephalus_Ventriculomegaly v0.18 B4GAT1 Zornitza Stark Classified gene: B4GAT1 as Amber List (moderate evidence)
Hydrocephalus_Ventriculomegaly v0.18 B4GAT1 Zornitza Stark Gene: b4gat1 has been classified as Amber List (Moderate Evidence).
Familial hypercholesterolaemia v0.11 CAV3 Zornitza Stark Marked gene: CAV3 as ready
Familial hypercholesterolaemia v0.11 CAV3 Zornitza Stark Gene: cav3 has been classified as Amber List (Moderate Evidence).
Familial hypercholesterolaemia v0.11 CAV3 Zornitza Stark Publications for gene: CAV3 were set to PMID: 32004987; 28807458
Familial hypercholesterolaemia v0.10 CAV3 Zornitza Stark Classified gene: CAV3 as Amber List (moderate evidence)
Familial hypercholesterolaemia v0.10 CAV3 Zornitza Stark Gene: cav3 has been classified as Amber List (Moderate Evidence).
Familial hypercholesterolaemia v0.9 CAV3 Elena Savva gene: CAV3 was added
gene: CAV3 was added to Familial hypercholesterolaemia. Sources: Literature
Mode of inheritance for gene: CAV3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CAV3 were set to PMID: 32004987; 28807458
Phenotypes for gene: CAV3 were set to Myopathy, distal, Tateyama type 614321; Rippling muscle disease 2 606072
Review for gene: CAV3 was set to AMBER
Added comment: PMID: 32004987 - 1 family (2 siblings) with elevated creatine kinase, myalgia and hypercholesterolemia. Onset was ~30 years old.

PMID: 28807458 - 1 patient with rippling muscle disease, who remains asymptomatic at 45 years old. Patient also had high LDL and CK levels and therefore hyperlipidemia.

Summary: 2 patients reported
Sources: Literature
Mendeliome v0.3075 SV2B Seb Lunke Marked gene: SV2B as ready
Mendeliome v0.3075 SV2B Seb Lunke Gene: sv2b has been classified as Red List (Low Evidence).
Mendeliome v0.3075 SV2B Seb Lunke gene: SV2B was added
gene: SV2B was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SV2B was set to Unknown
Publications for gene: SV2B were set to 23617838; 23937191
Phenotypes for gene: SV2B were set to seizures
Review for gene: SV2B was set to RED
Added comment: Multiply described in Epilepsy studies investigating role of SV2 gene family, however no patients directly attributed to variants in this gene and mouse models indicate viability without seizures. Sources: Literature
Sources: Literature
Genetic Epilepsy v0.727 SV2B Seb Lunke Marked gene: SV2B as ready
Genetic Epilepsy v0.727 SV2B Seb Lunke Gene: sv2b has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.727 SV2B Seb Lunke gene: SV2B was added
gene: SV2B was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: SV2B was set to Unknown
Publications for gene: SV2B were set to 23617838; 23937191
Phenotypes for gene: SV2B were set to seizures
Review for gene: SV2B was set to RED
Added comment: Multiply described in Epilepsy studies investigating role of SV2 gene family, however no patients directly attributed to variants in this gene and mouse models indicate viability without seizures.
Sources: Literature
Hydrocephalus_Ventriculomegaly v0.17 B4GAT1 Elena Savva gene: B4GAT1 was added
gene: B4GAT1 was added to Hydrocephalus_Ventriculomegaly. Sources: Expert list
Mode of inheritance for gene: B4GAT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: B4GAT1 were set to PMID: 23359570; 23877401
Phenotypes for gene: B4GAT1 were set to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 13 615287
Review for gene: B4GAT1 was set to AMBER
Added comment: aka B3GNT1 (OMIM)

PMID: 23359570 - One family with congenital muscular dystrophy. Index patient had hydrocephalus, seizures, severe hypotonia and retinal dysplasia. Patients were homozygous for TWO missense

PMID: 23877401 - One family with congenital onset Walker-warburg syndrome and hydrocephalus, seizure and cognitive impairment.

Summary: 2 families with hydrocephalus
Sources: Expert list
Mendeliome v0.3074 ADGRG1 Elena Savva reviewed gene: ADGRG1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 24531968; Phenotypes: Polymicrogyria, bilateral frontoparietal 606854, Polymicrogyria, bilateral perisylvian 615752; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3074 SI Elena Savva reviewed gene: SI: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 3149304, 31557950; Phenotypes: Sucrase-isomaltase deficiency, congenital #222900; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.3074 RYR3 Zornitza Stark Marked gene: RYR3 as ready
Mendeliome v0.3074 RYR3 Zornitza Stark Gene: ryr3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3074 RYR3 Zornitza Stark Classified gene: RYR3 as Amber List (moderate evidence)
Mendeliome v0.3074 RYR3 Zornitza Stark Gene: ryr3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3073 RYR3 Zornitza Stark gene: RYR3 was added
gene: RYR3 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: RYR3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RYR3 were set to 29498452; 32451403; 31230720
Phenotypes for gene: RYR3 were set to Nemaline myopathy; fetal akinesia; arthrogryposis
Review for gene: RYR3 was set to AMBER
Added comment: One family reported with nemaline myopathy and other cases reported as part of large fetal akinesia/arthrogryposis discovery cohorts reporting multiple novel gene candidates.
Sources: Expert list
Arthrogryposis v0.61 ASCC1 Elena Savva gene: ASCC1 was added
gene: ASCC1 was added to Arthrogryposis. Sources: Literature
Mode of inheritance for gene: ASCC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ASCC1 were set to PMID: 28218388; 30327447; 26924529
Phenotypes for gene: ASCC1 were set to Spinal muscular atrophy with congenital bone fractures 2 MIM#616867
Review for gene: ASCC1 was set to GREEN
Added comment: PMID: 28218388 - 1 Portuguese child with a homozygous PTC and mild arthrogryposis, and ongenital generalized hypotonia, lack of spontaneous movements and atrophic muscle fibres. Papers reviews another report (PMID: 26924529) where the Turkish patient also had arthrogryposis and the same homozygous PTC

