ClinVar Miner

Submissions for variant NM_000540.3(RYR1):c.2485C>T (p.Arg829Ter)

dbSNP: rs778320565
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Total submissions: 3
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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 RCV000784912 SCV000923453 pathogenic RYR1-related disorder 2019-01-01 criteria provided, single submitter research
Labcorp Genetics (formerly Invitae), Labcorp RCV000784912 SCV004520354 pathogenic RYR1-related disorder 2023-09-06 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg829*) in the RYR1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in RYR1 are known to be pathogenic (PMID: 23919265, 25960145, 28818389, 30611313). 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. ClinVar contains an entry for this variant (Variation ID: 634439). For these reasons, this variant has been classified as Pathogenic.
All of Us Research Program, National Institutes of Health RCV004001537 SCV004827263 uncertain significance Malignant hyperthermia, susceptibility to, 1 2023-07-19 criteria provided, single submitter clinical testing This variant changes 1 nucleotide in exon 20 of the RYR1 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. 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: 634439). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of RYR1 function due to truncation variants is not an established disease mechanism for autosomal dominant malignant hyperthermia susceptibility, although it is associated with other phenotype(s) (clinicalgenome.org). Due to insufficient evidence, this variant is classified as a Variant of Uncertain Significance for malignant hyperthermia susceptibility.

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