ClinVar Miner

Submissions for variant NM_000540.3(RYR1):c.5340dup (p.Cys1781fs)

dbSNP: rs1969271215
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001065579 SCV001230544 pathogenic RYR1-related disorder 2019-03-04 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in RYR1 are known to be pathogenic (PMID: 20583297, 20839240, 23919265, 28818389). This variant has not been reported in the literature in individuals with RYR1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Cys1781Leufs*77) in the RYR1 gene. It is expected to result in an absent or disrupted protein product.
All of Us Research Program, National Institutes of Health RCV004000148 SCV004820854 uncertain significance Malignant hyperthermia, susceptibility to, 1 2022-12-05 criteria provided, single submitter clinical testing This pathogenicity assessment is for autosomal dominant malignant hyperthermia susceptibility phenotype. This frameshift variant is predicted to result in an absent RYR1 protein product. Loss of RYR1 function due to haploinsufficiency is associated with congenital myopathy (https://clinicalgenome.org/), but it is not an established disease mechanism for autosomal dominant malignant hyperthermia susceptibility. Therefore, this variant is classified as a Variant of Uncertain Significance for malignant hyperthermia susceptibility.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.