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Mendeliome v1.2263 TRPM7 Zornitza Stark edited their review of gene: TRPM7: Added comment: Protein expressed in the distal tubule, related to TRPM6. Postulated link with hypoMg with secondary hypoCa. PMID 35561741: two families reported with dominant inheritance. F1: three affected individuals with splicing variant; some supportive functional data. F2: single affected individual, de novo missense variant. PMID 35712613: de novo missense variant in an individual with hypoMg. PMID 39099563: three affected individuals with missense variants, all de novo. Probands had DD, two had seizures.; Changed rating: GREEN; Changed publications: 32503408, 31423533, 35561741, 35712613, 39099563; Changed phenotypes: Familial primary hypomagnesemia, MONDO:0018100, TRPM7-related, {Amyotrophic lateral sclerosis-parkinsonism/dementia complex, susceptibility to}, MIM# 105500, Cardiac arrhythmia, stillbirth
Mendeliome v1.1954 FIG4 Zornitza Stark gene: FIG4 was added
gene: FIG4 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: FIG4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FIG4 were set to 23623387; 17572665; 21705420; 24878229; 18758830; 24598713
Phenotypes for gene: FIG4 were set to Yunis-Varon syndrome - MIM#216340; Polymicrogyria with epilepsy MIM# 612691; Charcot-Marie-Tooth disease, type 4J 611228; Amyotrophic lateral sclerosis 11, MIM# 612577
Review for gene: FIG4 was set to GREEN
Added comment: Associations between biallelic variants and CMT and Yunis Varon syndrome are well established.

Limited evidence for association with brain malformations and with ALS/FTD.
Sources: Expert Review
Mendeliome v1.1554 NEK1 Zornitza Stark Phenotypes for gene: NEK1 were changed from Short-rib thoracic dysplasia 6 with or without polydactyly, MIM# 263520; Amyotrophic lateral sclerosis, susceptibility to, 24, MIM# 617892 to Short-rib thoracic dysplasia 6 with or without polydactyly, MIM# 263520; Orofaciodigital syndrome II , MIM# 252100; Amyotrophic lateral sclerosis, susceptibility to, 24, MIM# 617892
Mendeliome v1.1552 NEK1 Zornitza Stark edited their review of gene: NEK1: Added comment: PMID 27530628: two brothers with OFD phenotype.; Changed publications: 21211617, 22499340, 25492405, 28123176, 27530628; Changed phenotypes: Short-rib thoracic dysplasia 6 with or without polydactyly, MIM# 263520, Orofaciodigital syndrome II , MIM# 252100, Amyotrophic lateral sclerosis, susceptibility to, 24, MIM# 617892
Mendeliome v1.891 SCN4A Zornitza Stark Phenotypes for gene: SCN4A were changed from Hyperkalemic periodic paralysis, type 2, MIM# 170500; Hypokalemic periodic paralysis, type 2, MIM# 613345; Myasthenic syndrome, congenital, 16, MIM# 614198; Myotonia congenita, atypical, acetazolamide-responsive , MIM#608390; Paramyotonia congenita , MIM#168300 to Congenital myopathy 22A, classic, MIM# 620351; Congenital myopathy 22B, severe fetal, MIM# 620369; Hyperkalemic periodic paralysis, type 2, MIM# 170500; Hypokalemic periodic paralysis, type 2, MIM# 613345; Myasthenic syndrome, congenital, 16, MIM# 614198; Myotonia congenita, atypical, acetazolamide-responsive , MIM#608390; Paramyotonia congenita , MIM#168300
Mendeliome v1.890 SCN4A Zornitza Stark edited their review of gene: SCN4A: Changed phenotypes: Congenital myopathy 22A, classic, MIM# 620351, Congenital myopathy 22B, severe fetal, MIM# 620369, Hyperkalemic periodic paralysis, type 2, MIM# 170500, Hypokalemic periodic paralysis, type 2, MIM# 613345, Myasthenic syndrome, congenital, 16, MIM# 614198, Myotonia congenita, atypical, acetazolamide-responsive , MIM#608390, Paramyotonia congenita , MIM#168300
