Congenital myopathy

Gene: TNNC2

Green List (high evidence)

The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.

Created: 1 Feb 2023, 5:10 p.m. | Last Modified: 1 Feb 2023, 5:10 p.m.

Panel Version: 3.14

Green List (high evidence)

Not associated with a phenotype in OMIM, Gen2Phen or MONDO. PMID: 33755597 reports two variants each in unrelated cases. The variant c.100G>T; p.Asp34Tyr segregates dominantly with congenital myopathy in three generations of Family 1, while c.237G>C; p.Met79Ile appear to be de novo in family 2. Detailed functional evidence is also presented in PMID: 33755597.

Created: 13 Dec 2022, 3:31 p.m. | Last Modified: 13 Dec 2022, 3:31 p.m.

Panel Version: 3.10

Green List (high evidence)

4 patients from 2 unrelated families described to date with mono-allelic variants in TNNC2 gene, presenting with a distinct, dominantly inherited congenital muscle disease. the clinical features are in keeping with a congenital myopathy with polyhydramnios during gestation, weakness, severe neonatal respiratory muscle involvement and external ophthalmoparesis. Feeding difficulties and scoliosis was also reported. muscle biopsy was myopathic with variation of fibre size and incrase in type 1 fibres. Functional data supports role of the changes, that are considered disrupting the binding sites for Ca2+ and troponin. overall, this evidence supports the upgrade to GREEN.

Created: 10 Nov 2022, 2:49 p.m. | Last Modified: 10 Nov 2022, 2:49 p.m.

Panel Version: 2.93

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
congenital myopathy

Mode of pathogenicity
Other

Comment on list classification: Promoted from Red to Amber. This gene is currently not associated with a phenotype in OMIM or Gene2Phenotype. There is enough evidence to support a gene-disease association. This gene should be rated Green at the next review.

Created: 12 Jul 2021, 9:24 a.m. | Last Modified: 12 Jul 2021, 9:24 a.m.

Panel Version: 2.51

Comment on publications: PMID:26924529 was incorrectly entered for TNNC2

Created: 12 Jul 2021, 8:59 a.m. | Last Modified: 12 Jul 2021, 8:59 a.m.

Panel Version: 2.49

Green List (high evidence)

Two families with congenital myopathy and dominantly inherited TNNC2 variants and details functional analysis reported in PMID: 33755597.

Created: 22 Jun 2021, 1:35 p.m. | Last Modified: 22 Jun 2021, 1:35 p.m.

Panel Version: 2.28

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Myopathy

Publications

• PMID: 33755597

Mode of pathogenicity
Other

I don't know

Note : The review uploaded on behalf of Rachael Mein (Viapath at Guy's Hospital) publication PMID: 26924529 is incorrect. The original file from London South GLH correctly associates PMID: 23746549 to the gene TRIP4, but for TNNC2 the publication field was blank (no data was supplied as evidence). The Green review rating for TNNC2 is the rating given by London South GLH. There is currently not enough evidence to support a Amber rating.

Created: 17 Oct 2019, 2:44 p.m. | Last Modified: 17 Oct 2019, 2:44 p.m.

Panel Version: 1.182

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.

I don't know

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
congenital myopathy

Publications

• 26924529