Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000150524 | SCV000197721 | uncertain significance | not specified | 2014-05-15 | criteria provided, single submitter | clinical testing | The Asp513Tyr variant in DSC2 has not been previously reported in individuals wi th cardiomyopathy, but has been identified in 1/4406 of African American chromos omes by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS/). Computational prediction tools and conservation analysis don?t provide strong ev idence for or against an impact to the protein. In summary, the clinical signifi cance of the Asp513Tyr variant is uncertain. |
Invitae | RCV000461667 | SCV000551492 | uncertain significance | Arrhythmogenic right ventricular dysplasia 11 | 2023-03-04 | 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 sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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 DSC2 protein function. ClinVar contains an entry for this variant (Variation ID: 163188). This variant has not been reported in the literature in individuals affected with DSC2-related conditions. This variant is present in population databases (rs373324195, gnomAD 0.01%). This sequence change replaces aspartic acid, which is acidic and polar, with tyrosine, which is neutral and polar, at codon 513 of the DSC2 protein (p.Asp513Tyr). |
Color Diagnostics, |
RCV001188342 | SCV001355379 | uncertain significance | Cardiomyopathy | 2019-09-12 | criteria provided, single submitter | clinical testing | This missense variant replaces aspartic acid with tyrosine at codon 513 of the DSC2 protein. Computational prediction tool is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 3/282436 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 | RCV002399524 | SCV002705029 | uncertain significance | Cardiovascular phenotype | 2021-11-04 | criteria provided, single submitter | clinical testing | The p.D513Y variant (also known as c.1537G>T), located in coding exon 11 of the DSC2 gene, results from a G to T substitution at nucleotide position 1537. The aspartic acid at codon 513 is replaced by tyrosine, an amino acid with highly dissimilar properties. This amino acid position is conserved. 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. |
CHEO Genetics Diagnostic Laboratory, |
RCV001188342 | SCV004240488 | uncertain significance | Cardiomyopathy | 2023-03-03 | criteria provided, single submitter | clinical testing |