ClinVar Miner

Submissions for variant NM_024422.6(DSC2):c.2393G>T (p.Arg798Leu) (rs61731921)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000226818 SCV000290731 uncertain significance Arrhythmogenic right ventricular cardiomyopathy, type 11 2018-12-18 criteria provided, single submitter clinical testing This sequence change replaces arginine with leucine at codon 798 of the DSC2 protein (p.Arg798Leu). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and leucine. This variant is present in population databases (rs61731921, ExAC 0.02%). This variant has not been reported in the literature in individuals with a DSC2-related disease. ClinVar contains an entry for this variant (Variation ID: 46179). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C25"). 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.
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000039422 SCV000063106 uncertain significance not specified 2013-01-11 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Benign. The Arg798Leu varia nt in DSC2 has not been reported in the literature nor previously identified by our laboratory. This variant has also not been identified in large and broad Eur opean American and African American populations by the NHLBI Exome Sequencing Pr oject ( However, we cannot exclude that it may be common in other populations. Arginine (Arg) at position 798 is not conserved in evolution, suggesting that a change may be tolerated. Computational analyses (biochemical amino acid properties, AlignGVGD, PolyPhen2, and SIFT) do not prov ide strong support for or against an impact to the protein. Although this data s upports that the Arg798Leu variant may be benign, additional studies are needed to fully assess its clinical significance.

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