Muscular dystrophy and myopathy_Paediatric

Gene: TNNT1

Green List (high evidence)

TNNT1 (troponin T1, slow skeletal type)
EnsemblGeneIds (GRCh38): ENSG00000105048
EnsemblGeneIds (GRCh37): ENSG00000105048
OMIM: 191041, Gene2Phenotype
TNNT1 is in 9 panels

2 reviews

Bryony Thompson (Royal Melbourne Hospital)

Comment 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

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Green List (high evidence)

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

Details

Mode of Inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Other
  • Expert Review Green
Phenotypes
  • Nemaline myopathy 5 MONDO:0011539
  • Nemaline myopathy MONDO:0018958
OMIM
191041
Clinvar variants
Variants in TNNT1
Penetrance
None
Publications
Panels with this gene

History Filter Activity

5 Jun 2023, Gel status: 3

Entity classified by Genomics England curator

Bryony Thompson (Royal Melbourne Hospital)

Gene: tnnt1 has been classified as Green List (High Evidence).

5 Jun 2023, Gel status: 3

Entity classified by Genomics England curator

Bryony Thompson (Royal Melbourne Hospital)

Gene: tnnt1 has been classified as Green List (High Evidence).

5 Jun 2023, Gel status: 1

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes

Bryony Thompson (Royal Melbourne Hospital)

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