ClinVar Miner

Submissions for variant NM_024422.6(DSC2):c.2245A>C (p.Lys749Gln) (rs765067237)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Fulgent Genetics,Fulgent Genetics RCV000765410 SCV000896692 uncertain significance Arrhythmogenic right ventricular cardiomyopathy, type 11 2018-10-31 criteria provided, single submitter clinical testing
GeneDx RCV000181161 SCV000233438 uncertain significance not specified 2015-10-21 criteria provided, single submitter clinical testing p.Lys749Gln (AAA>CAA): c.2245 A>C in exon 14 of the DSC2 gene (NM_024422.3). At least 12% of patients with autosomal dominant arrhythmogenic right ventricular cardiomyopathy have been reported to have a mutation in the DSG2 gene (McNally E et al., 2009).A variant of unknown significance has been identified in the DSC2 gene. The K749Q variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The K749Q variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The K749Q variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is class conserved in mammals. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. No missense mutations in nearby residues have been reported in association with cardiomyopathy, suggesting this region of the protein may be tolerant of change. 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, ARRHYTHMIA panel(s).

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