ClinVar Miner

Submissions for variant NM_000540.3(RYR1):c.1670C>T (p.Ser557Phe)

dbSNP: rs1967329033
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001059952 SCV001224607 pathogenic RYR1-Related Disorders 2020-01-06 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This missense change is located in a region of the RYR1 protein where a significant number of previously reported RYR1 missense mutations are found (PMID: 16084090). These observations suggest that this may be a clinically significant region of the protein. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). This variant has been observed in individual(s) with malignant hyperthermia (Invitae). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (ExAC no frequency). This sequence change replaces serine with phenylalanine at codon 557 of the RYR1 protein (p.Ser557Phe). The serine residue is highly conserved and there is a large physicochemical difference between serine and phenylalanine.

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