ClinVar Miner

Submissions for variant NM_000540.3(RYR1):c.8446A>G (p.Met2816Val)

dbSNP: rs775492883
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genomic Research Center, Shahid Beheshti University of Medical Sciences RCV000626286 SCV000746944 likely pathogenic Congenital myopathy with fiber type disproportion 2020-05-03 criteria provided, single submitter clinical testing
Ambry Genetics RCV002529788 SCV003574941 uncertain significance Inborn genetic diseases 2021-08-02 criteria provided, single submitter clinical testing The c.8446A>G (p.M2816V) alteration is located in exon 54 (coding exon 54) of the RYR1 gene. This alteration results from a A to G substitution at nucleotide position 8446, causing the methionine (M) at amino acid position 2816 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Revvity Omics, Revvity RCV003133414 SCV003814400 uncertain significance not provided 2021-03-19 criteria provided, single submitter clinical testing
GeneDx RCV003133414 SCV005391423 uncertain significance not provided 2025-01-22 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; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 12668474)
All of Us Research Program, National Institutes of Health RCV004802305 SCV005425142 uncertain significance Malignant hyperthermia, susceptibility to, 1 2024-08-13 criteria provided, single submitter clinical testing This missense variant replaces methionine with valine at codon 2816 of the RYR1 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function. 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: 523076). This variant has been identified in 1/251422 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Due to insufficient evidence, this variant is classified as a Variant of Uncertain Significance for autosomal dominant malignant hyperthermia.

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