Congenital myopathy
Gene: TNNT1
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
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
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.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
nemaline myopathy; Nemaline Myopathy, Recessive; Nemaline myopathy 5, Amish type, 605355
Publications
Variants in this GENE are reported as part of current diagnostic practice
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 mechanismCreated: 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
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
Publications for gene: TNNT1 were set to 26296490; 25430424; 32994279
Tag Q2_23_MOI tag was added to gene: TNNT1. Tag Q2_23_NHS_review tag was added to gene: TNNT1.
Tag Q2_23_promote_green was removed from gene: TNNT1. Tag Q2_23_NHS_review was removed from gene: TNNT1.
Tag Q2_23_promote_green tag was added to gene: TNNT1. Tag Q2_23_NHS_review tag was added to gene: TNNT1.
Mode of inheritance for gene: TNNT1 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TNNT1 were set to 26296490; 25430424
Phenotypes for gene: TNNT1 were changed from nemaline myopathy; Nemaline Myopathy, Recessive; Nemaline myopathy 5, Amish type, 605355 to Nemaline myopathy 5, Amish type, OMIM:605355
Source NHS GMS was added to TNNT1.
Source London South GLH was added to TNNT1. Rating Changed from Green List (high evidence) to Green List (high evidence)
Promoted 22/02/2017 after curation discussion and further review with members of the Genomics England curation team. Participants who are offered this panel will automatically be offered the following three panels: 1) Congenital muscular dystrophy 2) Congenital myasthenia and 3) Paediatric motor neuronopathy as this will cover a large range of differentials for a weak infant, for where the strict inclusion criteria are not applicable in view of the availability of muscle biopsy testing in peripheral paediatric units.
This gene has been classified as Green List (High Evidence).
Publications for TNNT1 were set to 26296490; 25430424
TNNT1 was added to Congenital myopathypanel. Sources: Expert
TNNT1 was added to Congenital myopathypanel. Sources: Radboud University Medical Center, Nijmegen
TNNT1 was added to Congenital myopathypanel. Sources: Illumina TruGenome Clinical Sequencing Services
TNNT1 was added to Congenital myopathypanel. Sources: UKGTN
TNNT1 was added to Congenital myopathypanel. Sources: Emory Genetics Laboratory