ClinVar Miner

Submissions for variant NM_001035.3(RYR2):c.9911A>G (p.Gln3304Arg) (rs794728766)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000182781 SCV000235167 uncertain significance not provided 2013-11-26 criteria provided, single submitter clinical testing p.Gln3304Arg (CAG>CGG): c.9911 A>G in exon 69 of the RYR2 gene (NM_001035.2). The Gln3304Arg variant in the RYR2 gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. Gln3304Arg was not observed in approximately 6000 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Although the Gln3304 residue is well conserved across species, it is not located in one of the three mutation hot spots in the RYR2 gene. In addition, mutations in nearby residues have not been reported in association with arrhythmia, indicating this region of the protein may tolerate change. The Gln3304Arg variant is a semi-conservative amino acid substitution as these residues share similar properties, but differ in size, charge, or other properties which may impact secondary structure. In silico algorithms are not consistent in their predictions but at least two concur that Gln3304Arg is benign to the protein structure/function. We cannot definitively determine if Gln3304Arg is a disease-causing mutation or a rare benign variant. The variant is found in ARVC panel(s).

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