ClinVar Miner

Submissions for variant NM_024422.6(DSC2):c.965A>G (p.Lys322Arg)

gnomAD frequency: 0.00002  dbSNP: rs1157312147
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV001189571 SCV001356882 uncertain significance Cardiomyopathy 2023-03-16 criteria provided, single submitter clinical testing This missense variant replaces lysine with arginine at codon 322 of the DSC2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with DSC2-related disorders in the literature. This variant has not been identified 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.
Invitae RCV001207317 SCV001378662 uncertain significance Arrhythmogenic right ventricular dysplasia 11 2021-08-30 criteria provided, single submitter clinical testing This sequence change replaces lysine with arginine at codon 322 of the DSC2 protein (p.Lys322Arg). The lysine residue is weakly conserved and there is a small physicochemical difference between lysine and arginine. 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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.
Ambry Genetics RCV003163469 SCV003853616 uncertain significance Cardiovascular phenotype 2023-01-01 criteria provided, single submitter clinical testing The p.K322R variant (also known as c.965A>G), located in coding exon 8 of the DSC2 gene, results from an A to G substitution at nucleotide position 965. The lysine at codon 322 is replaced by arginine, 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.

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