Total submissions: 8
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000463843 | SCV000541925 | uncertain significance | Hypertrophic cardiomyopathy 2; Dilated cardiomyopathy 1D; Cardiomyopathy, familial restrictive, 3 | 2023-12-18 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 250 of the TNNT2 protein (p.Leu250Pro). This variant is present in population databases (rs376037051, gnomAD 0.0009%). This missense change has been observed in individual(s) with clinical features of TNNT2-related conditions (Invitae). ClinVar contains an entry for this variant (Variation ID: 404398). 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, |
RCV001181624 | SCV001346807 | uncertain significance | Cardiomyopathy | 2023-03-15 | criteria provided, single submitter | clinical testing | This missense variant replaces leucine with proline at codon 250 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 TNNT2-related disorders in the literature. This variant has been identified in 2/251478 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. |
Ambry Genetics | RCV002393080 | SCV002672561 | uncertain significance | Cardiovascular phenotype | 2023-02-20 | criteria provided, single submitter | clinical testing | The p.L250P variant (also known as c.749T>C), located in coding exon 13 of the TNNT2 gene, results from a T to C substitution at nucleotide position 749. The leucine at codon 250 is replaced by proline, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Gene |
RCV003441858 | SCV004170196 | uncertain significance | not provided | 2023-10-13 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
Genome- |
RCV003449117 | SCV004180543 | uncertain significance | Dilated cardiomyopathy 1D | 2023-04-11 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV003449118 | SCV004180544 | uncertain significance | Cardiomyopathy, familial restrictive, 3 | 2023-04-11 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV003449116 | SCV004180545 | uncertain significance | Hypertrophic cardiomyopathy 2 | 2023-04-11 | criteria provided, single submitter | clinical testing | |
All of Us Research Program, |
RCV001181624 | SCV004821972 | uncertain significance | Cardiomyopathy | 2023-12-18 | criteria provided, single submitter | clinical testing | This missense variant replaces leucine with proline at codon 250 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 TNNT2-related disorders in the literature. This variant has been identified in 2/251478 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. |