ClinVar Miner

Submissions for variant NM_001035.3(RYR2):c.14278G>A (p.Val4760Ile) (rs794728831)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000182894 SCV000235283 likely pathogenic not provided 2011-11-28 criteria provided, single submitter clinical testing This variant is denoted Va4760Ile (aka V4760I) at the protein level and c.14278 G>A at the cDNA level. The Val4760Ile variant in the RYR2 gene has not been reported previously as a disease-causing mutation or as a benign polymorphism, to our knowledge. Although Val4760Ile results in a conservative amino acid substitution of one non-polar amino acid for another, the Val4760 residue is conserved across species throughout evolution. In addition, a mutation in a nearby codon (His4762Pro) has been reported in association with CPVT, further supporting the functional importance of this region of the protein, and in silico analysis (Polyphen) predicts this variant to be probably damaging to protein structure/function. Val4760Ile was also not observed in up to 200 control alleles from individuals of African American ancestry tested at GeneDx, indicating it is not a common benign variant in this population. In summary, while Val4760Ile is a good candidate for a disease-causing mutation, we cannot unequivocally determine the clinical significance of this variant. The variant is found in CPVT panel(s).

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