Muscular dystrophy and myopathy_Paediatric
Gene: TNNT1Comment on list classification: Biallelic Nemaline myopathy is classified as definitive by ClinGen Congenital Myopathies VCEP (reviewed 07/05/2020) with a LoF mechanism of disease, whereas monoallelic Nemaline myopathy is classified as limited (reviewed 22/06/2020) with an expected GoF mechanism of disease.Created: 5 Jun 2023, 5:31 a.m. | Last Modified: 5 Jun 2023, 5:31 a.m.
Panel Version: 0.196
Additional evidence for mono-allelic variants causing myopathy:
PMID: 29178646 - one large family segregating c.311A>T (p.E104V) dominantly and muscle biopsies consistent with nemaline myopathy. Dominant-negative effect was the suggested mechanism of disease. PMID: 35510366 - a novel missense c.194A>C/p.(Asp65Ala) was identified de novo in a woman with muscle hypotrophy and muscle weakness. The variant segregated to her affected son. In vitro functional assays demonstrated enhanced complex formation of the D65A mutant with tropomyosin and that E104V differentially affected co-immunoprecipitation of TnT1 with TPM3.Created: 13 Jul 2022, 5:28 a.m. | Last Modified: 13 Jul 2022, 5:28 a.m.
Panel Version: 1.32
Bi-allelic variants initially identified in Amish, but multiple families from different ethnicities now reported. Ovine animal model.
Single family segregating a mono-allelic variant reported in PMID 29178646.Created: 16 Oct 2020, 9:49 a.m. | Last Modified: 16 Oct 2020, 9:49 a.m.
Panel Version: 0.304
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes
Nemaline myopathy 5, Amish type, MIM# 605355; Nemaline myopathy-5B with rigid spine and respiratory insufficiency (NEM5B), MIM#620386; nemaline myopathy-5C (NEM5C), autosomal dominant, MIMD620389
Publications
Gene: tnnt1 has been classified as Green List (High Evidence).
Gene: tnnt1 has been classified as Green List (High Evidence).
gene: TNNT1 was added gene: TNNT1 was added to Muscular dystrophy_Paediatric. Sources: Other Mode of inheritance for gene: TNNT1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: TNNT1 were set to 10952871; 32994279; 32819427; 31970803; 31604653; 29931346; 29178646 Phenotypes for gene: TNNT1 were set to Nemaline myopathy 5 MONDO:0011539; Nemaline myopathy MONDO:0018958