ClinVar Miner

Submissions for variant NM_001035.3(RYR2):c.6829T>C (p.Cys2277Arg) (rs794727676)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000435115 SCV000230672 uncertain significance not provided 2014-09-09 criteria provided, single submitter clinical testing
GeneDx RCV000435115 SCV000530405 likely pathogenic not provided 2016-07-28 criteria provided, single submitter clinical testing The C2277R variant in the RYR2 gene has been reported previously in this family, where it was found to co-segregate with a CPVT phenotype in 7 of 8 heterozygous carriers; this family also had a history of sudden cardiac death in multiple individuals (Domingo et al., 2015). The C2277R variant was not observed in approximately 6,100 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The C2277R variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, we interpret C2277R as a strong candidate for a pathogenic variant.

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