Mendeliome v1.732 SPTLC1 Zornitza Stark Phenotypes for gene: SPTLC1 were changed from Neuropathy, hereditary sensory and autonomic, type IA, MIM# 162400; Serine palmitoyl transferase deficiency (Disorders of complex lipid synthesis) to Juvenile amyotrophic lateral sclerosis-27, MIM#620285; Neuropathy, hereditary sensory and autonomic, type IA, MIM# 162400; Serine palmitoyl transferase deficiency (Disorders of complex lipid synthesis)
Mendeliome v1.731 SPTLC1 Zornitza Stark edited their review of gene: SPTLC1: Changed phenotypes: Juvenile amyotrophic lateral sclerosis-27, MIM#620285, Neuropathy, hereditary sensory and autonomic, type IA, MIM# 162400, Serine palmitoyl transferase deficiency (Disorders of complex lipid synthesis)
Mendeliome v0.14672 TIA1 Elena Savva Phenotypes for gene: TIA1 were changed from Amyotrophic lateral sclerosis 26 with or without frontotemporal dementia, MIM# 619133; Welander distal myopathy (MIM#604454) to Amyotrophic lateral sclerosis 26 with or without frontotemporal dementia, MIM# 619133; Welander distal myopathy (MIM#604454)
Mendeliome v0.14667 TIA1 Elena Savva Phenotypes for gene: TIA1 were changed from to Amyotrophic lateral sclerosis 26 with or without frontotemporal dementia, MIM# 619133; Welander distal myopathy (MIM#604454)
Mendeliome v0.14422 MATR3 Zornitza Stark Phenotypes for gene: MATR3 were changed from to Amyotrophic lateral sclerosis 21, MIM# 606070; Distal myopathy
Mendeliome v0.14419 MATR3 Zornitza Stark reviewed gene: MATR3: Rating: GREEN; Mode of pathogenicity: None; Publications: 19344878, 24686783, 35205163, 34659085, 34173818, 26493020; Phenotypes: Amyotrophic lateral sclerosis 21, MIM# 606070, Distal myopathy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14229 MYOT Zornitza Stark Marked gene: MYOT as ready
Mendeliome v0.14229 MYOT Zornitza Stark Gene: myot has been classified as Green List (High Evidence).
Mendeliome v0.14229 MYOT Zornitza Stark Phenotypes for gene: MYOT were changed from to Myopathy, myofibrillar, 3, MIM# 609200; Myopathy, spheroid body, MIM# 182920
Mendeliome v0.14228 MYOT Zornitza Stark Publications for gene: MYOT were set to
Mendeliome v0.14227 MYOT Zornitza Stark Mode of inheritance for gene: MYOT was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14226 MYOT Zornitza Stark reviewed gene: MYOT: Rating: GREEN; Mode of pathogenicity: None; Publications: 10958653, 15111675, 16380616, 33250842, 32509353, 29924655; Phenotypes: Myopathy, myofibrillar, 3, MIM# 609200, Myopathy, spheroid body, MIM# 182920; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.13699 HNRNPA1 Zornitza Stark Phenotypes for gene: HNRNPA1 were changed from to Amyotrophic lateral sclerosis 20 MIM#615426
Mendeliome v0.13696 HNRNPA1 Zornitza Stark reviewed gene: HNRNPA1: Rating: GREEN; Mode of pathogenicity: None; Publications: 23455423, 34291734; Phenotypes: Amyotrophic lateral sclerosis 20 MIM#615426; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.13289 HSPG2 Zornitza Stark changed review comment from: Allelic disorders with some phenotypic overlap.

Schwartz-Jampel syndrome (SJS) is a rare autosomal recessive condition defined by the association of myotonia with chondrodysplasia; blepharophimosis is a key feature. More than 20 families reported.

Silverman-Handmaker dyssegmental dysplasia (DDSH) is a lethal autosomal recessive skeletal dysplasia with anisospondyly and micromelia. Individuals with DDSH also have a flat face, micrognathia, cleft palate and reduced joint mobility, and frequently have an encephalocele. The endochondral growth plate is short, the calcospherites (spherical calcium-phosphorus crystals produced by hypertrophic chondrocytes) are unfused, and there is mucoid degeneration of the resting cartilage. Two families reported.; to: Allelic disorders with some phenotypic overlap.

Schwartz-Jampel syndrome (SJS) is a rare autosomal recessive condition defined by the association of myotonia with chondrodysplasia; blepharophimosis is a key feature. More than 20 families reported.

