Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV002006738 | SCV002295080 | uncertain significance | Arrhythmogenic right ventricular dysplasia 11 | 2021-10-06 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine with serine at codon 413 of the DSC2 protein (p.Asn413Ser). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and serine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with DSC2-related conditions. 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. 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. |
All of Us Research Program, |
RCV004011123 | SCV004823222 | uncertain significance | Familial isolated arrhythmogenic right ventricular dysplasia | 2023-10-23 | criteria provided, single submitter | clinical testing | This missense variant replaces asparagine with serine at codon 413 of the DSC2 protein. Computational prediction 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). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 1/31386 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 | RCV004046178 | SCV005028714 | uncertain significance | Cardiovascular phenotype | 2023-09-18 | criteria provided, single submitter | clinical testing | The p.N413S variant (also known as c.1238A>G), located in coding exon 9 of the DSC2 gene, results from an A to G substitution at nucleotide position 1238. The asparagine at codon 413 is replaced by serine, an amino acid with highly 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. |