ClinVar Miner

Submissions for variant NM_001035.3(RYR2):c.5096G>A (p.Arg1699His) (rs779464111)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000182872 SCV000235260 uncertain significance not provided 2014-09-05 criteria provided, single submitter clinical testing p.Arg1699His (CGT>CAT): c.5096 G>A in exon 37 of the RYR2 gene (NM_001035.2). A variant of unknown significance has been identified in the RYR2 gene. The R1699H variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The R1699H variant was not observed in approximately 6,400 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 across species and in silico analysis predicts this variant is probably damaging to the protein structure/function. However, R1699H is located in a region of the RYR2 protein that contains few reported mutations and R1699H is not located in any of the three mutation hot spots" in the RYR2 gene (Medeiros-Domingo A et al., 2009). Additionally, the R1699H variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. This The variant is found in ARRHYTHMIA panel(s)."

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