ClinVar Miner

Submissions for variant NM_024422.6(DSC2):c.1091T>G (p.Val364Gly) (rs368089478)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000039402 SCV000063086 uncertain significance not specified 2010-01-04 criteria provided, single submitter clinical testing
GeneDx RCV000766662 SCV000582459 uncertain significance not provided 2017-11-22 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the DSC2 gene. The V364G variant has not been published as pathogenic or been reported as benign to our knowledge. The V364G variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. However, the V364G variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties.
Invitae RCV000823602 SCV000964467 uncertain significance Arrhythmogenic right ventricular cardiomyopathy, type 11 2018-07-05 criteria provided, single submitter clinical testing This sequence change replaces valine with glycine at codon 364 of the DSC2 protein (p.Val364Gly). The valine residue is highly conserved and there is a moderate physicochemical difference between valine and glycine. This variant is present in population databases (rs368089478, ExAC 0.002%). This variant has not been reported in the literature in individuals with DSC2-related disease. ClinVar contains an entry for this variant (Variation ID: 46162). 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. 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.
Center for Advanced Laboratory Medicine, UC San Diego Health,University of California San Diego RCV000852470 SCV000995164 uncertain significance Dilated cardiomyopathy 2017-08-21 criteria provided, single submitter clinical testing

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