Silverman-Handmaker dyssegmental dysplasia (DDSH) is a lethal autosomal recessive skeletal dysplasia with anisospondyly and micromelia. Individuals with DDSH also have a flat face, micrognathia, cleft palate and reduced joint mobility, and frequently have an encephalocele. The endochondral growth plate is short, the calcospherites (spherical calcium-phosphorus crystals produced by hypertrophic chondrocytes) are unfused, and there is mucoid degeneration of the resting cartilage. Two families reported. Appears associated with null variants.
Mendeliome v0.12973 PRPH Zornitza Stark Phenotypes for gene: PRPH were changed from to {Amyotrophic lateral sclerosis, susceptibility to}, 105400
Mendeliome v0.12969 PRPH Zornitza Stark reviewed gene: PRPH: Rating: AMBER; Mode of pathogenicity: None; Publications: 20363051, 15322088, 15446584; Phenotypes: {Amyotrophic lateral sclerosis, susceptibility to}, 105400; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.12295 TIA1 Zornitza Stark reviewed gene: TIA1: Rating: AMBER; Mode of pathogenicity: None; Publications: 29235362, 29886022, 29773329, 29699721, 29216908, 24659297, 29457785, 28817800, 23401021, 23401021; Phenotypes: Amyotrophic lateral sclerosis 26 with or without frontotemporal dementia, MIM# 619133, Welander distal myopathy (MIM#604454); Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.11193 ERBB4 Bryony Thompson Phenotypes for gene: ERBB4 were changed from Amyotrophic lateral sclerosis 19, MIM# MIM#615515; Intellectual disability to Amyotrophic lateral sclerosis 19, MIM# MIM#615515; Intellectual disability MONDO:0001071
Mendeliome v0.10999 TBK1 Chern Lim reviewed gene: TBK1: Rating: RED; Mode of pathogenicity: None; Publications: 25803835, 26581300; Phenotypes: Frontotemporal dementia and/or amyotrophic lateral sclerosis 4 (MIM#616439), AD; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v0.10554 PPIA Naomi Baker gene: PPIA was added
gene: PPIA was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PPIA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PPIA were set to PMID: 34972208
Phenotypes for gene: PPIA were set to amyotrophic lateral sclerosis, MONDO:0004976
Review for gene: PPIA was set to RED
Added comment: Paper characterizes a knockout mouse model that recapitulates key features of ALS-FTD. Also identified a heterozygous missense variant in one patient with sporadic amyotrophic lateral sclerosis. Functional studies of the missense variant suggest loss-of-function.
Sources: Literature
Mendeliome v0.10414 SCN4A Zornitza Stark Phenotypes for gene: SCN4A were changed from to Hyperkalemic periodic paralysis, type 2, MIM# 170500; Hypokalemic periodic paralysis, type 2, MIM# 613345; Myasthenic syndrome, congenital, 16, MIM# 614198; Myotonia congenita, atypical, acetazolamide-responsive , MIM#608390; Paramyotonia congenita , MIM#168300
Mendeliome v0.10411 SCN4A Zornitza Stark reviewed gene: SCN4A: Rating: GREEN; Mode of pathogenicity: None; Publications: 34671263; Phenotypes: Hyperkalemic periodic paralysis, type 2, MIM# 170500, Hypokalemic periodic paralysis, type 2, MIM# 613345, Myasthenic syndrome, congenital, 16, MIM# 614198, Myotonia congenita, atypical, acetazolamide-responsive , MIM#608390, Paramyotonia congenita , MIM#168300; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.9402 TBK1 Zornitza Stark Phenotypes for gene: TBK1 were changed from to Frontotemporal dementia and/or amyotrophic lateral sclerosis 4, MIM# 616439
Mendeliome v0.9392 TBK1 Lucy Spencer reviewed gene: TBK1: Rating: ; Mode of pathogenicity: None; Publications: PMID: 31000212, 25943890; Phenotypes: Frontotemporal dementia, amyotrophic lateral sclerosis; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.9312 ERBB4 Zornitza Stark Phenotypes for gene: ERBB4 were changed from to Amyotrophic lateral sclerosis 19, MIM# MIM#615515; Intellectual disability
Mendeliome v0.9309 ERBB4 Zornitza Stark reviewed gene: ERBB4: Rating: GREEN; Mode of pathogenicity: None; Publications: 24119685, 28889094, 33603162; Phenotypes: Amyotrophic lateral sclerosis 19, MIM# MIM#615515, Intellectual disability; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8835 ALS2 Teresa Zhao gene: ALS2 was added
gene: ALS2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ALS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ALS2 were set to PMID: 30128655; 33409823
Phenotypes for gene: ALS2 were set to Infantile onset ascending spastic paralysis (MIM#607225); Juvenile amyotrophic lateral sclerosis 2 (MIM#205100); Juvenile primary lateral sclerosis (MIM#606353)
Review for gene: ALS2 was set to GREEN
Added comment: >50 variants reported in multiple individuals with Infantile onset ascending spastic paralysis, mostly originated from the Middle East and Mediterranean countries.
