Submissions for variant NM_001276345.2(TNNT2):c.347_348delinsCT (p.Ile116Thr)

dbSNP: rs1553282523

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV001836834	SCV000621578	uncertain significance	not provided	2023-04-19	criteria provided, single submitter	clinical testing	Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD)
Invitae	RCV000646067	SCV000767824	uncertain significance	Hypertrophic cardiomyopathy 2; Dilated cardiomyopathy 1D; Cardiomyopathy, familial restrictive, 3	2023-10-28	criteria provided, single submitter	clinical testing	This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 106 of the TNNT2 protein (p.Ile106Thr). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with TNNT2-related conditions. ClinVar contains an entry for this variant (Variation ID: 452747). An algorithm developed specifically for the TNNT2 gene suggests that this missense change is likely to be deleterious (PMID: 21310275). 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.
Color Diagnostics, LLC DBA Color Health	RCV001524972	SCV001734958	uncertain significance	Cardiomyopathy	2021-05-10	criteria provided, single submitter	clinical testing	This missense variant replaces isoleucine with threonine at codon 106 of the TNNT2 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Ambry Genetics	RCV002323893	SCV002609605	uncertain significance	Cardiovascular phenotype	2019-05-08	criteria provided, single submitter	clinical testing	The c.317_318delTCinsCT variant (also known as p.I106T), located in coding exon 8 of the TNNT2 gene, results from an in-frame deletion of TC and insertion of CT at nucleotide positions 317 to 318. This results in the substitution of the isoleucine residue for a threonine residue at codon 106, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Genome-Nilou Lab	RCV003449496	SCV004181458	uncertain significance	Dilated cardiomyopathy 1D	2023-04-11	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV003449497	SCV004181459	uncertain significance	Cardiomyopathy, familial restrictive, 3	2023-04-11	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV003449495	SCV004181460	uncertain significance	Hypertrophic cardiomyopathy 2	2023-04-11	criteria provided, single submitter	clinical testing