Total submissions: 8
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000556705 | SCV000646920 | uncertain significance | Hypertrophic cardiomyopathy 2; Dilated cardiomyopathy 1D; Cardiomyopathy, familial restrictive, 3 | 2024-01-11 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 285 of the TNNT2 protein (p.Gly285Arg). This variant is present in population databases (rs147940106, gnomAD 0.009%). This missense change has been observed in individual(s) with hypertrophic cardiomyopathy (PMID: 31513939). ClinVar contains an entry for this variant (Variation ID: 180555). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt TNNT2 protein function with a positive predictive value of 95%. 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, |
RCV001191325 | SCV001359100 | uncertain significance | Cardiomyopathy | 2023-04-19 | criteria provided, single submitter | clinical testing | This missense variant replaces glycine with arginine at codon 285 of the TNNT2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with hypertrophic cardiomyopathy (PMID: 32492895). This variant has been identified in 9/274990 chromosomes 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. |
Gene |
RCV000788740 | SCV002050532 | uncertain significance | not provided | 2022-03-17 | criteria provided, single submitter | clinical testing | Identified in a patient with HCM in the published literature (Kim et al., 2020); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 32492895) |
Ambry Genetics | RCV002408709 | SCV002675492 | uncertain significance | Cardiovascular phenotype | 2021-12-22 | criteria provided, single submitter | clinical testing | The p.G285R variant (also known as c.853G>A), located in coding exon 15 of the TNNT2 gene, results from a G to A substitution at nucleotide position 853. The glycine at codon 285 is replaced by arginine, an amino acid with dissimilar properties. This alteration has been reported in a hypertrophic cardiomyopathy (HCM) cohort; however, clinical details were limited (Kim HY et al. J Clin Med, 2020 Jun;9:[ePub ahead of print]). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Genome- |
RCV003453210 | SCV004180482 | uncertain significance | Dilated cardiomyopathy 1D | 2023-04-11 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV003453211 | SCV004180483 | uncertain significance | Cardiomyopathy, familial restrictive, 3 | 2023-04-11 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV003453209 | SCV004180484 | uncertain significance | Hypertrophic cardiomyopathy 2 | 2023-04-11 | criteria provided, single submitter | clinical testing | |
Blueprint Genetics | RCV000157541 | SCV000207287 | uncertain significance | Primary familial hypertrophic cardiomyopathy | 2014-10-07 | no assertion criteria provided | clinical testing |