ClinVar Miner

Submissions for variant NM_001035.3(RYR2):c.14804G>C (p.Gly4935Ala) (rs794728809)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000182851 SCV000235239 likely pathogenic not provided 2012-09-04 criteria provided, single submitter clinical testing p.Gly4935Ala (GGA>GCA):c.14804 G>C in exon 104 of the RYR2 gene (NM_001035.2). The Gly4935Ala variant in the RYR2 gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. However, a more significant amino acid substitution at the same codon (Gly4935Arg) has been reported in association with CPVT (Medeiros-Domingo A et al., 2009). Gly4935Ala results in a conservative substitution of one non-polar amino acid for another at a position that is conserved across species. In silico analysis predicts Gly4935Ala is probably damaging to the protein structure/function. In addition, the NHLBI ESP Exome Variant Server reports Gly4935Ala was not observed in approximately 6,000 samples from individuals of European and African American backgrounds, indicating it is not a common benign variant in these populations. In summary, while the Gly4935Ala variant in the RYR2 gene is likely a disease-causing mutation, the possibility it is a rare benign variant cannot be excluded. The variant is found in POSTMORTEM panel(s).

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