ClinVar Miner

Submissions for variant NM_000540.3(RYR1):c.2533C>T (p.Leu845Phe)

gnomAD frequency: 0.00001  dbSNP: rs201545585
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Biesecker Lab/Clinical Genomics Section, National Institutes of Health RCV000210013 SCV000265696 uncertain significance Malignant hyperthermia, susceptibility to, 1 2013-07-01 criteria provided, single submitter research
Labcorp Genetics (formerly Invitae), Labcorp RCV002515574 SCV003503292 uncertain significance RYR1-related disorder 2022-05-24 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 845 of the RYR1 protein (p.Leu845Phe). This variant is present in population databases (rs201545585, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with RYR1-related conditions. ClinVar contains an entry for this variant (Variation ID: 224374). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt RYR1 protein function. 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.

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