ClinVar Miner

Submissions for variant NM_000540.2(RYR1):c.7192C>T (p.Arg2398Cys) (rs751654689)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000558376 SCV000660019 uncertain significance RYR1-Related Disorders 2017-03-07 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 2398 of the RYR1 protein (p.Arg2398Cys). The arginine residue is moderately conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs751654689, ExAC 0.007%) 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. There is no indication that it causes disease, but 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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