PMID: 30327447 - 3 unrelated families with severe prenatal onset muscle weakness, neonatal hypotonia and arthrogryposis. All families had biallelic PTCs, where one family was homozygous and another compound heterozygous for the recurring p.Glu53fs*19 mutation.
Sources: Literature
Long QT Syndrome v0.59 KCNE2 Zornitza Stark Mode of inheritance for gene: KCNE2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3072 SCN3A Zornitza Stark Marked gene: SCN3A as ready
Mendeliome v0.3072 SCN3A Zornitza Stark Gene: scn3a has been classified as Green List (High Evidence).
Mendeliome v0.3072 SCN3A Zornitza Stark Phenotypes for gene: SCN3A were changed from to Epilepsy, familial focal, with variable foci 4, MIM# 617935; Epileptic encephalopathy, early infantile, 62, MIM# 617938; Intellectual disability; Malformations of cortical development
Mendeliome v0.3071 SCN3A Zornitza Stark Publications for gene: SCN3A were set to
Mendeliome v0.3070 SCN3A Zornitza Stark Mode of pathogenicity for gene: SCN3A was changed from to Other
Mendeliome v0.3069 SCN3A Zornitza Stark Mode of inheritance for gene: SCN3A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3068 SCN3A Zornitza Stark reviewed gene: SCN3A: Rating: GREEN; Mode of pathogenicity: Other; Publications: 32515017; Phenotypes: Epilepsy, familial focal, with variable foci 4, MIM# 617935, Epileptic encephalopathy, early infantile, 62, MIM# 617938, Intellectual disability, Malformations of cortical development; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2698 SCN3A Zornitza Stark Marked gene: SCN3A as ready
Intellectual disability syndromic and non-syndromic v0.2698 SCN3A Zornitza Stark Gene: scn3a has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2698 SCN3A Zornitza Stark Phenotypes for gene: SCN3A were changed from to Epilepsy, familial focal, with variable foci 4, MIM# 617935; Epileptic encephalopathy, early infantile, 62, MIM# 617938; Intellectual disability; Malformations of cortical development
Intellectual disability syndromic and non-syndromic v0.2697 SCN3A Zornitza Stark Publications for gene: SCN3A were set to
Intellectual disability syndromic and non-syndromic v0.2696 SCN3A Zornitza Stark Mode of pathogenicity for gene: SCN3A was changed from to Other
Intellectual disability syndromic and non-syndromic v0.2695 SCN3A Zornitza Stark Mode of inheritance for gene: SCN3A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2694 SCN3A Zornitza Stark reviewed gene: SCN3A: Rating: GREEN; Mode of pathogenicity: Other; Publications: 32515017; Phenotypes: Epilepsy, familial focal, with variable foci 4, MIM# 617935, Epileptic encephalopathy, early infantile, 62, MIM# 617938, Intellectual disability, Malformations of cortical development; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.726 SCN3A Zornitza Stark Marked gene: SCN3A as ready
Genetic Epilepsy v0.726 SCN3A Zornitza Stark Gene: scn3a has been classified as Green List (High Evidence).
Genetic Epilepsy v0.726 SCN3A Zornitza Stark Phenotypes for gene: SCN3A were changed from to Epilepsy, familial focal, with variable foci 4, MIM# 617935; Epileptic encephalopathy, early infantile, 62, MIM# 617938; Intellectual disability; Malformations of cortical development
Genetic Epilepsy v0.725 SCN3A Zornitza Stark Publications for gene: SCN3A were set to
Genetic Epilepsy v0.724 SCN3A Zornitza Stark Mode of pathogenicity for gene: SCN3A was changed from to Other
Genetic Epilepsy v0.723 SCN3A Zornitza Stark Mode of inheritance for gene: SCN3A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.722 SCN3A Zornitza Stark reviewed gene: SCN3A: Rating: GREEN; Mode of pathogenicity: Other; Publications: 32515017; Phenotypes: Epilepsy, familial focal, with variable foci 4, MIM# 617935, Epileptic encephalopathy, early infantile, 62, MIM# 617938, Intellectual disability, Malformations of cortical development; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3068 HMGA2 Zornitza Stark Phenotypes for gene: HMGA2 were changed from Silver-Russel syndrome to Silver-Russel syndrome, MIM#618908
Mendeliome v0.3067 HMGA2 Zornitza Stark Publications for gene: HMGA2 were set to 29655892; 25809938
Mendeliome v0.3066 HMGA2 Zornitza Stark Classified gene: HMGA2 as Green List (high evidence)
Mendeliome v0.3066 HMGA2 Zornitza Stark Gene: hmga2 has been classified as Green List (High Evidence).
Mendeliome v0.3065 HMGA2 Zornitza Stark edited their review of gene: HMGA2: Added comment: At least four families reported with SNVs.; Changed rating: GREEN; Changed publications: 29655892, 25809938, 29453418, 29655892, 28796236; Changed phenotypes: Silver-Russel syndrome, MIM#618908
Mendeliome v0.3065 PLAG1 Zornitza Stark Marked gene: PLAG1 as ready
Mendeliome v0.3065 PLAG1 Zornitza Stark Gene: plag1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3065 PLAG1 Zornitza Stark Phenotypes for gene: PLAG1 were changed from to Silver-Russell syndrome, MIM#618907
Mendeliome v0.3064 PLAG1 Zornitza Stark Publications for gene: PLAG1 were set to
Mendeliome v0.3063 PLAG1 Zornitza Stark Mode of inheritance for gene: PLAG1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3062 PLAG1 Zornitza Stark Classified gene: PLAG1 as Amber List (moderate evidence)
Mendeliome v0.3062 PLAG1 Zornitza Stark Gene: plag1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3061 PLAG1 Zornitza Stark reviewed gene: PLAG1: Rating: AMBER; Mode of pathogenicity: None; Publications: 28796236, 29913240; Phenotypes: Silver-Russell syndrome, MIM#618907; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Autoinflammatory Disorders v0.83 MEFV Zornitza Stark Marked gene: MEFV as ready
Autoinflammatory Disorders v0.83 MEFV Zornitza Stark Gene: mefv has been classified as Green List (High Evidence).
Autoinflammatory Disorders v0.83 MEFV Zornitza Stark Phenotypes for gene: MEFV were changed from to Familial Mediterranean fever, AD, MIM# 134610; Familial Mediterranean fever, AR, MIM# 249100; Neutrophilic dermatosis, MIM#608068
Autoinflammatory Disorders v0.82 MEFV Zornitza Stark Publications for gene: MEFV were set to
Autoinflammatory Disorders v0.81 MEFV Zornitza Stark Mode of inheritance for gene: MEFV was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Autoinflammatory Disorders v0.80 MEFV Zornitza Stark reviewed gene: MEFV: Rating: GREEN; Mode of pathogenicity: None; Publications: 27030597, 28835462; Phenotypes: Familial Mediterranean fever, AD, MIM# 134610, Familial Mediterranean fever, AR, MIM# 249100, Neutrophilic dermatosis, MIM#608068; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2694 KIF1BP Zornitza Stark Marked gene: KIF1BP as ready
Intellectual disability syndromic and non-syndromic v0.2694 KIF1BP Zornitza Stark Added comment: Comment when marking as ready: HGNC approved name KIFBP.
Intellectual disability syndromic and non-syndromic v0.2694 KIF1BP Zornitza Stark Gene: kif1bp has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2694 KIF1BP Zornitza Stark Tag new gene name tag was added to gene: KIF1BP.
Polymicrogyria and Schizencephaly v0.88 KIF1BP Zornitza Stark Marked gene: KIF1BP as ready
Polymicrogyria and Schizencephaly v0.88 KIF1BP Zornitza Stark Added comment: Comment when marking as ready: HGNC approved name is KIFBP.
Polymicrogyria and Schizencephaly v0.88 KIF1BP Zornitza Stark Gene: kif1bp has been classified as Green List (High Evidence).
Polymicrogyria and Schizencephaly v0.88 KIF1BP Zornitza Stark Phenotypes for gene: KIF1BP were changed from Goldberg-Shprintzen megacolon syndrome MIM#609460 to Goldberg-Shprintzen megacolon syndrome MIM#609460
Polymicrogyria and Schizencephaly v0.87 KIF1BP Zornitza Stark Phenotypes for gene: KIF1BP were changed from to Goldberg-Shprintzen megacolon syndrome MIM#609460
Polymicrogyria and Schizencephaly v0.86 KIF1BP Zornitza Stark Mode of inheritance for gene: KIF1BP was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Polymicrogyria and Schizencephaly v0.86 KIF1BP Zornitza Stark Mode of inheritance for gene: KIF1BP was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Polymicrogyria and Schizencephaly v0.85 KIF1BP Zornitza Stark Publications for gene: KIF1BP were set to
Polymicrogyria and Schizencephaly v0.84 KIF1BP Zornitza Stark Tag new gene name tag was added to gene: KIF1BP.
Polymicrogyria and Schizencephaly v0.84 KIF1BP Zornitza Stark Mode of inheritance for gene: KIF1BP was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Polymicrogyria and Schizencephaly v0.84 KIF1BP Zornitza Stark Mode of inheritance for gene: KIF1BP was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3061 NEFH Zornitza Stark Marked gene: NEFH as ready
Mendeliome v0.3061 NEFH Zornitza Stark Gene: nefh has been classified as Green List (High Evidence).
Mendeliome v0.3061 NEFH Zornitza Stark Phenotypes for gene: NEFH were changed from to Charcot-Marie-Tooth disease, axonal, type 2CC, MIM#616924
Mendeliome v0.3060 NEFH Zornitza Stark Publications for gene: NEFH were set to
Mendeliome v0.3059 NEFH Zornitza Stark Mode of pathogenicity for gene: NEFH was changed from to Other
Mendeliome v0.3058 NEFH Zornitza Stark Mode of inheritance for gene: NEFH was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2694 SLC6A1 Zornitza Stark Marked gene: SLC6A1 as ready
Intellectual disability syndromic and non-syndromic v0.2694 SLC6A1 Zornitza Stark Gene: slc6a1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2694 SLC6A1 Zornitza Stark Phenotypes for gene: SLC6A1 were changed from to Myoclonic-atonic epilepsy, MIM#616421
Intellectual disability syndromic and non-syndromic v0.2693 SLC6A1 Zornitza Stark Publications for gene: SLC6A1 were set to
Autism v0.100 SLC6A1 Zornitza Stark Marked gene: SLC6A1 as ready
Autism v0.100 SLC6A1 Zornitza Stark Gene: slc6a1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2692 SLC6A1 Zornitza Stark Mode of inheritance for gene: SLC6A1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Autism v0.100 SLC6A1 Zornitza Stark Phenotypes for gene: SLC6A1 were changed from to Myoclonic-atonic epilepsy, MIM#616421
Intellectual disability syndromic and non-syndromic v0.2691 SLC6A1 Zornitza Stark reviewed gene: SLC6A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 29315614; Phenotypes: Myoclonic-atonic epilepsy, MIM#616421; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Autism v0.99 SLC6A1 Zornitza Stark Publications for gene: SLC6A1 were set to
Autism v0.98 SLC6A1 Zornitza Stark Mode of inheritance for gene: SLC6A1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Autism v0.97 SLC6A1 Zornitza Stark reviewed gene: SLC6A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 29315614; Phenotypes: Myoclonic-atonic epilepsy, MIM#616421; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.722 SLC6A1 Zornitza Stark Marked gene: SLC6A1 as ready
Genetic Epilepsy v0.722 SLC6A1 Zornitza Stark Gene: slc6a1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.722 SLC6A1 Zornitza Stark Phenotypes for gene: SLC6A1 were changed from to Myoclonic-atonic epilepsy, MIM#616421
Genetic Epilepsy v0.721 SLC6A1 Zornitza Stark Publications for gene: SLC6A1 were set to
Genetic Epilepsy v0.720 SLC6A1 Zornitza Stark Mode of inheritance for gene: SLC6A1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.719 SLC6A1 Zornitza Stark reviewed gene: SLC6A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 29315614; Phenotypes: Myoclonic-atonic epilepsy, MIM#616421; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3057 SLC6A1 Zornitza Stark Marked gene: SLC6A1 as ready
Mendeliome v0.3057 SLC6A1 Zornitza Stark Gene: slc6a1 has been classified as Green List (High Evidence).
Mendeliome v0.3057 SLC6A1 Zornitza Stark Phenotypes for gene: SLC6A1 were changed from to Myoclonic-atonic epilepsy, MIM#616421
Mendeliome v0.3056 SLC6A1 Zornitza Stark Publications for gene: SLC6A1 were set to
Mendeliome v0.3055 SLC6A1 Zornitza Stark Mode of inheritance for gene: SLC6A1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3054 GATM Zornitza Stark Marked gene: GATM as ready
Mendeliome v0.3054 GATM Zornitza Stark Gene: gatm has been classified as Green List (High Evidence).
Mendeliome v0.3054 GATM Zornitza Stark Phenotypes for gene: GATM were changed from to Cerebral creatine deficiency syndrome 3, MIM# 612718; Fanconi renotubular syndrome 1, MIM# 134600
Mendeliome v0.3053 GATM Zornitza Stark Publications for gene: GATM were set to
Mendeliome v0.3052 GATM Zornitza Stark Mode of inheritance for gene: GATM was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.3051 GATM Zornitza Stark reviewed gene: GATM: Rating: GREEN; Mode of pathogenicity: None; Publications: 12468279, 20682460, 22386973, 29654216; Phenotypes: Cerebral creatine deficiency syndrome 3, MIM# 612718, Fanconi renotubular syndrome 1, MIM# 134600; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Regression v0.121 GATM Zornitza Stark Marked gene: GATM as ready
Regression v0.121 GATM Zornitza Stark Gene: gatm has been classified as Green List (High Evidence).
Regression v0.121 GATM Zornitza Stark Phenotypes for gene: GATM were changed from to Cerebral creatine deficiency syndrome 3, MIM# 612718
Regression v0.120 GATM Zornitza Stark Publications for gene: GATM were set to
Regression v0.119 GATM Zornitza Stark Mode of inheritance for gene: GATM was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Regression v0.118 GATM Zornitza Stark reviewed gene: GATM: Rating: GREEN; Mode of pathogenicity: None; Publications: 12468279, 20682460, 22386973; Phenotypes: Cerebral creatine deficiency syndrome 3, MIM# 612718; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2691 GATM Zornitza Stark Marked gene: GATM as ready
Intellectual disability syndromic and non-syndromic v0.2691 GATM Zornitza Stark Gene: gatm has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2691 GATM Zornitza Stark Phenotypes for gene: GATM were changed from to Cerebral creatine deficiency syndrome 3, MIM# 612718
Intellectual disability syndromic and non-syndromic v0.2690 GATM Zornitza Stark Publications for gene: GATM were set to
Intellectual disability syndromic and non-syndromic v0.2689 GATM Zornitza Stark Mode of inheritance for gene: GATM was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2688 GATM Zornitza Stark reviewed gene: GATM: Rating: GREEN; Mode of pathogenicity: None; Publications: 12468279, 20682460, 22386973; Phenotypes: Cerebral creatine deficiency syndrome 3, MIM# 612718; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Susceptibility to Viral Infections v0.61 FUT2 Zornitza Stark Marked gene: FUT2 as ready
Susceptibility to Viral Infections v0.61 FUT2 Zornitza Stark Gene: fut2 has been classified as Red List (Low Evidence).
Susceptibility to Viral Infections v0.61 FUT2 Zornitza Stark gene: FUT2 was added
gene: FUT2 was added to Susceptibility to Viral Infections. Sources: Expert list
Mode of inheritance for gene: FUT2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: FUT2 were set to Norwalk virus infection, resistance to
Review for gene: FUT2 was set to RED
Added comment: Not a monogenic condition, but individuals homozygous for p.(Trp143Ter) are resistant to norovirus infection.
Sources: Expert list
Susceptibility to Viral Infections v0.60 CCR5 Zornitza Stark Marked gene: CCR5 as ready
Susceptibility to Viral Infections v0.60 CCR5 Zornitza Stark Gene: ccr5 has been classified as Green List (High Evidence).
Susceptibility to Viral Infections v0.60 CCR5 Zornitza Stark Classified gene: CCR5 as Green List (high evidence)
Susceptibility to Viral Infections v0.60 CCR5 Zornitza Stark Gene: ccr5 has been classified as Green List (High Evidence).
Susceptibility to Viral Infections v0.59 CCR5 Zornitza Stark gene: CCR5 was added
gene: CCR5 was added to Susceptibility to Viral Infections. Sources: Expert list
Mode of inheritance for gene: CCR5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: CCR5 were set to {Hepatitis C virus, resistance to} 609532; {HIV infection, susceptibility/resistance to}; {West nile virus, susceptibility to}MIM# 610379
Review for gene: CCR5 was set to GREEN
Added comment: Particular SNVs in this gene are well established as conferring resistance to certain viral infections, notably HIV.
Sources: Expert list
Susceptibility to Viral Infections v0.58 TNFRSF4 Zornitza Stark Marked gene: TNFRSF4 as ready
Susceptibility to Viral Infections v0.58 TNFRSF4 Zornitza Stark Gene: tnfrsf4 has been classified as Red List (Low Evidence).
Susceptibility to Viral Infections v0.58 TNFRSF4 Zornitza Stark gene: TNFRSF4 was added
gene: TNFRSF4 was added to Susceptibility to Viral Infections. Sources: Expert list
Mode of inheritance for gene: TNFRSF4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TNFRSF4 were set to 23897980
Phenotypes for gene: TNFRSF4 were set to Immunodeficiency 16, MIM# 615593
Review for gene: TNFRSF4 was set to RED
Added comment: Single case report in an individual with childhood-onset Kaposi's sarcoma (susceptibility to HHV8), homozygous missense variant, plausible biological candidate but direct evidence of causality limited.
Sources: Expert list
Susceptibility to Viral Infections v0.57 MAGT1 Zornitza Stark Marked gene: MAGT1 as ready
Susceptibility to Viral Infections v0.57 MAGT1 Zornitza Stark Gene: magt1 has been classified as Green List (High Evidence).
Susceptibility to Viral Infections v0.57 MAGT1 Zornitza Stark Classified gene: MAGT1 as Green List (high evidence)
Susceptibility to Viral Infections v0.57 MAGT1 Zornitza Stark Gene: magt1 has been classified as Green List (High Evidence).
Susceptibility to Viral Infections v0.56 MAGT1 Zornitza Stark gene: MAGT1 was added
gene: MAGT1 was added to Susceptibility to Viral Infections. Sources: Expert list
Mode of inheritance for gene: MAGT1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: MAGT1 were set to 21796205; 24550228; 25504528
Phenotypes for gene: MAGT1 were set to Immunodeficiency, X-linked, with magnesium defect, Epstein-Barr virus infection and neoplasia, MIM# 300853
Review for gene: MAGT1 was set to GREEN
Added comment: Multiple unrelated families reported.
Sources: Expert list
Mendeliome v0.3051 TRIM69 Zornitza Stark Marked gene: TRIM69 as ready
Mendeliome v0.3051 TRIM69 Zornitza Stark Gene: trim69 has been classified as Red List (Low Evidence).
Mendeliome v0.3051 TRIM69 Zornitza Stark gene: TRIM69 was added
gene: TRIM69 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: TRIM69 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: TRIM69 were set to 22105173
Phenotypes for gene: TRIM69 were set to Susceptibility to herpes simplex encephalitis
Review for gene: TRIM69 was set to RED
Added comment: One individual with bi-allelic and one individual with mono-allelic variants in this gene described.
Sources: Expert list
Susceptibility to Viral Infections v0.55 TRIM69 Zornitza Stark Marked gene: TRIM69 as ready
Susceptibility to Viral Infections v0.55 TRIM69 Zornitza Stark Gene: trim69 has been classified as Red List (Low Evidence).
Susceptibility to Viral Infections v0.55 TRIM69 Zornitza Stark gene: TRIM69 was added
gene: TRIM69 was added to Susceptibility to Viral Infections. Sources: Expert list
Mode of inheritance for gene: TRIM69 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: TRIM69 were set to 22105173
Phenotypes for gene: TRIM69 were set to Susceptibility to herpes simplex encephalitis
Review for gene: TRIM69 was set to RED
Added comment: One individual with bi-allelic and one individual with mono-allelic variants in this gene described.
Sources: Expert list
Mendeliome v0.3050 SLC6A1 Chern Lim reviewed gene: SLC6A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 29315614; Phenotypes: Myoclonic-atonic epilepsy, MIM#616421; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v0.3050 NEFH Chern Lim reviewed gene: NEFH: Rating: GREEN; Mode of pathogenicity: Other; Publications: 30992180, 27040688, 28709447; Phenotypes: Charcot-Marie-Tooth disease, axonal, type 2CC, MIM#616924; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Polymicrogyria and Schizencephaly v0.83 KIF1BP Chloe Stutterd reviewed gene: KIF1BP: Rating: GREEN; Mode of pathogenicity: None; Publications: 23427148, 15883926; Phenotypes: Polymicrogryia in Goldberg-Shprintzen megacolon syndrome MIM#609460; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Spastic Paraplegia v0.101 TUBB4A Zornitza Stark Marked gene: TUBB4A as ready
Hereditary Spastic Paraplegia v0.101 TUBB4A Zornitza Stark Gene: tubb4a has been classified as Green List (High Evidence).
Hereditary Spastic Paraplegia v0.101 TUBB4A Zornitza Stark Classified gene: TUBB4A as Green List (high evidence)
Hereditary Spastic Paraplegia v0.101 TUBB4A Zornitza Stark Gene: tubb4a has been classified as Green List (High Evidence).
Hereditary Spastic Paraplegia v0.100 TUBB4A Zornitza Stark gene: TUBB4A was added
gene: TUBB4A was added to Hereditary Spastic Paraplegia - paediatric. Sources: Expert list
Mode of inheritance for gene: TUBB4A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TUBB4A were set to 23582646; 24850488
Phenotypes for gene: TUBB4A were set to Leukodystrophy, hypomyelinating, 6, MIM# 612438
Review for gene: TUBB4A was set to GREEN
Added comment: Complex neurological disorder with childhood onset, spasticity is a feature.
Sources: Expert list
Hereditary Spastic Paraplegia v0.99 RTN2 Zornitza Stark Marked gene: RTN2 as ready
Hereditary Spastic Paraplegia v0.99 RTN2 Zornitza Stark Gene: rtn2 has been classified as Green List (High Evidence).
Hereditary Spastic Paraplegia v0.99 RTN2 Zornitza Stark Classified gene: RTN2 as Green List (high evidence)
Hereditary Spastic Paraplegia v0.99 RTN2 Zornitza Stark Gene: rtn2 has been classified as Green List (High Evidence).
Hereditary Spastic Paraplegia v0.98 RTN2 Zornitza Stark gene: RTN2 was added
gene: RTN2 was added to Hereditary Spastic Paraplegia - paediatric. Sources: Expert list
Mode of inheritance for gene: RTN2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RTN2 were set to 22232211; 27165006
Phenotypes for gene: RTN2 were set to Spastic paraplegia 12, autosomal dominant, MIM# 604805
Review for gene: RTN2 was set to GREEN
Added comment: At least 5 unrelated families reported. Variable age of onset from childhood to early adulthood.
Sources: Expert list
Hereditary Spastic Paraplegia v0.97 PNPLA6 Zornitza Stark Marked gene: PNPLA6 as ready
Hereditary Spastic Paraplegia v0.97 PNPLA6 Zornitza Stark Gene: pnpla6 has been classified as Amber List (Moderate Evidence).
Hereditary Spastic Paraplegia v0.97 PNPLA6 Zornitza Stark Classified gene: PNPLA6 as Amber List (moderate evidence)
Hereditary Spastic Paraplegia v0.97 PNPLA6 Zornitza Stark Gene: pnpla6 has been classified as Amber List (Moderate Evidence).
Hereditary Spastic Paraplegia v0.96 PNPLA6 Zornitza Stark gene: PNPLA6 was added
gene: PNPLA6 was added to Hereditary Spastic Paraplegia - paediatric. Sources: Expert list
Mode of inheritance for gene: PNPLA6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PNPLA6 were set to 18313024
Phenotypes for gene: PNPLA6 were set to Spastic paraplegia 39, autosomal recessive, MIM# 612020
Review for gene: PNPLA6 was set to AMBER
Added comment: Bi-allelic variants cause a range of complex phenotypes, including ataxia, retinal dystrophy, spasticity and hypogonadotrophic hypogonadism. Symptom onset is generally in adulthood, although at least one family with onset of spasticity in childhood reported.
Sources: Expert list
Hereditary Spastic Paraplegia v0.95 OPA3 Zornitza Stark Marked gene: OPA3 as ready
Hereditary Spastic Paraplegia v0.95 OPA3 Zornitza Stark Gene: opa3 has been classified as Green List (High Evidence).
Hereditary Spastic Paraplegia v0.95 OPA3 Zornitza Stark Classified gene: OPA3 as Green List (high evidence)
Hereditary Spastic Paraplegia v0.95 OPA3 Zornitza Stark Gene: opa3 has been classified as Green List (High Evidence).
Hereditary Spastic Paraplegia v0.94 OPA3 Zornitza Stark gene: OPA3 was added
gene: OPA3 was added to Hereditary Spastic Paraplegia - paediatric. Sources: Expert list
Mode of inheritance for gene: OPA3 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: OPA3 were set to 3-methylglutaconic aciduria, type III, MIM# 258501
Review for gene: OPA3 was set to GREEN
Added comment: Onset of optic atrophy generally precedes other features including spasticity, which generally begins in the second decade.
Sources: Expert list
Hereditary Spastic Paraplegia v0.93 AP5Z1 Zornitza Stark Marked gene: AP5Z1 as ready
Hereditary Spastic Paraplegia v0.93 AP5Z1 Zornitza Stark Gene: ap5z1 has been classified as Amber List (Moderate Evidence).
Hereditary Spastic Paraplegia v0.93 AP5Z1 Zornitza Stark Classified gene: AP5Z1 as Amber List (moderate evidence)
Hereditary Spastic Paraplegia v0.93 AP5Z1 Zornitza Stark Gene: ap5z1 has been classified as Amber List (Moderate Evidence).
Hereditary Spastic Paraplegia v0.92 AP5Z1 Zornitza Stark gene: AP5Z1 was added
gene: AP5Z1 was added to Hereditary Spastic Paraplegia - paediatric. Sources: Expert list
Mode of inheritance for gene: AP5Z1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AP5Z1 were set to 26085577
Phenotypes for gene: AP5Z1 were set to Spastic paraplegia 48, autosomal recessive, MIM# 613647
Review for gene: AP5Z1 was set to AMBER
Added comment: Onset is generally in adulthood though at least one individual with childhood onset reported.
Sources: Expert list
Hereditary Spastic Paraplegia v0.91 ALDH18A1 Zornitza Stark Marked gene: ALDH18A1 as ready
Hereditary Spastic Paraplegia v0.91 ALDH18A1 Zornitza Stark Gene: aldh18a1 has been classified as Green List (High Evidence).
Hereditary Spastic Paraplegia v0.91 ALDH18A1 Zornitza Stark Phenotypes for gene: ALDH18A1 were changed from Spastic paraplegia 9B, autosomal recessive, MIM# 616586 to Spastic paraplegia 9B, autosomal recessive, MIM# 616586; Spastic paraplegia 9A, autosomal dominant, MIM# 601162
Hereditary Spastic Paraplegia v0.90 ALDH18A1 Zornitza Stark Classified gene: ALDH18A1 as Green List (high evidence)
Hereditary Spastic Paraplegia v0.90 ALDH18A1 Zornitza Stark Gene: aldh18a1 has been classified as Green List (High Evidence).
Hereditary Spastic Paraplegia v0.89 ALDH18A1 Zornitza Stark edited their review of gene: ALDH18A1: Changed phenotypes: Spastic paraplegia 9B, autosomal recessive, MIM# 616586, Spastic paraplegia 9A, autosomal dominant, MIM# 601162
Hereditary Spastic Paraplegia v0.89 ALDH18A1 Zornitza Stark gene: ALDH18A1 was added
gene: ALDH18A1 was added to Hereditary Spastic Paraplegia - paediatric. Sources: Expert list
Mode of inheritance for gene: ALDH18A1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: ALDH18A1 were set to 26026163; 29915212
Phenotypes for gene: ALDH18A1 were set to Spastic paraplegia 9B, autosomal recessive, MIM# 616586
Review for gene: ALDH18A1 was set to GREEN
Added comment: At least four unrelated families reported with bi-allelic complex HSP, including microcephaly and ID. Mono-allelic variants are also associated with HSP (at least 15 patients from 3 families) but this tends to be with adult onset, although some childhood onset also reported.
Sources: Expert list
Early-onset Parkinson disease v0.31 PSEN2 Bryony Thompson changed review comment from: Parkinson disease and parkinsonism is not a prominent feature of Alzheimer disease caused by PSEN2. A couple of isolated cases with parkinsonism as a feature of the condition and a single family have been reported with established pathogenic variants and a VUS (PMID: 22118943, 26422362, 18427071). VUS or now likely benign/benign missense variants have been identified in a Parkinson Disease cases used in case-control studies (PMID: 29692703, 26522186).
Sources: Other; to: Parkinson disease and parkinsonism is not a prominent feature of Alzheimer disease caused by PSEN2. A couple of isolated cases with VUS and parkinsonism as a feature of the condition and a single family with multiple members with parkinsonism with pathogenic missense variant have been reported (PMID: 22118943, 26422362, 18427071). VUS or now likely benign/benign missense variants have been identified in Parkinson Disease cases used in case-control studies (PMID: 29692703, 26522186).
Sources: Other
Early-onset Parkinson disease v0.31 PSEN2 Bryony Thompson changed review comment from: Parkinson disease and parkinsonism is not a prominent feature of Alzheimer disease caused by PSEN2. A couple of isolated cases with parkinsonism as a feature of the condition and a single family have been reported with established pathogenic or probable pathogenic variants (PMID: 22118943, 26422362, 18427071). VUS or now likely benign/benign missense variants have been identified in a Parkinson Disease cases used in case-control studies (PMID: 29692703, 26522186).
Sources: Other; to: Parkinson disease and parkinsonism is not a prominent feature of Alzheimer disease caused by PSEN2. A couple of isolated cases with parkinsonism as a feature of the condition and a single family have been reported with established pathogenic variants and a VUS (PMID: 22118943, 26422362, 18427071). VUS or now likely benign/benign missense variants have been identified in a Parkinson Disease cases used in case-control studies (PMID: 29692703, 26522186).
Sources: Other
Early-onset Parkinson disease v0.31 PSEN2 Bryony Thompson Marked gene: PSEN2 as ready
Early-onset Parkinson disease v0.31 PSEN2 Bryony Thompson Gene: psen2 has been classified as Red List (Low Evidence).
Early-onset Parkinson disease v0.31 PSEN2 Bryony Thompson gene: PSEN2 was added
gene: PSEN2 was added to Early-onset Parkinson disease. Sources: Other
Mode of inheritance for gene: PSEN2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PSEN2 were set to 22118943; 26422362; 18427071; 29692703
Phenotypes for gene: PSEN2 were set to Parkinsonism; Alzheimer disease-4 MIM#606889
Review for gene: PSEN2 was set to RED
Added comment: Parkinson disease and parkinsonism is not a prominent feature of Alzheimer disease caused by PSEN2. A couple of isolated cases with parkinsonism as a feature of the condition and a single family have been reported with established pathogenic or probable pathogenic variants (PMID: 22118943, 26422362, 18427071). VUS or now likely benign/benign missense variants have been identified in a Parkinson Disease cases used in case-control studies (PMID: 29692703, 26522186).
Sources: Other
Mendeliome v0.3050 LIMS2 Zornitza Stark Marked gene: LIMS2 as ready
Mendeliome v0.3050 LIMS2 Zornitza Stark Gene: lims2 has been classified as Red List (Low Evidence).
Mendeliome v0.3050 LIMS2 Zornitza Stark gene: LIMS2 was added
gene: LIMS2 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: LIMS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LIMS2 were set to 25589244; 16317048
Phenotypes for gene: LIMS2 were set to Muscular dystrophy, autosomal recessive, with cardiomyopathy and triangular tongue MIM#616827
Review for gene: LIMS2 was set to RED
Added comment: Only one family reported and Pinch2 -/- mice were viable and fertile with no apparent phenotype.
Sources: Expert list
Mendeliome v0.3049 FAN1 Elena Savva reviewed gene: FAN1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 22772369; Phenotypes: Interstitial nephritis, karyomegalic 614817; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.3049 RAD21 Elena Savva reviewed gene: RAD21: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31334757, 25575569, 32193685; Phenotypes: ?Mungan syndrome, 611376, Cornelia de Lange syndrome 4, 614701, Holoprocencephaly; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Holoprosencephaly and septo-optic dysplasia v0.23 RAD21 Zornitza Stark Marked gene: RAD21 as ready
Holoprosencephaly and septo-optic dysplasia v0.23 RAD21 Zornitza Stark Gene: rad21 has been classified as Green List (High Evidence).
Holoprosencephaly and septo-optic dysplasia v0.23 RAD21 Zornitza Stark Classified gene: RAD21 as Green List (high evidence)
Holoprosencephaly and septo-optic dysplasia v0.23 RAD21 Zornitza Stark Gene: rad21 has been classified as Green List (High Evidence).
Holoprosencephaly and septo-optic dysplasia v0.22 RAD21 Zornitza Stark gene: RAD21 was added
gene: RAD21 was added to Holoprosencephaly and septo-optic dysplasia. Sources: Literature
Mode of inheritance for gene: RAD21 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RAD21 were set to 31334757
Phenotypes for gene: RAD21 were set to Holoprosencephaly; Septo-optic dysplasia
Review for gene: RAD21 was set to GREEN
Added comment: Three individuals reported with variants in this gene and HPE phenotype. Note paper reports variants in other cohesinopathy genes also.
Sources: Literature
Mendeliome v0.3049 PSMB1 Zornitza Stark Marked gene: PSMB1 as ready
Mendeliome v0.3049 PSMB1 Zornitza Stark Gene: psmb1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3049 PSMB1 Zornitza Stark Classified gene: PSMB1 as Amber List (moderate evidence)
Mendeliome v0.3049 PSMB1 Zornitza Stark Gene: psmb1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3048 PSMB1 Zornitza Stark gene: PSMB1 was added
gene: PSMB1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PSMB1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PSMB1 were set to 32129449
Phenotypes for gene: PSMB1 were set to Intellectual disability; microcephaly
Review for gene: PSMB1 was set to AMBER
Added comment: Two siblings reported with a homozygous missense variant in this gene; supportive experimental evidence including zebrafish model.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2688 PSMB1 Zornitza Stark Marked gene: PSMB1 as ready
Intellectual disability syndromic and non-syndromic v0.2688 PSMB1 Zornitza Stark Gene: psmb1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2688 PSMB1 Zornitza Stark Classified gene: PSMB1 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2688 PSMB1 Zornitza Stark Gene: psmb1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2687 PSMB1 Zornitza Stark gene: PSMB1 was added
gene: PSMB1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: PSMB1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PSMB1 were set to 32129449
Phenotypes for gene: PSMB1 were set to Intellectual disability; microcephaly
Review for gene: PSMB1 was set to AMBER
Added comment: Two siblings reported with a homozygous missense variant in this gene; supportive experimental evidence including zebrafish model.
Sources: Literature
Mendeliome v0.3047 SLC12A6 Zornitza Stark Marked gene: SLC12A6 as ready
Mendeliome v0.3047 SLC12A6 Zornitza Stark Gene: slc12a6 has been classified as Green List (High Evidence).
Mendeliome v0.3047 SLC12A6 Zornitza Stark Phenotypes for gene: SLC12A6 were changed from to Andermann syndrome; Hereditary Motor and Sensory Neuropathy with Agenesis of the Corpus Callosum; Intermediate CMT
Mendeliome v0.3046 SLC12A6 Zornitza Stark Publications for gene: SLC12A6 were set to
Mendeliome v0.3045 SLC12A6 Zornitza Stark Mode of inheritance for gene: SLC12A6 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.3044 SLC12A6 Zornitza Stark reviewed gene: SLC12A6: Rating: GREEN; Mode of pathogenicity: None; Publications: 31439721; Phenotypes: Andermann syndrome, Hereditary Motor and Sensory Neuropathy with Agenesis of the Corpus Callosum, Intermediate CMT; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hereditary Neuropathy v0.63 SLC12A6 Zornitza Stark Marked gene: SLC12A6 as ready
Hereditary Neuropathy v0.63 SLC12A6 Zornitza Stark Gene: slc12a6 has been classified as Green List (High Evidence).
Hereditary Neuropathy v0.63 SLC12A6 Zornitza Stark Phenotypes for gene: SLC12A6 were changed from Andermann syndrome; Hereditary Motor and Sensory Neuropathy with Agenesis of the Corpus Callosum; HMSN to Andermann syndrome; Hereditary Motor and Sensory Neuropathy with Agenesis of the Corpus Callosum; Intermediate CMT
Hereditary Neuropathy v0.62 SLC12A6 Zornitza Stark Publications for gene: SLC12A6 were set to
Hereditary Neuropathy v0.61 SLC12A6 Zornitza Stark Mode of inheritance for gene: SLC12A6 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hereditary Neuropathy v0.60 SLC12A6 Zornitza Stark reviewed gene: SLC12A6: Rating: GREEN; Mode of pathogenicity: None; Publications: 31439721; Phenotypes: Agenesis of the corpus callosum with peripheral neuropathy, MM# 218000, Intermediate CMT; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Anophthalmia_Microphthalmia_Coloboma v0.58 C16orf62 Zornitza Stark Marked gene: C16orf62 as ready
Anophthalmia_Microphthalmia_Coloboma v0.58 C16orf62 Zornitza Stark Gene: c16orf62 has been classified as Amber List (Moderate Evidence).
Anophthalmia_Microphthalmia_Coloboma v0.58 C16orf62 Zornitza Stark Classified gene: C16orf62 as Amber List (moderate evidence)
Anophthalmia_Microphthalmia_Coloboma v0.58 C16orf62 Zornitza Stark Gene: c16orf62 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2686 C16orf62 Zornitza Stark changed review comment from: HGNC approved name: VPS35L. Two variants have been reported as compound heterozygotes in two sibs with features of 3C/Ritscher-Schinzel syndrome. Functional studies show that loss of VPS35L function results in impared autophagy and VPS35L knockout mouse resulted in early embrionic lethality (PMID 25434475).
Sources: Expert list; to: HGNC approved name: VPS35L. Two variants have been reported as compound heterozygotes in two sibs with features of 3C/Ritscher-Schinzel syndrome. Functional studies show that loss of VPS35L function results in impared autophagy and VPS35L knockout mouse resulted in early embrionic lethality (PMID 25434475;31712251).
Sources: Expert list
Anophthalmia_Microphthalmia_Coloboma v0.57 C16orf62 Zornitza Stark gene: C16orf62 was added
gene: C16orf62 was added to Anophthalmia_Microphthalmia_Coloboma. Sources: Literature
Mode of inheritance for gene: C16orf62 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C16orf62 were set to 25434475; 31712251
Phenotypes for gene: C16orf62 were set to 3C/Ritscher-Schinzel-like syndrome
Review for gene: C16orf62 was set to AMBER
Added comment: HGNC approved name: VPS35L. Two variants have been reported as compound heterozygotes in two sibs with features of 3C/Ritscher-Schinzel syndrome. Functional studies show that loss of VPS35L function results in impared autophagy and VPS35L knockout mouse resulted in early embrionic lethality (PMID 25434475;31712251).
Sources: Literature
Mendeliome v0.3044 C16orf62 Zornitza Stark changed review comment from: HGNC approved name: VPS35L. Two variants have been reported as compound heterozygotes in two sibs with features of 3C/Ritscher-Schinzel syndrome. Functional studies show that loss of VPS35L function results in impared autophagy and VPS35L knockout mouse resulted in early embrionic lethality (PMID 25434475).
Sources: Expert list; to: HGNC approved name: VPS35L. Two variants have been reported as compound heterozygotes in two sibs with features of 3C/Ritscher-Schinzel syndrome. Functional studies show that loss of VPS35L function results in impared autophagy and VPS35L knockout mouse resulted in early embrionic lethality (PMID 25434475;31712251).
Sources: Expert list
Mendeliome v0.3044 C16orf62 Zornitza Stark edited their review of gene: C16orf62: Changed publications: 25434475, 31712251
Intellectual disability syndromic and non-syndromic v0.2686 C16orf62 Zornitza Stark Publications for gene: C16orf62 were set to 25434475; 31712251
Intellectual disability syndromic and non-syndromic v0.2685 C16orf62 Zornitza Stark Publications for gene: C16orf62 were set to 25434475
Intellectual disability syndromic and non-syndromic v0.2684 C16orf62 Zornitza Stark edited their review of gene: C16orf62: Changed publications: 25434475, 31712251
Mendeliome v0.3044 EWSR1 Seb Lunke Marked gene: EWSR1 as ready
Mendeliome v0.3044 EWSR1 Seb Lunke Gene: ewsr1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3044 EWSR1 Seb Lunke Phenotypes for gene: EWSR1 were changed from to Amyotrophic lateral sclerosis
Mendeliome v0.3043 EWSR1 Seb Lunke Publications for gene: EWSR1 were set to
Mendeliome v0.3042 EWSR1 Seb Lunke Mode of inheritance for gene: EWSR1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3041 EWSR1 Seb Lunke Classified gene: EWSR1 as Amber List (moderate evidence)
Mendeliome v0.3041 EWSR1 Seb Lunke Gene: ewsr1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3040 EWSR1 Seb Lunke reviewed gene: EWSR1: Rating: AMBER; Mode of pathogenicity: None; Publications: 29731676, 22454397; Phenotypes: Amyotrophic lateral sclerosis; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Craniosynostosis v0.39 FGF10 Tiong Tan Publications for gene: FGF10 were set to
Craniosynostosis v0.38 FGF10 Tiong Tan Marked gene: FGF10 as ready
Craniosynostosis v0.38 FGF10 Tiong Tan Gene: fgf10 has been classified as Amber List (Moderate Evidence).
Craniosynostosis v0.38 FGF10 Tiong Tan Classified gene: FGF10 as Amber List (moderate evidence)
Craniosynostosis v0.38 FGF10 Tiong Tan Added comment: Comment on list classification: Two unrelated individuals in large craniosynostosis cohort with pathogenic variants in FGF10.
Craniosynostosis v0.38 FGF10 Tiong Tan Gene: fgf10 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3040 TRPM7 Zornitza Stark Marked gene: TRPM7 as ready
Mendeliome v0.3040 TRPM7 Zornitza Stark Gene: trpm7 has been classified as Red List (Low Evidence).
Mendeliome v0.3040 TRPM7 Zornitza Stark Phenotypes for gene: TRPM7 were changed from to {Amyotrophic lateral sclerosis-parkinsonism/dementia complex, susceptibility to}, MIM# 105500
Mendeliome v0.3039 TRPM7 Zornitza Stark Classified gene: TRPM7 as Red List (low evidence)
Mendeliome v0.3039 TRPM7 Zornitza Stark Gene: trpm7 has been classified as Red List (Low Evidence).
Mendeliome v0.3038 TRPM7 Zornitza Stark reviewed gene: TRPM7: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: {Amyotrophic lateral sclerosis-parkinsonism/dementia complex, susceptibility to}, MIM# 105500; Mode of inheritance: None
Mendeliome v0.3038 C16orf62 Zornitza Stark Tag new gene name tag was added to gene: C16orf62.
Intellectual disability syndromic and non-syndromic v0.2684 C16orf62 Zornitza Stark Tag new gene name tag was added to gene: C16orf62.
Genetic Epilepsy v0.719 SMC1A Zornitza Stark Marked gene: SMC1A as ready
Genetic Epilepsy v0.719 SMC1A Zornitza Stark Gene: smc1a has been classified as Green List (High Evidence).
Genetic Epilepsy v0.719 SMC1A Zornitza Stark Phenotypes for gene: SMC1A were changed from to Epileptic encephalopathy, early infantile, 85, with or without midline brain defects, MIM# 301044
Genetic Epilepsy v0.718 SMC1A Zornitza Stark Publications for gene: SMC1A were set to
Genetic Epilepsy v0.717 SMC1A Zornitza Stark Mode of inheritance for gene: SMC1A was changed from Unknown to Other
Genetic Epilepsy v0.716 SMC1A Zornitza Stark reviewed gene: SMC1A: Rating: GREEN; Mode of pathogenicity: None; Publications: 31334757, 28166369; Phenotypes: Epileptic encephalopathy, early infantile, 85, with or without midline brain defects, MIM# 301044; Mode of inheritance: Other
Holoprosencephaly and septo-optic dysplasia v0.21 SMC1A Zornitza Stark Marked gene: SMC1A as ready
Holoprosencephaly and septo-optic dysplasia v0.21 SMC1A Zornitza Stark Gene: smc1a has been classified as Green List (High Evidence).
Holoprosencephaly and septo-optic dysplasia v0.21 SMC1A Zornitza Stark Classified gene: SMC1A as Green List (high evidence)
Holoprosencephaly and septo-optic dysplasia v0.21 SMC1A Zornitza Stark Gene: smc1a has been classified as Green List (High Evidence).
Holoprosencephaly and septo-optic dysplasia v0.20 SMC1A Zornitza Stark gene: SMC1A was added
gene: SMC1A was added to Holoprosencephaly and septo-optic dysplasia. Sources: Literature
Mode of inheritance for gene: SMC1A was set to Other
Publications for gene: SMC1A were set to 31334757; 28166369
Phenotypes for gene: SMC1A were set to Epileptic encephalopathy, early infantile, 85, with or without midline brain defects, MIM# 301044
Review for gene: SMC1A was set to GREEN
Added comment: Multiple females reported with EE/HPE and LOF variants in this gene. Note gene also causes CdL.
Sources: Literature
Holoprosencephaly and septo-optic dysplasia v0.19 STAG2 Zornitza Stark Marked gene: STAG2 as ready
Holoprosencephaly and septo-optic dysplasia v0.19 STAG2 Zornitza Stark Gene: stag2 has been classified as Green List (High Evidence).
Holoprosencephaly and septo-optic dysplasia v0.19 STAG2 Zornitza Stark Phenotypes for gene: STAG2 were changed from Holoprosencephaly to Holoprosencephaly 13, X-linked, MIM# 301043
Holoprosencephaly and septo-optic dysplasia v0.18 STAG2 Zornitza Stark Classified gene: STAG2 as Green List (high evidence)
Holoprosencephaly and septo-optic dysplasia v0.18 STAG2 Zornitza Stark Gene: stag2 has been classified as Green List (High Evidence).
Holoprosencephaly and septo-optic dysplasia v0.17 STAG2 Zornitza Stark gene: STAG2 was added
gene: STAG2 was added to Holoprosencephaly and septo-optic dysplasia. Sources: Literature
Mode of inheritance for gene: STAG2 was set to Other
Publications for gene: STAG2 were set to 31334757
Phenotypes for gene: STAG2 were set to Holoprosencephaly
Review for gene: STAG2 was set to GREEN
Added comment: Six females reported with LoF variants in this gene and HPE spectrum disorders.
Sources: Literature
Mendeliome v0.3038 C16orf62 Zornitza Stark Marked gene: C16orf62 as ready
Mendeliome v0.3038 C16orf62 Zornitza Stark Gene: c16orf62 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3038 C16orf62 Zornitza Stark Classified gene: C16orf62 as Amber List (moderate evidence)
Mendeliome v0.3038 C16orf62 Zornitza Stark Gene: c16orf62 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3037 C16orf62 Zornitza Stark gene: C16orf62 was added
gene: C16orf62 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: C16orf62 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C16orf62 were set to 25434475
Phenotypes for gene: C16orf62 were set to 3C/Ritscher-Schinzel-like syndrome
Review for gene: C16orf62 was set to AMBER
Added comment: HGNC approved name: VPS35L. Two variants have been reported as compound heterozygotes in two sibs with features of 3C/Ritscher-Schinzel syndrome. Functional studies show that loss of VPS35L function results in impared autophagy and VPS35L knockout mouse resulted in early embrionic lethality (PMID 25434475).
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.2684 C16orf62 Zornitza Stark Marked gene: C16orf62 as ready
Intellectual disability syndromic and non-syndromic v0.2684 C16orf62 Zornitza Stark Gene: c16orf62 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2684 C16orf62 Zornitza Stark Classified gene: C16orf62 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2684 C16orf62 Zornitza Stark Gene: c16orf62 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2683 C16orf62 Zornitza Stark gene: C16orf62 was added
gene: C16orf62 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list
Mode of inheritance for gene: C16orf62 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C16orf62 were set to 25434475
Phenotypes for gene: C16orf62 were set to 3C/Ritscher-Schinzel-like syndrome
Review for gene: C16orf62 was set to AMBER
Added comment: HGNC approved name: VPS35L. Two variants have been reported as compound heterozygotes in two sibs with features of 3C/Ritscher-Schinzel syndrome. Functional studies show that loss of VPS35L function results in impared autophagy and VPS35L knockout mouse resulted in early embrionic lethality (PMID 25434475).
Sources: Expert list
Mendeliome v0.3036 RHOBTB2 Zornitza Stark Marked gene: RHOBTB2 as ready
Mendeliome v0.3036 RHOBTB2 Zornitza Stark Gene: rhobtb2 has been classified as Green List (High Evidence).
Mendeliome v0.3036 RHOBTB2 Zornitza Stark Phenotypes for gene: RHOBTB2 were changed from to Epileptic encephalopathy, early infantile, 64, MIM#618004
Mendeliome v0.3035 RHOBTB2 Zornitza Stark Publications for gene: RHOBTB2 were set to
Mendeliome v0.3034 RHOBTB2 Zornitza Stark Mode of pathogenicity for gene: RHOBTB2 was changed from to Other
Mendeliome v0.3033 RHOBTB2 Zornitza Stark Mode of inheritance for gene: RHOBTB2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3032 RHOBTB2 Elena Savva reviewed gene: RHOBTB2: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID:29276004, 29768694; Phenotypes: Epileptic encephalopathy, early infantile, 64, 618004; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Intellectual disability syndromic and non-syndromic v0.2682 PPP1CB Zornitza Stark Marked gene: PPP1CB as ready
Intellectual disability syndromic and non-syndromic v0.2682 PPP1CB Zornitza Stark Gene: ppp1cb has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2682 PPP1CB Zornitza Stark Phenotypes for gene: PPP1CB were changed from to Noonan syndrome-like disorder with loose anlagen hair 2, OMIM # 617506
Intellectual disability syndromic and non-syndromic v0.2681 PPP1CB Zornitza Stark Publications for gene: PPP1CB were set to
Intellectual disability syndromic and non-syndromic v0.2680 PPP1CB Zornitza Stark Mode of inheritance for gene: PPP1CB was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2679 PPP1CB Zornitza Stark reviewed gene: PPP1CB: Rating: GREEN; Mode of pathogenicity: None; Publications: 32476286, 28211982, 27264673, 27681385, 27868344; Phenotypes: Noonan syndrome-like disorder with loose anlagen hair 2, OMIM # 617506; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3032 PPP1CB Zornitza Stark Marked gene: PPP1CB as ready
Mendeliome v0.3032 PPP1CB Zornitza Stark Gene: ppp1cb has been classified as Green List (High Evidence).
Mendeliome v0.3032 PPP1CB Zornitza Stark Phenotypes for gene: PPP1CB were changed from to Noonan syndrome-like disorder with loose anagen hair 2, OMIM # 617506
Mendeliome v0.3031 PPP1CB Zornitza Stark Publications for gene: PPP1CB were set to
Mendeliome v0.3030 PPP1CB Zornitza Stark Mode of inheritance for gene: PPP1CB was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3029 PPP1CB Zornitza Stark reviewed gene: PPP1CB: Rating: GREEN; Mode of pathogenicity: None; Publications: 32476286, 28211982, 27264673, 27681385, 27868344; Phenotypes: Noonan syndrome-like disorder with loose anagen hair 2, OMIM # 617506; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Rasopathy v0.17 PPP1CB Zornitza Stark Marked gene: PPP1CB as ready
Rasopathy v0.17 PPP1CB Zornitza Stark Gene: ppp1cb has been classified as Green List (High Evidence).
Rasopathy v0.17 PPP1CB Chirag Patel Classified gene: PPP1CB as Green List (high evidence)
Rasopathy v0.17 PPP1CB Chirag Patel Gene: ppp1cb has been classified as Green List (High Evidence).
Rasopathy v0.16 PPP1CB Chirag Patel gene: PPP1CB was added
gene: PPP1CB was added to Rasopathy. Sources: Literature
Mode of inheritance for gene: PPP1CB was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PPP1CB were set to PMID: 32476286; 28211982; 27264673; 27681385; 27868344
Phenotypes for gene: PPP1CB were set to Noonan syndrome-like disorder with loose anagen hair 2; OMIM # 617506
Review for gene: PPP1CB was set to GREEN
Added comment: > 20 patients reported from different families and different ethnicities with Noonan syndrome-like features and hair abnormalities. All patients so far with missense variants.
Sources: Literature
Mendeliome v0.3029 NUP88 Zornitza Stark Marked gene: NUP88 as ready
Mendeliome v0.3029 NUP88 Zornitza Stark Gene: nup88 has been classified as Green List (High Evidence).
Mendeliome v0.3029 NUP88 Zornitza Stark Classified gene: NUP88 as Green List (high evidence)
Mendeliome v0.3029 NUP88 Zornitza Stark Gene: nup88 has been classified as Green List (High Evidence).
Mendeliome v0.3028 NUP88 Zornitza Stark gene: NUP88 was added
gene: NUP88 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NUP88 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NUP88 were set to 30543681
Phenotypes for gene: NUP88 were set to Fetal akinesia deformation sequence 4, MIM# 618393
Review for gene: NUP88 was set to GREEN
Added comment: Two unrelated families, functional data on the variants support pathogenicity as does a zebrafish model.
Sources: Literature
Arthrogryposis v0.61 NUP88 Zornitza Stark Marked gene: NUP88 as ready
Arthrogryposis v0.61 NUP88 Zornitza Stark Gene: nup88 has been classified as Green List (High Evidence).
Arthrogryposis v0.61 NUP88 Zornitza Stark Classified gene: NUP88 as Green List (high evidence)
Arthrogryposis v0.61 NUP88 Zornitza Stark Gene: nup88 has been classified as Green List (High Evidence).
Arthrogryposis v0.60 NUP88 Zornitza Stark changed review comment from: Two unrelated families and a zebrafish model reported.
Sources: Literature; to: Two unrelated families, functional data on the variants support pathogenicity as does a zebrafish model.
Sources: Literature
Arthrogryposis v0.60 NUP88 Zornitza Stark edited their review of gene: NUP88: Changed rating: GREEN; Changed phenotypes: Fetal akinesia deformation sequence 4, MIM# 618393
Arthrogryposis v0.60 NUP88 Zornitza Stark gene: NUP88 was added
gene: NUP88 was added to Arthrogryposis. Sources: Literature
Mode of inheritance for gene: NUP88 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NUP88 were set to 30543681
Phenotypes for gene: NUP88 were set to Fetal akinesia deformation sequence 4, MIM# 618393
Review for gene: NUP88 was set to AMBER
Added comment: Two unrelated families and a zebrafish model reported.
Sources: Literature
Microcephaly v0.129 SMO Zornitza Stark Marked gene: SMO as ready
Microcephaly v0.129 SMO Zornitza Stark Gene: smo has been classified as Green List (High Evidence).
Microcephaly v0.129 SMO Zornitza Stark Classified gene: SMO as Green List (high evidence)
Microcephaly v0.129 SMO Zornitza Stark Gene: smo has been classified as Green List (High Evidence).
Microcephaly v0.128 SMO Zornitza Stark gene: SMO was added
gene: SMO was added to Microcephaly. Sources: 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
Review for gene: SMO was set to GREEN
Added comment: Bi-allelic loss-of-function variations in SMO reported in seven individuals from five independent families. Wide phenotypic spectrum of developmental anomalies affecting the brain (hypothalamic hamartoma and microcephaly), heart (atrioventricular septal defect), skeleton (postaxial polydactyly, narrow chest, and shortening of long bones), and enteric nervous system (aganglionosis).
Sources: Literature
Callosome v0.147 SMO Zornitza Stark Tag somatic tag was added to gene: SMO.
Hirschsprung disease v0.3 SMO Zornitza Stark Marked gene: SMO as ready
Hirschsprung disease v0.3 SMO Zornitza Stark Gene: smo has been classified as Green List (High Evidence).
Hirschsprung disease v0.3 SMO Zornitza Stark Classified gene: SMO as Green List (high evidence)
Hirschsprung disease v0.3 SMO Zornitza Stark Gene: smo has been classified as Green List (High Evidence).
Hirschsprung disease v0.2 SMO Zornitza Stark gene: SMO was added
gene: SMO was added to Hirschsprung disease. Sources: 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
Review for gene: SMO was set to GREEN
Added comment: Bi-allelic loss-of-function variations in SMO reported in seven individuals from five independent families. Wide phenotypic spectrum of developmental anomalies affecting the brain (hypothalamic hamartoma and microcephaly), heart (atrioventricular septal defect), skeleton (postaxial polydactyly, narrow chest, and shortening of long bones), and enteric nervous system (aganglionosis).
Sources: Literature
Congenital Heart Defect v0.48 SMO Zornitza Stark Marked gene: SMO as ready
Congenital Heart Defect v0.48 SMO Zornitza Stark Gene: smo has been classified as Green List (High Evidence).
Congenital Heart Defect v0.48 SMO Zornitza Stark Classified gene: SMO as Green List (high evidence)
Congenital Heart Defect v0.48 SMO Zornitza Stark Gene: smo has been classified as Green List (High Evidence).
Congenital Heart Defect v0.47 SMO Zornitza Stark gene: SMO was added
gene: SMO was added to Congenital Heart Defect. Sources: 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
Review for gene: SMO was set to GREEN
Added comment: Bi-allelic loss-of-function variations in SMO reported in seven individuals from five independent families. Wide phenotypic spectrum of developmental anomalies affecting the brain (hypothalamic hamartoma and microcephaly), heart (atrioventricular septal defect), skeleton (postaxial polydactyly, narrow chest, and shortening of long bones), and enteric nervous system (aganglionosis).
Sources: Literature
Congenital Heart Defect v0.46 Zornitza Stark Panel types changed to Victorian Clinical Genetics Services; Rare Disease
Callosome v0.147 SMO Zornitza Stark Marked gene: SMO as ready
Callosome v0.147 SMO Zornitza Stark Gene: smo has been classified as Green List (High Evidence).
Callosome v0.147 SMO Zornitza Stark Phenotypes for gene: SMO were changed from to Curry-Jones syndrome, somatic mosaic 601707
Callosome v0.146 SMO Zornitza Stark Publications for gene: SMO were set to
Callosome v0.145 SMO Zornitza Stark Mode of inheritance for gene: SMO was changed from Unknown to Other
Callosome v0.144 SMO Zornitza Stark reviewed gene: SMO: Rating: GREEN; Mode of pathogenicity: None; Publications: 27236920; Phenotypes: Curry-Jones syndrome, somatic mosaic 601707; Mode of inheritance: Other
Anophthalmia_Microphthalmia_Coloboma v0.56 SMO Zornitza Stark Tag somatic tag was added to gene: SMO.
Polydactyly v0.36 SMO Zornitza Stark Marked gene: SMO as ready
Polydactyly v0.36 SMO Zornitza Stark Gene: smo has been classified as Green List (High Evidence).
Polydactyly v0.36 SMO Zornitza Stark Phenotypes for gene: SMO were changed from to Microcephaly, congenital heart disease, polydactyly, aganglionosis; Curry-Jones syndrome, somatic mosaic 601707
Polydactyly v0.35 SMO Zornitza Stark Publications for gene: SMO were set to
Polydactyly v0.34 SMO Zornitza Stark Mode of inheritance for gene: SMO was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Polydactyly v0.33 SMO Zornitza Stark reviewed gene: SMO: Rating: GREEN; Mode of pathogenicity: None; Publications: 32413283, 27236920; Phenotypes: Microcephaly, congenital heart disease, polydactyly, aganglionosis, Curry-Jones syndrome, somatic mosaic 601707; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.3027 SMO Zornitza Stark Marked gene: SMO as ready
Mendeliome v0.3027 SMO Zornitza Stark Gene: smo has been classified as Green List (High Evidence).
Mendeliome v0.3027 SMO Zornitza Stark Phenotypes for gene: SMO were changed from to Microcephaly, congenital heart disease, polydactyly, aganglionosis; Curry-Jones syndrome, somatic mosaic 601707
Mendeliome v0.3026 SMO Zornitza Stark Publications for gene: SMO were set to
Mendeliome v0.3025 SMO Zornitza Stark Mode of inheritance for gene: SMO was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.3024 SMO Zornitza Stark reviewed gene: SMO: Rating: GREEN; Mode of pathogenicity: None; Publications: 32413283, 27236920; Phenotypes: Microcephaly, congenital heart disease, polydactyly, aganglionosis, Curry-Jones syndrome, somatic mosaic 601707; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.3024 RBL2 Zornitza Stark Marked gene: RBL2 as ready
Mendeliome v0.3024 RBL2 Zornitza Stark Gene: rbl2 has been classified as Red List (Low Evidence).
Mendeliome v0.3024 RBL2 Zornitza Stark gene: RBL2 was added
gene: RBL2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RBL2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RBL2 were set to 32105419; 9806916
Phenotypes for gene: RBL2 were set to Intellectual disability
Review for gene: RBL2 was set to RED
Added comment: Single family reported with pair of affected siblings. Supportive mouse model.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2679 RBL2 Zornitza Stark Marked gene: RBL2 as ready
Intellectual disability syndromic and non-syndromic v0.2679 RBL2 Zornitza Stark Gene: rbl2 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.2679 RBL2 Zornitza Stark gene: RBL2 was added
gene: RBL2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: RBL2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RBL2 were set to 32105419; 9806916
Phenotypes for gene: RBL2 were set to Intellectual disability
Review for gene: RBL2 was set to RED
Added comment: Single family reported with pair of affected siblings. Supportive mouse model.
Sources: Literature
Microcephaly v0.127 GRM7 Zornitza Stark Marked gene: GRM7 as ready
Microcephaly v0.127 GRM7 Zornitza Stark Gene: grm7 has been classified as Green List (High Evidence).
Microcephaly v0.127 GRM7 Zornitza Stark Classified gene: GRM7 as Green List (high evidence)
Microcephaly v0.127 GRM7 Zornitza Stark Gene: grm7 has been classified as Green List (High Evidence).
Microcephaly v0.126 GRM7 Zornitza Stark gene: GRM7 was added
gene: GRM7 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: GRM7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GRM7 were set to 32286009; 32248644
Phenotypes for gene: GRM7 were set to Epilepsy, microcephaly, developmental delay
Review for gene: GRM7 was set to GREEN
Added comment: Eleven individuals from six families reported, three different homozygous variants (two missense, one LoF). Developmental delay, neonatal‐ or infantile‐onset epilepsy, and microcephaly were universal. Supportive mouse model.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2678 GRM7 Zornitza Stark Marked gene: GRM7 as ready
Intellectual disability syndromic and non-syndromic v0.2678 GRM7 Zornitza Stark Gene: grm7 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2678 GRM7 Zornitza Stark Classified gene: GRM7 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2678 GRM7 Zornitza Stark Gene: grm7 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2677 GRM7 Zornitza Stark gene: GRM7 was added
gene: GRM7 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: GRM7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GRM7 were set to 32286009; 32248644
Phenotypes for gene: GRM7 were set to Epilepsy, microcephaly, developmental delay
Review for gene: GRM7 was set to GREEN
Added comment: Eleven individuals from six families reported, three different homozygous variants (two missense, one LoF). Developmental delay, neonatal‐ or infantile‐onset epilepsy, and microcephaly were universal. Supportive mouse model.
Sources: Literature
Genetic Epilepsy v0.716 GRM7 Zornitza Stark Marked gene: GRM7 as ready
Genetic Epilepsy v0.716 GRM7 Zornitza Stark Gene: grm7 has been classified as Green List (High Evidence).
Mendeliome v0.3023 GRM7 Zornitza Stark Marked gene: GRM7 as ready
Mendeliome v0.3023 GRM7 Zornitza Stark Gene: grm7 has been classified as Green List (High Evidence).
Mendeliome v0.3023 GRM7 Zornitza Stark Classified gene: GRM7 as Green List (high evidence)
Mendeliome v0.3023 GRM7 Zornitza Stark Gene: grm7 has been classified as Green List (High Evidence).
Mendeliome v0.3022 GRM7 Zornitza Stark gene: GRM7 was added
gene: GRM7 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GRM7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GRM7 were set to 32286009; 32248644
Phenotypes for gene: GRM7 were set to Epilepsy, microcephaly, developmental delay
Review for gene: GRM7 was set to GREEN
Added comment: Eleven individuals from six families reported, three different homozygous variants (two missense, one LoF). Developmental delay, neonatal‐ or infantile‐onset epilepsy, and microcephaly were universal. Supportive mouse model.
Sources: Literature
Genetic Epilepsy v0.716 GRM7 Zornitza Stark Classified gene: GRM7 as Green List (high evidence)
Genetic Epilepsy v0.716 GRM7 Zornitza Stark Gene: grm7 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.715 GRM7 Zornitza Stark gene: GRM7 was added
gene: GRM7 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: GRM7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GRM7 were set to 32286009; 32248644
Phenotypes for gene: GRM7 were set to Epilepsy, microcephaly, developmental delay
Review for gene: GRM7 was set to GREEN
Added comment: Eleven individuals from six families reported, three different homozygous variants (two missense, one LoF). Developmental delay, neonatal‐ or infantile‐onset epilepsy, and microcephaly were universal.
Sources: Literature
Glycogen Storage Diseases v0.8 PYGM Zornitza Stark Marked gene: PYGM as ready
Glycogen Storage Diseases v0.8 PYGM Zornitza Stark Gene: pygm has been classified as Green List (High Evidence).
Glycogen Storage Diseases v0.8 PYGM Zornitza Stark Publications for gene: PYGM were set to 32386344
Mendeliome v0.3021 PYGM Zornitza Stark Marked gene: PYGM as ready
Mendeliome v0.3021 PYGM Zornitza Stark Gene: pygm has been classified as Green List (High Evidence).
Mendeliome v0.3021 PYGM Zornitza Stark Phenotypes for gene: PYGM were changed from to McArdle disease, MIM# 232600; Glycogen storage disease, autosomal dominant
Mendeliome v0.3020 PYGM Zornitza Stark Publications for gene: PYGM were set to
Mendeliome v0.3019 PYGM Zornitza Stark Mode of inheritance for gene: PYGM was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Glycogen Storage Diseases v0.7 PYGM Zornitza Stark Phenotypes for gene: PYGM were changed from to McArdle disease, MIM# 232600; Glycogen storage disease, autosomal dominant
Mendeliome v0.3018 PYGM Zornitza Stark reviewed gene: PYGM: Rating: GREEN; Mode of pathogenicity: None; Publications: 32386344; Phenotypes: McArdle disease, MIM# 232600, Glycogen storage disease, autosomal dominant; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Glycogen Storage Diseases v0.6 PYGM Zornitza Stark Publications for gene: PYGM were set to 32386344
Glycogen Storage Diseases v0.6 PYGM Zornitza Stark Publications for gene: PYGM were set to
Glycogen Storage Diseases v0.5 PYGM Zornitza Stark Mode of inheritance for gene: PYGM was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Glycogen Storage Diseases v0.4 PYGM Zornitza Stark reviewed gene: PYGM: Rating: GREEN; Mode of pathogenicity: None; Publications: 32386344; Phenotypes: McArdle disease, MIM# 232600, Glycogen storage disease, autosomal dominant; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.3018 PERP Zornitza Stark Marked gene: PERP as ready
Mendeliome v0.3018 PERP Zornitza Stark Gene: perp has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3018 PERP Zornitza Stark Classified gene: PERP as Amber List (moderate evidence)
Mendeliome v0.3018 PERP Zornitza Stark Gene: perp has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3017 PERP Zornitza Stark gene: PERP was added
gene: PERP was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PERP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PERP were set to 31898316
Phenotypes for gene: PERP were set to Erythrokeratoderma, no OMIM # yet
Review for gene: PERP was set to AMBER
Added comment: One extended multiplex consanguineous family with Erythrokeratoderma (striking similarity to that observed in Perp −/− mice), and a novel homozygous variant (c.466G>A; p.Gly156Arg) in PERP that fully segregated with the phenotype. Functional analysis of patient‐ and control‐derived keratinocytes revealed a deleterious effect of the identified variant on the intracellular localization of PERP. A previous report showed that PERP mutation causes a dominant form of keratoderma but a single patient in that report with a homozygous variant in PERP suggests that recessive inheritance is also possible.
Sources: Literature
Palmoplantar Keratoderma and Erythrokeratoderma v0.7 PERP Zornitza Stark Marked gene: PERP as ready
Palmoplantar Keratoderma and Erythrokeratoderma v0.7 PERP Zornitza Stark Added comment: Comment when marking as ready: One family and a mouse model, upgrade to Amber.
Palmoplantar Keratoderma and Erythrokeratoderma v0.7 PERP Zornitza Stark Gene: perp has been classified as Amber List (Moderate Evidence).
Palmoplantar Keratoderma and Erythrokeratoderma v0.7 PERP Zornitza Stark Classified gene: PERP as Amber List (moderate evidence)
Palmoplantar Keratoderma and Erythrokeratoderma v0.7 PERP Zornitza Stark Gene: perp has been classified as Amber List (Moderate Evidence).
Early-onset Dementia v0.52 GBA Zornitza Stark Marked gene: GBA as ready
Early-onset Dementia v0.52 GBA Zornitza Stark Gene: gba has been classified as Amber List (Moderate Evidence).
Early-onset Dementia v0.52 GBA Zornitza Stark Phenotypes for gene: GBA were changed from to {Lewy body dementia, susceptibility to} (MIM# 127750)
Early-onset Dementia v0.51 GBA Zornitza Stark Publications for gene: GBA were set to
Early-onset Dementia v0.50 GBA Zornitza Stark Mode of inheritance for gene: GBA was changed from Unknown to Other
Early-onset Dementia v0.49 GBA Zornitza Stark Classified gene: GBA as Amber List (moderate evidence)
Early-onset Dementia v0.49 GBA Zornitza Stark Gene: gba has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3016 ADCY6 Zornitza Stark Marked gene: ADCY6 as ready
Mendeliome v0.3016 ADCY6 Zornitza Stark Gene: adcy6 has been classified as Green List (High Evidence).
Mendeliome v0.3016 ADCY6 Zornitza Stark Classified gene: ADCY6 as Green List (high evidence)
Mendeliome v0.3016 ADCY6 Zornitza Stark Gene: adcy6 has been classified as Green List (High Evidence).
Mendeliome v0.3015 ADCY6 Zornitza Stark gene: ADCY6 was added
gene: ADCY6 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ADCY6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADCY6 were set to 24319099; 26257172; 31846058
Phenotypes for gene: ADCY6 were set to Lethal congenital contracture syndrome 8, OMIM # 616287
Review for gene: ADCY6 was set to GREEN
Added comment: Laquerriere et al. (2014): 2 sibs from a consanguineous family with an axoglial form of lethal congenital contracture syndrome, and homozygous missense ADCY6 mutation (R1116C). The parents were heterozygous for the mutation. Knocked down ADCY6 orthologs in zebrafish showed a loss of myelin basic protein expression in the peripheral nervous system but no defects in Schwann cell migration and axonal growth. Gonzaga‐Jauregui et al. (2015): 1 patient with congenital hypotonia, distal joint contractures, hypomyelinating neuropathy, and vocal cord paralysis, and a homozygous missense ADCY6 variant. No functional studies. Deceased sister with a similar phenotype with hypotonia, areflexia, and hypomyelinating neuropathy who died at 18 months of respiratory insufficiency. Agolini et al. (2020): 1 patient with severe form of AMC, with two novel compound heterozygous variants in ADCY6 (parents confirmed carriers), but no functional studies.
Sources: Literature
Arthrogryposis v0.59 ADCY6 Zornitza Stark Marked gene: ADCY6 as ready
Arthrogryposis v0.59 ADCY6 Zornitza Stark Gene: adcy6 has been classified as Green List (High Evidence).
Early-onset Dementia v0.48 GBA Ain Roesley reviewed gene: GBA: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 23588557, 32439597, 31010158; Phenotypes: {Lewy body dementia, susceptibility to} (MIM# 127750); Mode of inheritance: Other
Arthrogryposis v0.59 ADCY6 Zornitza Stark Phenotypes for gene: ADCY6 were changed from ?Lethal congenital contracture syndrome 8, OMIM # 616287 to Lethal congenital contracture syndrome 8, OMIM # 616287
Mendeliome v0.3014 DSCR3 Zornitza Stark Marked gene: DSCR3 as ready
Mendeliome v0.3014 DSCR3 Zornitza Stark Gene: dscr3 has been classified as Red List (Low Evidence).
Mendeliome v0.3014 DSCR3 Zornitza Stark gene: DSCR3 was added
gene: DSCR3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: DSCR3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DSCR3 were set to 31845315
Phenotypes for gene: DSCR3 were set to Intellectual disability, no OMIM # yet
Review for gene: DSCR3 was set to RED
Added comment: 1 family/2 cousins with cognitive impairment, growth failure, skeletal abnormalities, and distinctive facial features. Both shared the homozygous nonsense variant c.178G>T (p.Glu60*) in the VPS26C gene. This gene encodes VPS26C, a member of the retriever integral membrane protein recycling pathway. The nature of the variant which is predicted to result in loss‐of‐function, expression studies revealing significant reduction in the mutant transcript, and the co‐segregation of the homozygous variant with the phenotype in two affected individuals.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2676 DSCR3 Zornitza Stark Marked gene: DSCR3 as ready
Intellectual disability syndromic and non-syndromic v0.2676 DSCR3 Zornitza Stark Gene: dscr3 has been classified as Red List (Low Evidence).
Mendeliome v0.3013 LEF1 Zornitza Stark Marked gene: LEF1 as ready
Mendeliome v0.3013 LEF1 Zornitza Stark Gene: lef1 has been classified as Red List (Low Evidence).
Mendeliome v0.3013 LEF1 Zornitza Stark gene: LEF1 was added
gene: LEF1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: LEF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: LEF1 were set to 32022899
Phenotypes for gene: LEF1 were set to Ectodermal dysplasia, no OMIM# yet
Review for gene: LEF1 was set to RED
Added comment: In mice, targeted inactivation of the LEF1 gene results in a complete block of development of multiple ectodermal appendages. One report of two unrelated patients with 4q25 de novo deletion encompassing LEF1 , associated with severe oligodontia of primary and permanent dentition, hypotrichosis and hypohidrosis compatible with hypohidrotic ectodermal dysplasia. So far, no pathogenic variants or variations involving the LEF1 gene have been reported in human.
Sources: Literature
Oligodontia v0.5 LEF1 Zornitza Stark Marked gene: LEF1 as ready
Oligodontia v0.5 LEF1 Zornitza Stark Gene: lef1 has been classified as Red List (Low Evidence).
Ectodermal Dysplasia v0.24 LEF1 Zornitza Stark Marked gene: LEF1 as ready
Ectodermal Dysplasia v0.24 LEF1 Zornitza Stark Gene: lef1 has been classified as Red List (Low Evidence).
Palmoplantar Keratoderma and Erythrokeratoderma v0.6 PERP Chirag Patel gene: PERP was added
gene: PERP was added to Palmoplantar Keratoderma and Erythrokeratoderma. Sources: Literature
Mode of inheritance for gene: PERP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PERP were set to PMID: 31898316
Phenotypes for gene: PERP were set to Erythrokeratoderma, no OMIM # yet
Review for gene: PERP was set to RED
Added comment: One extended multiplex consanguineous family with Erythrokeratoderma (striking similarity to that observed in Perp −/− mice), and a novel homozygous variant (c.466G>A; p.Gly156Arg) in PERP that fully segregated with the phenotype. Functional analysis of patient‐ and control‐derived keratinocytes revealed a deleterious effect of the identified variant on the intracellular localization of PERP.

