Congenital myopathy

Gene: TNNT1

Green List (high evidence)

The mode of inheritance of this gene has been updated to BOTH monoallelic and biallelic, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.

Created: 26 Sep 2024, 10:39 a.m. | Last Modified: 26 Sep 2024, 10:39 a.m.

Panel Version: 4.42

Comment on mode of inheritance: As reviewed by Anna Sarkozy, monoallelic variants in TNNT1 have been reported in two unrelated families with nemaline myopathy and supported by in vitro functional studies. There is sufficient evidence available for updating the MOI from "BIALLELIC, autosomal or pseudoautosomal" to "BOTH monoallelic and biallelic, autosomal or pseudoautosomal" in the next GMS review.

Created: 4 Apr 2023, 9:04 a.m. | Last Modified: 4 Apr 2023, 9:04 a.m.

Panel Version: 4.23

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Nemaline myopathy 5, Amish type, OMIM:605355

Publications

• 29178646
• 35510366

Green List (high evidence)

- PMID: 25430424 (2015) - 2 year old Hispanic male diagnosed with nemaline myopathy and a homozygous variant c.323C>G (p.S108X) in the TNNT1 gene. Patient had low muscle tone, global muscle weakness (proximal more than distal), hip and knee contractures and developmental delay. Muscle biopsy confirmed nemaline myopathy.

- PMID: 12732643 (2003) - a lethal form of nemaline myopathy (known as ANM - Amish nemaline myopathy) found in family with a homozygous nonsense variant Glu180 in TNNT1 (previously known as TNT). ANM presents with tremors at birth, proximal contractures and hypotonia, and progressive weakness often leading to death from respiratory insufficiency.

Created: 18 Jun 2025, 3:59 p.m. | Last Modified: 18 Jun 2025, 3:59 p.m.

Panel Version: 6.4

PMID: 32994279 - Three additional unrelated cases with nemaline myopathy due to different biallelic variants in TNNT1. The variants comprised a homozygous deletion of exons 8 and 9; two compound het nonsense and splice-site variants; and a homozygous nonsense variant. Western blot analysis revealed the total absence of the troponin protein in all three cases.

Created: 5 Oct 2020, 9:33 a.m. | Last Modified: 5 Oct 2020, 9:33 a.m.

Panel Version: 2.7

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Nemaline myopathy 5, Amish type, 605355; Nemaline Myopathy

Publications

• 32994279

I don't know

Gene rating and review submitted by Rachael Mein, Viapath Guy's Hospital February 2019 on on behalf of London South GLH for the GMS Neurology specialist test group.

Created: 30 Apr 2019, 10:09 a.m.

Green List (high evidence)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
nemaline myopathy; Nemaline Myopathy, Recessive; Nemaline myopathy 5, Amish type, 605355

Publications

• 26296490
• 25430424

Variants in this GENE are reported as part of current diagnostic practice

Green List (high evidence)

comment re inheritance: both dominant and recessive TNNT1 gene variants have now been reported in patients with congenital myopathies. Dominant mutations are likely acting via a dominant negative mechanism

Created: 24 Mar 2023, 1:02 p.m. | Last Modified: 24 Mar 2023, 1:02 p.m.

Panel Version: 4.2

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
nemaline myopathy; Nemaline Myopathy, Recessive; Nemaline myopathy 5, Amish type, 605355; autpsomal dominant nemaline myopathy

Publications

• 26296490
• 25430424
• 35510366
• 29178646

Green List (high evidence)

Comment when marking as ready: several families in 3 populations.

Created: 2 Feb 2017, 12:03 p.m.

Initially described in Amish population only, with founder effect. Recently described in 7 Palestinian families (single mutation) and Hispanic individual. In view of the number of families and an appropriate phenotype, considered green. However, founder mutations make up the majority of reported cases to date.

Created: 26 Jan 2017, 11:59 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Nemaline myopathy 5, Amish type 605355

Publications

• PMID 26296490
• 25430424