Sources: Literature
Mendeliome v0.8606 VRK1 Zornitza Stark changed review comment from: Complex phenotype with mixed peripheral and central neurological features. Two families reported where PCH was prominent and accompanied by ataxia. At least three families also reported where peripheral neuropathy dominated the clinical picture without PCH/ataxia.; to: Complex phenotype with mixed peripheral and central neurological features. Two families reported where PCH was prominent and accompanied by ataxia. At least three families also reported where peripheral neuropathy dominated the clinical picture without PCH/ataxia.

Further delineation of phenotype 2021:
PMID 34169149: expanding spectrum of neurologic disorders associated with VRK1. Two Hispanic individuals, one homozygous (R321C: VUS and LP/P in ClinVar) and one cHet (R321C+V236M, latter P and more recently VUS in ClinVar), with slowly progressive weakness and a clinical syndrome consistent with adult-onset spinal muscular atrophy WITHOUT pontocerebellar atrophy. No hom in gnomAD and both have been reported in cHet individuals with other features: R321C in association with adult-onset amyotrophic lateral sclerosis and V236M with rapidly progressive sensorimotor polyneuropathy and microcephaly. Authors suggest PMID 26583493 and 31837156 have similar reports. PMID 26583493 reports a 32yo Hispanic individual, cHet H119R+R321C, with early-onset amyotrophic lateral sclerosis, 5 years progressive weakness. PMID 31837156 reports two patients with adult-onset length-dependent motor neuropathy from unrelated consanguineous families of Moroccan Jewish descent, both hom for R387H.
Mendeliome v0.7615 SEPT9 Zornitza Stark edited their review of gene: SEPT9: Added comment: Hereditary neuralgic amyotrophy (HNA) is an autosomal dominant form of recurrent focal neuropathy characterized clinically by acute, recurrent episodes of brachial plexus neuropathy with muscle weakness and atrophy preceded by severe pain in the affected arm. Multiple founder variants, including p.Arg88Trp. Also note intragenic duplication and 5'UTR variant reported, which may not be detectable by all NGS assays.; Changed publications: 16186812, 19451530, 19939853, 19139049
Mendeliome v0.7491 NEK1 Zornitza Stark Phenotypes for gene: NEK1 were changed from to Short-rib thoracic dysplasia 6 with or without polydactyly, MIM# 263520; Amyotrophic lateral sclerosis, susceptibility to, 24, MIM# 617892
Mendeliome v0.7488 NEK1 Zornitza Stark reviewed gene: NEK1: Rating: GREEN; Mode of pathogenicity: None; Publications: 21211617, 22499340, 25492405, 28123176; Phenotypes: Short-rib thoracic dysplasia 6 with or without polydactyly, MIM# 263520, Amyotrophic lateral sclerosis, susceptibility to, 24, MIM# 617892; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7488 NEK1 Eleanor Williams reviewed gene: NEK1: Rating: GREEN; Mode of pathogenicity: None; Publications: 33445179; Phenotypes: {Amyotrophic lateral sclerosis, susceptibility to, 24}, OMIM:617892; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.7479 HINT1 Zornitza Stark Phenotypes for gene: HINT1 were changed from to Neuromyotonia and axonal neuropathy, autosomal recessive, MIM# 137200; Gamstorp-Wohlfart syndrome, MONDO:0007646
Mendeliome v0.7476 HINT1 Zornitza Stark reviewed gene: HINT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 22961002, 33663550, 33404983, 31848916; Phenotypes: Neuromyotonia and axonal neuropathy, autosomal recessive, MIM# 137200, Gamstorp-Wohlfart syndrome, MONDO:0007646; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.6843 DM2 Bryony Thompson STR: DM2 was added
STR: DM2 was added to Mendeliome. Sources: Expert list
Mode of inheritance for STR: DM2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: DM2 were set to 20301639; 29325606
