ClinVar Miner

Submissions for variant NM_001035.3(RYR2):c.8205C>A (p.Asp2735Glu) (rs794728823)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000182878 SCV000235266 uncertain significance not provided 2017-06-09 criteria provided, single submitter clinical testing p.Asp2735Glu (GAC>GAA): c.8205 C>A in exon 54 of the RYR2 gene (NM_001035.2). The D2735E variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The D2735E variant was not observed in approximately 5,800 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. This substitution occurs at a position that is conserved in most mammals. However, the D2735E variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. Additionally, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Furthermore, missense mutations in nearby residues have not been reported, indicating 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 ARVC panel(s).

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