ClinVar Miner

Submissions for variant NM_024422.6(DSC2):c.321G>T (p.Lys107Asn) (rs140856220)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000254167 SCV000318897 uncertain significance Cardiovascular phenotype 2016-09-15 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Stanford Center for Inherited Cardiovascular Disease, Stanford University RCV000786114 SCV000924767 uncertain significance not provided 2016-08-01 no assertion criteria provided provider interpretation p.Lys107Asn (c.321 G>T) in DSC2. We have seen the variant in one adult with unexplained cardiac arrest and mild biventricular systolic dysfunction. We re-reviewed the variant on August 1st, 2016. This variant is located in coding exon 3 of the DSC2 gene. The lysine at codon 107 is replaced by asparagine, an amino acid with some similar properties. This variant has not been reported in association with cardiomyopathy (as of August 1st, 2016). In silico analysis with PolyPhen-2 predicts the variant to be probably damaging. Mutation Taster predicts this variant to be disease-causing. The lysine at codon 107 is not well conserved across species. No other variants have been reported in association with disease at this codon. A nearby codon (Glu102Lys) has been reported in one individual with ARVC (Beffangna et al. 2007). The variant was reported online in 1 of 60495 individuals in the Exome Aggregation Consortium dataset (http://exac.broadinstitute.org/), which currently includes variant calls on ~64,000 individuals of European, African, Latino and Asian descent (as of August 1, 2016). Specifically, the variant was observed in 1 of 5144 African individuals (AF 0.00009720). The phenotype of that individuals is not publicly available. The dataset is comprised of multiple cohorts, some of which were recruited from the general population, others were enriched for common cardiovascular disease. Note that other variants with strong evidence for pathogenicity have been seen at similar frequencies in datasets like this so this does not necessarily rule out pathogenicity (Pan et al 2012).

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