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| Congenital myaesthenic syndrome v3.3 | TOR1AIP1 |
Arina Puzriakova changed review comment from: At least 5 individuals from 2 unrelated families reported (PMID: 33215087; 34164833) specifically with a myasthenic syndrome in association with different homozygous LoF variants in this gene (c.127delC, p.Pro43fs and c.63dupC, p.Arg22Glnfs*88, respectively). Electromyography in patients revealed decremental responses on repetitive nerve stimulation. Muscle biopsy from one proband showed the protein encoded by TOR1AIP1 was absent in myonuclei. Knockout mice exhibited fatigable muscle weakness and also decrement on repetitive nerve stimulation. Neuromuscular junctions were enlarged and fragmented, and the number of subsynaptic nuclei was significantly increased signifying impaired synaptic transmission.; to: At least 5 individuals from 2 unrelated families reported (PMID: 33215087; 34164833) specifically with a myasthenic syndrome in association with different homozygous LoF variants in this gene (c.127delC, p.Pro43fs and c.63dupC, p.Arg22Glnfs*88, respectively). Electromyography in patients revealed decremental responses on repetitive nerve stimulation. Muscle biopsy from one proband showed the protein encoded by TOR1AIP1 was absent in myonuclei. Both variants were shown to truncate the muscle isoform (termed LAP1B) while the LAP1C isoform remained intact. Knockout mice exhibited fatigable muscle weakness and also decrement on repetitive nerve stimulation. Neuromuscular junctions were enlarged and fragmented, and the number of subsynaptic nuclei was significantly increased signifying impaired synaptic transmission. |
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| Congenital myaesthenic syndrome v3.3 | TOR1AIP1 |
Arina Puzriakova changed review comment from: Associated with relevant phenotype in OMIM, but currently not in Gene2Phenotype. At least 5 individuals from 2 unrelated families reported (PMID: 33215087; 34164833) specifically with a myasthenic syndrome in association with different homozygous LoF variants in this gene (c.127delC, p.Pro43fs and c.63dupC, p.Arg22Glnfs*88, respectively). Electromyography in patients revealed decremental responses on repetitive nerve stimulation. Muscle biopsy from one proband showed the protein encoded by TOR1AIP1 was absent in myonuclei. Knockout mice exhibited fatigable muscle weakness and also decrement on repetitive nerve stimulation. Neuromuscular junctions were enlarged and fragmented, and the number of subsynaptic nuclei was significantly increased signifying impaired synaptic transmission.; to: At least 5 individuals from 2 unrelated families reported (PMID: 33215087; 34164833) specifically with a myasthenic syndrome in association with different homozygous LoF variants in this gene (c.127delC, p.Pro43fs and c.63dupC, p.Arg22Glnfs*88, respectively). Electromyography in patients revealed decremental responses on repetitive nerve stimulation. Muscle biopsy from one proband showed the protein encoded by TOR1AIP1 was absent in myonuclei. Knockout mice exhibited fatigable muscle weakness and also decrement on repetitive nerve stimulation. Neuromuscular junctions were enlarged and fragmented, and the number of subsynaptic nuclei was significantly increased signifying impaired synaptic transmission. |
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| Congenital myaesthenic syndrome v3.3 | TOR1AIP1 | Arina Puzriakova Classified gene: TOR1AIP1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Congenital myaesthenic syndrome v3.3 | TOR1AIP1 | Arina Puzriakova Added comment: Comment on list classification: At least two unrelated multiplex families reported with muscle fatigability, limb girdle weakness and impaired transmission at the neuromuscular synapse. Given the strong functional support including a concordant mouse model, this gene can be promoted to Green status on this panel at the next GMS panel update. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Congenital myaesthenic syndrome v3.3 | TOR1AIP1 | Arina Puzriakova Gene: tor1aip1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Congenital myaesthenic syndrome v3.2 | TOR1AIP1 | Arina Puzriakova Tag Q4_22_promote_green tag was added to gene: TOR1AIP1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Congenital myaesthenic syndrome v3.2 | TOR1AIP1 | Arina Puzriakova Publications for gene: TOR1AIP1 were set to 24856141; 31299614 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Congenital myaesthenic syndrome v3.1 | TOR1AIP1 | Arina Puzriakova edited their review of gene: TOR1AIP1: Changed publications to: 33215087, 34164833 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Congenital myaesthenic syndrome v3.1 | TOR1AIP1 | Arina Puzriakova reviewed gene: TOR1AIP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24856141, 27342937, 30723199, 31299614, 32055997; Phenotypes: Congenital myasthenic syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Congenital myaesthenic syndrome v2.7 | TOR1AIP1 | Arina Puzriakova Publications for gene: TOR1AIP1 were set to 24856141 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Congenital myaesthenic syndrome v2.6 | TOR1AIP1 | Arina Puzriakova Phenotypes for gene: TOR1AIP1 were changed from Muscular dystrophy, autosomal recessive, with rigid spine and distal joint contractures, 617072 to Muscular dystrophy, autosomal recessive, with rigid spine and distal joint contractures, OMIM:617072; Autosomal recessive limb-girdle muscular dystrophy type 2Y, MONDO:0014900 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Congenital myaesthenic syndrome v1.74 | TOR1AIP1 | Louise Daugherty Classified gene: TOR1AIP1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Congenital myaesthenic syndrome v1.74 | TOR1AIP1 | Louise Daugherty Added comment: Comment on list classification: Info from Tracy Lester: TOR1AIP1 – should be amber on R80, not red, there is an unpublished case. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Congenital myaesthenic syndrome v1.74 | TOR1AIP1 | Louise Daugherty Gene: tor1aip1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Congenital myaesthenic syndrome v1.60 | TOR1AIP1 | Louise Daugherty edited their review of gene: TOR1AIP1: Added comment: Applicable to panel, but currently not enough evidence to support Amber/Green rating; Changed rating: RED | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Congenital myaesthenic syndrome v1.60 | TOR1AIP1 | Louise Daugherty Publications for gene: TOR1AIP1 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Congenital myaesthenic syndrome v1.59 | TOR1AIP1 | Louise Daugherty Phenotypes for gene: TOR1AIP1 were changed from to Muscular dystrophy, autosomal recessive, with rigid spine and distal joint contractures, 617072 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Congenital myaesthenic syndrome v1.34 | TOR1AIP1 | Louise Daugherty reviewed gene: TOR1AIP1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Congenital myaesthenic syndrome v1.16 | TOR1AIP1 | Louise Daugherty Mode of inheritance for gene: TOR1AIP1 was changed from to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Congenital myaesthenic syndrome v1.14 | TOR1AIP1 | Michael Oldridge reviewed gene: TOR1AIP1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Congenital myaesthenic syndrome v1.13 | TOR1AIP1 | Louise Daugherty Source NHS GMS was added to TOR1AIP1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Congenital myaesthenic syndrome v1.12 | TOR1AIP1 |
Louise Daugherty gene: TOR1AIP1 was added gene: TOR1AIP1 was added to Congenital myaesthenic syndrome. Sources: Wessex and West Midlands GLH Mode of inheritance for gene: TOR1AIP1 was set to |
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