Submissions for variant NM_001276345.2(TNNT2):c.614A>G (p.Glu205Gly)

dbSNP: rs1658740460

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001201673	SCV001372755	uncertain significance	Hypertrophic cardiomyopathy 2; Dilated cardiomyopathy 1D; Cardiomyopathy, familial restrictive, 3	2019-05-10	criteria provided, single submitter	clinical testing	In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with TNNT2-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamic acid with glycine at codon 195 of the TNNT2 protein (p.Glu195Gly). The glutamic acid residue is moderately conserved and there is a moderate physicochemical difference between glutamic acid and glycine.
GeneDx	RCV001751367	SCV001996741	uncertain significance	not provided	2019-11-06	criteria provided, single submitter	clinical testing	Has not been previously published as pathogenic or benign to our knowledge; Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect
3billion	RCV002051921	SCV002318892	uncertain significance	Hypertrophic cardiomyopathy 2	2022-03-22	criteria provided, single submitter	clinical testing	Different pathogenic/likely pathogenic amino acid change has been reported with supporting evidence at the same codon (PMID:24111713). In silico tool predictions suggest damaging effect of the variant on gene or gene product (3CNET: 0.965>=0.75). A missense variant is a common mechanism . It is not observed in the gnomAD v2.1.1 dataset. Therefore, this variant is classified as uncertain significance according to the recommendation of ACMG/AMP guideline.
Genome-Nilou Lab	RCV003449642	SCV004181277	uncertain significance	Dilated cardiomyopathy 1D	2023-04-11	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV003449643	SCV004181278	uncertain significance	Cardiomyopathy, familial restrictive, 3	2023-04-11	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV002051921	SCV004181279	uncertain significance	Hypertrophic cardiomyopathy 2	2023-04-11	criteria provided, single submitter	clinical testing