ClinVar Miner

Submissions for variant NM_000540.3(RYR1):c.10493G>A (p.Arg3498His)

gnomAD frequency: 0.00003  dbSNP: rs529215921
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001658858 SCV001874036 uncertain significance not provided 2021-09-11 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 27535533)
Labcorp Genetics (formerly Invitae), Labcorp RCV002032640 SCV002216237 uncertain significance RYR1-related disorder 2021-09-01 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 3498 of the RYR1 protein (p.Arg3498His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs529215921, ExAC 0.02%). This variant has not been reported in the literature in individuals affected with RYR1-related conditions. 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: "Benign"; Align-GVGD: "Class C0"). 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.
Revvity Omics, Revvity RCV001658858 SCV003812507 uncertain significance not provided 2019-06-17 criteria provided, single submitter clinical testing

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