Phenotypes for STR: DM2 were set to Myotonic dystrophy 2 MIM#602668
Review for STR: DM2 was set to GREEN
STR: DM2 was marked as clinically relevant
Added comment: HGVS nomenclature: NM_003418.4:c.-14-833_-14-830[X]
Toxic gain of function RNA expected mechanism of disease
Normal: ≤30 uninterrupted CCTG repeats, 11-26 CCTG repeats with any GCTC or TCTG interruptions
Unknown significance (normal vs. mutable): 27-29 CCTG repeats
Mutable normal (premutation) alleles. ~30-~54 CCTG repeats
Unknown significance (premutation vs pathogenic): ~55-74 CCTG repeats
Pathogenic: ~75-11,000 CCTG repeats
Sources: Expert list
Mendeliome v0.6840 DM1 Bryony Thompson STR: DM1 was added
STR: DM1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for STR: DM1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: DM1 were set to 20301344; 29325606
Phenotypes for STR: DM1 were set to Myotonic dystrophy 1 MIM#160900
Review for STR: DM1 was set to GREEN
STR: DM1 was marked as clinically relevant
Added comment: HGVS nomenclature: NM_001081560.2:c.*224_*226CTG[X]
RNA toxic gain of function is mechanism of disease
Premutation: 35-49 repeats, no clinical signs
Mild: 50-~150 repeats, age of onset 20-70 yrs, clinical signs - cataracts, mild myotonia
Classic: ~100-~1,000 repeats, age of onset 10-30 yrs, clinical signs - weakness, myotonia, cataracts, balding, cardiac arrhythmia
Congenital: >1,000 repeats, age of onset birth-10 yrs , clinical signs - infantile hypotonia, respiratory deficits, intellectual disability, classic signs in adults
Sources: Expert list
Mendeliome v0.6070 CLCN1 Zornitza Stark Phenotypes for gene: CLCN1 were changed from to Myotonia congenita, dominant 160800; Myotonia congenita, recessive 255700
Mendeliome v0.6067 CLCN1 Zornitza Stark reviewed gene: CLCN1: Rating: GREEN; Mode of pathogenicity: None; Publications: 1379744, 7981750, 8533761; Phenotypes: Myotonia congenita, dominant 160800, Myotonia congenita, recessive 255700; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.6028 CYLD Zornitza Stark Phenotypes for gene: CYLD were changed from Brooke-Spiegler syndrome, 605041; Cylindromatosis, familial, 132700; Trichoepithelioma, multiple familial, 1, 601606; Frontotemporal dementia and amyotrophic lateral sclerosis to Brooke-Spiegler syndrome, 605041; Cylindromatosis, familial, 132700; Trichoepithelioma, multiple familial, 1, 601606; Frontotemporal dementia and/or amytrophic lateral sclerosis 8, MIM# 619132
Mendeliome v0.4722 PFN1 Zornitza Stark Phenotypes for gene: PFN1 were changed from to Amyotrophic lateral sclerosis 18 (MIM# 614808); Paget’s disease of bone
Mendeliome v0.4720 PFN1 Zornitza Stark reviewed gene: PFN1: Rating: GREEN; Mode of pathogenicity: None; Publications: 31802421, 31611772, 31401564, 30203378, 28040732, 22801503; Phenotypes: Amyotrophic lateral sclerosis 18, MIM# 614808; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4714 PFN1 Ain Roesley reviewed gene: PFN1: Rating: GREEN; Mode of pathogenicity: None; Publications: 23141414, 22801503, 25499087, 24309268, 22801503, 26908597; Phenotypes: Amyotrophic lateral sclerosis 18 (MIM# 614808); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4257 DNAJC7 Seb Lunke gene: DNAJC7 was added
gene: DNAJC7 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: DNAJC7 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: DNAJC7 were set to 31768050
Phenotypes for gene: DNAJC7 were set to amyotrophic lateral sclerosis
Review for gene: DNAJC7 was set to AMBER
Added comment: Two cohort studies in ALS patients identified 11 and 1 patient, respectively, with variants in DNAJC7. Seven of these are putative PTVs. However gene described as risk factor, unclear why.

