ClinVar Miner

Submissions for variant NM_001035.3(RYR2):c.2038G>A (p.Asp680Asn) (rs794728727)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000182694 SCV000235073 uncertain significance not provided 2013-08-26 criteria provided, single submitter clinical testing p.Asp680Asn (GAC>AAC): c.2038 G>A in exon 20 of the RYR2 gene (NM_001035.2). The D680N variant in the RYR2 gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. D680N results in a semi-conservative amino acid substitution of a negatively charged Aspartic acid to a neutral, polar Asparagine at a position that is well conserved across species. In silico analysis predicts D680N is damaging to the protein structure/function. The D680N variant was not observed in approximately 6,000 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Nevertheless, D680N does not occur in one of the mutation hot spot regions of the RYR2 gene (Medeiros-Domingo A et al., 2009), and no mutations in nearby residues have been reported in association with arrhythmia. With the clinical and molecular information available at this time, we cannot definitively determine if D680N is a disease-causing mutation or a rare benign variant. The variant is found in POSTMORTEM panel(s).

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