A previous report showed that PERP mutation causes a dominant form of keratoderma but a single patient in that report with a homozygous variant in PERP suggests that recessive inheritance is also possible.
Sources: Literature
Mendeliome v0.3012 OTUD7A Zornitza Stark Marked gene: OTUD7A as ready
Mendeliome v0.3012 OTUD7A Zornitza Stark Gene: otud7a has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.2676 OTUD7A Zornitza Stark Phenotypes for gene: OTUD7A were changed from Epileptic encephalopathy, no OMIM# yet to Epileptic encephalopathy, intellectual disability, no OMIM# yet
Intellectual disability syndromic and non-syndromic v0.2675 OTUD7A Zornitza Stark Publications for gene: OTUD7A were set to PMID: 31997314
Intellectual disability syndromic and non-syndromic v0.2674 OTUD7A Zornitza Stark reviewed gene: OTUD7A: Rating: RED; Mode of pathogenicity: None; Publications: 29395075, 29395074; Phenotypes: ; Mode of inheritance: None
Mendeliome v0.3012 OTUD7A Zornitza Stark Phenotypes for gene: OTUD7A were changed from Epileptic encephalopathy, no OMIM# yet to Epileptic encephalopathy, intellectual disability, no OMIM# yet
Mendeliome v0.3011 OTUD7A Zornitza Stark Publications for gene: OTUD7A were set to 31997314
Mendeliome v0.3010 OTUD7A Zornitza Stark edited their review of gene: OTUD7A: Changed publications: 31997314, 29395075, 29395074
Mendeliome v0.3010 OTUD7A Zornitza Stark gene: OTUD7A was added
gene: OTUD7A was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: OTUD7A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: OTUD7A were set to 31997314
Phenotypes for gene: OTUD7A were set to Epileptic encephalopathy, no OMIM# yet
Review for gene: OTUD7A was set to RED
Added comment: One patient with severe global developmental delay, language impairment and epileptic encephalopathy. Homozygous OTUD7A missense variant (c.697C>T, p.Leu233Phe), predicted to alter an ultraconserved amino acid, lying within the OTU catalytic domain. Its subsequent segregation analysis revealed that the parents, presenting with learning disability, and brother were heterozygous carriers. Biochemical assays demonstrated that proteasome complex formation and function were significantly reduced in patient‐derived fibroblasts and in OTUD7A knockout HAP1 cell line. Gene lies in the chromosome 15q13.3 region. Heterozygous microdeletions of chromosome 15q13.3 show incomplete penetrance and are associated with a highly variable phenotype that may include intellectual disability, epilepsy, facial dysmorphism and digit anomalies.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2674 OTUD7A Zornitza Stark Marked gene: OTUD7A as ready
Intellectual disability syndromic and non-syndromic v0.2674 OTUD7A Zornitza Stark Gene: otud7a has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.714 OTUD7A Zornitza Stark Marked gene: OTUD7A as ready
Genetic Epilepsy v0.714 OTUD7A Zornitza Stark Gene: otud7a has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.2674 GATAD2B Zornitza Stark Marked gene: GATAD2B as ready
Intellectual disability syndromic and non-syndromic v0.2674 GATAD2B Zornitza Stark Gene: gatad2b has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2674 GATAD2B Zornitza Stark Phenotypes for gene: GATAD2B were changed from to Mental retardation, autosomal dominant 18, OMIM # 615074
Intellectual disability syndromic and non-syndromic v0.2673 GATAD2B Zornitza Stark Publications for gene: GATAD2B were set to
Intellectual disability syndromic and non-syndromic v0.2672 GATAD2B Zornitza Stark Mode of inheritance for gene: GATAD2B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3009 GATAD2B Zornitza Stark Marked gene: GATAD2B as ready
Mendeliome v0.3009 GATAD2B Zornitza Stark Gene: gatad2b has been classified as Green List (High Evidence).
Mendeliome v0.3009 GATAD2B Zornitza Stark Phenotypes for gene: GATAD2B were changed from to Mental retardation, autosomal dominant 18, OMIM # 615074
Mendeliome v0.3008 GATAD2B Zornitza Stark Publications for gene: GATAD2B were set to
Mendeliome v0.3007 GATAD2B Zornitza Stark Mode of inheritance for gene: GATAD2B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3006 GATAD2B Zornitza Stark reviewed gene: GATAD2B: Rating: GREEN; Mode of pathogenicity: None; Publications: 31949314; Phenotypes: Mental retardation, autosomal dominant 18, OMIM # 615074; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Macrocephaly_Megalencephaly v0.33 GATAD2B Zornitza Stark Marked gene: GATAD2B as ready
Macrocephaly_Megalencephaly v0.33 GATAD2B Zornitza Stark Gene: gatad2b has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2671 KMT2D Zornitza Stark Marked gene: KMT2D as ready
Intellectual disability syndromic and non-syndromic v0.2671 KMT2D Zornitza Stark Gene: kmt2d has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2671 KMT2D Zornitza Stark Phenotypes for gene: KMT2D were changed from Kabuki syndrome 1, MIM# 147920; KMT2D-associated syndrome to Kabuki syndrome 1, MIM# 147920; KMT2D-associated syndrome
Intellectual disability syndromic and non-syndromic v0.2671 KMT2D Zornitza Stark Phenotypes for gene: KMT2D were changed from Kabuki syndrome 1, MIM# 147920; KMT2D-associated neurodevelopmental syndrome to Kabuki syndrome 1, MIM# 147920; KMT2D-associated syndrome
Mendeliome v0.3006 KMT2D Zornitza Stark Phenotypes for gene: KMT2D were changed from Kabuki syndrome 1, MIM# 147920; KMT2D-associated neurodevelopmental syndrome to Kabuki syndrome 1, MIM# 147920; KMT2D-associated syndrome
Intellectual disability syndromic and non-syndromic v0.2670 KMT2D Zornitza Stark reviewed gene: KMT2D: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Kabuki syndrome 1, MIM# 147920, KMT2D-associated syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2670 KMT2D Zornitza Stark Deleted their review
Mendeliome v0.3005 KMT2D Zornitza Stark Marked gene: KMT2D as ready
Mendeliome v0.3005 KMT2D Zornitza Stark Gene: kmt2d has been classified as Green List (High Evidence).
Mendeliome v0.3005 KMT2D Zornitza Stark Phenotypes for gene: KMT2D were changed from to Kabuki syndrome 1, MIM# 147920; KMT2D-associated neurodevelopmental syndrome
Mendeliome v0.3004 KMT2D Zornitza Stark Publications for gene: KMT2D were set to
Mendeliome v0.3003 KMT2D Zornitza Stark Mode of inheritance for gene: KMT2D was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3002 KMT2D Zornitza Stark reviewed gene: KMT2D: Rating: GREEN; Mode of pathogenicity: None; Publications: 31949313; Phenotypes: Kabuki syndrome 1, MIM# 147920, KMT2D-associated neurodevelopmental syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2670 KMT2D Zornitza Stark Phenotypes for gene: KMT2D were changed from to Kabuki syndrome 1, MIM# 147920; KMT2D-associated neurodevelopmental syndrome
Intellectual disability syndromic and non-syndromic v0.2669 KMT2D Zornitza Stark Publications for gene: KMT2D were set to
Craniosynostosis v0.37 TLK2 Bryony Thompson reviewed gene: TLK2: Rating: AMBER; Mode of pathogenicity: None; Publications: 29861108; Phenotypes: Mental retardation, autosomal dominant 57 MIM#618050; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2668 KMT2D Zornitza Stark Mode of inheritance for gene: KMT2D was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2667 KMT2D Zornitza Stark reviewed gene: KMT2D: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Kabuki syndrome 1, MIM# 147920, KMT2D-associated neurodevelopmental syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v0.32 COG4 Zornitza Stark Marked gene: COG4 as ready
Skeletal dysplasia v0.32 COG4 Zornitza Stark Gene: cog4 has been classified as Green List (High Evidence).
Skeletal dysplasia v0.32 COG4 Zornitza Stark Phenotypes for gene: COG4 were changed from Saul-Wilson syndrome, OMIM #618150; Congenital disorder of glycosylation, type IIj, OMIM #613489 to Saul-Wilson syndrome, OMIM #618150
Skeletal dysplasia v0.31 COG4 Zornitza Stark Mode of inheritance for gene: COG4 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v0.31 COG4 Zornitza Stark Mode of inheritance for gene: COG4 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2667 COG4 Zornitza Stark Publications for gene: COG4 were set to
Intellectual disability syndromic and non-syndromic v0.2666 COG4 Zornitza Stark Mode of inheritance for gene: COG4 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2665 COG4 Zornitza Stark Deleted their review
Intellectual disability syndromic and non-syndromic v0.2665 COG4 Zornitza Stark reviewed gene: COG4: Rating: GREEN; Mode of pathogenicity: None; Publications: 31949312, 30290151, 19494034, 21185756; Phenotypes: Saul-Wilson syndrome, OMIM #618150, Congenital disorder of glycosylation, type IIj, OMIM #613489; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.3002 COG4 Zornitza Stark Marked gene: COG4 as ready
Mendeliome v0.3002 COG4 Zornitza Stark Gene: cog4 has been classified as Green List (High Evidence).
Mendeliome v0.3002 COG4 Zornitza Stark Phenotypes for gene: COG4 were changed from to Saul-Wilson syndrome, OMIM #618150; Congenital disorder of glycosylation, type IIj, OMIM #613489
Mendeliome v0.3001 COG4 Zornitza Stark Publications for gene: COG4 were set to
Mendeliome v0.3000 COG4 Zornitza Stark Mode of inheritance for gene: COG4 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.2999 COG4 Zornitza Stark reviewed gene: COG4: Rating: GREEN; Mode of pathogenicity: None; Publications: 31949312, 30290151, 19494034, 21185756; Phenotypes: Saul-Wilson syndrome, OMIM #618150, Congenital disorder of glycosylation, type IIj, OMIM #613489; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Congenital Disorders of Glycosylation v0.53 COG4 Zornitza Stark Marked gene: COG4 as ready
Congenital Disorders of Glycosylation v0.53 COG4 Zornitza Stark Gene: cog4 has been classified as Green List (High Evidence).
Congenital Disorders of Glycosylation v0.53 COG4 Zornitza Stark Phenotypes for gene: COG4 were changed from to Congenital disorder of glycosylation, type IIj 613489
Congenital Disorders of Glycosylation v0.52 COG4 Zornitza Stark Publications for gene: COG4 were set to
Congenital Disorders of Glycosylation v0.51 COG4 Zornitza Stark Mode of inheritance for gene: COG4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Congenital Disorders of Glycosylation v0.50 COG4 Zornitza Stark reviewed gene: COG4: Rating: GREEN; Mode of pathogenicity: None; Publications: 21185756, 19494034; Phenotypes: Congenital disorder of glycosylation, type IIj 613489; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cataract v0.143 COG4 Zornitza Stark Marked gene: COG4 as ready
Cataract v0.143 COG4 Zornitza Stark Gene: cog4 has been classified as Green List (High Evidence).
Cataract v0.143 COG4 Zornitza Stark Publications for gene: COG4 were set to Saul-Wilson syndrome, OMIM #618150; Congenital disorder of glycosylation, type IIj, OMIM #613489
Cataract v0.142 COG4 Zornitza Stark Phenotypes for gene: COG4 were changed from PMID: 31949312; 30290151 to Saul-Wilson syndrome, OMIM #618150; Congenital disorder of glycosylation, type IIj, OMIM #613489
Differences of Sex Development v0.30 NR2F2 Zornitza Stark Marked gene: NR2F2 as ready
Differences of Sex Development v0.30 NR2F2 Zornitza Stark Gene: nr2f2 has been classified as Green List (High Evidence).
Differences of Sex Development v0.30 NR2F2 Zornitza Stark Classified gene: NR2F2 as Green List (high evidence)
Differences of Sex Development v0.30 NR2F2 Zornitza Stark Gene: nr2f2 has been classified as Green List (High Evidence).
Differences of Sex Development v0.29 NR2F2 Zornitza Stark gene: NR2F2 was added
gene: NR2F2 was added to Disorders of Sex Differentiation. Sources: Expert list
Mode of inheritance for gene: NR2F2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NR2F2 were set to 29478779; 31687637
Phenotypes for gene: NR2F2 were set to 46,XX disorder of sex development (DSD) and congenital heart defects
Review for gene: NR2F2 was set to GREEN
Added comment: Four unrelated individuals reported. Note two had the same 7bp deletion, c.97_103delCCGCCCG, NM_021005.3, and the third individual had an adjacent deletion, c.103_109delGGCGCCC, NM_021005.3. All three were of very different ancestries, making founder effect unlikely. Fourth individual had a larger deletion encompassing this gene. Gene is also linked with isolated CHD (Congenital heart defects, multiple types, 4, MIM# 615779)
Sources: Expert list
Arthrogryposis v0.58 ADCY6 Chirag Patel Classified gene: ADCY6 as Green List (high evidence)
Arthrogryposis v0.58 ADCY6 Chirag Patel Gene: adcy6 has been classified as Green List (High Evidence).
Arthrogryposis v0.57 ADCY6 Chirag Patel Classified gene: ADCY6 as Green List (high evidence)
Arthrogryposis v0.57 ADCY6 Chirag Patel Gene: adcy6 has been classified as Green List (High Evidence).
Arthrogryposis v0.56 ADCY6 Chirag Patel gene: ADCY6 was added
gene: ADCY6 was added to Arthrogryposis. Sources: Literature
Mode of inheritance for gene: ADCY6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADCY6 were set to PMID: 24319099, 26257172, 31846058
Phenotypes for gene: ADCY6 were set to ?Lethal congenital contracture syndrome 8, OMIM # 616287
Review for gene: ADCY6 was set to GREEN
Added comment: Laquerriere et al. (2014): 2 sibs from a consanguineous family with an axoglial form of lethal congenital contracture syndrome, and homozygous missense ADCY6 mutation (R1116C). The parents were heterozygous for the mutation. Knocked down ADCY6 orthologs in zebrafish showed a loss of myelin basic protein expression in the peripheral nervous system but no defects in Schwann cell migration and axonal growth.

Gonzaga‐Jauregui et al. (2015): 1 patient with congenital hypotonia, distal joint contractures, hypomyelinating neuropathy, and vocal cord paralysis, and a homozygous missense ADCY6 variant. No functional studies. Deceased sister with a similar phenotype with hypotonia, areflexia, and hypomyelinating neuropathy who died at 18 months of respiratory insufficiency.

Agolini et al. (2020): 1 patient with severe form of AMC, with two novel compound heterozygous variants in ADCY6 (parents confirmed carriers), but no functional studies.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2665 DSCR3 Chirag Patel gene: DSCR3 was added
gene: DSCR3 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: DSCR3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DSCR3 were set to PMID: 31845315
Phenotypes for gene: DSCR3 were set to Intellectual disability, no OMIM # yet
Review for gene: DSCR3 was set to RED
Added comment: 1 family/2 cousins with cognitive impairment, growth failure, skeletal abnormalities, and distinctive facial features. Both shared the homozygous nonsense variant c.178G>T (p.Glu60*) in the VPS26C gene. This gene encodes VPS26C, a member of the retriever integral membrane protein recycling pathway. The nature of the variant which is predicted to result in loss‐of‐function, expression studies revealing significant reduction in the mutant transcript, and the co‐segregation of the homozygous variant with the phenotype in two affected individuals.
Sources: Literature
Oligodontia v0.5 LEF1 Chirag Patel gene: LEF1 was added
gene: LEF1 was added to Oligodontia. Sources: Literature
Mode of inheritance for gene: LEF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: LEF1 were set to PMID: 32022899
Phenotypes for gene: LEF1 were set to Ectodermal dysplasia, no OMIM# yet
Review for gene: LEF1 was set to RED
Added comment: In mice, targeted inactivation of the LEF1 gene results in a complete block of development of multiple ectodermal appendages. One report of two unrelated patients with 4q25 de novo deletion encompassing LEF1 , associated with severe oligodontia of primary and permanent dentition, hypotrichosis and hypohidrosis compatible with hypohidrotic ectodermal dysplasia. So far, no pathogenic variants or variations involving the LEF1 gene have been reported in human.
Sources: Literature
Ectodermal Dysplasia v0.24 LEF1 Chirag Patel gene: LEF1 was added
gene: LEF1 was added to Ectodermal Dysplasia. Sources: Literature
Mode of inheritance for gene: LEF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: LEF1 were set to PMID: 32022899
Phenotypes for gene: LEF1 were set to Ectodermal dysplasia, no OMIM# yet
Added comment: In mice, targeted inactivation of the LEF1 gene results in a complete block of development of multiple ectodermal appendages. One report of two unrelated patients with 4q25 de novo deletion encompassing LEF1 , associated with severe oligodontia of primary and permanent dentition, hypotrichosis and hypohidrosis compatible with hypohidrotic ectodermal dysplasia. So far, no pathogenic variants or variations involving the LEF1 gene have been reported in human.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2664 OTUD7A Chirag Patel gene: OTUD7A was added
gene: OTUD7A was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: OTUD7A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: OTUD7A were set to PMID: 31997314
Phenotypes for gene: OTUD7A were set to Epileptic encephalopathy, no OMIM# yet
Review for gene: OTUD7A was set to RED
Added comment: One patient with severe global developmental delay, language impairment and epileptic encephalopathy. Homozygous OTUD7A missense variant (c.697C>T, p.Leu233Phe), predicted to alter an ultraconserved amino acid, lying within the OTU catalytic domain. Its subsequent segregation analysis revealed that the parents, presenting with learning disability, and brother were heterozygous carriers. Biochemical assays demonstrated that proteasome complex formation and function were significantly reduced in patient‐derived fibroblasts and in OTUD7A knockout HAP1 cell line. We provide evidence that biallelic pathogenic OTUD7A variation is linked to early‐onset epileptic encephalopathy and proteasome dysfunction. Gene lies in the chromosome 15q13.3 region. Heterozygous microdeletions of chromosome 15q13.3 show incomplete penetrance and are associated with a highly variable phenotype that may include intellectual disability, epilepsy, facial dysmorphism and digit anomalies.
Sources: Literature
Genetic Epilepsy v0.714 OTUD7A Chirag Patel gene: OTUD7A was added
gene: OTUD7A was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: OTUD7A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: OTUD7A were set to PMID: 31997314
Phenotypes for gene: OTUD7A were set to Epileptic encephalopathy, no OMIM# yet
Review for gene: OTUD7A was set to RED
Added comment: One patient with severe global developmental delay, language impairment and epileptic encephalopathy. Homozygous OTUD7A missense variant (c.697C>T, p.Leu233Phe), predicted to alter an ultraconserved amino acid, lying within the OTU catalytic domain. Its subsequent segregation analysis revealed that the parents, presenting with learning disability, and brother were heterozygous carriers. Biochemical assays demonstrated that proteasome complex formation and function were significantly reduced in patient‐derived fibroblasts and in OTUD7A knockout HAP1 cell line. We provide evidence that biallelic pathogenic OTUD7A variation is linked to early‐onset epileptic encephalopathy and proteasome dysfunction. Gene lies in the chromosome 15q13.3 region. Heterozygous microdeletions of chromosome 15q13.3 show incomplete penetrance and are associated with a highly variable phenotype that may include intellectual disability, epilepsy, facial dysmorphism and digit anomalies.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2663 GATAD2B Chirag Patel reviewed gene: GATAD2B: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31949314; Phenotypes: Mental retardation, autosomal dominant 18, OMIM # 615074; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Macrocephaly_Megalencephaly v0.33 GATAD2B Chirag Patel Classified gene: GATAD2B as Green List (high evidence)
Macrocephaly_Megalencephaly v0.33 GATAD2B Chirag Patel Gene: gatad2b has been classified as Green List (High Evidence).
Macrocephaly_Megalencephaly v0.32 GATAD2B Chirag Patel gene: GATAD2B was added
gene: GATAD2B was added to Macrocephaly_Megalencephaly. Sources: Literature
Mode of inheritance for gene: GATAD2B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GATAD2B were set to PMID: 31949314
Phenotypes for gene: GATAD2B were set to Mental retardation, autosomal dominant 18, OMIM # 615074
Review for gene: GATAD2B was set to GREEN
Added comment: 50 patients reported in series in 2020:
- loss-of-function and missense variants
- clinical features of hypotonia, intellectual disability, strabismus, cardiac defects, characteristic facies, childhood apraxia of speech, and macrocephaly.
Sources: Literature
Craniosynostosis v0.37 SLC25A24 Bryony Thompson Marked gene: SLC25A24 as ready
Craniosynostosis v0.37 SLC25A24 Bryony Thompson Gene: slc25a24 has been classified as Green List (High Evidence).
Craniosynostosis v0.37 SLC25A24 Bryony Thompson Phenotypes for gene: SLC25A24 were changed from to Fontaine progeroid syndrome MIM#612289
Craniosynostosis v0.36 SLC25A24 Bryony Thompson Publications for gene: SLC25A24 were set to
Craniosynostosis v0.35 SLC25A24 Bryony Thompson Mode of inheritance for gene: SLC25A24 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Craniosynostosis v0.34 SLC25A24 Bryony Thompson reviewed gene: SLC25A24: Rating: GREEN; Mode of pathogenicity: Other; Publications: 29100093; Phenotypes: Fontaine progeroid syndrome MIM#612289; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2663 KMT2D Chirag Patel changed review comment from: KMT2D missense variants located in a specific region spanning exons 38 and 39 and affecting highly conserved residues cause a novel multiple malformations syndrome distinct from Kabuki syndrome, through a dominant negative mechanism.; to: KMT2D missense variants located in a specific region spanning exons 38 and 39 and affecting highly conserved residues cause a novel multiple malformations syndrome distinct from Kabuki syndrome, through a dominant negative mechanism.
- 7 unrelated families with choanal atresia, athelia or hypoplastic nipples, branchial sinus abnormalities, neck pits, lacrimal duct anomalies, hearing loss, external ear malformations, and thyroid abnormalities. None of the individuals had intellectual disability.
Intellectual disability syndromic and non-syndromic v0.2663 KMT2D Chirag Patel reviewed gene: KMT2D: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31949313; Phenotypes: ; Mode of inheritance: None
Skeletal dysplasia v0.30 COG4 Chirag Patel Classified gene: COG4 as Green List (high evidence)
Skeletal dysplasia v0.30 COG4 Chirag Patel Gene: cog4 has been classified as Green List (High Evidence).
Skeletal dysplasia v0.29 COG4 Chirag Patel changed review comment from: Saul-Wilson syndrome (AD)
14 patients reported with DD, skeletal changes, cataracts, and growth retardation (progeriod like)
All have a recurrent de novo heterozygous missense variant (p.Gly516Arg)

Congenital disorder of glycosylation, type IIj (AR)
Sources: Literature; to: Saul-Wilson syndrome (AD)
14 patients reported with DD, skeletal dysplasia changes, cataracts, and growth retardation (progeriod like)
All have a recurrent de novo heterozygous missense variant (p.Gly516Arg)

Congenital disorder of glycosylation, type IIj (AR)
Sources: Literature
Skeletal dysplasia v0.29 COG4 Chirag Patel gene: COG4 was added
gene: COG4 was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: COG4 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: COG4 were set to PMID: 31949312; 30290151
Phenotypes for gene: COG4 were set to Saul-Wilson syndrome, OMIM #618150; Congenital disorder of glycosylation, type IIj, OMIM #613489
Review for gene: COG4 was set to GREEN
Added comment: Saul-Wilson syndrome (AD)
14 patients reported with DD, skeletal changes, cataracts, and growth retardation (progeriod like)
All have a recurrent de novo heterozygous missense variant (p.Gly516Arg)

Congenital disorder of glycosylation, type IIj (AR)
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2663 COG4 Chirag Patel reviewed gene: COG4: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31949312, 30290151; Phenotypes: Saul-Wilson syndrome, OMIM #618150, Congenital disorder of glycosylation, type IIj, OMIM #613489; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Cataract v0.141 COG4 Chirag Patel Classified gene: COG4 as Green List (high evidence)
Cataract v0.141 COG4 Chirag Patel Gene: cog4 has been classified as Green List (High Evidence).
Cataract v0.140 COG4 Chirag Patel Classified gene: COG4 as Green List (high evidence)
Cataract v0.140 COG4 Chirag Patel Gene: cog4 has been classified as Green List (High Evidence).
Cataract v0.140 COG4 Chirag Patel Classified gene: COG4 as Green List (high evidence)
Cataract v0.140 COG4 Chirag Patel Gene: cog4 has been classified as Green List (High Evidence).
Cataract v0.140 COG4 Chirag Patel Classified gene: COG4 as Green List (high evidence)
Cataract v0.140 COG4 Chirag Patel Gene: cog4 has been classified as Green List (High Evidence).
Cataract v0.140 COG4 Chirag Patel Classified gene: COG4 as Green List (high evidence)
Cataract v0.140 COG4 Chirag Patel Gene: cog4 has been classified as Green List (High Evidence).
Cataract v0.139 COG4 Chirag Patel gene: COG4 was added
gene: COG4 was added to Cataract. Sources: Literature
Mode of inheritance for gene: COG4 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: COG4 were set to Saul-Wilson syndrome, OMIM #618150; Congenital disorder of glycosylation, type IIj, OMIM #613489
Phenotypes for gene: COG4 were set to PMID: 31949312; 30290151
Review for gene: COG4 was set to GREEN
Added comment: Saul-Wilson syndrome (AD)
14 patients reported with DD, skeletal changes, cataracts, and growth retardation (progeriod like)
All have a recurrent de novo heterozygous missense variant (p.Gly516Arg)

