ClinVar Miner

Submissions for variant NM_024422.6(DSC2):c.2636A>G (p.Asp879Gly) (rs143342988)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000619644 SCV000734914 uncertain significance Cardiovascular phenotype 2016-06-27 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
GeneDx RCV000181169 SCV000233446 uncertain significance not specified 2015-10-28 criteria provided, single submitter clinical testing p.Asp879Gly (GAT>GGT): c.2636 A>G in exon 16 of the DSC2 gene (NM_024422.3). Although rare, mutations in the DSC2 gene have been reported in association with arrhythmogenic right ventricular cardiomyopathy (ARVC) (McNally et al., 2009).A variant of unknown significance has been identified in the DSC2 gene. The D879G variant has not been reported in association with cardiomyopathy, to our knowledge. However, this sequence variant was observed in 1/427 healthy control individuals (Kapplinger Jet al., 2011), in 2/128 alleles from individuals of Mexican ancestry reported in the 1000 Genomes Project, and in 11/2192 alleles from individuals of African American ancestry reported in the NHLBI Exome Sequencing Project, suggesting D879G may be a rare benign variant in these populations. Moreover, no missense mutations in nearby residues have been reported in association with cardiomyopathy, indicating this region of the protein may be tolerant of change. Nevertheless, the D879G variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is completely conserved across species. Moreover, in silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. The variant is found in CARDIOMYOPATHY panel(s).
Invitae RCV000475212 SCV000561697 likely benign Arrhythmogenic right ventricular cardiomyopathy, type 11 2017-09-26 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000181169 SCV000270163 likely benign not specified 2015-05-16 criteria provided, single submitter clinical testing p.Asp879Gly in exon 16 of DSC2: This variant is not expected to have clinical si gnificance because it has been identified in 0.3% (35/10398) of African chromoso mes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; d bSNP rs143342988).

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