ClinVar Miner

Submissions for variant NM_001035.3(RYR2):c.1832T>C (p.Leu611Pro) (rs794728726)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000182692 SCV000235071 uncertain significance not provided 2016-07-19 criteria provided, single submitter clinical testing The Leu611Pro variant in the RYR2 gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. Leu611Pro results in a semi-conservative amino acid substitution of a nonpolar Leucine with a non-polar, sterically constrained Proline at a position that is conserved across species. In silico analysis predicts Leu611Pro is probably damaging to the protein structure/function. The Leu611Pro variant was not observed in approximately 6,000 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. A mutation in a nearby residue (Ser616Leu) has been reported in association with CPVT, however, Leu611Pro does not occur in or near any of the mutation hotspot regions of the RYR2 gene (Medeiros-Domingo A et al., 2009). With the clinical and molecular information available at this time, we cannot definitively determine if Leu611Pro is a disease-causing mutation or a rare benign variant.

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