ClinVar Miner

Submissions for variant NM_000540.3(RYR1):c.15089G>A (p.Arg5030His)

gnomAD frequency: 0.00002  dbSNP: rs747155223
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
PreventionGenetics, part of Exact Sciences RCV000721413 SCV000852475 uncertain significance not provided 2013-10-30 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001317525 SCV001508190 uncertain significance RYR1-related disorder 2024-10-25 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 5030 of the RYR1 protein (p.Arg5030His). This variant is present in population databases (rs747155223, gnomAD 0.06%). This missense change has been observed in individual(s) with clinical features of central core myopathy (PMID: 36697461; internal data). ClinVar contains an entry for this variant (Variation ID: 590481). Invitae Evidence 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 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.
Revvity Omics, Revvity RCV000721413 SCV003813167 uncertain significance not provided 2022-06-15 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV003999826 SCV004816295 uncertain significance Malignant hyperthermia, susceptibility to, 1 2023-12-01 criteria provided, single submitter clinical testing This missense variant replaces arginine with histidine at codon 5030 of the RYR1 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with autosomal dominant malignant hyperthermia in the literature, although it is associated with other phenotype(s) (ClinVar Variation ID: 590481, SCV001508190.3). This variant has been identified in 13/251442 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Center of Excellence for Medical Genomics, Chulalongkorn University RCV002281645 SCV002546539 likely pathogenic Central core myopathy 2022-09-08 no assertion criteria provided research

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