DOI: https://doi.org/10.1212/NXG.0000000000000503
Sources: Literature
Mendeliome v0.4101 TRPM7 Zornitza Stark Phenotypes for gene: TRPM7 were changed from {Amyotrophic lateral sclerosis-parkinsonism/dementia complex, susceptibility to}, MIM# 105500 to {Amyotrophic lateral sclerosis-parkinsonism/dementia complex, susceptibility to}, MIM# 105500; Cardiac arrhythmia, stillbirth
Mendeliome v0.4097 TRPM7 Zornitza Stark edited their review of gene: TRPM7: Added comment: Ion channel expressed in the nervous and cardiac systems. The variant associated with ALS/dementia in the Guam population, p.Thr1482Ile is present in >23,000 hets in gnomad, which is out of keeping for a rare Mendelian disorder. Note recent publication associating missense variants with cardiac arrhythmia and stillbirth, with some functional data provided to substantiate effect of variant on protein function but not necessarily establish gene-disease association.; Changed rating: AMBER; Changed publications: 32503408, 31423533; Changed phenotypes: {Amyotrophic lateral sclerosis-parkinsonism/dementia complex, susceptibility to}, MIM# 105500, Cardiac arrhythmia, stillbirth; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4097 CHCHD10 Zornitza Stark Phenotypes for gene: CHCHD10 were changed from to Frontotemporal dementia and/or amyotrophic lateral sclerosis 2 615911; Spinal muscular atrophy, Jokela type 615048; Myopathy, isolated mitochondrial, autosomal dominant 616209
Mendeliome v0.4093 CHCHD10 Zornitza Stark reviewed gene: CHCHD10: Rating: GREEN; Mode of pathogenicity: Other; Publications: 24934289, 25428574, 25193783, 32042922, 31690696, 30877432, 30874923; Phenotypes: Frontotemporal dementia and/or amyotrophic lateral sclerosis 2 615911, Spinal muscular atrophy, Jokela type 615048, Myopathy, isolated mitochondrial, autosomal dominant 616209; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3189 EMILIN1 Naomi Baker changed review comment from: Missense mutations identified in two families. First family, proband presented with ascending and descending aortic aneurysms, bilateral lower leg and foot sensorimotor peripheral neuropathy, arthropathy, and increased skin elasticity. Variant segregated with disease in the affected proband, mother, and son. Second family, father and three affected children showed amyotrophy and weakness of the distal lower limbs, dating back to early childhood. Some functional studies performed in patient fibroblasts and zebrafish, however these were not conclusive as the two missense mutations are at different locations within the protein.
Sources: Literature; to: Missense mutations identified in two families. First family, proband presented with ascending and descending aortic aneurysms, bilateral lower leg and foot sensorimotor peripheral neuropathy, arthropathy, and increased skin elasticity. Variant segregated with disease in the affected proband, mother, and son. Second family, father and three affected children showed amyotrophy and weakness of the distal lower limbs, dating back to early childhood. Some functional studies performed in patient fibroblasts and zebrafish, however these were not conclusive as the two missense mutations are at different locations within the protein.
Sources: Literature
Mendeliome v0.3189 EMILIN1 Naomi Baker gene: EMILIN1 was added
gene: EMILIN1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: EMILIN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: EMILIN1 were set to PMID: 31978608; 26462740.
Phenotypes for gene: EMILIN1 were set to peripheral neuropathy
Penetrance for gene: EMILIN1 were set to unknown
Review for gene: EMILIN1 was set to AMBER
Added comment: Missense mutations identified in two families. First family, proband presented with ascending and descending aortic aneurysms, bilateral lower leg and foot sensorimotor peripheral neuropathy, arthropathy, and increased skin elasticity. Variant segregated with disease in the affected proband, mother, and son. Second family, father and three affected children showed amyotrophy and weakness of the distal lower limbs, dating back to early childhood. Some functional studies performed in patient fibroblasts and zebrafish, however these were not conclusive as the two missense mutations are at different locations within the protein.
