ClinVar Miner

Submissions for variant NM_001035.3(RYR2):c.6950C>A (p.Ala2317Glu) (rs794728750)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000182752 SCV000235137 likely pathogenic not provided 2016-03-04 criteria provided, single submitter clinical testing The A2317E likely pathogenic variant in the RYR2 gene has been reported as de novo in a 4 year-old individual with CPVT (van der Werf et al., 2012). In addition, this 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. The A2317E 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. Moreover, this substitution occurs at a position that is conserved across species. Consequently, in silico analysis predicts this variant is probably damaging to the protein structure/function. Furthermore, the A2317E variant is located in one of the three hot-spot regions of the RYR2 gene, where the majority of pathogenic missense variants occur (Medeiros-Domingo et al., 2009).Therefore, this variant is likely pathogenic

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