ClinVar Miner

Submissions for variant NM_001035.3(RYR2):c.5857A>C (p.Met1953Leu) (rs1057518592)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000413746 SCV000492380 uncertain significance not specified 2016-12-09 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the RYR2 gene. The M1953L variant has not been publishedas a pathogenic variant, nor has it been reported as a benign variant to our knowledge. This variant was not observedin approximately 6,200 individuals of European and African American ancestry in the NHLBI Exome SequencingProject, indicating it is not a common benign variant in these populations. This substitution occurs at a position thatis conserved across species and in silico analysis predicts this variant is probably damaging to the proteinstructure/function. However, the M1953L variant is a conservative amino acid substitution, which is not likely toimpact secondary protein structure as these residues share similar properties. Finally, the M1953L variant is notlocated in one of the three hot-spot regions of the RYR2 gene, where the majority of pathogenic missense variantsoccur (Medeiros-Domingo et al., 2009).

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