Congenital disorder of glycosylation, type IIj (AR)
Sources: Literature
Catecholaminergic Polymorphic Ventricular Tachycardia v0.26 TECRL Zornitza Stark Marked gene: TECRL as ready
Catecholaminergic Polymorphic Ventricular Tachycardia v0.26 TECRL Zornitza Stark Gene: tecrl has been classified as Green List (High Evidence).
Catecholaminergic Polymorphic Ventricular Tachycardia v0.26 TECRL Zornitza Stark Phenotypes for gene: TECRL were changed from CPVT to Ventricular tachycardia, catecholaminergic polymorphic, 3, MIM# 614021
Catecholaminergic Polymorphic Ventricular Tachycardia v0.25 TECRL Zornitza Stark Classified gene: TECRL as Green List (high evidence)
Catecholaminergic Polymorphic Ventricular Tachycardia v0.25 TECRL Zornitza Stark Gene: tecrl has been classified as Green List (High Evidence).
Catecholaminergic Polymorphic Ventricular Tachycardia v0.24 CALM1 Zornitza Stark Marked gene: CALM1 as ready
Catecholaminergic Polymorphic Ventricular Tachycardia v0.24 CALM1 Zornitza Stark Gene: calm1 has been classified as Green List (High Evidence).
Catecholaminergic Polymorphic Ventricular Tachycardia v0.24 CALM1 Zornitza Stark Phenotypes for gene: CALM1 were changed from to Long QT syndrome 14 616247; Ventricular tachycardia, catecholaminergic polymorphic, 4 614916
Catecholaminergic Polymorphic Ventricular Tachycardia v0.23 CALM1 Zornitza Stark Publications for gene: CALM1 were set to
Catecholaminergic Polymorphic Ventricular Tachycardia v0.22 CALM1 Zornitza Stark Mode of inheritance for gene: CALM1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Catecholaminergic Polymorphic Ventricular Tachycardia v0.21 CALM2 Zornitza Stark Marked gene: CALM2 as ready
Catecholaminergic Polymorphic Ventricular Tachycardia v0.21 CALM2 Zornitza Stark Gene: calm2 has been classified as Green List (High Evidence).
Catecholaminergic Polymorphic Ventricular Tachycardia v0.21 CALM2 Zornitza Stark Phenotypes for gene: CALM2 were changed from to Long QT syndrome 15 616249; sudden unexplained death; idopathic VF
Catecholaminergic Polymorphic Ventricular Tachycardia v0.20 CALM2 Zornitza Stark Publications for gene: CALM2 were set to
Catecholaminergic Polymorphic Ventricular Tachycardia v0.19 CALM3 Zornitza Stark Publications for gene: CALM3 were set to 27516456
Catecholaminergic Polymorphic Ventricular Tachycardia v0.18 CALM3 Zornitza Stark Classified gene: CALM3 as Amber List (moderate evidence)
Catecholaminergic Polymorphic Ventricular Tachycardia v0.18 CALM3 Zornitza Stark Gene: calm3 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2663 ARL13B Zornitza Stark Marked gene: ARL13B as ready
Intellectual disability syndromic and non-syndromic v0.2663 ARL13B Zornitza Stark Gene: arl13b has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2663 ARL13B Zornitza Stark Phenotypes for gene: ARL13B were changed from to Joubert syndrome 8, MIM# 612291
Intellectual disability syndromic and non-syndromic v0.2662 ARL13B Zornitza Stark Publications for gene: ARL13B were set to
Intellectual disability syndromic and non-syndromic v0.2661 ARL13B Zornitza Stark Mode of inheritance for gene: ARL13B was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2660 ARL13B Zornitza Stark reviewed gene: ARL13B: Rating: GREEN; Mode of pathogenicity: None; Publications: 18674751, 25138100, 26092869, 27894351, 29255182, 17488627; Phenotypes: Joubert syndrome 8, MIM# 612291; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Regression v0.118 ARL13B Zornitza Stark Marked gene: ARL13B as ready
Regression v0.118 ARL13B Zornitza Stark Gene: arl13b has been classified as Red List (Low Evidence).
Regression v0.118 ARL13B Zornitza Stark Phenotypes for gene: ARL13B were changed from to Joubert syndrome 8, MIM# 612291
Regression v0.117 ARL13B Zornitza Stark Classified gene: ARL13B as Red List (low evidence)
Regression v0.117 ARL13B Zornitza Stark Gene: arl13b has been classified as Red List (Low Evidence).
Regression v0.116 ARL13B Zornitza Stark reviewed gene: ARL13B: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Joubert syndrome 8, MIM# 612291; Mode of inheritance: None
Renal Ciliopathies and Nephronophthisis v0.106 ARL13B Zornitza Stark Marked gene: ARL13B as ready
Renal Ciliopathies and Nephronophthisis v0.106 ARL13B Zornitza Stark Gene: arl13b has been classified as Green List (High Evidence).
Renal Ciliopathies and Nephronophthisis v0.106 ARL13B Zornitza Stark Phenotypes for gene: ARL13B were changed from to Joubert syndrome 8, MIM# 612291
Renal Ciliopathies and Nephronophthisis v0.105 ARL13B Zornitza Stark Publications for gene: ARL13B were set to
Renal Ciliopathies and Nephronophthisis v0.104 ARL13B Zornitza Stark Mode of inheritance for gene: ARL13B was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Renal Ciliopathies and Nephronophthisis v0.103 ARL13B Zornitza Stark reviewed gene: ARL13B: Rating: GREEN; Mode of pathogenicity: None; Publications: 18674751, 25138100, 26092869, 27894351, 29255182, 17488627; Phenotypes: Joubert syndrome 8, MIM# 612291; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2999 ARL13B Zornitza Stark Marked gene: ARL13B as ready
Mendeliome v0.2999 ARL13B Zornitza Stark Gene: arl13b has been classified as Green List (High Evidence).
Mendeliome v0.2999 ARL13B Zornitza Stark Phenotypes for gene: ARL13B were changed from to Joubert syndrome 8, MIM# 612291
Mendeliome v0.2998 ARL13B Zornitza Stark Publications for gene: ARL13B were set to
Mendeliome v0.2997 ARL13B Zornitza Stark Mode of inheritance for gene: ARL13B was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2996 ARL13B Zornitza Stark Deleted their comment
Mendeliome v0.2996 ARL13B Zornitza Stark edited their review of gene: ARL13B: Added comment: Eight families reported in the literature. Many are homozygous missense variants in consanguineous families with no further supporting evidence, but sufficient number have functional evidence at protein level. Gene has appropriate tissue expression. Zebrafish model: curved tails and cystic kidneys. Hennin mouse model discovered in ENU mutagenesis screen: has polydactyly, ciliary defect, and much more severe neurological phenotype (neural tube defect).; Changed publications: 18674751, 25138100, 26092869, 27894351, 29255182, 17488627
Ciliopathies v0.190 ARL13B Zornitza Stark Marked gene: ARL13B as ready
Ciliopathies v0.190 ARL13B Zornitza Stark Gene: arl13b has been classified as Green List (High Evidence).
Ciliopathies v0.190 ARL13B Zornitza Stark Phenotypes for gene: ARL13B were changed from to Joubert syndrome 8, MIM# 612291
Ciliopathies v0.189 ARL13B Zornitza Stark Publications for gene: ARL13B were set to
Ciliopathies v0.188 ARL13B Zornitza Stark Mode of inheritance for gene: ARL13B was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Ciliopathies v0.187 ARL13B Zornitza Stark reviewed gene: ARL13B: Rating: GREEN; Mode of pathogenicity: None; Publications: 18674751, 25138100, 26092869, 27894351, 29255182, 17488627; Phenotypes: Joubert syndrome 8, MIM# 612291; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Joubert syndrome and other neurological ciliopathies v0.83 CENPF Zornitza Stark Marked gene: CENPF as ready
Joubert syndrome and other neurological ciliopathies v0.83 CENPF Zornitza Stark Gene: cenpf has been classified as Amber List (Moderate Evidence).
Joubert syndrome and other neurological ciliopathies v0.83 CENPF Zornitza Stark Classified gene: CENPF as Amber List (moderate evidence)
Joubert syndrome and other neurological ciliopathies v0.83 CENPF Zornitza Stark Gene: cenpf has been classified as Amber List (Moderate Evidence).
Joubert syndrome and other neurological ciliopathies v0.82 ARL13B Zornitza Stark Marked gene: ARL13B as ready
Joubert syndrome and other neurological ciliopathies v0.82 ARL13B Zornitza Stark Gene: arl13b has been classified as Green List (High Evidence).
Joubert syndrome and other neurological ciliopathies v0.82 ARL13B Zornitza Stark Phenotypes for gene: ARL13B were changed from to Joubert syndrome 8, MIM# 612291
Joubert syndrome and other neurological ciliopathies v0.81 ARL13B Zornitza Stark Publications for gene: ARL13B were set to
Joubert syndrome and other neurological ciliopathies v0.80 ARL13B Zornitza Stark Mode of inheritance for gene: ARL13B was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Joubert syndrome and other neurological ciliopathies v0.79 ARL13B Zornitza Stark reviewed gene: ARL13B: Rating: GREEN; Mode of pathogenicity: None; Publications: 18674751, 25138100, 26092869, 27894351, 29255182, 17488627; Phenotypes: Joubert syndrome 8, MIM# 612291; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Craniosynostosis v0.34 RAB23 Tiong Tan Marked gene: RAB23 as ready
Craniosynostosis v0.34 RAB23 Tiong Tan Gene: rab23 has been classified as Green List (High Evidence).
Craniosynostosis v0.34 RAB23 Tiong Tan Classified gene: RAB23 as Green List (high evidence)
Craniosynostosis v0.34 RAB23 Tiong Tan Gene: rab23 has been classified as Green List (High Evidence).
Craniosynostosis v0.33 RAB23 Tiong Tan gene: RAB23 was added
gene: RAB23 was added to Craniosynostosis. Sources: Literature
Mode of inheritance for gene: RAB23 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RAB23 were set to 17503333
Phenotypes for gene: RAB23 were set to 201000 CARPENTER SYNDROME
Penetrance for gene: RAB23 were set to Complete
Review for gene: RAB23 was set to GREEN
Added comment: Craniosynostosis is an established feature of Carpenter syndrome
Sources: Literature
Craniosynostosis v0.32 HNRNPK Tiong Tan Marked gene: HNRNPK as ready
Craniosynostosis v0.32 HNRNPK Tiong Tan Gene: hnrnpk has been classified as Green List (High Evidence).
Craniosynostosis v0.32 HNRNPK Tiong Tan Classified gene: HNRNPK as Green List (high evidence)
Craniosynostosis v0.32 HNRNPK Tiong Tan Added comment: Comment on list classification: Amazing reviewer
Craniosynostosis v0.32 HNRNPK Tiong Tan Gene: hnrnpk has been classified as Green List (High Evidence).
Craniosynostosis v0.31 HNRNPK Tiong Tan gene: HNRNPK was added
gene: HNRNPK was added to Craniosynostosis. Sources: Literature
Mode of inheritance for gene: HNRNPK was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HNRNPK were set to 26173930; 26954065; 29904177
Phenotypes for gene: HNRNPK were set to Au-Kline syndrome
Penetrance for gene: HNRNPK were set to Complete
Review for gene: HNRNPK was set to GREEN
Added comment: Multiple unrelated individuals with Au-Kline (approx 1/3 have craniosynostosis - sagittal, metric, lambdoid)
Sources: Literature
Craniosynostosis v0.30 ESCO2 Tiong Tan Marked gene: ESCO2 as ready
Craniosynostosis v0.30 ESCO2 Tiong Tan Gene: esco2 has been classified as Amber List (Moderate Evidence).
Craniosynostosis v0.30 ESCO2 Tiong Tan Classified gene: ESCO2 as Amber List (moderate evidence)
Craniosynostosis v0.30 ESCO2 Tiong Tan Gene: esco2 has been classified as Amber List (Moderate Evidence).
Craniosynostosis v0.29 ESCO2 Tiong Tan gene: ESCO2 was added
gene: ESCO2 was added to Craniosynostosis. Sources: Literature
Mode of inheritance for gene: ESCO2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ESCO2 were set to 31192177
Phenotypes for gene: ESCO2 were set to 268300 ROBERTS SYNDROME
Penetrance for gene: ESCO2 were set to Complete
Review for gene: ESCO2 was set to AMBER
Added comment: Two unrelated individuals with Roberts syndrome and craniosynostosis
Sources: Literature
Craniosynostosis v0.28 EFNA4 Tiong Tan Marked gene: EFNA4 as ready
Craniosynostosis v0.28 EFNA4 Tiong Tan Gene: efna4 has been classified as Amber List (Moderate Evidence).
Craniosynostosis v0.28 EFNA4 Tiong Tan Classified gene: EFNA4 as Amber List (moderate evidence)
Craniosynostosis v0.28 EFNA4 Tiong Tan Gene: efna4 has been classified as Amber List (Moderate Evidence).
Craniosynostosis v0.27 EFNA4 Tiong Tan reviewed gene: EFNA4: Rating: AMBER; Mode of pathogenicity: None; Publications: 29168297, 29215649; Phenotypes: Coronal and metopic craniosynostosis; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Craniosynostosis v0.27 DPH1 Tiong Tan Marked gene: DPH1 as ready
Craniosynostosis v0.27 DPH1 Tiong Tan Gene: dph1 has been classified as Amber List (Moderate Evidence).
Craniosynostosis v0.27 DPH1 Tiong Tan Classified gene: DPH1 as Amber List (moderate evidence)
Craniosynostosis v0.27 DPH1 Tiong Tan Added comment: Comment on list classification: I agree!
Craniosynostosis v0.27 DPH1 Tiong Tan Gene: dph1 has been classified as Amber List (Moderate Evidence).
Craniosynostosis v0.26 DPH1 Tiong Tan gene: DPH1 was added
gene: DPH1 was added to Craniosynostosis. Sources: Literature
Mode of inheritance for gene: DPH1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DPH1 were set to 25558065; 26220823
Phenotypes for gene: DPH1 were set to 616901 DEVELOPMENTAL DELAY WITH SHORT STATURE, DYSMORPHIC FACIAL FEATURES, AND SPARSE HAIR
Penetrance for gene: DPH1 were set to Complete
Review for gene: DPH1 was set to AMBER
Added comment: Multiple sibs from two unrelated families with DEDSSH syndrome, of which craniosynostosis was a component in some affected individuals.
Sources: Literature
Craniosynostosis v0.25 CYP26B1 Tiong Tan Marked gene: CYP26B1 as ready
Craniosynostosis v0.25 CYP26B1 Tiong Tan Gene: cyp26b1 has been classified as Green List (High Evidence).
Craniosynostosis v0.25 CYP26B1 Tiong Tan Classified gene: CYP26B1 as Green List (high evidence)
Craniosynostosis v0.25 CYP26B1 Tiong Tan Gene: cyp26b1 has been classified as Green List (High Evidence).
Craniosynostosis v0.24 CYP26B1 Tiong Tan gene: CYP26B1 was added
gene: CYP26B1 was added to Craniosynostosis. Sources: Literature
Mode of inheritance for gene: CYP26B1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CYP26B1 were set to 27410456; 22019272
Phenotypes for gene: CYP26B1 were set to 614416 RADIOHUMERAL FUSIONS WITH OTHER SKELETAL AND CRANIOFACIAL ANOMALIES
Penetrance for gene: CYP26B1 were set to Complete
Review for gene: CYP26B1 was set to GREEN
Added comment: Three unrelated families in two publications, the first of which also demonstrated robust functional work in murine embryos, zebrafish and in vitro assays suggesting aberrant osteoblast-osteocyte transition.
Sources: Literature
Craniosynostosis v0.23 COLEC11 Tiong Tan Marked gene: COLEC11 as ready
Craniosynostosis v0.23 COLEC11 Tiong Tan Gene: colec11 has been classified as Green List (High Evidence).
Craniosynostosis v0.23 COLEC11 Tiong Tan Classified gene: COLEC11 as Green List (high evidence)
Craniosynostosis v0.23 COLEC11 Tiong Tan Gene: colec11 has been classified as Green List (High Evidence).
Craniosynostosis v0.22 COLEC11 Tiong Tan gene: COLEC11 was added
gene: COLEC11 was added to Craniosynostosis. Sources: Literature
Mode of inheritance for gene: COLEC11 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COLEC11 were set to 21258343
Phenotypes for gene: COLEC11 were set to 265050 3MC SYNDROME 2
Penetrance for gene: COLEC11 were set to Complete
Review for gene: COLEC11 was set to GREEN
Added comment: Craniosynostosis occurs in 20-30% of individuals with 3MC syndrome
Sources: Literature
Craniosynostosis v0.21 CHST3 Tiong Tan edited their review of gene: CHST3: Changed rating: RED
Craniosynostosis v0.21 CHST3 Tiong Tan Classified gene: CHST3 as Red List (low evidence)
Craniosynostosis v0.21 CHST3 Tiong Tan Gene: chst3 has been classified as Red List (Low Evidence).
Craniosynostosis v0.20 CHST3 Tiong Tan Marked gene: CHST3 as ready
Craniosynostosis v0.20 CHST3 Tiong Tan Gene: chst3 has been classified as Red List (Low Evidence).
Craniosynostosis v0.20 CHST3 Tiong Tan gene: CHST3 was added
gene: CHST3 was added to Craniosynostosis. Sources: Literature
Mode of inheritance for gene: CHST3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CHST3 were set to 24300290
Phenotypes for gene: CHST3 were set to 143095 SPONDYLOEPIPHYSEAL DYSPLASIA WITH CONGENITAL JOINT DISLOCATIONS
Penetrance for gene: CHST3 were set to Complete
Review for gene: CHST3 was set to AMBER
Added comment: Single case report of craniosynostosis in single individual with SEDCJD
Sources: Literature
Catecholaminergic Polymorphic Ventricular Tachycardia v0.17 TECRL Ivan Macciocca gene: TECRL was added
gene: TECRL was added to Catecholaminergic Polymorphic Ventricular Tachycardia. Sources: Literature
Mode of inheritance for gene: TECRL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TECRL were set to 17666061; 27861123; 30790670
Phenotypes for gene: TECRL were set to CPVT
Penetrance for gene: TECRL were set to Complete
Review for gene: TECRL was set to GREEN
Added comment: As at 03/06/2020, not assessed by ClinGen for association with CPVT; and is associated with CPVT3 in OMIM. Amber on GEL PanelApp
Homozygous or cpd heterozygous pathogenic variants in TECRL have been identified in patients with CPVT in at least 3 families in the literature with functional evidence.
- 17666061 one consanguineous family with 4 affected relatives (siblings or 1stcousins)
- 27861123 consanguineous family with 8 affected relatives (siblings or 1stcousins)
- 30790670 reported in a single family with one child with features of CPVT
This gene meets criteria for green.
Sources: Literature
Craniosynostosis v0.19 B3GAT3 Tiong Tan Classified gene: B3GAT3 as Green List (high evidence)
Craniosynostosis v0.19 B3GAT3 Tiong Tan Gene: b3gat3 has been classified as Green List (High Evidence).
Craniosynostosis v0.18 B3GAT3 Tiong Tan Marked gene: B3GAT3 as ready
Craniosynostosis v0.18 B3GAT3 Tiong Tan Gene: b3gat3 has been classified as Red List (Low Evidence).
Craniosynostosis v0.18 B3GAT3 Tiong Tan gene: B3GAT3 was added
gene: B3GAT3 was added to Craniosynostosis. Sources: Literature
Mode of inheritance for gene: B3GAT3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: B3GAT3 were set to 31438591
Phenotypes for gene: B3GAT3 were set to 245600 MULTIPLE JOINT DISLOCATIONS, SHORT STATURE, AND CRANIOFACIAL DYSMORPHISM WITH OR WITHOUT CONGENITAL HEART DEFECTS
Penetrance for gene: B3GAT3 were set to Complete
Review for gene: B3GAT3 was set to GREEN
Added comment: Craniosynostosis is a feature of B3GAT3-related joint dislocations. Reported in multiple unrelated individuals and summarised in PMID 31438591 (2019)
Sources: Literature
Craniosynostosis v0.17 ALPL Tiong Tan Classified gene: ALPL as Green List (high evidence)
Craniosynostosis v0.17 ALPL Tiong Tan Added comment: Comment on list classification: Known manifestation of hypophosphatasia. Can precede other features
Craniosynostosis v0.17 ALPL Tiong Tan Gene: alpl has been classified as Green List (High Evidence).
Craniosynostosis v0.17 ALPL Tiong Tan Classified gene: ALPL as Red List (low evidence)
Craniosynostosis v0.17 ALPL Tiong Tan Added comment: Comment on list classification: Known manifestation of hypophosphatasia. Can precede other features
Craniosynostosis v0.17 ALPL Tiong Tan Gene: alpl has been classified as Red List (Low Evidence).
Craniosynostosis v0.16 ALPL Tiong Tan Classified gene: ALPL as Green List (high evidence)
Craniosynostosis v0.16 ALPL Tiong Tan Added comment: Comment on list classification: Known manifestation of hypophosphatasia; can precede other features
Craniosynostosis v0.16 ALPL Tiong Tan Gene: alpl has been classified as Green List (High Evidence).
Craniosynostosis v0.15 ALPL Tiong Tan Marked gene: ALPL as ready
Craniosynostosis v0.15 ALPL Tiong Tan Gene: alpl has been classified as Red List (Low Evidence).
Craniosynostosis v0.15 ALPL Tiong Tan gene: ALPL was added
gene: ALPL was added to Craniosynostosis. Sources: Literature
Mode of inheritance for gene: ALPL was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: ALPL were set to 29405940; 26590809; 30979546; 31754721
Phenotypes for gene: ALPL were set to 241500 HYPOPHOSPHATASIA, INFANTILE
Penetrance for gene: ALPL were set to unknown
Review for gene: ALPL was set to GREEN
Added comment: Sources: Literature
Catecholaminergic Polymorphic Ventricular Tachycardia v0.17 TRDN Ivan Macciocca reviewed gene: TRDN: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 30649896, 25922419, 22422768; Phenotypes: triadin knockout syndrome, LQTS, CPVT; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.55 ZC4H2 Zornitza Stark Marked gene: ZC4H2 as ready
Arthrogryposis v0.55 ZC4H2 Zornitza Stark Gene: zc4h2 has been classified as Green List (High Evidence).
Arthrogryposis v0.55 ZC4H2 Zornitza Stark Phenotypes for gene: ZC4H2 were changed from to Wieacker-Wolff syndrome (MIM#314580)
Arthrogryposis v0.54 ZC4H2 Zornitza Stark Publications for gene: ZC4H2 were set to
Arthrogryposis v0.53 ZC4H2 Zornitza Stark Mode of inheritance for gene: ZC4H2 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Catecholaminergic Polymorphic Ventricular Tachycardia v0.17 CASQ2 Zornitza Stark Marked gene: CASQ2 as ready
Catecholaminergic Polymorphic Ventricular Tachycardia v0.17 CASQ2 Zornitza Stark Gene: casq2 has been classified as Green List (High Evidence).
Catecholaminergic Polymorphic Ventricular Tachycardia v0.17 CASQ2 Zornitza Stark Phenotypes for gene: CASQ2 were changed from to Ventricular tachycardia, catecholaminergic polymorphic, 2, MIM# 611938
Catecholaminergic Polymorphic Ventricular Tachycardia v0.16 CASQ2 Zornitza Stark Publications for gene: CASQ2 were set to
Catecholaminergic Polymorphic Ventricular Tachycardia v0.15 CASQ2 Zornitza Stark Mode of inheritance for gene: CASQ2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Catecholaminergic Polymorphic Ventricular Tachycardia v0.14 KCNJ2 Zornitza Stark Marked gene: KCNJ2 as ready
Catecholaminergic Polymorphic Ventricular Tachycardia v0.14 KCNJ2 Zornitza Stark Gene: kcnj2 has been classified as Amber List (Moderate Evidence).
Catecholaminergic Polymorphic Ventricular Tachycardia v0.14 KCNJ2 Zornitza Stark Phenotypes for gene: KCNJ2 were changed from to Andersen Tawil syndrome, LQTS
Catecholaminergic Polymorphic Ventricular Tachycardia v0.13 KCNJ2 Zornitza Stark Publications for gene: KCNJ2 were set to
Catecholaminergic Polymorphic Ventricular Tachycardia v0.12 KCNJ2 Zornitza Stark Mode of inheritance for gene: KCNJ2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Catecholaminergic Polymorphic Ventricular Tachycardia v0.11 KCNJ2 Zornitza Stark Classified gene: KCNJ2 as Amber List (moderate evidence)
Catecholaminergic Polymorphic Ventricular Tachycardia v0.11 KCNJ2 Zornitza Stark Gene: kcnj2 has been classified as Amber List (Moderate Evidence).
Cholestasis v0.27 VPS33B Zornitza Stark Marked gene: VPS33B as ready
Cholestasis v0.27 VPS33B Zornitza Stark Gene: vps33b has been classified as Green List (High Evidence).
Cholestasis v0.27 VPS33B Zornitza Stark Phenotypes for gene: VPS33B were changed from to Arthrogryposis, renal dysfunction, and cholestasis 1 (MIM#208085)
Cholestasis v0.26 VPS33B Zornitza Stark Publications for gene: VPS33B were set to
Cholestasis v0.25 VPS33B Zornitza Stark Mode of inheritance for gene: VPS33B was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Cholestasis v0.24 VPS33B Zornitza Stark reviewed gene: VPS33B: Rating: GREEN; Mode of pathogenicity: None; Publications: 31240160, 31777725, 24415890, 15052268; Phenotypes: Arthrogryposis, renal dysfunction, and cholestasis 1 (MIM#208085); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.52 VPS33B Zornitza Stark Marked gene: VPS33B as ready
Arthrogryposis v0.52 VPS33B Zornitza Stark Gene: vps33b has been classified as Green List (High Evidence).
Arthrogryposis v0.52 VPS33B Zornitza Stark Phenotypes for gene: VPS33B were changed from to Arthrogryposis, renal dysfunction, and cholestasis 1 (MIM#208085)
Arthrogryposis v0.51 VPS33B Zornitza Stark Publications for gene: VPS33B were set to
Arthrogryposis v0.50 VPS33B Zornitza Stark Mode of inheritance for gene: VPS33B was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Craniosynostosis v0.14 ALX4 Zornitza Stark Marked gene: ALX4 as ready
Craniosynostosis v0.14 ALX4 Zornitza Stark Gene: alx4 has been classified as Green List (High Evidence).
Craniosynostosis v0.14 HUWE1 Bryony Thompson Marked gene: HUWE1 as ready
Craniosynostosis v0.14 HUWE1 Bryony Thompson Gene: huwe1 has been classified as Green List (High Evidence).
Craniosynostosis v0.14 HUWE1 Bryony Thompson Phenotypes for gene: HUWE1 were changed from to Mental retardation, X-linked syndromic, Turner type MIM#309590
Craniosynostosis v0.13 HUWE1 Bryony Thompson Mode of inheritance for gene: HUWE1 was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Craniosynostosis v0.12 HUWE1 Bryony Thompson reviewed gene: HUWE1: Rating: GREEN; Mode of pathogenicity: None; Publications: 29180823; Phenotypes: Mental retardation, X-linked syndromic, Turner type MIM#309590; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Craniosynostosis v0.12 FGF9 Bryony Thompson Marked gene: FGF9 as ready
Craniosynostosis v0.12 FGF9 Bryony Thompson Gene: fgf9 has been classified as Amber List (Moderate Evidence).
Craniosynostosis v0.12 FGF9 Bryony Thompson Phenotypes for gene: FGF9 were changed from to Multiple synostoses syndrome 3 MIM#612961
Craniosynostosis v0.11 FGF9 Bryony Thompson Mode of inheritance for gene: FGF9 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Craniosynostosis v0.10 FGF9 Bryony Thompson Classified gene: FGF9 as Amber List (moderate evidence)
Craniosynostosis v0.10 FGF9 Bryony Thompson Gene: fgf9 has been classified as Amber List (Moderate Evidence).
Craniosynostosis v0.9 FGF9 Bryony Thompson reviewed gene: FGF9: Rating: AMBER; Mode of pathogenicity: None; Publications: 19219044, 28730625; Phenotypes: Multiple synostoses syndrome 3 MIM#612961; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Craniosynostosis v0.9 CDC45 Bryony Thompson Marked gene: CDC45 as ready
Craniosynostosis v0.9 CDC45 Bryony Thompson Gene: cdc45 has been classified as Green List (High Evidence).
Craniosynostosis v0.9 CDC45 Bryony Thompson Phenotypes for gene: CDC45 were changed from to Meier-Gorlin syndrome 7 MIM#617063
Craniosynostosis v0.8 CDC45 Bryony Thompson Publications for gene: CDC45 were set to
Craniosynostosis v0.7 CDC45 Bryony Thompson Mode of inheritance for gene: CDC45 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Craniosynostosis v0.6 CDC45 Bryony Thompson Mode of inheritance for gene: CDC45 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Craniosynostosis v0.6 CDC45 Bryony Thompson Mode of inheritance for gene: CDC45 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Craniosynostosis v0.5 CDC45 Bryony Thompson edited their review of gene: CDC45: Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Craniosynostosis v0.5 CDC45 Bryony Thompson reviewed gene: CDC45: Rating: GREEN; Mode of pathogenicity: None; Publications: 27374770; Phenotypes: Meier-Gorlin syndrome 7 MIM#617063; Mode of inheritance: None
Craniosynostosis v0.5 ALX4 Bryony Thompson Classified gene: ALX4 as Green List (high evidence)
Craniosynostosis v0.5 ALX4 Bryony Thompson Gene: alx4 has been classified as Green List (High Evidence).
Craniosynostosis v0.4 ALX4 Bryony Thompson gene: ALX4 was added
gene: ALX4 was added to Craniosynostosis. Sources: Expert list
Mode of inheritance for gene: ALX4 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: ALX4 were set to 19692347; 29215649; 22829454
Phenotypes for gene: ALX4 were set to Frontonasal dysplasia 2 MIM#613451; Parietal foramina 2 MIM#609597
Review for gene: ALX4 was set to GREEN
Added comment: Craniosynostosis has been reported in 2 cases with monoallelic likely LoF variants and as a feature of a syndromic condition in 2 consanguineous families with homozygous LoF variants. 2 putative gain of function missense variants were identified in 2 probands with non-syndromic craniosynostosis, but were also identified in unaffected parents.
Sources: Expert list
Arthrogryposis v0.49 VPS33B Crystle Lee reviewed gene: VPS33B: Rating: GREEN; Mode of pathogenicity: None; Publications: 31240160, 31777725, 24415890, 15052268; Phenotypes: Arthrogryposis, renal dysfunction, and cholestasis 1 (MIM#208085); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Catecholaminergic Polymorphic Ventricular Tachycardia v0.10 KCNJ2 Ivan Macciocca reviewed gene: KCNJ2: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 31020160, 22589293, 26322597; Phenotypes: Andersen Tawil syndrome, LQTS; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Catecholaminergic Polymorphic Ventricular Tachycardia v0.10 CASQ2 Ivan Macciocca changed review comment from: not curated by ClinGen as at 03/05/2020
Green in PanelApp GEL

Homozygous or compound heterozygous variants have been reported in at least 3 families. Heterozygotes are typically not affected. Functional studies on the variants identified in these families support a deleterious effect. Variants reported in the orgiginal gene discovery papers are either no present, or present at very low frequency (2 or less) in GnomAD/Exac.; to: not curated by ClinGen as at 03/05/2020
Green in PanelApp GEL

Homozygous or compound heterozygous variants have been reported in at least 3 families. Heterozygotes are typically not affected, although there is at least 1 report of a multi-generation family with affected heterozygotes (PMID: 27157848) - this variant is absent from Gnomad as at 03/06/2020). Functional studies on the variants identified in these families support a deleterious effect. Variants reported in the original gene discovery papers are either no present, or present at very low frequency (2 or less) in GnomAD/Exac.
Catecholaminergic Polymorphic Ventricular Tachycardia v0.10 CASQ2 Ivan Macciocca changed review comment from: not curated by ClinGen as at 03/05/2020
Green in PanelApp GEL

Homozygous or compound heterozygous variants have been reported in at least 3 families. Heterozygotes are typically not affected. Functional studies on the variants identified in these families support a deleterious effect.; to: not curated by ClinGen as at 03/05/2020
Green in PanelApp GEL

Homozygous or compound heterozygous variants have been reported in at least 3 families. Heterozygotes are typically not affected. Functional studies on the variants identified in these families support a deleterious effect. Variants reported in the orgiginal gene discovery papers are either no present, or present at very low frequency (2 or less) in GnomAD/Exac.
Arthrogryposis v0.49 ZC4H2 Crystle Lee reviewed gene: ZC4H2: Rating: GREEN; Mode of pathogenicity: None; Publications: 23623388, 31885220; Phenotypes: Wieacker-Wolff syndrome (MIM#314580); Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Catecholaminergic Polymorphic Ventricular Tachycardia v0.10 CASQ2 Ivan Macciocca reviewed gene: CASQ2: Rating: GREEN; Mode of pathogenicity: None; Publications: OMID: 611938, 611938; Phenotypes: CPVT; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Catecholaminergic Polymorphic Ventricular Tachycardia v0.10 CALM2 Ivan Macciocca edited their review of gene: CALM2: Changed publications: PMID: 31170290; Changed phenotypes: LQTS, sudden unexplained death, idopathic VF
Catecholaminergic Polymorphic Ventricular Tachycardia v0.10 CALM2 Ivan Macciocca changed review comment from: Not assessed by ClinGen as at 03.05.2020.
Green in PanelApp GEL

Pathogenic and likely pathogenic CALM 1, 2 and 3 variants have been asscoiated with CPVT, LQTS and Idopathic VF (incldundg sudden unexplained death) in a review paper formt he CALM registry (PMID: 31170290). For CPVT at least:
- 7 families have been reported with one of 2 CALM1 P/LP variants, both variants caused overlapping phenotype of LQTS, CPVT and/or SUD
- 8 families have been reported with one of 4 CALM2 P/LP variants, 3 of which caused overlapping phenotype of LQTS, CPVT and/or SUD
- 2 families have been reported with one of 2 CALM3 P/LP variants, both of which caused CPVT exclusively.

Calmodulin is an essential calcium-sensing, signal-transducing protein. Three calmodulin genes, CALM1, CALM2 and CALM3, have unique nucleotide sequences but encode identical 149-amino acid calmodulin proteins with 4 EF-hand calcium-binding loops. (OMIM: https://omim.org/entry/114180?search=CALM1&highlight=calm1#7, accessed 03.05.2020); to: Not assessed by ClinGen as at 03.05.2020.
Green in PanelApp GEL

Pathogenic and likely pathogenic CALM 1, 2 and 3 variants have been asscoiated with CPVT, LQTS and Idopathic VF (incldundg sudden unexplained death) in a review paper formt he CALM registry (PMID: 31170290). For CPVT at least:
- 7 families have been reported with one of 2 CALM1 P/LP variants, both variants caused overlapping phenotype of LQTS, CPVT and/or SUD
- 8 families have been reported with one of 4 CALM2 P/LP variants, 3 of which caused overlapping phenotype of LQTS, CPVT and/or SUD
- 2 families have been reported with one of 2 CALM3 P/LP variants, both of which caused CPVT exclusively.

Calmodulin is an essential calcium-sensing, signal-transducing protein. Three calmodulin genes, CALM1, CALM2 and CALM3, have unique nucleotide sequences but encode identical 149-amino acid calmodulin proteins with 4 EF-hand calcium-binding loops. (OMIM: https://omim.org/entry/114180?search=CALM1&highlight=calm1#7, accessed 03.05.2020)
Catecholaminergic Polymorphic Ventricular Tachycardia v0.10 CALM3 Ivan Macciocca reviewed gene: CALM3: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 31170290; Phenotypes: LQTS, idiopathic VF, sudden unexplained death; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Catecholaminergic Polymorphic Ventricular Tachycardia v0.10 CALM2 Ivan Macciocca commented on gene: CALM2
Catecholaminergic Polymorphic Ventricular Tachycardia v0.10 CALM1 Ivan Macciocca reviewed gene: CALM1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31170290; Phenotypes: CPVT, LQTS, idiopathic VF; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Ciliary Dyskinesia v0.113 HYDIN Crystle Lee reviewed gene: HYDIN: Rating: GREEN; Mode of pathogenicity: None; Publications: 23022101, 23849777, 28441829, 31116566; Phenotypes: Ciliary dyskinesia, primary, 5 (MIM#608647); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Heterotaxy v0.103 HYDIN Crystle Lee reviewed gene: HYDIN: Rating: RED; Mode of pathogenicity: None; Publications: 23022101, 23849777; Phenotypes: Ciliary dyskinesia, primary, 5 (MIM#08647); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disease v0.448 MT-CO3 Chern Lim gene: MT-CO3 was added
gene: MT-CO3 was added to Mitochondrial disease. Sources: Literature
Mode of inheritance for gene gene: MT-CO3 was set to MITOCHONDRIAL
Publications for gene: MT-CO3 were set to 20525945; 9634511; 11063732; 12414820
Phenotypes for gene: MT-CO3 were set to Leigh syndrome; Leigh-like syndrome; Myopathy; Encephalopathy and myopathy
Review for gene: MT-CO3 was set to GREEN
gene: MT-CO3 was marked as current diagnostic
Added comment: Reported in at least 3 unrelated families (PMIDs: 20525945, 9634511, 11063732, 12414820).
Sources: Literature
Heterotaxy v0.103 LRRC56 Elena Savva gene: LRRC56 was added
gene: LRRC56 was added to Heterotaxy. Sources: Expert list
Mode of inheritance for gene: LRRC56 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LRRC56 were set to PMID: 30388400
Phenotypes for gene: LRRC56 were set to Ciliary dyskinesia, primary, 39 618254
Review for gene: LRRC56 was set to GREEN
Added comment: PMID: 30388400 - 3 unrelated families reported with either homozygous splice, missense or chet (nonsense/splice). All patients had dextrocardia, atrial situs inversus and abdominal/thoracic situs inversus
Sources: Expert list
Heterotaxy v0.103 LZTFL1 Crystle Lee gene: LZTFL1 was added
gene: LZTFL1 was added to Heterotaxy. Sources: Expert Review
Mode of inheritance for gene: LZTFL1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LZTFL1 were set to 22510444; 23692385; 27312011; 22072986
Phenotypes for gene: LZTFL1 were set to Bardet-Biedl syndrome 17 (MIM#615994)
Review for gene: LZTFL1 was set to AMBER
Added comment: Only 1 family of the 2 currently reported presented with situs invertus

PMID: 22510444; Marion 2012: Hom variant reported in BBS family, presenting with situs invertus. Supporting functional studies performed. Variant not present in gnomad

PMID: 23692385; Schaefer 2014: Compound heterozygous variants reported in twins with BBS, with supporting functional studies. Situs invertus not reported. Variants not in gnomAD at unexpected frquencies.

PMID: 27312011; Jiang 2016: Knockout mice model showed retinal defects and differences in weight compared to wild-type mice.

