ClinVar Miner

Submissions for variant NM_000540.3(RYR1):c.11071G>A (p.Glu3691Lys)

gnomAD frequency: 0.00001  dbSNP: rs1459249278
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV003756682 SCV004514984 uncertain significance RYR1-related disorder 2024-07-16 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 3691 of the RYR1 protein (p.Glu3691Lys). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with RYR1-related conditions. 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 with a negative predictive value of 95%. 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.
All of Us Research Program, National Institutes of Health RCV004005817 SCV004835317 uncertain significance Malignant hyperthermia, susceptibility to, 1 2023-11-30 criteria provided, single submitter clinical testing

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