Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001890721 | SCV002151132 | uncertain significance | Arrhythmogenic right ventricular dysplasia 11 | 2021-03-15 | 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 missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with DSC2-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces serine with alanine at codon 636 of the DSC2 protein (p.Ser636Ala). The serine residue is moderately conserved and there is a moderate physicochemical difference between serine and alanine. |
Ambry Genetics | RCV003303287 | SCV004001541 | uncertain significance | Cardiovascular phenotype | 2023-03-31 | criteria provided, single submitter | clinical testing | The p.S636A variant (also known as c.1906T>G), located in coding exon 13 of the DSC2 gene, results from a T to G substitution at nucleotide position 1906. The serine at codon 636 is replaced by alanine, an amino acid with similar properties. This amino acid position is conserved. 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. |