PMID: 22072986; Seo 2011: LZTFL1 interacts with BBS protein complex and is an important regulator of BBSome ciliary trafficking
Sources: Expert Review
Bardet Biedl syndrome v0.28 LZTFL1 Crystle Lee reviewed gene: LZTFL1: Rating: GREEN; Mode of pathogenicity: None; Publications: 22510444, 23692385, 27312011, 22072986; Phenotypes: Bardet-Biedl syndrome 17 (MIM#615994); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Vascular Malformations_Germline v0.94 PTPN14 Zornitza Stark Publications for gene: PTPN14 were set to
Vascular Malformations_Germline v0.93 PTPN11 Zornitza Stark Marked gene: PTPN11 as ready
Vascular Malformations_Germline v0.93 PTPN11 Zornitza Stark Added comment: Comment when marking as ready: No evidence for association between germline variants and vascular malformations.
Vascular Malformations_Germline v0.93 PTPN11 Zornitza Stark Gene: ptpn11 has been classified as Red List (Low Evidence).
Vascular Malformations_Germline v0.93 PIK3R2 Zornitza Stark Marked gene: PIK3R2 as ready
Vascular Malformations_Germline v0.93 PIK3R2 Zornitza Stark Gene: pik3r2 has been classified as Red List (Low Evidence).
Vascular Malformations_Germline v0.93 PIK3R1 Zornitza Stark Marked gene: PIK3R1 as ready
Vascular Malformations_Germline v0.93 PIK3R1 Zornitza Stark Gene: pik3r1 has been classified as Red List (Low Evidence).
Vascular Malformations_Germline v0.93 NRAS Zornitza Stark Marked gene: NRAS as ready
Vascular Malformations_Germline v0.93 NRAS Zornitza Stark Gene: nras has been classified as Red List (Low Evidence).
Vascular Malformations_Germline v0.93 MTOR Zornitza Stark Marked gene: MTOR as ready
Vascular Malformations_Germline v0.93 MTOR Zornitza Stark Gene: mtor has been classified as Red List (Low Evidence).
Vascular Malformations_Germline v0.93 MAP3K3 Zornitza Stark Marked gene: MAP3K3 as ready
Vascular Malformations_Germline v0.93 MAP3K3 Zornitza Stark Gene: map3k3 has been classified as Red List (Low Evidence).
Vascular Malformations_Germline v0.93 MAP2K1 Zornitza Stark Marked gene: MAP2K1 as ready
Vascular Malformations_Germline v0.93 MAP2K1 Zornitza Stark Gene: map2k1 has been classified as Red List (Low Evidence).
Vascular Malformations_Germline v0.93 KRAS Zornitza Stark Marked gene: KRAS as ready
Vascular Malformations_Germline v0.93 KRAS Zornitza Stark Gene: kras has been classified as Red List (Low Evidence).
Vascular Malformations_Germline v0.93 HRAS Zornitza Stark Marked gene: HRAS as ready
Vascular Malformations_Germline v0.93 HRAS Zornitza Stark Gene: hras has been classified as Red List (Low Evidence).
Vascular Malformations_Germline v0.93 GNAQ Zornitza Stark Marked gene: GNAQ as ready
Vascular Malformations_Germline v0.93 GNAQ Zornitza Stark Gene: gnaq has been classified as Red List (Low Evidence).
Vascular Malformations_Germline v0.93 GNA14 Zornitza Stark Marked gene: GNA14 as ready
Vascular Malformations_Germline v0.93 GNA14 Zornitza Stark Gene: gna14 has been classified as Red List (Low Evidence).
Vascular Malformations_Germline v0.93 GNA11 Zornitza Stark Marked gene: GNA11 as ready
Vascular Malformations_Germline v0.93 GNA11 Zornitza Stark Gene: gna11 has been classified as Red List (Low Evidence).
Vascular Malformations_Germline v0.93 GNA11 Zornitza Stark Mode of pathogenicity for gene: GNA11 was changed from to Other
Vascular Malformations_Germline v0.92 GNA11 Zornitza Stark Mode of inheritance for gene: GNA11 was changed from to Other
Vascular Malformations_Germline v0.91 BRAF Zornitza Stark Marked gene: BRAF as ready
Vascular Malformations_Germline v0.91 BRAF Zornitza Stark Gene: braf has been classified as Red List (Low Evidence).
Vascular Malformations_Germline v0.91 AKT1 Zornitza Stark Marked gene: AKT1 as ready
Vascular Malformations_Germline v0.91 AKT1 Zornitza Stark Gene: akt1 has been classified as Red List (Low Evidence).
Vascular Malformations_Germline v0.91 KDR Zornitza Stark Marked gene: KDR as ready
Vascular Malformations_Germline v0.91 KDR Zornitza Stark Gene: kdr has been classified as Amber List (Moderate Evidence).
Vascular Malformations_Germline v0.91 ELMO2 Zornitza Stark Marked gene: ELMO2 as ready
Vascular Malformations_Germline v0.91 ELMO2 Zornitza Stark Gene: elmo2 has been classified as Green List (High Evidence).
Vascular Malformations_Germline v0.91 ELMO2 Zornitza Stark Publications for gene: ELMO2 were set to
Vascular Malformations_Germline v0.89 SOS1 Zornitza Stark Marked gene: SOS1 as ready
Vascular Malformations_Germline v0.89 SOS1 Zornitza Stark Added comment: Comment when marking as ready: Somatic variants in Rasopathy genes have been associated with vascular malformations.
Vascular Malformations_Germline v0.89 SOS1 Zornitza Stark Gene: sos1 has been classified as Red List (Low Evidence).
Vascular Malformations_Germline v0.89 SOS1 Zornitza Stark Tag somatic tag was added to gene: SOS1.
Mendeliome v0.2996 DNAL1 Zornitza Stark Marked gene: DNAL1 as ready
Mendeliome v0.2996 DNAL1 Zornitza Stark Gene: dnal1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2996 DNAL1 Zornitza Stark Phenotypes for gene: DNAL1 were changed from to Ciliary dyskinesia, primary, 16, MIM# 614017
Mendeliome v0.2995 DNAL1 Zornitza Stark Publications for gene: DNAL1 were set to
Mendeliome v0.2994 DNAL1 Zornitza Stark Mode of inheritance for gene: DNAL1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2993 DNAL1 Zornitza Stark Classified gene: DNAL1 as Amber List (moderate evidence)
Mendeliome v0.2993 DNAL1 Zornitza Stark Gene: dnal1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2992 DNAL1 Zornitza Stark Tag founder tag was added to gene: DNAL1.
Mendeliome v0.2992 DNAL1 Zornitza Stark reviewed gene: DNAL1: Rating: AMBER; Mode of pathogenicity: None; Publications: 21496787; Phenotypes: Ciliary dyskinesia, primary, 16, MIM# 614017; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ciliary Dyskinesia v0.113 DNAL1 Zornitza Stark Tag founder tag was added to gene: DNAL1.
Heterotaxy v0.103 DNAL1 Zornitza Stark Marked gene: DNAL1 as ready
Heterotaxy v0.103 DNAL1 Zornitza Stark Gene: dnal1 has been classified as Amber List (Moderate Evidence).
Heterotaxy v0.103 DNAL1 Zornitza Stark Phenotypes for gene: DNAL1 were changed from to Ciliary dyskinesia, primary, 16, MIM# 614017
Heterotaxy v0.102 DNAL1 Zornitza Stark Publications for gene: DNAL1 were set to
Heterotaxy v0.101 DNAL1 Zornitza Stark Mode of inheritance for gene: DNAL1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Heterotaxy v0.100 DNAL1 Zornitza Stark Tag founder tag was added to gene: DNAL1.
Heterotaxy v0.100 DNAL1 Zornitza Stark Classified gene: DNAL1 as Amber List (moderate evidence)
Heterotaxy v0.100 DNAL1 Zornitza Stark Gene: dnal1 has been classified as Amber List (Moderate Evidence).
Ciliary Dyskinesia v0.113 DNAL1 Zornitza Stark changed review comment from: Single family reported with homozygous missense variant, some functional data.; to: Two Bedouin families reported with same homozygous missense variant (founder), some functional data.
Heterotaxy v0.99 DNAL1 Zornitza Stark reviewed gene: DNAL1: Rating: AMBER; Mode of pathogenicity: None; Publications: 21496787; Phenotypes: Ciliary dyskinesia, primary, 16, MIM# 614017; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ciliary Dyskinesia v0.113 DNAL1 Zornitza Stark Marked gene: DNAL1 as ready
Ciliary Dyskinesia v0.113 DNAL1 Zornitza Stark Gene: dnal1 has been classified as Amber List (Moderate Evidence).
Ciliary Dyskinesia v0.113 DNAL1 Zornitza Stark Phenotypes for gene: DNAL1 were changed from to Ciliary dyskinesia, primary, 16, MIM# 614017
Ciliary Dyskinesia v0.112 DNAL1 Zornitza Stark Publications for gene: DNAL1 were set to
Ciliary Dyskinesia v0.111 DNAL1 Zornitza Stark Mode of inheritance for gene: DNAL1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Ciliary Dyskinesia v0.110 DNAL1 Zornitza Stark Classified gene: DNAL1 as Amber List (moderate evidence)
Ciliary Dyskinesia v0.110 DNAL1 Zornitza Stark Gene: dnal1 has been classified as Amber List (Moderate Evidence).
Ciliary Dyskinesia v0.109 DNAL1 Zornitza Stark reviewed gene: DNAL1: Rating: AMBER; Mode of pathogenicity: None; Publications: 21496787; Phenotypes: Ciliary dyskinesia, primary, 16, MIM# 614017; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2992 DNAH8 Zornitza Stark Marked gene: DNAH8 as ready
Mendeliome v0.2992 DNAH8 Zornitza Stark Gene: dnah8 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2992 DNAH8 Zornitza Stark Phenotypes for gene: DNAH8 were changed from to Asthenozoospermia; primary ciliary dyskinesia
Mendeliome v0.2991 DNAH8 Zornitza Stark Publications for gene: DNAH8 were set to
Mendeliome v0.2990 DNAH8 Zornitza Stark Mode of inheritance for gene: DNAH8 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2989 DNAH8 Zornitza Stark Classified gene: DNAH8 as Amber List (moderate evidence)
Mendeliome v0.2989 DNAH8 Zornitza Stark Gene: dnah8 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2988 DNAH8 Zornitza Stark reviewed gene: DNAH8: Rating: AMBER; Mode of pathogenicity: None; Publications: 31178125, 24307375; Phenotypes: Asthenozoospermia, primary ciliary dyskinesia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Heterotaxy v0.99 GAS8 Zornitza Stark changed review comment from: Heterotaxy is not part of the phenotype of this PCD.; to: Heterotaxy is not part of the phenotype of this PCD in the individuals reported, though note zebrafish model had LR axis abnormalities.
Heterotaxy v0.99 GAS8 Zornitza Stark edited their review of gene: GAS8: Changed publications: 19043402, 26387594
Heterotaxy v0.99 GAS8 Zornitza Stark Marked gene: GAS8 as ready
Heterotaxy v0.99 GAS8 Zornitza Stark Gene: gas8 has been classified as Red List (Low Evidence).
Heterotaxy v0.99 GAS8 Zornitza Stark Phenotypes for gene: GAS8 were changed from to Ciliary dyskinesia, primary, 33, MIM# 616726
Heterotaxy v0.98 GAS8 Zornitza Stark Mode of inheritance for gene: GAS8 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Heterotaxy v0.97 GAS8 Zornitza Stark Classified gene: GAS8 as Red List (low evidence)
Heterotaxy v0.97 GAS8 Zornitza Stark Gene: gas8 has been classified as Red List (Low Evidence).
Heterotaxy v0.96 GAS8 Zornitza Stark reviewed gene: GAS8: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Ciliary dyskinesia, primary, 33, MIM# 616726; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2988 TTC5 Zornitza Stark Marked gene: TTC5 as ready
Mendeliome v0.2988 TTC5 Zornitza Stark Gene: ttc5 has been classified as Green List (High Evidence).
Mendeliome v0.2988 TTC5 Zornitza Stark Classified gene: TTC5 as Green List (high evidence)
Mendeliome v0.2988 TTC5 Zornitza Stark Gene: ttc5 has been classified as Green List (High Evidence).
Mendeliome v0.2987 TTC5 Zornitza Stark gene: TTC5 was added
gene: TTC5 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TTC5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TTC5 were set to 29302074; 32439809
Phenotypes for gene: TTC5 were set to Central hypotonia; Global developmental delay; Intellectual disability; Abnormality of nervous system morphology; Microcephaly; Abnormality of the face; Behavioral abnormality; Abnormality of the genitourinary system
Review for gene: TTC5 was set to GREEN
Added comment: Eleven individuals from seven families reported.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2660 TTC5 Zornitza Stark Marked gene: TTC5 as ready
Intellectual disability syndromic and non-syndromic v0.2660 TTC5 Zornitza Stark Gene: ttc5 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2660 TTC5 Zornitza Stark Classified gene: TTC5 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2660 TTC5 Zornitza Stark Gene: ttc5 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2659 TTC5 Konstantinos Varvagiannis gene: TTC5 was added
gene: TTC5 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: TTC5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TTC5 were set to 29302074; 32439809
Phenotypes for gene: TTC5 were set to Central hypotonia; Global developmental delay; Intellectual disability; Abnormality of nervous system morphology; Microcephaly; Abnormality of the face; Behavioral abnormality; Abnormality of the genitourinary system
Penetrance for gene: TTC5 were set to Complete
Review for gene: TTC5 was set to GREEN
Added comment: Hu et al (2019 - PMID: 29302074) reported briefly on 3 individuals from 2 consanguineous families (from Turkey and Iran) with biallelic TTC5 variants. Features included DD (3/3), ID (severe in 2/2 with relevant age), microcephaly (3/3), brain abnormalities, etc. A nonsense and a variant affecting splice site were identified by WES/WGS.

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In a recent report, Rasheed et al (2020 - PMID: 32439809) report on the phenotype of 8 individuals - belonging to 5 consanguineous families - all 8 harboring homozygous TTC5 mutations.

Frequent features included hypotonia (6/8), motor and speech delay, moderate to severe ID (10/10 of relevant age - inclusion of less severely affected subjects was not considered by study design), brain MRI abnormalities (8/8). Other findings included microcephaly in some (6/11), behavioral abnormalities in few (autistic behavior in 2/8, aggression in 2/8), genitourinary anomalies (2/8), seizures (1/11). Facial phenotype incl. thin V-shaped upper lip, low-set ears (in most) and/or additional features.

TTC5 encodes a 440 aa protein, functioning as a scaffold to stabilise p300-JMY interactions. Apart from this role in nucleus, it has functions in the cytoplasm (inhibiting actin nucleataion, autophagosome formation, etc).

The gene has ubiquitous expression, highest in brain.

All variants were identified following WES - as the best candidates - in affected individuals with compatible Sanger studies in all affected family members and carrier parents.

2 missense and 2 nonsense variants were identified with the 2 missense SNVs localizing within TPR domains. qRT-PCR studies for a nonsense variant localizing 19 nt before the last exon, revealed fourfold decreased expression in affected individuals compared to carriers.

Families from Egypt shared a homozygous ~6.3 Mb haplotype block spanning TTC5, suggesting that p.(Arg263Ter) is likely a founder mutation.

The authors underscore some phenotypic (though not facial) similarities with Rubinstein-Taybi syndrome 2 due to EP300 mutations (in line with the role of TTC5).

Biallelic variants in genes encoding other members of the TTC family (containing a TPR motif), e.g. TTC8 or TTC15 cause disorders with neurologic manifestations (and DD/ID).
Sources: Literature
Vascular Malformations_Germline v0.89 CDKN1C Zornitza Stark Marked gene: CDKN1C as ready
Vascular Malformations_Germline v0.89 CDKN1C Zornitza Stark Gene: cdkn1c has been classified as Amber List (Moderate Evidence).
Vascular Malformations_Germline v0.89 CDKN1C Zornitza Stark Phenotypes for gene: CDKN1C were changed from Beckwith-Wiedemann syndrome 130650; IMAGE syndrome 614732 to Beckwith-Wiedemann syndrome 130650
Vascular Malformations_Germline v0.88 CDKN1C Zornitza Stark Classified gene: CDKN1C as Amber List (moderate evidence)
Vascular Malformations_Germline v0.88 CDKN1C Zornitza Stark Gene: cdkn1c has been classified as Amber List (Moderate Evidence).
Vascular Malformations_Germline v0.87 CDKN1C Zornitza Stark reviewed gene: CDKN1C: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Beckwith-Wiedemann syndrome, MIM# 130650; Mode of inheritance: None
Vascular Malformations_Germline v0.85 SOS1 Zornitza Stark Marked gene: SOS1 as ready
Vascular Malformations_Germline v0.85 SOS1 Zornitza Stark Gene: sos1 has been classified as Red List (Low Evidence).
Vascular Malformations_Germline v0.84 Zornitza Stark Panel types changed to Victorian Clinical Genetics Services; Royal Melbourne Hospital; Rare Disease
Mendeliome v0.2986 ACAD11 Zornitza Stark Marked gene: ACAD11 as ready
Mendeliome v0.2986 ACAD11 Zornitza Stark Gene: acad11 has been classified as Red List (Low Evidence).
Mendeliome v0.2986 ACAD11 Zornitza Stark Classified gene: ACAD11 as Red List (low evidence)
Mendeliome v0.2986 ACAD11 Zornitza Stark Gene: acad11 has been classified as Red List (Low Evidence).
Mendeliome v0.2985 ACAD11 Zornitza Stark reviewed gene: ACAD11: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Heterotaxy v0.96 Zornitza Stark Panel types changed to Victorian Clinical Genetics Services; Rare Disease
Long QT Syndrome v0.57 KCNE1 Zornitza Stark Phenotypes for gene: KCNE1 were changed from long QT syndrome; acquired LQTS to Jervell and Lange-Nielsen syndrome 2, MIM# 612347; Long QT syndrome 5, MIM# 613695; Acquired LQTS
Long QT Syndrome v0.56 KCNE1 Zornitza Stark Marked gene: KCNE1 as ready
Long QT Syndrome v0.56 KCNE1 Zornitza Stark Added comment: Comment when marking as ready: Rated as MODERATE by ClinGen for bi-allelic disease. Evidence for mono-allelic disease is limited.
Long QT Syndrome v0.56 KCNE1 Zornitza Stark Gene: kcne1 has been classified as Amber List (Moderate Evidence).
Long QT Syndrome v0.56 SNTA1 Zornitza Stark Marked gene: SNTA1 as ready
Long QT Syndrome v0.56 SNTA1 Zornitza Stark Gene: snta1 has been classified as Red List (Low Evidence).
Long QT Syndrome v0.56 SNTA1 Zornitza Stark Phenotypes for gene: SNTA1 were changed from to Long QT syndrome 12, MIM# 612955
Long QT Syndrome v0.55 SNTA1 Zornitza Stark Publications for gene: SNTA1 were set to
Long QT Syndrome v0.54 SNTA1 Zornitza Stark Mode of inheritance for gene: SNTA1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Long QT Syndrome v0.53 SNTA1 Zornitza Stark Classified gene: SNTA1 as Red List (low evidence)
Long QT Syndrome v0.53 SNTA1 Zornitza Stark Gene: snta1 has been classified as Red List (Low Evidence).
Long QT Syndrome v0.52 SNTA1 Zornitza Stark Tag disputed tag was added to gene: SNTA1.
Long QT Syndrome v0.52 TRDN Zornitza Stark Marked gene: TRDN as ready
Long QT Syndrome v0.52 TRDN Zornitza Stark Gene: trdn has been classified as Green List (High Evidence).
Long QT Syndrome v0.52 TRDN Zornitza Stark Publications for gene: TRDN were set to long QT syndrome
Long QT Syndrome v0.51 TRDN Zornitza Stark Phenotypes for gene: TRDN were changed from PMID: 31983240; 25922419 to Long QT syndrome; Ventricular tachycardia, catecholaminergic polymorphic, 5, with or without muscle weakness, MIM# 615441
Long QT Syndrome v0.50 TRDN Zornitza Stark Classified gene: TRDN as Green List (high evidence)
Long QT Syndrome v0.50 TRDN Zornitza Stark Gene: trdn has been classified as Green List (High Evidence).
Long QT Syndrome v0.49 CALM2 Zornitza Stark Marked gene: CALM2 as ready
Long QT Syndrome v0.49 CALM2 Zornitza Stark Gene: calm2 has been classified as Green List (High Evidence).
Long QT Syndrome v0.49 CALM2 Zornitza Stark Phenotypes for gene: CALM2 were changed from long QT syndrome to Long QT syndrome 15, MIM# 616249
Long QT Syndrome v0.48 CALM2 Zornitza Stark Classified gene: CALM2 as Green List (high evidence)
Long QT Syndrome v0.48 CALM2 Zornitza Stark Gene: calm2 has been classified as Green List (High Evidence).
Long QT Syndrome v0.46 CALM1 Zornitza Stark Marked gene: CALM1 as ready
Long QT Syndrome v0.46 CALM1 Zornitza Stark Gene: calm1 has been classified as Green List (High Evidence).
Long QT Syndrome v0.46 CALM1 Zornitza Stark Phenotypes for gene: CALM1 were changed from long QT syndrome to Long QT syndrome 14, MIM# 616247
Long QT Syndrome v0.45 CALM1 Zornitza Stark Classified gene: CALM1 as Green List (high evidence)
Long QT Syndrome v0.45 CALM1 Zornitza Stark Gene: calm1 has been classified as Green List (High Evidence).
Long QT Syndrome v0.44 SCN4B Zornitza Stark Marked gene: SCN4B as ready
Long QT Syndrome v0.44 SCN4B Zornitza Stark Gene: scn4b has been classified as Red List (Low Evidence).
Long QT Syndrome v0.44 SCN4B Zornitza Stark Phenotypes for gene: SCN4B were changed from to Long QT syndrome 10, MIM# 611819
Long QT Syndrome v0.43 SCN4B Zornitza Stark Publications for gene: SCN4B were set to
Long QT Syndrome v0.42 SCN4B Zornitza Stark Mode of inheritance for gene: SCN4B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Long QT Syndrome v0.41 SCN4B Zornitza Stark Classified gene: SCN4B as Red List (low evidence)
Long QT Syndrome v0.41 SCN4B Zornitza Stark Gene: scn4b has been classified as Red List (Low Evidence).
Long QT Syndrome v0.40 SCN4B Zornitza Stark Tag disputed tag was added to gene: SCN4B.
Long QT Syndrome v0.40 Zornitza Stark Panel types changed to Victorian Clinical Genetics Services; Rare Disease
Long QT Syndrome v0.39 KCNJ5 Zornitza Stark Marked gene: KCNJ5 as ready
Long QT Syndrome v0.39 KCNJ5 Zornitza Stark Gene: kcnj5 has been classified as Red List (Low Evidence).
Long QT Syndrome v0.39 KCNJ5 Zornitza Stark Phenotypes for gene: KCNJ5 were changed from to Long QT syndrome 13, MIM# 613485
Long QT Syndrome v0.38 KCNJ5 Zornitza Stark Publications for gene: KCNJ5 were set to
Long QT Syndrome v0.37 KCNJ5 Zornitza Stark Mode of inheritance for gene: KCNJ5 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Long QT Syndrome v0.36 KCNJ5 Zornitza Stark Tag disputed tag was added to gene: KCNJ5.
Long QT Syndrome v0.36 KCNJ5 Zornitza Stark Classified gene: KCNJ5 as Red List (low evidence)
Long QT Syndrome v0.36 KCNJ5 Zornitza Stark Gene: kcnj5 has been classified as Red List (Low Evidence).
Heterotaxy v0.95 NPHP4 Zornitza Stark Marked gene: NPHP4 as ready
Heterotaxy v0.95 NPHP4 Zornitza Stark Gene: nphp4 has been classified as Amber List (Moderate Evidence).
Heterotaxy v0.95 NPHP4 Zornitza Stark Mode of inheritance for gene: NPHP4 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Heterotaxy v0.95 NPHP4 Zornitza Stark Mode of inheritance for gene: NPHP4 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Heterotaxy v0.94 NPHP4 Zornitza Stark Classified gene: NPHP4 as Amber List (moderate evidence)
Heterotaxy v0.94 NPHP4 Zornitza Stark Gene: nphp4 has been classified as Amber List (Moderate Evidence).
Congenital Heart Defect v0.45 NKX2-5 Zornitza Stark Marked gene: NKX2-5 as ready
Congenital Heart Defect v0.45 NKX2-5 Zornitza Stark Gene: nkx2-5 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.45 NKX2-5 Zornitza Stark Phenotypes for gene: NKX2-5 were changed from to Ventricular septal defect 3 (MIM#614432); Tetralogy of Fallot (MIM#187500)
Congenital Heart Defect v0.44 NKX2-5 Zornitza Stark Publications for gene: NKX2-5 were set to
Congenital Heart Defect v0.43 NKX2-5 Zornitza Stark Mode of inheritance for gene: NKX2-5 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital Heart Defect v0.43 NKX2-5 Zornitza Stark Mode of inheritance for gene: NKX2-5 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Heterotaxy v0.93 CCNO Zornitza Stark Marked gene: CCNO as ready
Heterotaxy v0.93 CCNO Zornitza Stark Gene: ccno has been classified as Red List (Low Evidence).
Heterotaxy v0.93 CCNO Zornitza Stark Phenotypes for gene: CCNO were changed from to Ciliary dyskinesia, primary, 29, MIM# 615872
Heterotaxy v0.92 CCNO Zornitza Stark Publications for gene: CCNO were set to
Heterotaxy v0.91 CCNO Zornitza Stark Mode of inheritance for gene: CCNO was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Heterotaxy v0.90 CCNO Zornitza Stark Classified gene: CCNO as Red List (low evidence)
Heterotaxy v0.90 CCNO Zornitza Stark Gene: ccno has been classified as Red List (Low Evidence).
Heterotaxy v0.89 CRELD1 Zornitza Stark Classified gene: CRELD1 as Amber List (moderate evidence)
Heterotaxy v0.89 CRELD1 Zornitza Stark Gene: creld1 has been classified as Amber List (Moderate Evidence).
Heterotaxy v0.88 CRELD1 Zornitza Stark changed review comment from: Three families reported with heterozygous missense variants and heterotaxy phenotype.
Sources: Expert list; to: Three families reported with heterozygous missense variants and heterotaxy phenotype. However, supporting evidence of pathogenicity for some of the variants is relatively weak.
Sources: Expert list
Heterotaxy v0.88 CRELD1 Zornitza Stark edited their review of gene: CRELD1: Changed rating: AMBER
Heterotaxy v0.88 DNAAF2 Zornitza Stark Marked gene: DNAAF2 as ready
Heterotaxy v0.88 DNAAF2 Zornitza Stark Gene: dnaaf2 has been classified as Green List (High Evidence).
Heterotaxy v0.88 DNAAF2 Zornitza Stark Phenotypes for gene: DNAAF2 were changed from to Ciliary dyskinesia, primary, 10 612518
Heterotaxy v0.87 DNAAF2 Zornitza Stark Publications for gene: DNAAF2 were set to
Heterotaxy v0.86 DNAAF2 Zornitza Stark Mode of inheritance for gene: DNAAF2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Heterotaxy v0.85 DNAH1 Zornitza Stark Marked gene: DNAH1 as ready
Heterotaxy v0.85 DNAH1 Zornitza Stark Gene: dnah1 has been classified as Red List (Low Evidence).
Heterotaxy v0.85 DNAH1 Zornitza Stark Classified gene: DNAH1 as Red List (low evidence)
Heterotaxy v0.85 DNAH1 Zornitza Stark Gene: dnah1 has been classified as Red List (Low Evidence).
Mendeliome v0.2985 DNAH6 Zornitza Stark Marked gene: DNAH6 as ready
Mendeliome v0.2985 DNAH6 Zornitza Stark Gene: dnah6 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2985 DNAH6 Zornitza Stark Classified gene: DNAH6 as Amber List (moderate evidence)
Mendeliome v0.2985 DNAH6 Zornitza Stark Gene: dnah6 has been classified as Amber List (Moderate Evidence).
Ciliary Dyskinesia v0.109 DNAH9 Zornitza Stark Marked gene: DNAH9 as ready
Ciliary Dyskinesia v0.109 DNAH9 Zornitza Stark Gene: dnah9 has been classified as Green List (High Evidence).
Ciliary Dyskinesia v0.109 DNAH9 Zornitza Stark Phenotypes for gene: DNAH9 were changed from to Ciliary dyskinesia, primary, 40, MIM# 618300
Ciliary Dyskinesia v0.108 DNAH9 Zornitza Stark Publications for gene: DNAH9 were set to
Ciliary Dyskinesia v0.107 DNAH9 Zornitza Stark Mode of inheritance for gene: DNAH9 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Ciliary Dyskinesia v0.106 DNAH9 Zornitza Stark reviewed gene: DNAH9: Rating: GREEN; Mode of pathogenicity: None; Publications: 30471717, 30471718; Phenotypes: Ciliary dyskinesia, primary, 40, MIM# 618300; Mode of inheritance: None
Heterotaxy v0.84 DNAH9 Zornitza Stark Marked gene: DNAH9 as ready
Heterotaxy v0.84 DNAH9 Zornitza Stark Gene: dnah9 has been classified as Green List (High Evidence).
Heterotaxy v0.84 DNAH9 Zornitza Stark Classified gene: DNAH9 as Green List (high evidence)
Heterotaxy v0.84 DNAH9 Zornitza Stark Gene: dnah9 has been classified as Green List (High Evidence).
Mendeliome v0.2984 DRC1 Zornitza Stark Marked gene: DRC1 as ready
Mendeliome v0.2984 DRC1 Zornitza Stark Gene: drc1 has been classified as Green List (High Evidence).
Mendeliome v0.2984 DRC1 Zornitza Stark Phenotypes for gene: DRC1 were changed from to Ciliary dyskinesia, primary, 21, MIM# 615294
Mendeliome v0.2983 DRC1 Zornitza Stark Publications for gene: DRC1 were set to
Mendeliome v0.2982 DRC1 Zornitza Stark Mode of inheritance for gene: DRC1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2981 DRC1 Zornitza Stark Tag SV/CNV tag was added to gene: DRC1.
Mendeliome v0.2981 DRC1 Zornitza Stark edited their review of gene: DRC1: Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2981 DRC1 Zornitza Stark reviewed gene: DRC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 31960620; Phenotypes: Ciliary dyskinesia, primary, 21, MIM# 615294; Mode of inheritance: None
Heterotaxy v0.83 DRC1 Zornitza Stark Marked gene: DRC1 as ready
Heterotaxy v0.83 DRC1 Zornitza Stark Gene: drc1 has been classified as Red List (Low Evidence).
Heterotaxy v0.83 DRC1 Zornitza Stark Phenotypes for gene: DRC1 were changed from to Ciliary dyskinesia, primary, 21, MIM# 615294
Heterotaxy v0.82 DRC1 Zornitza Stark Publications for gene: DRC1 were set to
Heterotaxy v0.81 DRC1 Zornitza Stark Mode of inheritance for gene: DRC1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Heterotaxy v0.80 DRC1 Zornitza Stark Classified gene: DRC1 as Red List (low evidence)
Heterotaxy v0.80 DRC1 Zornitza Stark Gene: drc1 has been classified as Red List (Low Evidence).
Congenital Heart Defect v0.42 TLL1 Zornitza Stark Marked gene: TLL1 as ready
Congenital Heart Defect v0.42 TLL1 Zornitza Stark Gene: tll1 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.42 TLL1 Zornitza Stark Publications for gene: TLL1 were set to
Congenital Heart Defect v0.41 TLL1 Zornitza Stark Mode of inheritance for gene: TLL1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital Heart Defect v0.40 TLL1 Zornitza Stark reviewed gene: TLL1: Rating: GREEN; Mode of pathogenicity: None; Publications: 18830233, 30538173, 27418595, 31570783; Phenotypes: Atrial septal defect; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2981 TLL1 Zornitza Stark Phenotypes for gene: TLL1 were changed from to Atrial septal defect
Mendeliome v0.2980 TLL1 Zornitza Stark Publications for gene: TLL1 were set to
Mendeliome v0.2979 TLL1 Zornitza Stark Mode of inheritance for gene: TLL1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2978 TLL1 Dean Phelan reviewed gene: TLL1: Rating: GREEN; Mode of pathogenicity: None; Publications: 18830233, 30538173, 27418595, 31570783; Phenotypes: Atrial septal defect; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2978 HIST1H4J Zornitza Stark Marked gene: HIST1H4J as ready
Mendeliome v0.2978 HIST1H4J Zornitza Stark Gene: hist1h4j has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2978 HIST1H4J Zornitza Stark Classified gene: HIST1H4J as Amber List (moderate evidence)
Mendeliome v0.2978 HIST1H4J Zornitza Stark Gene: hist1h4j has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2977 HIST1H4J Zornitza Stark gene: HIST1H4J was added
gene: HIST1H4J was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: HIST1H4J was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HIST1H4J were set to 31804630
Phenotypes for gene: HIST1H4J were set to microcephaly; intellectual disability; dysmorphic features
Review for gene: HIST1H4J was set to AMBER
Added comment: Single case report but with functional evidence in zebrafish and phenotypic similarity to other HIST1H4C phenotype
Sources: Literature
Mendeliome v0.2976 MCIDAS Zornitza Stark Marked gene: MCIDAS as ready
Mendeliome v0.2976 MCIDAS Zornitza Stark Gene: mcidas has been classified as Green List (High Evidence).
Mendeliome v0.2976 MCIDAS Zornitza Stark Phenotypes for gene: MCIDAS were changed from to Ciliary dyskinesia, primary, 42 (MIM#618695)
Mendeliome v0.2975 MCIDAS Zornitza Stark Publications for gene: MCIDAS were set to
Mendeliome v0.2974 MCIDAS Zornitza Stark Mode of inheritance for gene: MCIDAS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2973 MCIDAS Zornitza Stark reviewed gene: MCIDAS: Rating: GREEN; Mode of pathogenicity: None; Publications: 25048963; Phenotypes: Ciliary dyskinesia, primary, 42 (MIM#618695); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Heterotaxy v0.79 MCIDAS Zornitza Stark Marked gene: MCIDAS as ready
Heterotaxy v0.79 MCIDAS Zornitza Stark Gene: mcidas has been classified as Red List (Low Evidence).
Heterotaxy v0.79 MCIDAS Zornitza Stark Phenotypes for gene: MCIDAS were changed from to Ciliary dyskinesia, primary, 42 (MIM#618695)
Heterotaxy v0.78 MCIDAS Zornitza Stark Publications for gene: MCIDAS were set to
Heterotaxy v0.77 MCIDAS Zornitza Stark Mode of inheritance for gene: MCIDAS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Heterotaxy v0.76 MCIDAS Zornitza Stark Classified gene: MCIDAS as Red List (low evidence)
Heterotaxy v0.76 MCIDAS Zornitza Stark Gene: mcidas has been classified as Red List (Low Evidence).
Ciliary Dyskinesia v0.106 MCIDAS Zornitza Stark Marked gene: MCIDAS as ready
Ciliary Dyskinesia v0.106 MCIDAS Zornitza Stark Gene: mcidas has been classified as Green List (High Evidence).
Ciliary Dyskinesia v0.106 MCIDAS Zornitza Stark Phenotypes for gene: MCIDAS were changed from to Ciliary dyskinesia, primary, 42 (MIM#618695)
Ciliary Dyskinesia v0.105 MCIDAS Zornitza Stark Publications for gene: MCIDAS were set to
Ciliary Dyskinesia v0.104 MCIDAS Zornitza Stark Mode of inheritance for gene: MCIDAS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2973 VWA3B Zornitza Stark Marked gene: VWA3B as ready
Mendeliome v0.2973 VWA3B Zornitza Stark Gene: vwa3b has been classified as Red List (Low Evidence).
Muscular dystrophy and myopathy_Paediatric v0.13 TOR1AIP1 Zornitza Stark Marked gene: TOR1AIP1 as ready
Muscular dystrophy and myopathy_Paediatric v0.13 TOR1AIP1 Zornitza Stark Gene: tor1aip1 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.13 TOR1AIP1 Zornitza Stark Classified gene: TOR1AIP1 as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v0.13 TOR1AIP1 Zornitza Stark Gene: tor1aip1 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.12 TOR1AIP1 Zornitza Stark gene: TOR1AIP1 was added
gene: TOR1AIP1 was added to Muscular dystrophy. Sources: Literature
Mode of inheritance for gene: TOR1AIP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TOR1AIP1 were set to 24856141; 31299614; 30723199; 27342937; 32055997
Phenotypes for gene: TOR1AIP1 were set to Muscular dystrophy, autosomal recessive, with rigid spine and distal joint contractures MIM#617072; Progeroid appearance; Cataracts; Microcephaly; Deafness; Contractures
Review for gene: TOR1AIP1 was set to GREEN
Added comment: Multiple families reported but highly variable phenotype; muscular dystrophy reported frequently.
Sources: Literature
Arthrogryposis v0.49 TOR1AIP1 Zornitza Stark Marked gene: TOR1AIP1 as ready
Arthrogryposis v0.49 TOR1AIP1 Zornitza Stark Gene: tor1aip1 has been classified as Green List (High Evidence).
Arthrogryposis v0.49 TOR1AIP1 Zornitza Stark Classified gene: TOR1AIP1 as Green List (high evidence)
Arthrogryposis v0.49 TOR1AIP1 Zornitza Stark Gene: tor1aip1 has been classified as Green List (High Evidence).
Arthrogryposis v0.48 TOR1AIP1 Zornitza Stark gene: TOR1AIP1 was added
gene: TOR1AIP1 was added to Arthrogryposis. Sources: Literature
Mode of inheritance for gene: TOR1AIP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TOR1AIP1 were set to 24856141; 31299614; 30723199; 27342937; 32055997
Phenotypes for gene: TOR1AIP1 were set to Muscular dystrophy, autosomal recessive, with rigid spine and distal joint contractures MIM#617072; Progeroid appearance; Cataracts; Microcephaly; Deafness; Contractures
Review for gene: TOR1AIP1 was set to GREEN
Added comment: Multiple families reported but highly variable phenotype; joint contractures observed in multiple individuals.
Sources: Literature
Mendeliome v0.2973 TOR1AIP1 Zornitza Stark Phenotypes for gene: TOR1AIP1 were changed from Muscular dystrophy, autosomal recessive, with rigid spine and distal joint contractures MIM#617072; Progeroid appearance; Cataracts; Microcephaly; Deafness to Muscular dystrophy, autosomal recessive, with rigid spine and distal joint contractures MIM#617072; Progeroid appearance; Cataracts; Microcephaly; Deafness; Contractures
Mendeliome v0.2972 TOR1AIP1 Zornitza Stark Phenotypes for gene: TOR1AIP1 were changed from Muscular dystrophy, autosomal recessive, with rigid spine and distal joint contractures MIM#617072 to Muscular dystrophy, autosomal recessive, with rigid spine and distal joint contractures MIM#617072; Progeroid appearance; Cataracts; Microcephaly; Deafness
Mendeliome v0.2971 TOR1AIP1 Zornitza Stark Marked gene: TOR1AIP1 as ready
Mendeliome v0.2971 TOR1AIP1 Zornitza Stark Added comment: Comment when marking as ready: Highly variable phenotype. Few of the features are consistently reported across affected individuals.
Mendeliome v0.2971 TOR1AIP1 Zornitza Stark Gene: tor1aip1 has been classified as Green List (High Evidence).
Mendeliome v0.2971 TOR1AIP1 Zornitza Stark Publications for gene: TOR1AIP1 were set to 24856141; 31299614; 30723199; 27342937
Leukodystrophy v0.127 CNP Zornitza Stark Marked gene: CNP as ready
Leukodystrophy v0.127 CNP Zornitza Stark Gene: cnp has been classified as Amber List (Moderate Evidence).
Leukodystrophy v0.127 CNP Zornitza Stark Classified gene: CNP as Amber List (moderate evidence)
Leukodystrophy v0.127 CNP Zornitza Stark Gene: cnp has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2970 EFEMP1 Zornitza Stark Marked gene: EFEMP1 as ready
Mendeliome v0.2970 EFEMP1 Zornitza Stark Gene: efemp1 has been classified as Green List (High Evidence).
Mendeliome v0.2970 EFEMP1 Zornitza Stark Phenotypes for gene: EFEMP1 were changed from to Doyne honeycomb degeneration of retina, MIM# 126600; EFEMP1-related connective tissue disorder
Mendeliome v0.2969 EFEMP1 Zornitza Stark Publications for gene: EFEMP1 were set to
Mendeliome v0.2968 EFEMP1 Zornitza Stark Mode of inheritance for gene: EFEMP1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.2967 ZFYVE27 Bryony Thompson Classified gene: ZFYVE27 as Red List (low evidence)
Mendeliome v0.2967 ZFYVE27 Bryony Thompson Gene: zfyve27 has been classified as Red List (Low Evidence).
Mendeliome v0.2966 ZFYVE27 Bryony Thompson reviewed gene: ZFYVE27: Rating: RED; Mode of pathogenicity: None; Publications: 16826525, 29980238, 18606302; Phenotypes: Spastic paraplegia 33, autosomal dominant MIM#610244; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2966 EFEMP1 Zornitza Stark reviewed gene: EFEMP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 32006683, 31792352; Phenotypes: Doyne honeycomb degeneration of retina, MIM# 126600, EFEMP1-related connective tissue disorder; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Aortopathy_Connective Tissue Disorders v0.25 EFEMP1 Zornitza Stark Marked gene: EFEMP1 as ready
Aortopathy_Connective Tissue Disorders v0.25 EFEMP1 Zornitza Stark Gene: efemp1 has been classified as Amber List (Moderate Evidence).
Aortopathy_Connective Tissue Disorders v0.25 EFEMP1 Zornitza Stark Classified gene: EFEMP1 as Amber List (moderate evidence)
Aortopathy_Connective Tissue Disorders v0.25 EFEMP1 Zornitza Stark Gene: efemp1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2966 TOR1AIP1 Kristin Rigbye reviewed gene: TOR1AIP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 32055997; Phenotypes: TOR1AIP1-associated nuclear envelopathy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v0.349 SLC12A2 Zornitza Stark Phenotypes for gene: SLC12A2 were changed from Kilquist syndrome; deafness; intellectual disability; dysmorphic features; absent salivation to Kilquist syndrome: deafness, intellectual disability, dysmorphic features, absent salivation; Congenital, severe to profound hearing loss; minor motor developmental delay
Deafness_IsolatedAndComplex v0.348 SLC12A2 Zornitza Stark Publications for gene: SLC12A2 were set to 30740830
Deafness_IsolatedAndComplex v0.347 SLC12A2 Zornitza Stark Mode of inheritance for gene: SLC12A2 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.2966 USP8 Bryony Thompson Classified gene: USP8 as Green List (high evidence)
Mendeliome v0.2966 USP8 Bryony Thompson Gene: usp8 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v0.346 SLC12A2 Zornitza Stark Classified gene: SLC12A2 as Green List (high evidence)
Deafness_IsolatedAndComplex v0.346 SLC12A2 Zornitza Stark Gene: slc12a2 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v0.24 EFEMP1 Michelle Torres gene: EFEMP1 was added
gene: EFEMP1 was added to Aortopathy_Connective Tissue Disorders. Sources: Literature
Mode of inheritance for gene: EFEMP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EFEMP1 were set to 32006683; 31792352
Phenotypes for gene: EFEMP1 were set to EFEMP1-related connective tissue disorder
Review for gene: EFEMP1 was set to AMBER
Added comment: New gene-disease association for EFEMP1: truncating variants (absent in gnomAD):

