Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001984765 | SCV002211942 | uncertain significance | Arrhythmogenic right ventricular dysplasia 11 | 2023-10-04 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 556 of the DSC2 protein (p.Gly556Glu). This variant is present in population databases (no rsID available, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with DSC2-related conditions. ClinVar contains an entry for this variant (Variation ID: 1434979). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The glutamic acid amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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 |
RCV002307798 | SCV002601402 | uncertain significance | not provided | 2022-05-10 | 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 |
Fulgent Genetics, |
RCV001984765 | SCV002786232 | uncertain significance | Arrhythmogenic right ventricular dysplasia 11 | 2021-09-28 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV003303451 | SCV004001794 | uncertain significance | Cardiovascular phenotype | 2023-06-09 | criteria provided, single submitter | clinical testing | The p.G556E variant (also known as c.1667G>A), located in coding exon 12 of the DSC2 gene, results from a G to A substitution at nucleotide position 1667. The glycine at codon 556 is replaced by glutamic acid, 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 tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |