ClinVar Miner

Submissions for variant NM_001035.3(RYR2):c.4736T>C (p.Val1579Ala)

gnomAD frequency: 0.00001  dbSNP: rs766750384
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000724282 SCV000229813 uncertain significance not provided 2014-10-13 criteria provided, single submitter clinical testing
GeneDx RCV000724282 SCV000235110 uncertain significance not provided 2016-01-07 criteria provided, single submitter clinical testing The V1579A variant has not been published as a mutation or been reported as a benign polymorphism to our knowledge. The V1579A 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. Although the V1579A variant is a conservative amino acid substitution of one non-polar amino acid to another; this substitution occurs at a position that is conserved among mammals. Nevertheless, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. No missense mutations in nearby residues have been reported in association with ARVC, suggesting this region of the protein may be tolerant to change. Furthermore, this variant is not located in one of the mutation hot spot regions in the RYR2 gene (Medeiros-Domingo A et al., 2009). Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant.

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