ClinVar Miner

Submissions for variant NM_000540.3(RYR1):c.9680G>A (p.Arg3227Gln)

gnomAD frequency: 0.00001  dbSNP: rs878984852
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000655576 SCV000777507 uncertain significance RYR1-related disorder 2024-04-24 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 3227 of the RYR1 protein (p.Arg3227Gln). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 544436). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on 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.
Mayo Clinic Laboratories, Mayo Clinic RCV002261162 SCV002541635 uncertain significance not provided 2021-08-11 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV004004151 SCV004826323 uncertain significance Malignant hyperthermia, susceptibility to, 1 2023-05-31 criteria provided, single submitter clinical testing
GeneDx RCV002261162 SCV005628496 uncertain significance not provided 2024-07-16 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; In silico analysis suggests this variant may impact gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; This variant is associated with the following publications: (PMID: 37273706)

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