ClinVar Miner

Submissions for variant NM_000540.2(RYR1):c.2450G>A (p.Arg817Gln) (rs759902314)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000531270 SCV000659891 uncertain significance RYR1-Related Disorders 2017-04-27 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 817 of the RYR1 protein (p.Arg817Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs759902314, ExAC 0.02%) but has not been reported in the literature in individuals with an RYR1-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). This sequence change is located in a region of the RYR1 protein where a significant number of previously reported RYR1 missense mutations are found (PMID: 16084090). In summary, this variant is a rare missense change with uncertain impact on protein function. Because it is found in the population at an appreciable frequency, this variant is not anticipated to cause disease. However, the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.

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