PMID 31792352 reports one man with a pronounced connective tissue phenotype presenting multiple and recurrent abdominal and thoracic herniae, myopia, hypermobile joints, scoliosis, and thin translucent skin. This individual has no clinical signs of retinal dystrophy.

PMID 32006683 reports 2 homozygous siblings (consanguinous) with multiple and recurrent herniae, pelvic and rectal prolapse, huge diverticula, marfanoid habitus, joint laxity, dorsal scoliosis, advanced bone age, pectus excavatum, dysmorphic facial features, and myopia. Both were homozygous for a truncating in VCPKMT, with no gene-disease association in OMIM, not in Panel App.

Both papers mention that studies on EFEMP1−/− mice revealed a phenotypic resemblance.
Sources: Literature
Mendeliome v0.2965 USP8 Bryony Thompson gene: USP8 was added
gene: USP8 was added to Mendeliome. Sources: Expert list
somatic tags were added to gene: USP8.
Mode of inheritance for gene: USP8 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: USP8 were set to 25675982; 24482476; 25485838; 25942478
Phenotypes for gene: USP8 were set to Pituitary adenoma 4, ACTH-secreting, somatic MIM#219090; hereditary spastic paraplegia
Review for gene: USP8 was set to GREEN
Added comment: Recurrent somatic gain of function missense variants in pituitary adenomas cause Cushing's disease.
A single family reported with spastic paraplegia with a homozygous variant, and a zebrafish model with a movement disorder.
Sources: Expert list
Deafness_IsolatedAndComplex v0.345 SLC12A2 Zornitza Stark Classified gene: SLC12A2 as Green List (high evidence)
Deafness_IsolatedAndComplex v0.345 SLC12A2 Zornitza Stark Gene: slc12a2 has been classified as Green List (High Evidence).
Mendeliome v0.2964 RIMS2 Zornitza Stark Marked gene: RIMS2 as ready
Mendeliome v0.2964 RIMS2 Zornitza Stark Gene: rims2 has been classified as Green List (High Evidence).
Mendeliome v0.2964 RIMS2 Zornitza Stark Phenotypes for gene: RIMS2 were changed from to nystagmus; retinal dysfunction; autism; night blindness
Mendeliome v0.2963 RIMS2 Zornitza Stark Classified gene: RIMS2 as Green List (high evidence)
Mendeliome v0.2963 RIMS2 Zornitza Stark Gene: rims2 has been classified as Green List (High Evidence).
Mendeliome v0.2962 RIMS2 Zornitza Stark reviewed gene: RIMS2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: nystagmus, retinal dysfunction, autism, night blindness; Mode of inheritance: None
Autism v0.97 RIMS2 Zornitza Stark Marked gene: RIMS2 as ready
Autism v0.97 RIMS2 Zornitza Stark Added comment: Comment when marking as ready: Most affected individuals reported as having autism.
Autism v0.97 RIMS2 Zornitza Stark Gene: rims2 has been classified as Green List (High Evidence).
Autism v0.97 RIMS2 Zornitza Stark Classified gene: RIMS2 as Green List (high evidence)
Autism v0.97 RIMS2 Zornitza Stark Gene: rims2 has been classified as Green List (High Evidence).
Congenital Stationary Night Blindness v0.3 RIMS2 Zornitza Stark Marked gene: RIMS2 as ready
Congenital Stationary Night Blindness v0.3 RIMS2 Zornitza Stark Gene: rims2 has been classified as Green List (High Evidence).
Congenital Stationary Night Blindness v0.3 RIMS2 Zornitza Stark Classified gene: RIMS2 as Green List (high evidence)
Congenital Stationary Night Blindness v0.3 RIMS2 Zornitza Stark Gene: rims2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2659 SOX6 Zornitza Stark Marked gene: SOX6 as ready
Intellectual disability syndromic and non-syndromic v0.2659 SOX6 Zornitza Stark Added comment: Comment when marking as ready: Most individuals had ID, ranging from mild to severe.
Intellectual disability syndromic and non-syndromic v0.2659 SOX6 Zornitza Stark Gene: sox6 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2659 SOX6 Zornitza Stark Classified gene: SOX6 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2659 SOX6 Zornitza Stark Gene: sox6 has been classified as Green List (High Evidence).
Hydrocephalus_Ventriculomegaly v0.17 TRIM71 Zornitza Stark Marked gene: TRIM71 as ready
Hydrocephalus_Ventriculomegaly v0.17 TRIM71 Zornitza Stark Gene: trim71 has been classified as Green List (High Evidence).
Hydrocephalus_Ventriculomegaly v0.17 TRIM71 Zornitza Stark Mode of pathogenicity for gene: TRIM71 was changed from Other to None
Leukodystrophy v0.126 CNP Kristin Rigbye gene: CNP was added
gene: CNP was added to Leukodystrophy - paediatric. Sources: Literature
Mode of inheritance for gene: CNP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CNP were set to 32128616; 12590258
Phenotypes for gene: CNP were set to Hypomyelinating leukodystrophy
Review for gene: CNP was set to AMBER
Added comment: Single consanguineous family described with homozygous missense in affected child (additional two affected deceased offspring unavailable for testing; healthy carrier parents and sibling).
Loss of protein by Western blot and defect in F-actin structure and organization observed in patient fibroblasts.
Deficiency of CNP in mouse has previously been shown to cause a lethal white matter neurodegenerative phenotype (PMID: 12590258), similar to the phenotype observed in this family.
Sources: Literature
Mendeliome v0.2962 TRIM71 Seb Lunke Mode of pathogenicity for gene: TRIM71 was changed from Other to None
Hydrocephalus_Ventriculomegaly v0.16 TRIM71 Zornitza Stark Classified gene: TRIM71 as Green List (high evidence)
Hydrocephalus_Ventriculomegaly v0.16 TRIM71 Zornitza Stark Gene: trim71 has been classified as Green List (High Evidence).
Mendeliome v0.2961 TRIM71 Seb Lunke Marked gene: TRIM71 as ready
Mendeliome v0.2961 TRIM71 Seb Lunke Gene: trim71 has been classified as Green List (High Evidence).
Mendeliome v0.2961 TRIM71 Seb Lunke Classified gene: TRIM71 as Green List (high evidence)
Mendeliome v0.2961 TRIM71 Seb Lunke Gene: trim71 has been classified as Green List (High Evidence).
Mendeliome v0.2960 SCYL2 Zornitza Stark Marked gene: SCYL2 as ready
Mendeliome v0.2960 SCYL2 Zornitza Stark Gene: scyl2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2960 SCYL2 Zornitza Stark Classified gene: SCYL2 as Amber List (moderate evidence)
Mendeliome v0.2960 SCYL2 Zornitza Stark Gene: scyl2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2959 SCYL2 Zornitza Stark gene: SCYL2 was added
gene: SCYL2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SCYL2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SCYL2 were set to 31960134; 26203146
Phenotypes for gene: SCYL2 were set to Arthrogryposis multiplex congenita (AMC); Zain syndrome
Review for gene: SCYL2 was set to AMBER
Added comment: Two unrelated families reported with AMC, variable other features including microcephaly.
Sources: Literature
Mendeliome v0.2958 CNP Seb Lunke Marked gene: CNP as ready
Mendeliome v0.2958 CNP Seb Lunke Gene: cnp has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2958 CNP Seb Lunke Classified gene: CNP as Amber List (moderate evidence)
Mendeliome v0.2958 CNP Seb Lunke Gene: cnp has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2957 VWA3B Bryony Thompson edited their review of gene: VWA3B: Changed rating: RED
Mendeliome v0.2957 VWA3B Bryony Thompson Classified gene: VWA3B as Red List (low evidence)
Mendeliome v0.2957 VWA3B Bryony Thompson Added comment: Comment on list classification: Single family and in vitro assay only
Mendeliome v0.2957 VWA3B Bryony Thompson Gene: vwa3b has been classified as Red List (Low Evidence).
Congenital Stationary Night Blindness v0.2 RIMS2 Paul De Fazio gene: RIMS2 was added
gene: RIMS2 was added to Congenital Stationary Night Blindness. Sources: Literature
Mode of inheritance for gene: RIMS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RIMS2 were set to 32470375
Phenotypes for gene: RIMS2 were set to nystagmus; retinal dysfunction; autism; night blindness
Review for gene: RIMS2 was set to GREEN
Added comment: Biallelic LoF variants segregate with Syndromic Congenital Cone-Rod Synaptic Disease in 7 individuals across 4 families. Some functional studies related to insulin secretion but they are non-significant. Several individuals had autism. One had night blindness.
Sources: Literature
Autism v0.96 RIMS2 Paul De Fazio changed review comment from: Biallelic LoF variants segregate with Syndromic Congenital Cone-Rod Synaptic Disease in 7 individuals across 4 families. Some functional studies related to insulin secretion but they are non-significant. Several individuals had autism.
Sources: Literature; to: Biallelic LoF variants segregate with Syndromic Congenital Cone-Rod Synaptic Disease in 7 individuals across 4 families. Some functional studies related to insulin secretion but they are non-significant. Several individuals had autism. One had night blindness.
Sources: Literature
Mendeliome v0.2956 RIMS2 Paul De Fazio changed review comment from: Biallelic LoF variants segregate with Syndromic Congenital Cone-Rod Synaptic Disease in 7 individuals across 4 families. Some functional studies related to insulin secretion but they are non-significant.
Sources: Literature; to: Biallelic LoF variants segregate with Syndromic Congenital Cone-Rod Synaptic Disease in 7 individuals across 4 families. Some functional studies related to insulin secretion but they are non-significant. Several individuals had autism. One had night blindness.
Sources: Literature
Arthrogryposis v0.47 SCYL2 Zornitza Stark Marked gene: SCYL2 as ready
Arthrogryposis v0.47 SCYL2 Zornitza Stark Gene: scyl2 has been classified as Amber List (Moderate Evidence).
Arthrogryposis v0.47 SCYL2 Zornitza Stark Classified gene: SCYL2 as Amber List (moderate evidence)
Arthrogryposis v0.47 SCYL2 Zornitza Stark Gene: scyl2 has been classified as Amber List (Moderate Evidence).
Autism v0.96 RIMS2 Paul De Fazio changed review comment from: Biallelic LoF variants segregate with Syndromic Congenital Cone-Rod Synaptic Disease in 7 individuals across 4 families. Some functional studies related to insulin secretion but they are non-significant.
Sources: Literature; to: Biallelic LoF variants segregate with Syndromic Congenital Cone-Rod Synaptic Disease in 7 individuals across 4 families. Some functional studies related to insulin secretion but they are non-significant. Several individuals had autism.
Sources: Literature
Autism v0.96 RIMS2 Paul De Fazio gene: RIMS2 was added
gene: RIMS2 was added to Autism. Sources: Literature
Mode of inheritance for gene: RIMS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RIMS2 were set to 32470375
Phenotypes for gene: RIMS2 were set to nystagmus; retinal dysfunction; autism; night blindness
Review for gene: RIMS2 was set to GREEN
Added comment: Biallelic LoF variants segregate with Syndromic Congenital Cone-Rod Synaptic Disease in 7 individuals across 4 families. Some functional studies related to insulin secretion but they are non-significant.
Sources: Literature
Mendeliome v0.2956 VWA3B Bryony Thompson Classified gene: VWA3B as Amber List (moderate evidence)
Mendeliome v0.2956 VWA3B Bryony Thompson Gene: vwa3b has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2955 VWA3B Bryony Thompson gene: VWA3B was added
gene: VWA3B was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: VWA3B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: VWA3B were set to 26157035
Phenotypes for gene: VWA3B were set to Spinocerebellar ataxia, autosomal recessive 22 MIM#616948
Review for gene: VWA3B was set to AMBER
Added comment: A homozygous missense variant was identified in 3 brothers from a single consanguineous Japanese family with autosomal recessive cerebellar ataxia. Transfection of the mutant VWA3B protein into several different cultured cell lines resulted in decreased cell viability.
Sources: Expert list
Deafness_IsolatedAndComplex v0.344 SLC12A2 Ee Ming Wong reviewed gene: SLC12A2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 32294086; Phenotypes: Congenital, severe to profound hearing loss, minor motor developmental delay; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2954 SLC12A2 Zornitza Stark Phenotypes for gene: SLC12A2 were changed from Kilquist syndrome; deafness; intellectual disability; dysmorphic features; absent salivation to Kilquist syndrome: deafness, intellectual disability, dysmorphic features, absent salivation; Congenital, severe to profound hearing loss
Mendeliome v0.2953 SOX6 Paul De Fazio changed review comment from: 6 LoF, 4 missense, and 6 intragenic deletion variants identified in individuals with a neurodevelopmental syndrome, however the number of families is unclear to me (paper says 19 individuals from 17 families). 12 were de novo.
Sources: Literature; to: 6 LoF, 4 missense, and 6 intragenic deletion variants identified in individuals with a neurodevelopmental syndrome. Paper says 19 individuals from 17 families. 12 were de novo.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2658 SOX6 Paul De Fazio changed review comment from: 6 LoF, 4 missense, and 6 intragenic deletion variants identified in individuals with a neurodevelopmental syndrome, however the number of families is unclear to me (paper says 19 individuals from 17 families). 12 were de novo.
Sources: Literature; to: 6 LoF, 4 missense, and 6 intragenic deletion variants identified in individuals with a neurodevelopmental syndrome. Paper says 19 individuals from 17 families. 12 were de novo.
Sources: Literature
Mendeliome v0.2953 SLC12A2 Zornitza Stark Publications for gene: SLC12A2 were set to 30740830
Mendeliome v0.2952 SOX6 Paul De Fazio changed review comment from: 6 LoF, 4 missense, and 6 intragenic deletion variants identified in individuals with a neurodevelopmental syndrome, however the number of families is unclear to me.
Sources: Literature; to: 6 LoF, 4 missense, and 6 intragenic deletion variants identified in individuals with a neurodevelopmental syndrome, however the number of families is unclear to me (paper says 19 individuals from 17 families). 12 were de novo.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2658 SOX6 Paul De Fazio changed review comment from: 6 LoF, 4 missense, and 6 intragenic deletion variants identified in individuals with a neurodevelopmental syndrome, however the number of families is unclear to me.
Sources: Literature; to: 6 LoF, 4 missense, and 6 intragenic deletion variants identified in individuals with a neurodevelopmental syndrome, however the number of families is unclear to me (paper says 19 individuals from 17 families). 12 were de novo.
Sources: Literature
Mendeliome v0.2952 SLC12A2 Zornitza Stark Mode of inheritance for gene: SLC12A2 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.2952 PLD3 Bryony Thompson Classified gene: PLD3 as Amber List (moderate evidence)
Mendeliome v0.2952 PLD3 Bryony Thompson Gene: pld3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2951 SLC12A2 Zornitza Stark Classified gene: SLC12A2 as Green List (high evidence)
Mendeliome v0.2951 SLC12A2 Zornitza Stark Gene: slc12a2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2658 SOX6 Paul De Fazio gene: SOX6 was added
gene: SOX6 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: SOX6 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SOX6 were set to 32442410
Phenotypes for gene: SOX6 were set to ADHD; Craniosynostosis; Osteochondromas
Review for gene: SOX6 was set to GREEN
Added comment: 6 LoF, 4 missense, and 6 intragenic deletion variants identified in individuals with a neurodevelopmental syndrome, however the number of families is unclear to me.
Sources: Literature
Mendeliome v0.2950 PLD3 Bryony Thompson gene: PLD3 was added
gene: PLD3 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: PLD3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PLD3 were set to 29053796; 30312375; 30312384
Phenotypes for gene: PLD3 were set to Spinocerebellar ataxia 46 MIM#617770
Review for gene: PLD3 was set to AMBER
Added comment: A heterozygous missense was identified in 8 affected members of a single family with spinocerebellar ataxia, and supporting in vitro functional assays.
Sources: Expert list
Mendeliome v0.2949 SOX6 Paul De Fazio changed review comment from: 6 LoF and 4 missense variants identified in individuals with a neurodevelopmental syndrome, however the number of families is unclear to me.
Sources: Literature; to: 6 LoF, 4 missense, and 6 intragenic deletion variants identified in individuals with a neurodevelopmental syndrome, however the number of families is unclear to me.
Sources: Literature
Mendeliome v0.2949 SPATA13 Zornitza Stark Marked gene: SPATA13 as ready
Mendeliome v0.2949 SPATA13 Zornitza Stark Added comment: Comment when marking as ready: Adult-onset.
Mendeliome v0.2949 SPATA13 Zornitza Stark Gene: spata13 has been classified as Green List (High Evidence).
Mendeliome v0.2949 SPATA13 Zornitza Stark Classified gene: SPATA13 as Green List (high evidence)
Mendeliome v0.2949 SPATA13 Zornitza Stark Gene: spata13 has been classified as Green List (High Evidence).
Mendeliome v0.2948 SPATA13 Zornitza Stark reviewed gene: SPATA13: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Craniosynostosis v0.3 SOX6 Seb Lunke Marked gene: SOX6 as ready
Craniosynostosis v0.3 SOX6 Seb Lunke Gene: sox6 has been classified as Green List (High Evidence).
Craniosynostosis v0.3 SOX6 Seb Lunke Classified gene: SOX6 as Green List (high evidence)
Craniosynostosis v0.3 SOX6 Seb Lunke Gene: sox6 has been classified as Green List (High Evidence).
Craniosynostosis v0.2 SOX6 Seb Lunke gene: SOX6 was added
gene: SOX6 was added to Craniosynostosis. Sources: Literature
Mode of inheritance for gene: SOX6 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SOX6 were set to 32442410
Phenotypes for gene: SOX6 were set to ADHD; Craniosynostosis; Osteochondromas
Review for gene: SOX6 was set to GREEN
gene: SOX6 was marked as current diagnostic
Added comment: 6 LoF and 4 missense variants identified in individuals with a neurodevelopmental syndrome, however the number of families is unclear to me. Sources: Literature
Sources: Literature
Mendeliome v0.2948 SOX6 Seb Lunke Marked gene: SOX6 as ready
Mendeliome v0.2948 SOX6 Seb Lunke Gene: sox6 has been classified as Green List (High Evidence).
Ciliopathies v0.187 KIF3B Zornitza Stark Marked gene: KIF3B as ready
Ciliopathies v0.187 KIF3B Zornitza Stark Gene: kif3b has been classified as Amber List (Moderate Evidence).
Ciliopathies v0.187 KIF3B Zornitza Stark Classified gene: KIF3B as Amber List (moderate evidence)
Ciliopathies v0.187 KIF3B Zornitza Stark Gene: kif3b has been classified as Amber List (Moderate Evidence).
Ciliopathies v0.186 KIF3B Zornitza Stark gene: KIF3B was added
gene: KIF3B was added to Ciliopathies. Sources: Literature
Mode of inheritance for gene: KIF3B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KIF3B were set to 32386558
Phenotypes for gene: KIF3B were set to hepatic fibrosis; retinitis pigmentosa; postaxial polydactyly
Review for gene: KIF3B was set to AMBER
Added comment: Two unrelated families with a ciliopathy phenotype and some functional data.
Sources: Literature
Mendeliome v0.2948 SOX6 Seb Lunke Classified gene: SOX6 as Green List (high evidence)
Mendeliome v0.2948 SOX6 Seb Lunke Gene: sox6 has been classified as Green List (High Evidence).
Mendeliome v0.2947 KIF3B Zornitza Stark Marked gene: KIF3B as ready
Mendeliome v0.2947 KIF3B Zornitza Stark Gene: kif3b has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2947 KIF3B Zornitza Stark Publications for gene: KIF3B were set to
Mendeliome v0.2946 KIF3B Zornitza Stark Classified gene: KIF3B as Amber List (moderate evidence)
Mendeliome v0.2946 KIF3B Zornitza Stark Gene: kif3b has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2945 KIF3B Zornitza Stark edited their review of gene: KIF3B: Changed rating: AMBER
Mendeliome v0.2945 KIF3B Zornitza Stark reviewed gene: KIF3B: Rating: RED; Mode of pathogenicity: None; Publications: 32386558; Phenotypes: hepatic fibrosis, retinitis pigmentosa, postaxial polydactyly; Mode of inheritance: None
Mendeliome v0.2945 POC5 Bryony Thompson Marked gene: POC5 as ready
Mendeliome v0.2945 POC5 Bryony Thompson Gene: poc5 has been classified as Green List (High Evidence).
Mendeliome v0.2945 POC5 Bryony Thompson Classified gene: POC5 as Green List (high evidence)
Mendeliome v0.2945 POC5 Bryony Thompson Gene: poc5 has been classified as Green List (High Evidence).
Mendeliome v0.2944 POC5 Bryony Thompson gene: POC5 was added
gene: POC5 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: POC5 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: POC5 were set to 25642776; 29272404
Phenotypes for gene: POC5 were set to Idiopathic scoliosis; retinitis pigmentosa; short stature; microcephaly; recurrent glomerulonephritis
Review for gene: POC5 was set to GREEN
Added comment: Three heterozygous missense variants identified in three families segregating with idiopathic scoliosis, and supporting zebrafish models for each of the missense variants.
Also, one case reported with retinitis pigmentosa, short stature, microcephaly, and recurrent glomerulonephritis with a homozygous truncating variant and a supporting zebrafish model.
Sources: Literature
Long QT Syndrome v0.35 KCNJ2 Zornitza Stark Marked gene: KCNJ2 as ready
Long QT Syndrome v0.35 KCNJ2 Zornitza Stark Gene: kcnj2 has been classified as Green List (High Evidence).
Long QT Syndrome v0.35 KCNJ2 Zornitza Stark Phenotypes for gene: KCNJ2 were changed from to long QT syndrome; Andersen-Tawil syndrome
Long QT Syndrome v0.34 KCNJ2 Zornitza Stark Publications for gene: KCNJ2 were set to
Long QT Syndrome v0.33 KCNJ2 Zornitza Stark Mode of inheritance for gene: KCNJ2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2943 KIF3B Paul De Fazio gene: KIF3B was added
gene: KIF3B was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: KIF3B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: KIF3B were set to hepatic fibrosis; retinitis pigmentosa; postaxial polydactyly
Review for gene: KIF3B was set to AMBER
Added comment: 2 families reported with missense variants, one de novo and one segregating in a six-generation pedigree. Functional studies in zebrafish showed the variants result in impaired rhodopsin trafficking.
Sources: Literature
Long QT Syndrome v0.32 KCNH2 Zornitza Stark Marked gene: KCNH2 as ready
Long QT Syndrome v0.32 KCNH2 Zornitza Stark Gene: kcnh2 has been classified as Green List (High Evidence).
Long QT Syndrome v0.32 KCNH2 Zornitza Stark Phenotypes for gene: KCNH2 were changed from to long QT syndrome
Long QT Syndrome v0.31 KCNH2 Zornitza Stark Publications for gene: KCNH2 were set to
Long QT Syndrome v0.30 KCNH2 Zornitza Stark Mode of inheritance for gene: KCNH2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Long QT Syndrome v0.29 KCNE2 Zornitza Stark Marked gene: KCNE2 as ready
Long QT Syndrome v0.29 KCNE2 Zornitza Stark Gene: kcne2 has been classified as Amber List (Moderate Evidence).
Long QT Syndrome v0.29 KCNE2 Zornitza Stark Phenotypes for gene: KCNE2 were changed from to Long QT syndrome
Mendeliome v0.2943 SPATA13 Ain Roesley changed review comment from: PMID: 32339198; 10 unrelated probands with missense except for 2 families with inframe del of 9bp.
Sources: Literature; to: PMID: 32339198; 10 unrelated probands with missense except for 2 families with inframe del of 9bp.
Sources: Literature
Long QT Syndrome v0.28 KCNE2 Zornitza Stark Publications for gene: KCNE2 were set to
Mendeliome v0.2943 SPATA13 Ain Roesley gene: SPATA13 was added
gene: SPATA13 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SPATA13 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SPATA13 were set to PMID: 32339198
Phenotypes for gene: SPATA13 were set to primary angle-closure glaucoma
Added comment: PMID: 32339198; 10 unrelated probands with missense except for 2 families with inframe del of 9bp.
Sources: Literature
Long QT Syndrome v0.27 KCNE2 Zornitza Stark Classified gene: KCNE2 as Amber List (moderate evidence)
Long QT Syndrome v0.27 KCNE2 Zornitza Stark Gene: kcne2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2943 SOX6 Paul De Fazio gene: SOX6 was added
gene: SOX6 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SOX6 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SOX6 were set to 32442410
Phenotypes for gene: SOX6 were set to ADHD; Craniosynostosis; Osteochondromas
Added comment: 6 LoF and 4 missense variants identified in individuals with a neurodevelopmental syndrome, however the number of families is unclear to me.
Sources: Literature
Long QT Syndrome v0.26 KCNE1 Zornitza Stark Marked gene: KCNE1 as ready
Long QT Syndrome v0.26 KCNE1 Zornitza Stark Gene: kcne1 has been classified as Amber List (Moderate Evidence).
Long QT Syndrome v0.26 KCNE1 Zornitza Stark Publications for gene: KCNE1 were set to
Long QT Syndrome v0.25 KCNE1 Zornitza Stark Phenotypes for gene: KCNE1 were changed from to long QT syndrome; acquired LQTS
Long QT Syndrome v0.24 KCNE1 Zornitza Stark Mode of inheritance for gene: KCNE1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.2943 CNP Kristin Rigbye gene: CNP was added
gene: CNP was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CNP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CNP were set to 32128616; 12590258
Phenotypes for gene: CNP were set to Hypomyelinating leukodystrophy
Review for gene: CNP was set to AMBER
Added comment: Single consanguineous family described with homozygous missense in affected child (additional two affected deceased offspring unavailable for testing; healthy carrier parents and sibling).
Loss of protein by Western blot and defect in F-actin structure and organization observed in patient fibroblasts.
Deficiency of CNP in mouse has previously been shown to cause a lethal white matter neurodegenerative phenotype (PMID: 12590258), similar to the phenotype observed in this family.
Sources: Literature
Long QT Syndrome v0.23 KCNE1 Zornitza Stark Classified gene: KCNE1 as Amber List (moderate evidence)
Long QT Syndrome v0.23 KCNE1 Zornitza Stark Gene: kcne1 has been classified as Amber List (Moderate Evidence).
Long QT Syndrome v0.22 CAV3 Zornitza Stark Marked gene: CAV3 as ready
Long QT Syndrome v0.22 CAV3 Zornitza Stark Gene: cav3 has been classified as Amber List (Moderate Evidence).
Long QT Syndrome v0.22 CAV3 Zornitza Stark Phenotypes for gene: CAV3 were changed from to Long QT syndrome 9, MIM# 611818
Long QT Syndrome v0.21 CAV3 Zornitza Stark Publications for gene: CAV3 were set to
Long QT Syndrome v0.20 CAV3 Zornitza Stark Mode of pathogenicity for gene: CAV3 was changed from to None
Long QT Syndrome v0.19 CAV3 Zornitza Stark Mode of inheritance for gene: CAV3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Long QT Syndrome v0.18 CAV3 Zornitza Stark Classified gene: CAV3 as Amber List (moderate evidence)
Long QT Syndrome v0.18 CAV3 Zornitza Stark Gene: cav3 has been classified as Amber List (Moderate Evidence).
Long QT Syndrome v0.17 CAV3 Zornitza Stark reviewed gene: CAV3: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Long QT syndrome 9, MIM# 611818; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2943 SLC12A2 Ee Ming Wong reviewed gene: SLC12A2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 32294086; Phenotypes: Congenital, severe to profound hearing loss, minor motor developmental delay; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Retinitis pigmentosa v0.55 Bryony Thompson removed gene:POC5 from the panel
Syndromic Retinopathy v0.72 POC5 Bryony Thompson Phenotypes for gene: POC5 were changed from to retinitis pigmentosa; short stature; microcephaly; recurrent glomerulonephritis
Syndromic Retinopathy v0.71 POC5 Bryony Thompson Publications for gene: POC5 were set to
Syndromic Retinopathy v0.70 POC5 Bryony Thompson Mode of inheritance for gene: POC5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Long QT Syndrome v0.17 CACNA1C Zornitza Stark Marked gene: CACNA1C as ready
Long QT Syndrome v0.17 CACNA1C Zornitza Stark Gene: cacna1c has been classified as Green List (High Evidence).
Long QT Syndrome v0.17 CACNA1C Zornitza Stark Phenotypes for gene: CACNA1C were changed from Long QT syndrome 8, MIM# 618447; Timothy syndrome, MIM# 601005 to Long QT syndrome 8, MIM# 618447; Timothy syndrome, MIM# 601005
Long QT Syndrome v0.16 CACNA1C Zornitza Stark Phenotypes for gene: CACNA1C were changed from to Long QT syndrome 8, MIM# 618447; Timothy syndrome, MIM# 601005
Hydrocephalus_Ventriculomegaly v0.15 TRIM71 Elena Savva gene: TRIM71 was added
gene: TRIM71 was added to Hydrocephalus_Ventriculomegaly. Sources: Literature
Mode of inheritance for gene: TRIM71 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: TRIM71 were set to PMID: 29983323; 32168371; 30975633
Phenotypes for gene: TRIM71 were set to Hydrocephalus, congenital communicating, 1 618667
Mode of pathogenicity for gene: TRIM71 was set to Other
Review for gene: TRIM71 was set to GREEN
Added comment: PMID: 29983323 - 3 unrelated patients with de novo missense and hydrocephalus with ventriculomegaly (p.Arg608His recurrent). One patient then transmitted the variant to an affected child.

PMID: 32168371 - refers to the gene as an established sources of neurodevelopmental disorder

PMID: 30975633 - identifies and proves by functional studies that TRIM71 is essential for neurodevelopment. Proposes a LOF mechanism.
Sources: Literature
Mendeliome v0.2943 TRIM71 Elena Savva reviewed gene: TRIM71: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 29983323, 32168371, 30975633; Phenotypes: Hydrocephalus, congenital communicating, 1 618667; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.2943 TRIM71 Elena Savva Deleted their review
Mendeliome v0.2943 RIMS2 Paul De Fazio changed review comment from: Segregates with Syndromic Congenital Cone-Rod Synaptic Disease in 7 individuals across 4 families. Some functional studies related to insulin secretion but they are non-significant.
Sources: Literature; to: Biallelic LoF variants segregate with Syndromic Congenital Cone-Rod Synaptic Disease in 7 individuals across 4 families. Some functional studies related to insulin secretion but they are non-significant.
Sources: Literature
Long QT Syndrome v0.15 CACNA1C Zornitza Stark Publications for gene: CACNA1C were set to
Mendeliome v0.2943 TRIM71 Elena Savva gene: TRIM71 was added
gene: TRIM71 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TRIM71 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: TRIM71 were set to PMID: 29983323; 32168371; 30975633
Phenotypes for gene: TRIM71 were set to Hydrocephalus, congenital communicating, 1 618667
Mode of pathogenicity for gene: TRIM71 was set to Other
Added comment: PMID: 29983323 - 3 unrelated patients with de novo missense and hydrocephalus with ventriculomegaly (p.Arg608His recurrent). One patient then transmitted the variant to an affected child.

