ClinVar Miner

Submissions for variant NM_000540.2(RYR1):c.7661T>C (p.Leu2554Pro) (rs1292252892)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000531104 SCV000660034 uncertain significance RYR1-Related Disorders 2017-07-12 criteria provided, single submitter clinical testing This sequence change replaces leucine with proline at codon 2554 of the RYR1 protein (p.Leu2554Pro). The leucine residue is moderately conserved and there is a moderate physicochemical difference between leucine and proline. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with 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, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
