ClinVar Miner

Submissions for variant NM_024422.6(DSC2):c.2498G>A (p.Arg833His) (rs370325533)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000244558 SCV000320492 uncertain significance Cardiovascular phenotype 2017-11-15 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Fulgent Genetics,Fulgent Genetics RCV000229598 SCV000611473 uncertain significance Arrhythmogenic right ventricular cardiomyopathy, type 11 2017-05-23 criteria provided, single submitter clinical testing
GeneDx RCV000766860 SCV000233444 uncertain significance not provided 2018-07-16 criteria provided, single submitter clinical testing Although the R833H variant in the DSC2 gene has not been published as pathogenic or been reported as benign to our knowledge, it has been identified in 1/427 healthy control individuals (Kapplinger et al., 2011). Furthermore, the R833H variant is observed in 20/10,406 alleles (0.2%) from individuals of African ancestry in the Exome Aggregation Consortium (ExAC) data set (Lek et al., 2016). The R833H variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. Additionally, this substitution occurs at a position where amino acids with similar properties to histidine (H) are tolerated across species, and arginine (R) is tolerated at this position in several species. Nevertheless, in silico analysis predicts this variant is probably damaging to the protein structure/function.
Invitae RCV000229598 SCV000290732 likely benign Arrhythmogenic right ventricular cardiomyopathy, type 11 2017-11-15 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000039425 SCV000063109 uncertain significance not specified 2012-04-11 criteria provided, single submitter clinical testing The Arg833His variant (DSC2) has been identified in 3/3738 African American chro mosomes from a broad population by the NHLBI Exome Sequencing Project (http://ev s.gs.washington.edu/EVS) as well as in 1 of 854 control chromosomes (Kapplinger 2011). Computational analyses (biochemical amino acid properties, conservation, AlignGVGD, PolyPhen2, and SIFT) do not provide strong support for or against an impact to the protein. Additional information is needed to fully assess the clin ical significance of the Arg833His variant.

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