Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001296876 | SCV001485853 | uncertain significance | Hypertrophic cardiomyopathy 2; Dilated cardiomyopathy 1D; Cardiomyopathy, familial restrictive, 3 | 2022-07-02 | criteria provided, single submitter | clinical testing | Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 1000713). This variant has not been reported in the literature in individuals affected with TNNT2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces aspartic acid, which is acidic and polar, with valine, which is neutral and non-polar, at codon 125 of the TNNT2 protein (p.Asp125Val). 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. |
Gene |
RCV002253802 | SCV002525307 | uncertain significance | not provided | 2022-05-27 | 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; In silico analysis, which includes splice predictors and evolutionary conservation, suggests this variant may impact gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; Has not been previously published as pathogenic or benign to our knowledge |
Ambry Genetics | RCV002350525 | SCV002622154 | uncertain significance | Cardiovascular phenotype | 2020-11-23 | criteria provided, single submitter | clinical testing | The p.D125V variant (also known as c.374A>T), located in coding exon 8 of the TNNT2 gene, results from an A to T substitution at nucleotide position 374. The aspartic acid at codon 125 is replaced by valine, an amino acid with highly dissimilar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Genome- |
RCV003449852 | SCV004181428 | uncertain significance | Dilated cardiomyopathy 1D | 2023-04-11 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV003449853 | SCV004181430 | uncertain significance | Cardiomyopathy, familial restrictive, 3 | 2023-04-11 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV003449851 | SCV004181431 | uncertain significance | Hypertrophic cardiomyopathy 2 | 2023-04-11 | criteria provided, single submitter | clinical testing |