Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002049911 | SCV002115534 | uncertain significance | Arrhythmogenic right ventricular dysplasia 10 | 2021-02-21 | 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 disruptive, 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 DSG2-related conditions. This variant is present in population databases (rs373542380, ExAC 0.01%). This sequence change replaces alanine with serine at codon 131 of the DSG2 protein (p.Ala131Ser). The alanine residue is highly conserved and there is a moderate physicochemical difference between alanine and serine. |
Ambry Genetics | RCV002370350 | SCV002624898 | uncertain significance | Cardiovascular phenotype | 2019-11-19 | criteria provided, single submitter | clinical testing | The p.A131S variant (also known as c.391G>T), located in coding exon 5 of the DSG2 gene, results from a G to T substitution at nucleotide position 391. The alanine at codon 131 is replaced by serine, an amino acid with similar properties. This amino acid position is highly 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. |