PMID: 32168371 - refers to the gene as an established sources of neurodevelopmental disorder

PMID: 30975633 - identifies and proves by functional studies that TRIM71 is essential for neurodevelopment. Proposes a LOF mechanism.
Sources: Literature
Long QT Syndrome v0.14 CACNA1C Zornitza Stark Mode of inheritance for gene: CACNA1C was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Long QT Syndrome v0.13 ANK2 Zornitza Stark edited their review of gene: ANK2: Changed phenotypes: Long QT syndrome 4, MIM# 600919
Long QT Syndrome v0.13 ANK2 Zornitza Stark Tag disputed tag was added to gene: ANK2.
Long QT Syndrome v0.13 ANK2 Zornitza Stark Marked gene: ANK2 as ready
Long QT Syndrome v0.13 ANK2 Zornitza Stark Gene: ank2 has been classified as Red List (Low Evidence).
Long QT Syndrome v0.13 ANK2 Zornitza Stark Phenotypes for gene: ANK2 were changed from to Long QT syndrome 4, MIM# 600919
Mendeliome v0.2943 RIMS2 Paul De Fazio gene: RIMS2 was added
gene: RIMS2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RIMS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RIMS2 were set to 32470375
Review for gene: RIMS2 was set to GREEN
Added comment: Segregates with Syndromic Congenital Cone-Rod Synaptic Disease in 7 individuals across 4 families. Some functional studies related to insulin secretion but they are non-significant.
Sources: Literature
Long QT Syndrome v0.12 ANK2 Zornitza Stark Publications for gene: ANK2 were set to
Long QT Syndrome v0.11 ANK2 Zornitza Stark Classified gene: ANK2 as Red List (low evidence)
Long QT Syndrome v0.11 ANK2 Zornitza Stark Gene: ank2 has been classified as Red List (Low Evidence).
Long QT Syndrome v0.10 ANK2 Zornitza Stark reviewed gene: ANK2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Arthrogryposis v0.46 SCYL2 Kristin Rigbye gene: SCYL2 was added
gene: SCYL2 was added to Arthrogryposis. Sources: Literature
Mode of inheritance for gene: SCYL2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SCYL2 were set to 31960134; 26203146
Phenotypes for gene: SCYL2 were set to Arthrogryposis multiplex congenita (AMC); Zain syndrome
Review for gene: SCYL2 was set to AMBER
Added comment: 2 unrelated consanguineous families reported with AMC (PMID: 31960134).
Constitutive mouse knockout of Scyl2 results in neonatal lethality and severe motor and sensory deficits (PMID: 26203146).
Sources: Literature
Incidentalome v0.31 AKAP9 Zornitza Stark Tag disputed tag was added to gene: AKAP9.
Incidentalome v0.31 AKAP9 Zornitza Stark Marked gene: AKAP9 as ready
Incidentalome v0.31 AKAP9 Zornitza Stark Gene: akap9 has been classified as Red List (Low Evidence).
Incidentalome v0.31 AKAP9 Zornitza Stark Phenotypes for gene: AKAP9 were changed from to Long QT syndrome 11, MIM# 611820
Incidentalome v0.30 AKAP9 Zornitza Stark Publications for gene: AKAP9 were set to
Incidentalome v0.29 AKAP9 Zornitza Stark Mode of inheritance for gene: AKAP9 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Incidentalome v0.28 AKAP9 Zornitza Stark Classified gene: AKAP9 as Red List (low evidence)
Incidentalome v0.28 AKAP9 Zornitza Stark Gene: akap9 has been classified as Red List (Low Evidence).
Incidentalome v0.27 AKAP9 Zornitza Stark reviewed gene: AKAP9: Rating: RED; Mode of pathogenicity: None; Publications: 31983240; Phenotypes: Long QT syndrome 11, MIM# 611820; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Long QT Syndrome v0.10 AKAP9 Zornitza Stark Tag disputed tag was added to gene: AKAP9.
Long QT Syndrome v0.10 AKAP9 Zornitza Stark Marked gene: AKAP9 as ready
Long QT Syndrome v0.10 AKAP9 Zornitza Stark Gene: akap9 has been classified as Red List (Low Evidence).
Long QT Syndrome v0.10 AKAP9 Zornitza Stark Phenotypes for gene: AKAP9 were changed from to long QT syndrome
Long QT Syndrome v0.9 AKAP9 Zornitza Stark Publications for gene: AKAP9 were set to
Long QT Syndrome v0.8 AKAP9 Zornitza Stark Classified gene: AKAP9 as Red List (low evidence)
Long QT Syndrome v0.8 AKAP9 Zornitza Stark Gene: akap9 has been classified as Red List (Low Evidence).
Mendeliome v0.2943 RBM7 Bryony Thompson Classified gene: RBM7 as Amber List (moderate evidence)
Mendeliome v0.2943 RBM7 Bryony Thompson Gene: rbm7 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2942 RBM7 Bryony Thompson gene: RBM7 was added
gene: RBM7 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: RBM7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RBM7 were set to 27193168
Phenotypes for gene: RBM7 were set to SMA-like spinal motor neuropathy; dHMN/dSMA
Review for gene: RBM7 was set to AMBER
Added comment: Single case with a homozygote variant, with functional assays in patient fibroblasts. Also, supporting zebrafish model.
Sources: Expert list
Mendeliome v0.2941 SORD Seb Lunke Marked gene: SORD as ready
Mendeliome v0.2941 SORD Seb Lunke Gene: sord has been classified as Green List (High Evidence).
Mendeliome v0.2941 SORD Seb Lunke Classified gene: SORD as Green List (high evidence)
Mendeliome v0.2941 SORD Seb Lunke Gene: sord has been classified as Green List (High Evidence).
Mendeliome v0.2940 SORD Seb Lunke gene: SORD was added
gene: SORD was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SORD was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SORD were set to 32367058
Phenotypes for gene: SORD were set to isolated hereditary neuropathy
Review for gene: SORD was set to GREEN
gene: SORD was marked as current diagnostic
Added comment: 45 individuals from 38 families across multiple ancestries carrying the nonsense c.757delG
(p.Ala253GlnfsTer27) variant in SORD, in either a homozygous or compound heterozygous state
Sources: Literature
Brugada syndrome v0.34 KCND3 Zornitza Stark Phenotypes for gene: KCND3 were changed from to Brugada syndrome
Brugada syndrome v0.33 KCND3 Zornitza Stark Tag disputed tag was added to gene: KCND3.
Brugada syndrome v0.33 CACNB2 Zornitza Stark Tag disputed tag was added to gene: CACNB2.
Brugada syndrome v0.33 CACNA2D1 Zornitza Stark Tag disputed tag was added to gene: CACNA2D1.
Brugada syndrome v0.33 CACNA1C Zornitza Stark Tag disputed tag was added to gene: CACNA1C.
Incidentalome v0.27 GPD1L Zornitza Stark Classified gene: GPD1L as Red List (low evidence)
Incidentalome v0.27 GPD1L Zornitza Stark Gene: gpd1l has been classified as Red List (Low Evidence).
Brugada syndrome v0.33 GPD1L Zornitza Stark Publications for gene: GPD1L were set to 17967977; 19666841
Brugada syndrome v0.32 GPD1L Zornitza Stark Classified gene: GPD1L as Red List (low evidence)
Brugada syndrome v0.32 GPD1L Zornitza Stark Gene: gpd1l has been classified as Red List (Low Evidence).
Brugada syndrome v0.31 SCN1B Zornitza Stark Marked gene: SCN1B as ready
Brugada syndrome v0.31 SCN1B Zornitza Stark Gene: scn1b has been classified as Red List (Low Evidence).
Brugada syndrome v0.31 SCN1B Zornitza Stark Publications for gene: SCN1B were set to
Brugada syndrome v0.30 SCN1B Zornitza Stark Classified gene: SCN1B as Red List (low evidence)
Brugada syndrome v0.30 SCN1B Zornitza Stark Gene: scn1b has been classified as Red List (Low Evidence).
Brugada syndrome v0.29 SCN1B Zornitza Stark Tag disputed tag was added to gene: SCN1B.
Brugada syndrome v0.29 SCN10A Zornitza Stark Marked gene: SCN10A as ready
Brugada syndrome v0.29 SCN10A Zornitza Stark Gene: scn10a has been classified as Red List (Low Evidence).
Brugada syndrome v0.29 SCN10A Zornitza Stark Phenotypes for gene: SCN10A were changed from to Brugada syndrome
Brugada syndrome v0.28 SCN10A Zornitza Stark Publications for gene: SCN10A were set to
Brugada syndrome v0.27 SCN10A Zornitza Stark Classified gene: SCN10A as Red List (low evidence)
Brugada syndrome v0.27 SCN10A Zornitza Stark Gene: scn10a has been classified as Red List (Low Evidence).
Brugada syndrome v0.26 SCN10A Zornitza Stark Tag disputed tag was added to gene: SCN10A.
Mendeliome v0.2940 KCNJ8 Zornitza Stark Marked gene: KCNJ8 as ready
Mendeliome v0.2940 KCNJ8 Zornitza Stark Gene: kcnj8 has been classified as Red List (Low Evidence).
Mendeliome v0.2940 KCNJ8 Zornitza Stark Phenotypes for gene: KCNJ8 were changed from to Brugada syndrome
Mendeliome v0.2939 KCNJ8 Zornitza Stark Publications for gene: KCNJ8 were set to
Mendeliome v0.2938 KCNJ8 Zornitza Stark Mode of inheritance for gene: KCNJ8 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2937 KCNJ8 Zornitza Stark Classified gene: KCNJ8 as Red List (low evidence)
Mendeliome v0.2937 KCNJ8 Zornitza Stark Gene: kcnj8 has been classified as Red List (Low Evidence).
Mendeliome v0.2936 KCNJ8 Zornitza Stark Tag disputed tag was added to gene: KCNJ8.
Mendeliome v0.2936 KCNJ8 Zornitza Stark reviewed gene: KCNJ8: Rating: RED; Mode of pathogenicity: None; Publications: 29959160; Phenotypes: Brugada syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Brugada syndrome v0.26 KCNJ8 Zornitza Stark Phenotypes for gene: KCNJ8 were changed from to Brugada syndrome
Brugada syndrome v0.25 KCNJ8 Zornitza Stark Marked gene: KCNJ8 as ready
Brugada syndrome v0.25 KCNJ8 Zornitza Stark Gene: kcnj8 has been classified as Red List (Low Evidence).
Brugada syndrome v0.25 KCNJ8 Zornitza Stark Tag disputed tag was added to gene: KCNJ8.
Mendeliome v0.2936 KCNE3 Zornitza Stark Marked gene: KCNE3 as ready
Mendeliome v0.2936 KCNE3 Zornitza Stark Gene: kcne3 has been classified as Red List (Low Evidence).
Mendeliome v0.2936 KCNE3 Zornitza Stark Phenotypes for gene: KCNE3 were changed from to Brugada syndrome
Mendeliome v0.2935 KCNE3 Zornitza Stark Publications for gene: KCNE3 were set to
Mendeliome v0.2934 KCNE3 Zornitza Stark Mode of inheritance for gene: KCNE3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Brugada syndrome v0.25 KCNJ8 Zornitza Stark Publications for gene: KCNJ8 were set to
Brugada syndrome v0.24 KCNJ8 Zornitza Stark Classified gene: KCNJ8 as Red List (low evidence)
Brugada syndrome v0.24 KCNJ8 Zornitza Stark Gene: kcnj8 has been classified as Red List (Low Evidence).
Brugada syndrome v0.23 KCNE3 Zornitza Stark Marked gene: KCNE3 as ready
Brugada syndrome v0.23 KCNE3 Zornitza Stark Gene: kcne3 has been classified as Red List (Low Evidence).
Brugada syndrome v0.23 KCNE3 Zornitza Stark Tag disputed tag was added to gene: KCNE3.
Mendeliome v0.2933 KCNE3 Zornitza Stark Classified gene: KCNE3 as Red List (low evidence)
Mendeliome v0.2933 KCNE3 Zornitza Stark Gene: kcne3 has been classified as Red List (Low Evidence).
Mendeliome v0.2932 KCNE3 Zornitza Stark reviewed gene: KCNE3: Rating: RED; Mode of pathogenicity: None; Publications: 29959160; Phenotypes: Brugada syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Brugada syndrome v0.23 KCNE3 Zornitza Stark Publications for gene: KCNE3 were set to
Brugada syndrome v0.22 KCNE3 Zornitza Stark Classified gene: KCNE3 as Red List (low evidence)
Brugada syndrome v0.22 KCNE3 Zornitza Stark Gene: kcne3 has been classified as Red List (Low Evidence).
Brugada syndrome v0.21 KCND3 Zornitza Stark Marked gene: KCND3 as ready
Brugada syndrome v0.21 KCND3 Zornitza Stark Gene: kcnd3 has been classified as Red List (Low Evidence).
Brugada syndrome v0.21 KCND3 Zornitza Stark Publications for gene: KCND3 were set to
Brugada syndrome v0.20 KCND3 Zornitza Stark Classified gene: KCND3 as Red List (low evidence)
Brugada syndrome v0.20 KCND3 Zornitza Stark Gene: kcnd3 has been classified as Red List (Low Evidence).
Brugada syndrome v0.19 CACNB2 Zornitza Stark Marked gene: CACNB2 as ready
Brugada syndrome v0.19 CACNB2 Zornitza Stark Gene: cacnb2 has been classified as Red List (Low Evidence).
Brugada syndrome v0.19 CACNB2 Zornitza Stark Publications for gene: CACNB2 were set to
Brugada syndrome v0.18 CACNB2 Zornitza Stark Classified gene: CACNB2 as Red List (low evidence)
Brugada syndrome v0.18 CACNB2 Zornitza Stark Gene: cacnb2 has been classified as Red List (Low Evidence).
Brugada syndrome v0.17 CACNA2D1 Zornitza Stark Marked gene: CACNA2D1 as ready
Brugada syndrome v0.17 CACNA2D1 Zornitza Stark Gene: cacna2d1 has been classified as Red List (Low Evidence).
Brugada syndrome v0.17 CACNA2D1 Zornitza Stark Publications for gene: CACNA2D1 were set to
Brugada syndrome v0.16 CACNA2D1 Zornitza Stark Classified gene: CACNA2D1 as Red List (low evidence)
Brugada syndrome v0.16 CACNA2D1 Zornitza Stark Gene: cacna2d1 has been classified as Red List (Low Evidence).
Brugada syndrome v0.15 CACNA1C Zornitza Stark Marked gene: CACNA1C as ready
Brugada syndrome v0.15 CACNA1C Zornitza Stark Gene: cacna1c has been classified as Red List (Low Evidence).
Brugada syndrome v0.15 CACNA1C Zornitza Stark Publications for gene: CACNA1C were set to
Brugada syndrome v0.14 CACNA1C Zornitza Stark Classified gene: CACNA1C as Red List (low evidence)
Brugada syndrome v0.14 CACNA1C Zornitza Stark Gene: cacna1c has been classified as Red List (Low Evidence).
Ciliary Dyskinesia v0.103 MCIDAS Crystle Lee reviewed gene: MCIDAS: Rating: GREEN; Mode of pathogenicity: None; Publications: 25048963; Phenotypes: Ciliary dyskinesia, primary, 42 (MIM#618695); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Heterotaxy v0.75 MCIDAS Crystle Lee changed review comment from: PCD without situs invertus (OMIM)

PMID: 25048963: 3 different homozygous variants reported in 4 unrelated families. Situs invertus not observed in any of the 9 individuals reported. Functional studies showed reduction of cilia; to: PCD without situs invertus (OMIM)

PMID: 25048963: 3 different homozygous variants reported in 4 unrelated families. Situs invertus not observed in any of the 9 individuals reported. Functional studies showed reduction of cilia. None of the variants identified were observed in gnomAD at unexpected frequency for a recessive condition.
Heterotaxy v0.75 MCIDAS Crystle Lee reviewed gene: MCIDAS: Rating: RED; Mode of pathogenicity: None; Publications: 25048963; Phenotypes: Ciliary dyskinesia, primary, 42 (MIM#618695); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2658 HIST1H4J Sue White Classified gene: HIST1H4J as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2658 HIST1H4J Sue White Gene: hist1h4j has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2657 HIST1H4J Sue White Marked gene: HIST1H4J as ready
Intellectual disability syndromic and non-syndromic v0.2657 HIST1H4J Sue White Gene: hist1h4j has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.2657 HIST1H4J Sue White gene: HIST1H4J was added
gene: HIST1H4J was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: HIST1H4J was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HIST1H4J were set to 31804630
Phenotypes for gene: HIST1H4J were set to microcephaly; intellectual disability; dysmorphic features
Penetrance for gene: HIST1H4J were set to Complete
Review for gene: HIST1H4J was set to AMBER
Added comment: single case report but with functional evidence in zebrafish and phenotypic similarity to other HIST1H4C phenotype
Sources: Literature
Chronic granulomatous disease v0.9 Bryony Thompson Panel status changed from internal to public
Panel types changed to Royal Melbourne Hospital; Rare Disease
Chronic granulomatous disease v0.8 NCF4 Bryony Thompson Classified gene: NCF4 as Green List (high evidence)
Chronic granulomatous disease v0.8 NCF4 Bryony Thompson Gene: ncf4 has been classified as Green List (High Evidence).
Chronic granulomatous disease v0.7 NCF4 Bryony Thompson reviewed gene: NCF4: Rating: GREEN; Mode of pathogenicity: None; Publications: 19692703, 16880254, 29969437; Phenotypes: Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type III MIM#613960; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Heterotaxy v0.75 DRC1 Elena Savva reviewed gene: DRC1: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 31960620, 32108610; Phenotypes: Ciliary dyskinesia, primary, 21, MIM# 615294; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Chronic granulomatous disease v0.7 C17orf62 Bryony Thompson edited their review of gene: C17orf62: Changed publications: 28600779, 30361506, 28351984, 30312704
Chronic granulomatous disease v0.7 C17orf62 Bryony Thompson Classified gene: C17orf62 as Green List (high evidence)
Chronic granulomatous disease v0.7 C17orf62 Bryony Thompson Gene: c17orf62 has been classified as Green List (High Evidence).
Chronic granulomatous disease v0.6 C17orf62 Bryony Thompson reviewed gene: C17orf62: Rating: GREEN; Mode of pathogenicity: None; Publications: 28600779, 30361506, 28351984; Phenotypes: Chronic granulomatous disease; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Chronic granulomatous disease v0.6 NOD2 Bryony Thompson Classified gene: NOD2 as Green List (high evidence)
Chronic granulomatous disease v0.6 NOD2 Bryony Thompson Gene: nod2 has been classified as Green List (High Evidence).
Chronic granulomatous disease v0.5 NCF2 Bryony Thompson Classified gene: NCF2 as Green List (high evidence)
Chronic granulomatous disease v0.5 NCF2 Bryony Thompson Gene: ncf2 has been classified as Green List (High Evidence).
Chronic granulomatous disease v0.4 NCF1 Bryony Thompson Classified gene: NCF1 as Green List (high evidence)
Chronic granulomatous disease v0.4 NCF1 Bryony Thompson Gene: ncf1 has been classified as Green List (High Evidence).
Chronic granulomatous disease v0.3 G6PD Bryony Thompson Classified gene: G6PD as Green List (high evidence)
Chronic granulomatous disease v0.3 G6PD Bryony Thompson Gene: g6pd has been classified as Green List (High Evidence).
Chronic granulomatous disease v0.2 CYBB Bryony Thompson Classified gene: CYBB as Green List (high evidence)
Chronic granulomatous disease v0.2 CYBB Bryony Thompson Gene: cybb has been classified as Green List (High Evidence).
Congenital Heart Defect v0.40 MYH6 Crystle Lee reviewed gene: MYH6: Rating: GREEN; Mode of pathogenicity: Other; Publications: 20656787, 29969989, 15735645; Phenotypes: Atrial septal defect 3 (MIM#614089); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Chronic granulomatous disease v0.1 CYBA Bryony Thompson Classified gene: CYBA as Green List (high evidence)
Chronic granulomatous disease v0.1 CYBA Bryony Thompson Gene: cyba has been classified as Green List (High Evidence).
Chronic granulomatous disease v0.0 NOD2 Bryony Thompson gene: NOD2 was added
gene: NOD2 was added to Chronic granulomatous disease. Sources: Expert list
Mode of inheritance for gene: NOD2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: NOD2 were set to Blau syndrome MIM#186580
Chronic granulomatous disease v0.0 NCF4 Bryony Thompson gene: NCF4 was added
gene: NCF4 was added to Chronic granulomatous disease. Sources: Expert list
Mode of inheritance for gene: NCF4 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NCF4 were set to Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type III MIM#613960
Chronic granulomatous disease v0.0 NCF2 Bryony Thompson gene: NCF2 was added
gene: NCF2 was added to Chronic granulomatous disease. Sources: Expert list
Mode of inheritance for gene: NCF2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NCF2 were set to Chronic granulomatous disease due to deficiency of NCF-2 MIM#233710
Chronic granulomatous disease v0.0 NCF1 Bryony Thompson gene: NCF1 was added
gene: NCF1 was added to Chronic granulomatous disease. Sources: Expert list
Mode of inheritance for gene: NCF1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NCF1 were set to Chronic granulomatous disease due to deficiency of NCF-1 MIM#233700
Chronic granulomatous disease v0.0 G6PD Bryony Thompson gene: G6PD was added
gene: G6PD was added to Chronic granulomatous disease. Sources: Expert list
Mode of inheritance for gene: G6PD was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Phenotypes for gene: G6PD were set to Hemolytic anemia, G6PD deficient (favism) MIM#300908
Chronic granulomatous disease v0.0 CYBB Bryony Thompson gene: CYBB was added
gene: CYBB was added to Chronic granulomatous disease. Sources: Expert list
Mode of inheritance for gene: CYBB was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: CYBB were set to Chronic granulomatous disease, X-linked MIM#306400
Chronic granulomatous disease v0.0 CYBA Bryony Thompson gene: CYBA was added
gene: CYBA was added to Chronic granulomatous disease. Sources: Expert list
Mode of inheritance for gene: CYBA was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CYBA were set to Chronic granulomatous disease, autosomal, due to deficiency of CYBA MIM#233690
Chronic granulomatous disease v0.0 C17orf62 Bryony Thompson gene: C17orf62 was added
gene: C17orf62 was added to Chronic granulomatous disease. Sources: Expert list
Mode of inheritance for gene: C17orf62 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C17orf62 were set to 30361506; 30312704
Phenotypes for gene: C17orf62 were set to Chronic granulomatous disease
Chronic granulomatous disease v0.0 Bryony Thompson Added panel Chronic granulomatous disease
Heterotaxy v0.75 DNAH9 Elena Savva gene: DNAH9 was added
gene: DNAH9 was added to Heterotaxy. Sources: Expert list
Mode of inheritance for gene: DNAH9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DNAH9 were set to PMID: 30471717; 30471718
Phenotypes for gene: DNAH9 were set to Ciliary dyskinesia, primary, 40 618300
Review for gene: DNAH9 was set to GREEN
Added comment: OMIM: Situs inversus of the heart

PMID: 30471717 - 4 patients (3 families) all with PCD and situs inversus.

PMID: 30471718 - 5 families with situs inversus totalis and/or heterotaxy
Sources: Expert list
Mendeliome v0.2932 DNAH6 Elena Savva gene: DNAH6 was added
gene: DNAH6 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: DNAH6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DNAH6 were set to PMID: 26918822
Phenotypes for gene: DNAH6 were set to Heterotaxy, Azoospermia
Review for gene: DNAH6 was set to AMBER
Added comment: PMID: 26918822 - zebrafish model has disrupted motile cilia and cilia length, with some body axis defects within embryos. Transfected human cells also had defective motile cilia and cilia width.
Two patients with heterotaxy, one homozygous (missense), the other heterozygous (missense), but the heterozygous carrier has an additional known PCD mutation in DNA1.

Summary: 1 convincing patient with animal model
Sources: Literature
Heterotaxy v0.75 DNAH1 Elena Savva gene: DNAH1 was added
gene: DNAH1 was added to Heterotaxy. Sources: Expert list
Mode of inheritance for gene: DNAH1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DNAH1 were set to PMID: 25927852; 24360805
Phenotypes for gene: DNAH1 were set to ?Ciliary dyskinesia, primary, 37 617577
Review for gene: DNAH1 was set to RED
Added comment: PMID: 25927852 - 2 homozygous siblings with a missense variant and PCD. Proband had situs invertus, sibling details unavailable.

PMID: 24360805 - 7 patients (4 different variants) with homozygous variants and infertility due to defective sperm. No mention of patients and situs inversus "Apart from infertility, none of the 20 individuals declared suffering from any of the principal PCD symptoms"

Summary: single report but emerging gene with limited reports
Sources: Expert list
Heterotaxy v0.75 DNAAF2 Elena Savva reviewed gene: DNAAF2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 19052621, 31107948; Phenotypes: Ciliary dyskinesia, primary, 10 612518; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Heterotaxy v0.75 CCNO Elena Savva reviewed gene: CCNO: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 24747639, 24824133, 31765523; Phenotypes: Ciliary dyskinesia, primary, 29 615872; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Heart Defect v0.40 NKX2-5 Crystle Lee reviewed gene: NKX2-5: Rating: GREEN; Mode of pathogenicity: None; Publications: 25742962, 26805889; Phenotypes: Ventricular septal defect 3 (MIM#614432), Tetralogy of Fallot (MIM#187500); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Heterotaxy v0.75 NPHP4 Crystle Lee gene: NPHP4 was added
gene: NPHP4 was added to Heterotaxy. Sources: Expert Review
Mode of inheritance for gene: NPHP4 was set to Unknown
Publications for gene: NPHP4 were set to 22550138
Phenotypes for gene: NPHP4 were set to Pleiotropic Heart Malformations (PMID: 22550138)
Review for gene: NPHP4 was set to AMBER
Added comment: Single publication in 2012 reported biallelic variants in a consanguineous family and additional heterozygous variants in sporadic patients with cardiac laterality defects. Knockdown nphp4 expression in zebrafish caused laterality defects.