Sources: Literature
Mendeliome v0.3044 EWSR1 Seb Lunke Phenotypes for gene: EWSR1 were changed from to Amyotrophic lateral sclerosis
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
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 v0.3038 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 v0.2466 SIGMAR1 Zornitza Stark Phenotypes for gene: SIGMAR1 were changed from to Amyotrophic lateral sclerosis 16, juvenile 614373; ?Spinal muscular atrophy, distal, autosomal recessive, 2 605726; distal hereditary motor neuropathy of Jerash type (HMNJ)
Mendeliome v0.2434 CYLD Zornitza Stark Phenotypes for gene: CYLD were changed from to Brooke-Spiegler syndrome, 605041; Cylindromatosis, familial, 132700; Trichoepithelioma, multiple familial, 1, 601606; Frontotemporal dementia and amyotrophic lateral sclerosis
Mendeliome v0.2392 SIGMAR1 Michelle Torres reviewed gene: SIGMAR1: Rating: GREEN; Mode of pathogenicity: None; Publications: 31511340; Phenotypes: ?Amyotrophic lateral sclerosis 16, juvenile 614373, ?Spinal muscular atrophy, distal, autosomal recessive, 2 605726, distal hereditary motor neuropathy of Jerash type (HMNJ); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2372 CYLD Kristin Rigbye reviewed gene: CYLD: Rating: GREEN; Mode of pathogenicity: None; Publications: 10835629, 16307661, 12950348, 19807742; Phenotypes: Brooke-Spiegler syndrome, 605041, Cylindromatosis, familial, 132700, Trichoepithelioma, multiple familial, 1, 601606, Frontotemporal dementia and amyotrophic lateral sclerosis; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2365 FUS Elena Savva gene: FUS was added
gene: FUS was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: FUS was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: FUS were set to PMID: 32281455; 20668259; 20385912
Phenotypes for gene: FUS were set to Amyotrophic lateral sclerosis 6, with or without frontotemporal dementia 608030; Essential tremor, hereditary, 4 614782
Mode of pathogenicity for gene: FUS was set to Other
Review for gene: FUS was set to GREEN
Added comment: PMID: 32281455 - Reports a case of Pediatric Amyotrophic Lateral Sclerosis. Reviews and shows multiple other reports of ALS casued by FUS

PMID: 20668259 - additional reports of ALS

PMID: 20385912 - postulated that disruption of this region may disrupt subcellular distribution of FUS, in turn affecting transcription and RNA processing and conferring a toxic gain of function.
Sources: Literature
Mendeliome v0.2365 C9orf72 Elena Savva gene: C9orf72 was added
gene: C9orf72 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: C9orf72 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: C9orf72 were set to PMID: 30120348; 23284068
Phenotypes for gene: C9orf72 were set to Frontotemporal dementia and/or amyotrophic lateral sclerosis 1 105550
Review for gene: C9orf72 was set to AMBER
Added comment: Possibly RED

Caused by expansion of GGGGCC repeats, dont know if these qualify for mendeliome
Sources: Literature
Mendeliome v0.1766 ANXA11 Bryony Thompson gene: ANXA11 was added
gene: ANXA11 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: ANXA11 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ANXA11 were set to 28469040; 29845112; 30109997
Phenotypes for gene: ANXA11 were set to Amytrophic lateral sclerosis 23 MIM#617839
Review for gene: ANXA11 was set to GREEN
Added comment: 4 different missense variants in 10 patients from 7 unrelated families with amyotrophic lateral sclerosis and functional assays supporting association.
Sources: Expert list
Mendeliome v0.1435 TBCE Zornitza Stark Phenotypes for gene: TBCE were changed from to Encephalopathy, progressive, with amyotrophy and optic atrophy; Hypoparathyroidism-retardation-dysmorphism syndrome; Kenny-Caffey syndrome, type 1
Mendeliome v0.1415 TBCE Elena Savva reviewed gene: TBCE: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 27666369; Phenotypes: Encephalopathy, progressive, with amyotrophy and optic atrophy, Hypoparathyroidism-retardation-dysmorphism syndrome, Kenny-Caffey syndrome, type 1; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.693 SEPT9 Zornitza Stark Phenotypes for gene: SEPT9 were changed from to Amyotrophy, hereditary neuralgic, MIM# 162100
Mendeliome v0.692 SEPT9 Zornitza Stark reviewed gene: SEPT9: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Amyotrophy, hereditary neuralgic, MIM# 162100; Mode of inheritance: None
Mendeliome v0.0 MYOT Zornitza Stark gene: MYOT was added
gene: MYOT was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: MYOT was set to Unknown