PMID: 22550138; Frenh 2012: Hom missense reported in a consang family with with cardiac laterality defects. 9 additional het sporadic cases reported with features of heterotaxy. p.(Ala1110Val) reported in one patient with abdominal situs inversus but variant is present in gnomAD (1007 hets and 3 hom), another missense, p.(Pro541Leu), reported in patient with midline liver and asplenia (variant is present 228x in gnomAD). Most of the variants in the sporadic cases either many hets or present in homozygosity.
Sources: Expert Review
Catecholaminergic Polymorphic Ventricular Tachycardia v0.10 RYR2 Ivan Macciocca changed review comment from: rated as definitive by ClinGen; to: rated as definitive by ClinGen 03/08/2017
Long QT Syndrome v0.7 TRDN Ivan Macciocca gene: TRDN was added
gene: TRDN was added to Long QT Syndrome. Sources: Expert list
Mode of inheritance for gene: TRDN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRDN were set to long QT syndrome
Phenotypes for gene: TRDN were set to PMID: 31983240; 25922419
Review for gene: TRDN was set to GREEN
gene: TRDN was marked as current diagnostic
Added comment: definitive as reported in Circulation. 2020 Feb 11;141(6):418-428 PMID: 31983240, by the International, Multicentered LQTS ClinGen Working Group:
Evidence for involvement of TRDN in LQTS was based mainly on a single publication demonstrating 5 cases with homozygous or compound heterozygous frameshift variants. All cases presented during early childhood (up to the age of 3 years) with QT prolongation, negative T waves in precordial leads, and exercise-induced arrhythmias, although typical
torsades de pointes was demonstrated only in 1 case. Experimental evidence demonstrated that TRDN loss of function may lead to arrhythmogenesis but did not specifically show prolongation of repolarization, which is the hallmark of LQTS. Accordingly, there was a debate
within the panel as to whether the TRDN-related cardiac phenotype should be classified as CPVT or as a unique syndrome, referred in the literature as triadin knockout syndrome. Because QT prolongation was the most easily discernable abnormality, it was decided to consider these cases as having an atypical LQTS phenotype. Furthermore, it was agreed that there was strong evidence for TRDN’s disease association.
Sources: Expert list
Long QT Syndrome v0.7 SNTA1 Ivan Macciocca reviewed gene: SNTA1: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 31983240; Phenotypes: long QT syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Long QT Syndrome v0.7 SCN5A Ivan Macciocca reviewed gene: SCN5A: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31983240; Phenotypes: long QT syndrome, Brugada syndrome, dilated cardiomyopathy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Long QT Syndrome v0.7 SCN4B Ivan Macciocca reviewed gene: SCN4B: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 31983240; Phenotypes: long QT syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Long QT Syndrome v0.7 KCNQ1 Ivan Macciocca reviewed gene: KCNQ1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31983240; Phenotypes: long QT syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Long QT Syndrome v0.7 KCNJ5 Ivan Macciocca reviewed gene: KCNJ5: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 31983240; Phenotypes: long QT syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Long QT Syndrome v0.7 KCNJ2 Ivan Macciocca reviewed gene: KCNJ2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31983240; Phenotypes: long QT syndrome, Andersen-Tawil syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Long QT Syndrome v0.7 KCNE2 Ivan Macciocca edited their review of gene: KCNE2: Set current diagnostic: yes
Long QT Syndrome v0.7 KCNH2 Ivan Macciocca reviewed gene: KCNH2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31983240; Phenotypes: long QT syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Long QT Syndrome v0.7 KCNE2 Ivan Macciocca reviewed gene: KCNE2: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 31983240, 28794082; Phenotypes: ; Mode of inheritance: None
Long QT Syndrome v0.7 KCNE1 Ivan Macciocca reviewed gene: KCNE1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: long QT syndrome, acquired LQTS; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Long QT Syndrome v0.7 CAV3 Ivan Macciocca reviewed gene: CAV3: Rating: AMBER; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: PMID: 31983240, 17060380; Phenotypes: long QT syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Long QT Syndrome v0.7 CALM2 Ivan Macciocca gene: CALM2 was added
gene: CALM2 was added to Long QT Syndrome. Sources: Expert list
Mode of inheritance for gene: CALM2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CALM2 were set to PMID: 31983240
Phenotypes for gene: CALM2 were set to long QT syndrome
Penetrance for gene: CALM2 were set to unknown
Review for gene: CALM2 was set to GREEN
gene: CALM2 was marked as current diagnostic
Added comment: strong evidence for causality in LQTS with atypical features presenting in childhood - presentation typically in infancy or early childhood (up to 5 years) with marked bradycardia or atrioventricular block associated with severe QT prolongation, a presentation that is seen only rarely in LQTS related to SCN5A and KCNH2 genetic defects as reported in Circulation. 2020 Feb 11;141(6):418-428 PMID: 31983240, by the International, Multicentered LQTS ClinGen Working Group
Sources: Expert list
Long QT Syndrome v0.7 CALM1 Ivan Macciocca gene: CALM1 was added
gene: CALM1 was added to Long QT Syndrome. Sources: Expert Review
Mode of inheritance for gene: CALM1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: CALM1 were set to long QT syndrome
Penetrance for gene: CALM1 were set to unknown
Review for gene: CALM1 was set to GREEN
gene: CALM1 was marked as current diagnostic
Added comment: strong evidence for causality in LQTS with atypical features presenting in childhood - presentation typically in infancy or early childhood (up to 5 years) with marked bradycardia or atrioventricular block associated with severe QT prolongation, a presentation that is seen only rarely in LQTS related to SCN5A and KCNH2 genetic defects as reported in Circulation. 2020 Feb 11;141(6):418-428 PMID: 31983240, by the International, Multicentered LQTS ClinGen Working Group
Sources: Expert Review
Long QT Syndrome v0.7 CALM3 Ivan Macciocca reviewed gene: CALM3: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31983240; Phenotypes: long QT syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Long QT Syndrome v0.7 CACNA1C Ivan Macciocca reviewed gene: CACNA1C: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31983240; Phenotypes: long QT syndrome, Timothy syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Long QT Syndrome v0.7 ANK2 Ivan Macciocca reviewed gene: ANK2: Rating: ; Mode of pathogenicity: None; Publications: PMID: 31983240; Phenotypes: ; Mode of inheritance: None
Long QT Syndrome v0.7 AKAP9 Ivan Macciocca reviewed gene: AKAP9: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 31983240; Phenotypes: long QT syndrome; Mode of inheritance: None
Brugada syndrome v0.13 SCN3B Ivan Macciocca reviewed gene: SCN3B: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 29959160; Phenotypes: Brugada syndrome; Mode of inheritance: None
Brugada syndrome v0.13 GPD1L Ivan Macciocca reviewed gene: GPD1L: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 29959160; Phenotypes: ; Mode of inheritance: None
Brugada syndrome v0.13 SCN5A Ivan Macciocca reviewed gene: SCN5A: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 29959160; Phenotypes: Brugada syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Brugada syndrome v0.13 SCN1B Ivan Macciocca reviewed gene: SCN1B: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 29959160; Phenotypes: ; Mode of inheritance: None
Brugada syndrome v0.13 SCN10A Ivan Macciocca reviewed gene: SCN10A: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 29959160; Phenotypes: ; Mode of inheritance: None
Brugada syndrome v0.13 KCNJ8 Ivan Macciocca reviewed gene: KCNJ8: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 29959160; Phenotypes: ; Mode of inheritance: None
Brugada syndrome v0.13 KCNE3 Ivan Macciocca reviewed gene: KCNE3: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 29959160; Phenotypes: ; Mode of inheritance: None
Brugada syndrome v0.13 CACNB2 Ivan Macciocca changed review comment from: disputed by ClinGen (21/11/2017) and recent publication: Circulation. 2018;138:1195–1205 (PMID: 29959160); to: disputed by ClinGen (21/11/2017) and as reported in Circulation. 2018;138:1195–1205 (PMID: 29959160)
Brugada syndrome v0.13 CACNA2D1 Ivan Macciocca changed review comment from: disputed by ClinGen (21/11/2017) and recent publication: Circulation. 2018;138:1195–1205; to: disputed by ClinGen (21/11/2017) and as reported in Circulation. 2018;138:1195–1205 (PMID: 29959160)
Brugada syndrome v0.13 CACNA1C Ivan Macciocca changed review comment from: disputed by ClinGen (21/11/2017) and recent publication: Circulation. 2018;138:1195–1205; to: disputed by ClinGen (21/11/2017) and as reported in Circulation. 2018;138:1195–1205 (PMID: 29959160)
Brugada syndrome v0.13 KCND3 Ivan Macciocca reviewed gene: KCND3: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 29959160; Phenotypes: ; Mode of inheritance: None
Brugada syndrome v0.13 CACNB2 Ivan Macciocca reviewed gene: CACNB2: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 29959160; Phenotypes: ; Mode of inheritance: None
Brugada syndrome v0.13 CACNA2D1 Ivan Macciocca reviewed gene: CACNA2D1: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 29959160; Phenotypes: ; Mode of inheritance: None
Brugada syndrome v0.13 CACNA1C Ivan Macciocca reviewed gene: CACNA1C: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 29959160; Phenotypes: ; Mode of inheritance: None
Malformations of cortical development_Superpanel v0.85 Bryony Thompson Panel name changed from Malformations of cortical development Superpanel to Malformations of cortical development
Malformations of cortical development_Superpanel v0.84 Bryony Thompson Panel types changed to Royal Melbourne Hospital; Rare Disease
Malformations of cortical development_Superpanel v0.83 Bryony Thompson Changed child panels to: Polymicrogyria and Schizencephaly; Lissencephaly and Band Heterotopia; Tuberous Sclerosis_Cortical Dysplasia_Hemimegalencephaly; Tubulinopathies; Cobblestone Malformations; Periventricular Grey Matter Heterotopia
Malformations of cortical development_Superpanel v0.82 Bryony Thompson Changed child panels to: Microcephaly; Polymicrogyria and Schizencephaly; Lissencephaly and Band Heterotopia; Tuberous Sclerosis_Cortical Dysplasia_Hemimegalencephaly; Tubulinopathies; Cobblestone Malformations; Periventricular Grey Matter Heterotopia
Microcephaly v0.125 CSNK2A1 Zornitza Stark Marked gene: CSNK2A1 as ready
Microcephaly v0.125 CSNK2A1 Zornitza Stark Gene: csnk2a1 has been classified as Green List (High Evidence).
Polymicrogyria and Schizencephaly v0.83 GPSM2 Bryony Thompson Marked gene: GPSM2 as ready
Polymicrogyria and Schizencephaly v0.83 GPSM2 Bryony Thompson Gene: gpsm2 has been classified as Green List (High Evidence).
Polymicrogyria and Schizencephaly v0.83 GPSM2 Bryony Thompson Classified gene: GPSM2 as Green List (high evidence)
Polymicrogyria and Schizencephaly v0.83 GPSM2 Bryony Thompson Gene: gpsm2 has been classified as Green List (High Evidence).
Polymicrogyria and Schizencephaly v0.82 GPSM2 Bryony Thompson gene: GPSM2 was added
gene: GPSM2 was added to Polymicrogyria and Schizencephaly. Sources: Expert list
Mode of inheritance for gene: GPSM2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GPSM2 were set to 22578326
Phenotypes for gene: GPSM2 were set to Chudley-McCullough syndrome MIM#604213
Review for gene: GPSM2 was set to GREEN
Added comment: Polymicrogyria is a prominent feature of the condtion, reported in at least 10/10 families.
Sources: Expert list
Malformations of cortical development_Superpanel v0.79 Bryony Thompson Changed child panels to: Microcephaly; Polymicrogyria and Schizencephaly; Lissencephaly and Band Heterotopia; Tuberous Sclerosis_Cortical Dysplasia_Hemimegalencephaly; Cobblestone Malformations; Periventricular Grey Matter Heterotopia
Microcephaly v0.125 CSNK2A1 Bryony Thompson Classified gene: CSNK2A1 as Green List (high evidence)
Microcephaly v0.125 CSNK2A1 Bryony Thompson Gene: csnk2a1 has been classified as Green List (High Evidence).
Microcephaly v0.124 CSNK2A1 Bryony Thompson gene: CSNK2A1 was added
gene: CSNK2A1 was added to Microcephaly. Sources: Expert list
Mode of inheritance for gene: CSNK2A1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CSNK2A1 were set to 29240241
Phenotypes for gene: CSNK2A1 were set to Okur-Chung neurodevelopmental syndrome MIM#617062
Review for gene: CSNK2A1 was set to GREEN
Added comment: Microcephaly is a feature of the condition in 8/14 cases with de novo variants.
Sources: Expert list
Polymicrogyria and Schizencephaly v0.81 CCND2 Bryony Thompson Marked gene: CCND2 as ready
Polymicrogyria and Schizencephaly v0.81 CCND2 Bryony Thompson Gene: ccnd2 has been classified as Green List (High Evidence).
Polymicrogyria and Schizencephaly v0.81 CCND2 Bryony Thompson Classified gene: CCND2 as Green List (high evidence)
Polymicrogyria and Schizencephaly v0.81 CCND2 Bryony Thompson Gene: ccnd2 has been classified as Green List (High Evidence).
Polymicrogyria and Schizencephaly v0.80 CCND2 Bryony Thompson gene: CCND2 was added
gene: CCND2 was added to Polymicrogyria and Schizencephaly. Sources: Expert list
Mode of inheritance for gene: CCND2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CCND2 were set to 24705253
Phenotypes for gene: CCND2 were set to Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 3 MIM#615938
Mode of pathogenicity for gene: CCND2 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: CCND2 was set to GREEN
Added comment: Polymicrogyria is a prominent feature of the condition. At least 12 cases with de novo or parental mosaic missense with expected gain of function.
Sources: Expert list
Malformations of cortical development_Superpanel v0.74 Bryony Thompson Changed child panels to: Microcephaly; Polymicrogyria and Schizencephaly; Lissencephaly and Band Heterotopia; Tuberous Sclerosis_Cortical Dysplasia_Hemimegalencephaly; Cobblestone Malformations
Intellectual disability syndromic and non-syndromic v0.2656 ADAM22 Zornitza Stark Classified gene: ADAM22 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2656 ADAM22 Zornitza Stark Gene: adam22 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2655 ADAM22 Zornitza Stark Marked gene: ADAM22 as ready
Intellectual disability syndromic and non-syndromic v0.2655 ADAM22 Zornitza Stark Gene: adam22 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.2655 RAX Zornitza Stark Marked gene: RAX as ready
Intellectual disability syndromic and non-syndromic v0.2655 RAX Zornitza Stark Gene: rax has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.2655 TUBA8 Zornitza Stark Marked gene: TUBA8 as ready
Intellectual disability syndromic and non-syndromic v0.2655 TUBA8 Zornitza Stark Gene: tuba8 has been classified as Red List (Low Evidence).
Mendeliome v0.2932 XIST Zornitza Stark Marked gene: XIST as ready
Mendeliome v0.2932 XIST Zornitza Stark Gene: xist has been classified as Green List (High Evidence).
Mendeliome v0.2932 XIST Zornitza Stark Phenotypes for gene: XIST were changed from to X-inactivation, familial skewed, MIM# 300087
Mendeliome v0.2931 XIST Zornitza Stark Mode of inheritance for gene: XIST was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.2930 XIST Zornitza Stark reviewed gene: XIST: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: X-inactivation, familial skewed, MIM# 300087; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.2655 XIST Zornitza Stark Marked gene: XIST as ready
Intellectual disability syndromic and non-syndromic v0.2655 XIST Zornitza Stark Gene: xist has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.2655 WFS1 Zornitza Stark Marked gene: WFS1 as ready
Intellectual disability syndromic and non-syndromic v0.2655 WFS1 Zornitza Stark Gene: wfs1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2655 RBM10 Zornitza Stark Marked gene: RBM10 as ready
Intellectual disability syndromic and non-syndromic v0.2655 RBM10 Zornitza Stark Gene: rbm10 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2655 RBM10 Zornitza Stark Phenotypes for gene: RBM10 were changed from to TARP syndrome, 311900 (3), X-linked recessive
Intellectual disability syndromic and non-syndromic v0.2654 RBM10 Zornitza Stark Publications for gene: RBM10 were set to
Intellectual disability syndromic and non-syndromic v0.2653 RBM10 Zornitza Stark Mode of inheritance for gene: RBM10 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.2930 SYNE2 Zornitza Stark Marked gene: SYNE2 as ready
Mendeliome v0.2930 SYNE2 Zornitza Stark Gene: syne2 has been classified as Red List (Low Evidence).
Mendeliome v0.2930 SYNE2 Zornitza Stark Phenotypes for gene: SYNE2 were changed from to Emery-Dreifuss muscular dystrophy 5, autosomal dominant MIM#612999
Mendeliome v0.2929 SYNE2 Zornitza Stark Publications for gene: SYNE2 were set to
Intellectual disability syndromic and non-syndromic v0.2652 RBM10 Michelle Torres reviewed gene: RBM10: Rating: GREEN; Mode of pathogenicity: None; Publications: 24259342, 24000153, 30462380; Phenotypes: TARP syndrome, 311900 (3), X-linked recessive; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females; Current diagnostic: yes
Rhabdomyolysis and Metabolic Myopathy v0.53 YARS2 Bryony Thompson Marked gene: YARS2 as ready
Rhabdomyolysis and Metabolic Myopathy v0.53 YARS2 Bryony Thompson Gene: yars2 has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.53 YARS2 Bryony Thompson Classified gene: YARS2 as Green List (high evidence)
Rhabdomyolysis and Metabolic Myopathy v0.53 YARS2 Bryony Thompson Gene: yars2 has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.52 YARS2 Bryony Thompson gene: YARS2 was added
gene: YARS2 was added to Rhabdomyolysis RMH. Sources: Expert list
Mode of inheritance for gene: YARS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: YARS2 were set to 28395030
Phenotypes for gene: YARS2 were set to Myopathy, lactic acidosis, and sideroblastic anemia 2 MIM#613561
Review for gene: YARS2 was set to GREEN
Added comment: Exercise intolerance is a prominent presenting feature of the condition.
Sources: Expert list
Rhabdomyolysis and Metabolic Myopathy v0.51 TYMP Bryony Thompson changed review comment from: Cannot find any evidence that rhabdomyolysis is a feature of the condition. This condition has features of a visceral myopathy.; to: Cannot find any evidence that rhabdomyolysis is a feature of the condition. One case reported with exercise intolerance as a presenting feature of the condition.
Rhabdomyolysis and Metabolic Myopathy v0.51 TYMP Bryony Thompson edited their review of gene: TYMP: Changed publications: 24199812
Rhabdomyolysis and Metabolic Myopathy v0.51 TTN Bryony Thompson gene: TTN was added
gene: TTN was added to Rhabdomyolysis RMH. Sources: Expert list
Mode of inheritance for gene: TTN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TTN were set to 31353864
Phenotypes for gene: TTN were set to Congenital titinopathy; exercise intolerance
Review for gene: TTN was set to RED
Added comment: Exercise intolerance only reported in two cases.
Sources: Expert list
Rhabdomyolysis and Metabolic Myopathy v0.50 TSFM Bryony Thompson edited their review of gene: TSFM: Changed rating: RED
Rhabdomyolysis and Metabolic Myopathy v0.50 TSFM Bryony Thompson edited their review of gene: TSFM: Changed rating: AMBER; Changed publications: 31267352, 17033963
Rhabdomyolysis and Metabolic Myopathy v0.50 TSEN54 Bryony Thompson edited their review of gene: TSEN54: Changed publications: 23177318; Changed phenotypes: Pontocerebellar hypoplasia type 2A MIM#277470
Rhabdomyolysis and Metabolic Myopathy v0.50 TSEN54 Bryony Thompson changed review comment from: Cannot find any evidence that rhabdomyolysis is a feature of the condition. Hypertonia reported which is neurogenic.; to: Single case reported with recurrent rhabdomyolysis and PCH with a homozygous variant.
Rhabdomyolysis and Metabolic Myopathy v0.50 TNNT1 Bryony Thompson Marked gene: TNNT1 as ready
Rhabdomyolysis and Metabolic Myopathy v0.50 TNNT1 Bryony Thompson Gene: tnnt1 has been classified as Amber List (Moderate Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.50 TNNT1 Bryony Thompson Classified gene: TNNT1 as Amber List (moderate evidence)
Rhabdomyolysis and Metabolic Myopathy v0.50 TNNT1 Bryony Thompson Gene: tnnt1 has been classified as Amber List (Moderate Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.49 TNNT1 Bryony Thompson gene: TNNT1 was added
gene: TNNT1 was added to Rhabdomyolysis RMH. Sources: Expert list
Mode of inheritance for gene: TNNT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TNNT1 were set to 31970803
Phenotypes for gene: TNNT1 were set to Nemaline myopathy 5, Amish type MIM#605355
Review for gene: TNNT1 was set to AMBER
Added comment: 4 individuals belonging to 3 apparently unrelated families of French Canadian ancestry
harbouring a novel homozygous TNNT1 (NM_003283.6:c.287T>C; p.Leu96Pro) missense with recurrent episodes of rhabdomyolysis.
Sources: Expert list
Rhabdomyolysis and Metabolic Myopathy v0.48 TAZ Bryony Thompson Classified gene: TAZ as Green List (high evidence)
Rhabdomyolysis and Metabolic Myopathy v0.48 TAZ Bryony Thompson Gene: taz has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.47 TAZ Bryony Thompson gene: TAZ was added
gene: TAZ was added to Rhabdomyolysis RMH. Sources: Expert list
Mode of inheritance for gene: TAZ was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: TAZ were set to 26845103
Phenotypes for gene: TAZ were set to Barth syndrome MIM#302060
Review for gene: TAZ was set to GREEN
Added comment: Exercise intolerance is a prominent feature of the condition.
Sources: Expert list
Mendeliome v0.2928 SYNE2 Bryony Thompson Classified gene: SYNE2 as Red List (low evidence)
Mendeliome v0.2928 SYNE2 Bryony Thompson Gene: syne2 has been classified as Red List (Low Evidence).
Mendeliome v0.2927 SYNE2 Bryony Thompson reviewed gene: SYNE2: Rating: RED; Mode of pathogenicity: None; Publications: 32184094, 17761684; Phenotypes: Emery-Dreifuss muscular dystrophy 5, autosomal dominant MIM#612999; Mode of inheritance: None
Rhabdomyolysis and Metabolic Myopathy v0.46 SLC25A20 Bryony Thompson gene: SLC25A20 was added
gene: SLC25A20 was added to Rhabdomyolysis RMH. Sources: Literature
Mode of inheritance for gene: SLC25A20 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC25A20 were set to 24088670
Phenotypes for gene: SLC25A20 were set to Carnitine-acylcarnitine translocase deficiency MIM#212138
Review for gene: SLC25A20 was set to RED
Added comment: Single case with rhabdomyolysis with biallelic variants.
Sources: Literature
Rhabdomyolysis and Metabolic Myopathy v0.45 SLC25A4 Bryony Thompson Marked gene: SLC25A4 as ready
Rhabdomyolysis and Metabolic Myopathy v0.45 SLC25A4 Bryony Thompson Gene: slc25a4 has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.45 SLC25A4 Bryony Thompson Classified gene: SLC25A4 as Green List (high evidence)
Rhabdomyolysis and Metabolic Myopathy v0.45 SLC25A4 Bryony Thompson Gene: slc25a4 has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.44 SLC25A4 Bryony Thompson gene: SLC25A4 was added
gene: SLC25A4 was added to Rhabdomyolysis RMH. Sources: Expert list
Mode of inheritance for gene: SLC25A4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC25A4 were set to 28823815
Phenotypes for gene: SLC25A4 were set to Mitochondrial DNA depletion syndrome 12B (cardiomyopathic type) AR MIM#615418
Review for gene: SLC25A4 was set to GREEN
Added comment: Five unrelated cases reported with exercise intolerance as a presenting feature of the condition.
Sources: Expert list
Rhabdomyolysis and Metabolic Myopathy v0.43 SGCA Bryony Thompson Marked gene: SGCA as ready
Rhabdomyolysis and Metabolic Myopathy v0.43 SGCA Bryony Thompson Gene: sgca has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.43 SGCA Bryony Thompson Classified gene: SGCA as Green List (high evidence)
Rhabdomyolysis and Metabolic Myopathy v0.43 SGCA Bryony Thompson Gene: sgca has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.42 SGCA Bryony Thompson gene: SGCA was added
gene: SGCA was added to Rhabdomyolysis RMH. Sources: Expert list
Mode of inheritance for gene: SGCA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SGCA were set to 27297959; 26453141; 23989969
Phenotypes for gene: SGCA were set to Muscular dystrophy, limb-girdle, autosomal recessive 3 MIM#608099
Review for gene: SGCA was set to GREEN
Added comment: Four unrelated cases reported with rhabdomyolysis or exercise intolerance.
Sources: Expert list
Rhabdomyolysis and Metabolic Myopathy v0.41 KCNJ11 Bryony Thompson gene: KCNJ11 was added
gene: KCNJ11 was added to Rhabdomyolysis RMH. Sources: Literature
Mode of inheritance for gene: KCNJ11 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: KCNJ11 were set to Hyperinsulinemic hypoglycemia, familial, 2 MIM#601820
Review for gene: KCNJ11 was set to RED
Added comment: Single consanguineous family reported with congenital hyperinsulinism and rhabdomyolysis
Sources: Literature
Mendeliome v0.2927 PRKAG3 Bryony Thompson Classified gene: PRKAG3 as Amber List (moderate evidence)
Mendeliome v0.2927 PRKAG3 Bryony Thompson Gene: prkag3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2926 PRKAG3 Bryony Thompson reviewed gene: PRKAG3: 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: 17878938, 10818001; Phenotypes: increased glycogen content in skeletal muscle; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2926 PAH Elena Savva reviewed gene: PAH: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Phenylketonuria 261600, [Hyperphenylalaninemia, non-PKU mild] 261600; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Rhabdomyolysis and Metabolic Myopathy v0.40 HMBS Bryony Thompson Marked gene: HMBS as ready
Rhabdomyolysis and Metabolic Myopathy v0.40 HMBS Bryony Thompson Gene: hmbs has been classified as Amber List (Moderate Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.40 HMBS Bryony Thompson Classified gene: HMBS as Amber List (moderate evidence)
Rhabdomyolysis and Metabolic Myopathy v0.40 HMBS Bryony Thompson Gene: hmbs has been classified as Amber List (Moderate Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.39 HMBS Bryony Thompson gene: HMBS was added
gene: HMBS was added to Rhabdomyolysis RMH. Sources: Literature
Mode of inheritance for gene: HMBS was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HMBS were set to 25389600; 18647325
Phenotypes for gene: HMBS were set to Porphyria, acute intermittent MIM#176000
Review for gene: HMBS was set to AMBER
Added comment: Two cases reported with rhabdomyolysis.
Sources: Literature
Rhabdomyolysis and Metabolic Myopathy v0.38 FDX2 Bryony Thompson Marked gene: FDX2 as ready
Rhabdomyolysis and Metabolic Myopathy v0.38 FDX2 Bryony Thompson Gene: fdx2 has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.38 FDX2 Bryony Thompson Classified gene: FDX2 as Green List (high evidence)
Rhabdomyolysis and Metabolic Myopathy v0.38 FDX2 Bryony Thompson Gene: fdx2 has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.37 FDX2 Bryony Thompson gene: FDX2 was added
gene: FDX2 was added to Rhabdomyolysis RMH. Sources: Literature
Mode of inheritance for gene: FDX2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FDX2 were set to 24281368; 30010796; 28803783
Phenotypes for gene: FDX2 were set to Mitochondrial myopathy, episodic, with optic atrophy and reversible leukoencephalopathy MIM#251900
Review for gene: FDX2 was set to GREEN
Added comment: Three unrelated cases reported with rhabdomyolysis/myoglobinuria.
Sources: Literature
Rhabdomyolysis and Metabolic Myopathy v0.36 DGUOK Bryony Thompson gene: DGUOK was added
gene: DGUOK was added to Rhabdomyolysis RMH. Sources: Literature
Mode of inheritance for gene: DGUOK was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DGUOK were set to 23043144
Phenotypes for gene: DGUOK were set to Rhabdomyolisis; lower limb weakness
Review for gene: DGUOK was set to RED
Added comment: Single case reported with rhabdomyolysis
Sources: Literature
Rhabdomyolysis and Metabolic Myopathy v0.35 CASQ1 Bryony Thompson Marked gene: CASQ1 as ready
Rhabdomyolysis and Metabolic Myopathy v0.35 CASQ1 Bryony Thompson Gene: casq1 has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.35 CASQ1 Bryony Thompson Classified gene: CASQ1 as Green List (high evidence)
Rhabdomyolysis and Metabolic Myopathy v0.35 CASQ1 Bryony Thompson Gene: casq1 has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.34 CASQ1 Bryony Thompson gene: CASQ1 was added
gene: CASQ1 was added to Rhabdomyolysis RMH. Sources: Literature
Mode of inheritance for gene: CASQ1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CASQ1 were set to 30258016
Phenotypes for gene: CASQ1 were set to Myopathy, vacuolar, with CASQ1 aggregates MIM#616231
Review for gene: CASQ1 was set to GREEN
Added comment: Exercise intolerance has been reported as the presenting symptom in at least 5 cases, mainly with the described founder mutation (p.Asp244Gly).
Sources: Literature
Rhabdomyolysis and Metabolic Myopathy v0.33 PNPLA2 Bryony Thompson Marked gene: PNPLA2 as ready
Rhabdomyolysis and Metabolic Myopathy v0.33 PNPLA2 Bryony Thompson Gene: pnpla2 has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.33 PNPLA2 Bryony Thompson Classified gene: PNPLA2 as Green List (high evidence)
Rhabdomyolysis and Metabolic Myopathy v0.33 PNPLA2 Bryony Thompson Gene: pnpla2 has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.32 PNPLA2 Bryony Thompson gene: PNPLA2 was added
gene: PNPLA2 was added to Rhabdomyolysis RMH. Sources: Expert list
Mode of inheritance for gene: PNPLA2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PNPLA2 were set to 18952067; 25287355; 25956450
Phenotypes for gene: PNPLA2 were set to Neutral lipid storage disease with myopathy MIM#610717
Review for gene: PNPLA2 was set to GREEN
Added comment: Three unrelated families reported with exercise intolerance as a presenting feature of the condition.
Sources: Expert list
Mendeliome v0.2926 ANO5 Zornitza Stark Marked gene: ANO5 as ready
Mendeliome v0.2926 ANO5 Zornitza Stark Gene: ano5 has been classified as Green List (High Evidence).
Mendeliome v0.2926 ANO5 Zornitza Stark Publications for gene: ANO5 were set to
Mendeliome v0.2925 ANO5 Zornitza Stark Phenotypes for gene: ANO5 were changed from to Gnathodiaphyseal dysplasia MIM#166260; Miyoshi muscular dystrophy 3 MIM#613319; Muscular dystrophy, limb-girdle, autosomal recessive 12 MIM#611307
Rhabdomyolysis and Metabolic Myopathy v0.31 AMACR Bryony Thompson gene: AMACR was added
gene: AMACR was added to Rhabdomyolysis RMH. Sources: Literature
Mode of inheritance for gene: AMACR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AMACR were set to 20921516
Phenotypes for gene: AMACR were set to rhabdomyolysis
Review for gene: AMACR was set to RED
Added comment: Single case with rahbdomyolysis reported, with a homozygous missense
Sources: Literature
Mendeliome v0.2924 ANO5 Zornitza Stark Mode of inheritance for gene: ANO5 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.2923 CPT1B Zornitza Stark Marked gene: CPT1B as ready
Mendeliome v0.2923 CPT1B Zornitza Stark Gene: cpt1b has been classified as Red List (Low Evidence).
Mendeliome v0.2923 CPT1B Zornitza Stark Publications for gene: CPT1B were set to
Mendeliome v0.2922 CPT1B Zornitza Stark Mode of inheritance for gene: CPT1B was changed from Unknown to Unknown
Rhabdomyolysis and Metabolic Myopathy v0.30 MYH3 Bryony Thompson gene: MYH3 was added
gene: MYH3 was added to Rhabdomyolysis RMH. Sources: Expert list
Mode of inheritance for gene: MYH3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MYH3 were set to 28779239
Phenotypes for gene: MYH3 were set to paresthesia; rhabdomyolysis
Review for gene: MYH3 was set to RED
Added comment: Single case with rhabdomyolysis reported.
Sources: Expert list
Rhabdomyolysis and Metabolic Myopathy v0.29 TWNK Bryony Thompson Classified gene: TWNK as Green List (high evidence)
Rhabdomyolysis and Metabolic Myopathy v0.29 TWNK Bryony Thompson Gene: twnk has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.28 TWNK Bryony Thompson gene: TWNK was added
gene: TWNK was added to Rhabdomyolysis RMH. Sources: Expert list
Mode of inheritance for gene: TWNK was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TWNK were set to 20880070
Phenotypes for gene: TWNK were set to Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3 MIM#609286
Review for gene: TWNK was set to GREEN
Added comment: Exercise intolerance reported as a presenting feature of the condition in at least 5 cases.
Sources: Expert list
Rhabdomyolysis and Metabolic Myopathy v0.27 AHCY Bryony Thompson gene: AHCY was added
gene: AHCY was added to Rhabdomyolysis RMH. Sources: Expert list
Mode of inheritance for gene: AHCY was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AHCY were set to 28779239
Phenotypes for gene: AHCY were set to Hypermethioninemia with deficiency of S-adenosylhomocysteine hydrolase MIM#613752
Review for gene: AHCY was set to RED
Added comment: Single case reported with rhabdomyolysis
Sources: Expert list
Rhabdomyolysis and Metabolic Myopathy v0.26 COQ8A Bryony Thompson Marked gene: COQ8A as ready
Rhabdomyolysis and Metabolic Myopathy v0.26 COQ8A Bryony Thompson Gene: coq8a has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.26 COQ8A Bryony Thompson Classified gene: COQ8A as Green List (high evidence)
Rhabdomyolysis and Metabolic Myopathy v0.26 COQ8A Bryony Thompson Gene: coq8a has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.25 COQ8A Bryony Thompson gene: COQ8A was added
gene: COQ8A was added to Rhabdomyolysis RMH. Sources: Expert list
Mode of inheritance for gene: COQ8A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COQ8A were set to 32337771
Phenotypes for gene: COQ8A were set to Coenzyme Q10 deficiency, primary, 4 MIM#612016
Review for gene: COQ8A was set to GREEN
gene: COQ8A was marked as current diagnostic
Added comment: Exercise intolerance is a presenting feature in 25% of cases (out of 59 total).
Sources: Expert list
Mendeliome v0.2921 MYF6 Bryony Thompson Classified gene: MYF6 as Red List (low evidence)
Mendeliome v0.2921 MYF6 Bryony Thompson Gene: myf6 has been classified as Red List (Low Evidence).
Mendeliome v0.2920 MYF6 Bryony Thompson reviewed gene: MYF6: Rating: RED; Mode of pathogenicity: None; Publications: 11053684; Phenotypes: Centronuclear myopathy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2920 MTMR14 Bryony Thompson Classified gene: MTMR14 as Red List (low evidence)
Mendeliome v0.2920 MTMR14 Bryony Thompson Added comment: Comment on list classification: No evidence of Mendelian disease
Mendeliome v0.2920 MTMR14 Bryony Thompson Gene: mtmr14 has been classified as Red List (Low Evidence).
Mendeliome v0.2919 MTMR14 Bryony Thompson reviewed gene: MTMR14: Rating: RED; Mode of pathogenicity: None; Publications: 17008356; Phenotypes: {Centronuclear myopathy, autosomal, modifier of} MIM#160150; Mode of inheritance: Unknown
Rhabdomyolysis and Metabolic Myopathy v0.22 GMPPB Bryony Thompson Marked gene: GMPPB as ready
Rhabdomyolysis and Metabolic Myopathy v0.22 GMPPB Bryony Thompson Gene: gmppb has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.22 GMPPB Bryony Thompson Classified gene: GMPPB as Green List (high evidence)
Rhabdomyolysis and Metabolic Myopathy v0.22 GMPPB Bryony Thompson Gene: gmppb has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.21 GMPPB Bryony Thompson gene: GMPPB was added
gene: GMPPB was added to Rhabdomyolysis RMH. Sources: Expert list
Mode of inheritance for gene: GMPPB was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GMPPB were set to 28456886; 27874200; 25681410
Phenotypes for gene: GMPPB were set to Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 14 MIM#615352; Limb myalgia; exercise intolerance; myoglobinuria
Review for gene: GMPPB was set to GREEN
Added comment: Three unrelated cases reported with rhabdomyolysis.
Sources: Expert list
Rhabdomyolysis and Metabolic Myopathy v0.20 DNA2 Bryony Thompson gene: DNA2 was added
gene: DNA2 was added to Rhabdomyolysis RMH. Sources: Expert list
Mode of inheritance for gene: DNA2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DNA2 were set to 31636600
Phenotypes for gene: DNA2 were set to Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 6 MIM#615156
Review for gene: DNA2 was set to RED
Added comment: Single case reported with rhabdomyolysis
Sources: Expert list
Rhabdomyolysis and Metabolic Myopathy v0.19 Bryony Thompson removed gene:CYP2C8 from the panel
Rhabdomyolysis and Metabolic Myopathy v0.18 CYP2C8 Bryony Thompson Classified gene: CYP2C8 as No list
Rhabdomyolysis and Metabolic Myopathy v0.18 CYP2C8 Bryony Thompson Gene: cyp2c8 has been removed from the panel.
Mendeliome v0.2919 CPT1B Bryony Thompson Classified gene: CPT1B as Red List (low evidence)
Mendeliome v0.2919 CPT1B Bryony Thompson Gene: cpt1b has been classified as Red List (Low Evidence).
Mendeliome v0.2918 CPT1B Bryony Thompson reviewed gene: CPT1B: Rating: RED; Mode of pathogenicity: None; Publications: 18023382; Phenotypes: ; Mode of inheritance: Unknown
Rhabdomyolysis and Metabolic Myopathy v0.17 COL4A1 Bryony Thompson gene: COL4A1 was added
gene: COL4A1 was added to Rhabdomyolysis RMH. Sources: Expert list
Mode of inheritance for gene: COL4A1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: COL4A1 were set to 31540749
Phenotypes for gene: COL4A1 were set to Recurrent rhabdomyolysis; infections; hypertrophic cardiomyopathy.
Review for gene: COL4A1 was set to RED
Added comment: Single case reported with rhabdomyolysis
Sources: Expert list
Rhabdomyolysis and Metabolic Myopathy v0.16 CHKB Bryony Thompson Marked gene: CHKB as ready
Rhabdomyolysis and Metabolic Myopathy v0.16 CHKB Bryony Thompson Gene: chkb has been classified as Red List (Low Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.16 CHKB Bryony Thompson gene: CHKB was added
gene: CHKB was added to Rhabdomyolysis RMH. Sources: Expert list
Mode of inheritance for gene: CHKB was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CHKB were set to 26782016
Phenotypes for gene: CHKB were set to Muscular dystrophy, congenital, megaconial type MIM#602541
Review for gene: CHKB was set to RED
Added comment: Single family reported with rhbdomyolysis
Sources: Expert list
Mendeliome v0.2918 ANO5 Bryony Thompson reviewed gene: ANO5: Rating: GREEN; Mode of pathogenicity: None; Publications: 32112655; Phenotypes: Gnathodiaphyseal dysplasia MIM#166260, Miyoshi muscular dystrophy 3 MIM#613319, Muscular dystrophy, limb-girdle, autosomal recessive 12 MIM#611307; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Renal Macrocystic Disease v0.31 SEC63 Zornitza Stark edited their review of gene: SEC63: Changed rating: RED
Renal Macrocystic Disease v0.31 PRKCSH Zornitza Stark Classified gene: PRKCSH as Amber List (moderate evidence)
Renal Macrocystic Disease v0.31 PRKCSH Zornitza Stark Gene: prkcsh has been classified as Amber List (Moderate Evidence).
Renal Macrocystic Disease v0.30 PRKCSH Zornitza Stark edited their review of gene: PRKCSH: Changed rating: AMBER
Renal Macrocystic Disease v0.30 ALG9 Zornitza Stark Marked gene: ALG9 as ready
Renal Macrocystic Disease v0.30 ALG9 Zornitza Stark Gene: alg9 has been classified as Amber List (Moderate Evidence).
Renal Macrocystic Disease v0.30 ALG9 Zornitza Stark Classified gene: ALG9 as Amber List (moderate evidence)
Renal Macrocystic Disease v0.30 ALG9 Zornitza Stark Gene: alg9 has been classified as Amber List (Moderate Evidence).
Renal Macrocystic Disease v0.29 ALG9 Zornitza Stark gene: ALG9 was added
gene: ALG9 was added to Renal Macrocystic Disease. Sources: Literature
Mode of inheritance for gene: ALG9 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: ALG9 were set to 31395617
Phenotypes for gene: ALG9 were set to Congenital disorder of glycosylation, type Il, MIM# 608776; Gillessen-Kaesbach-Nishimura syndrome, MIM#263210; Polycystic kidney disease
Review for gene: ALG9 was set to AMBER
Added comment: Two individuals with mono-allelic variants reported with polycystic kidney disease, and ALG9 LOF variants over-represented in a population-based cohort. However, penetrance and expressivity seem variable, and also it is unclear whether parents of children affected by the AR CDG have renal cysts. Bi-allelic variants cause CDG: kidney cysts reported as part of phenotype but note this is generally a severe multi-system disorder.
Sources: Literature
Renal Macrocystic Disease v0.28 PRKCSH Zornitza Stark changed review comment from: Well established gene-disease relationship, >50 reported families.; to: Well established gene-disease relationship, >50 reported families. Liver cystic disease predominates the clinical presentation, generally a small number of kidney cysts.
Renal Macrocystic Disease v0.28 PRKCSH Zornitza Stark Phenotypes for gene: PRKCSH were changed from Polycystic liver disease 1, MIM# 174050, with or without kidney cysts to Polycystic liver disease 1, MIM# 174050, with or without kidney cysts
Renal Macrocystic Disease v0.28 PRKCSH Zornitza Stark Marked gene: PRKCSH as ready
Renal Macrocystic Disease v0.28 PRKCSH Zornitza Stark Gene: prkcsh has been classified as Green List (High Evidence).
Renal Macrocystic Disease v0.28 PRKCSH Zornitza Stark Phenotypes for gene: PRKCSH were changed from to Polycystic liver disease 1, MIM# 174050, with or without kidney cysts
Renal Macrocystic Disease v0.27 PRKCSH Zornitza Stark Publications for gene: PRKCSH were set to
Renal Macrocystic Disease v0.26 PRKCSH Zornitza Stark Mode of inheritance for gene: PRKCSH was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Renal Macrocystic Disease v0.25 PRKCSH Zornitza Stark reviewed gene: PRKCSH: Rating: GREEN; Mode of pathogenicity: None; Publications: 12577059; Phenotypes: Polycystic liver disease 1, MIM# 174050, with or without kidney cysts; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2918 DNAJB11 Zornitza Stark Marked gene: DNAJB11 as ready
Mendeliome v0.2918 DNAJB11 Zornitza Stark Gene: dnajb11 has been classified as Green List (High Evidence).
Mendeliome v0.2918 DNAJB11 Zornitza Stark Phenotypes for gene: DNAJB11 were changed from to Polycystic kidney disease 6 with or without polycystic liver disease, MIM#618061
Mendeliome v0.2917 DNAJB11 Zornitza Stark Publications for gene: DNAJB11 were set to
Mendeliome v0.2916 DNAJB11 Zornitza Stark Mode of inheritance for gene: DNAJB11 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2915 DNAJB11 Zornitza Stark reviewed gene: DNAJB11: Rating: GREEN; Mode of pathogenicity: None; Publications: 29706351, 29777155; Phenotypes: Polycystic kidney disease 6 with or without polycystic liver disease, MIM#618061; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Polymicrogyria and Schizencephaly v0.79 RAB3GAP1 Zornitza Stark Marked gene: RAB3GAP1 as ready
Polymicrogyria and Schizencephaly v0.79 RAB3GAP1 Zornitza Stark Gene: rab3gap1 has been classified as Green List (High Evidence).
Polymicrogyria and Schizencephaly v0.79 RAB3GAP1 Zornitza Stark Phenotypes for gene: RAB3GAP1 were changed from to Warburg micro syndrome 1, MIM# 600118
Polymicrogyria and Schizencephaly v0.78 RAB3GAP1 Zornitza Stark Publications for gene: RAB3GAP1 were set to
Polymicrogyria and Schizencephaly v0.77 RAB3GAP1 Zornitza Stark Mode of inheritance for gene: RAB3GAP1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Polymicrogyria and Schizencephaly v0.76 RAB18 Zornitza Stark Marked gene: RAB18 as ready
Polymicrogyria and Schizencephaly v0.76 RAB18 Zornitza Stark Gene: rab18 has been classified as Green List (High Evidence).
Polymicrogyria and Schizencephaly v0.76 RAB18 Zornitza Stark Phenotypes for gene: RAB18 were changed from to Warburg micro syndrome 3, MIM# 614222
Polymicrogyria and Schizencephaly v0.75 RAB18 Zornitza Stark Publications for gene: RAB18 were set to
Polymicrogyria and Schizencephaly v0.74 RAB18 Zornitza Stark Mode of inheritance for gene: RAB18 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Tuberous Sclerosis_Focal Cortical Dysplasia_Hemimegalencephaly v0.10 PTEN Zornitza Stark Marked gene: PTEN as ready
Tuberous Sclerosis_Focal Cortical Dysplasia_Hemimegalencephaly v0.10 PTEN Zornitza Stark Gene: pten has been classified as Green List (High Evidence).
Tuberous Sclerosis_Focal Cortical Dysplasia_Hemimegalencephaly v0.10 PTEN Zornitza Stark Phenotypes for gene: PTEN were changed from to Cowden syndrome 1 158350; Lhermitte-Duclos syndrome 158350; Macrocephaly/autism syndrome 605309
Tuberous Sclerosis_Focal Cortical Dysplasia_Hemimegalencephaly v0.9 PTEN Zornitza Stark Publications for gene: PTEN were set to
Tuberous Sclerosis_Focal Cortical Dysplasia_Hemimegalencephaly v0.8 PTEN Zornitza Stark Mode of inheritance for gene: PTEN was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v0.28 ANO5 Zornitza Stark Marked gene: ANO5 as ready
Skeletal dysplasia v0.28 ANO5 Zornitza Stark Gene: ano5 has been classified as Green List (High Evidence).
Skeletal dysplasia v0.28 ANO5 Zornitza Stark Publications for gene: ANO5 were set to
Skeletal dysplasia v0.27 ANO5 Zornitza Stark Mode of pathogenicity for gene: ANO5 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
Skeletal dysplasia v0.26 ANO5 Zornitza Stark Mode of inheritance for gene: ANO5 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v0.26 ANO5 Zornitza Stark Mode of inheritance for gene: ANO5 was changed from BIALLELIC, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v0.25 ANO5 Zornitza Stark Mode of inheritance for gene: ANO5 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v0.25 ANO5 Zornitza Stark Mode of inheritance for gene: ANO5 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.2915 GPR143 Zornitza Stark Marked gene: GPR143 as ready
Mendeliome v0.2915 GPR143 Zornitza Stark Gene: gpr143 has been classified as Green List (High Evidence).
Mendeliome v0.2915 GPR143 Zornitza Stark Phenotypes for gene: GPR143 were changed from to congenital nystagmus 6, MIM 300814; type I ocular albinism, Nettleship-Falls type, MIM 300500