ClinVar Miner

Submissions for variant NM_000540.3(RYR1):c.2697C>A (p.Asn899Lys)

dbSNP: rs201401814
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Biesecker Lab/Clinical Genomics Section, National Institutes of Health RCV000209958 SCV000265697 uncertain significance Malignant hyperthermia, susceptibility to, 1 2013-07-01 criteria provided, single submitter research
Invitae RCV001853349 SCV002171078 uncertain significance RYR1-related disorder 2022-09-01 criteria provided, single submitter clinical testing This sequence change replaces asparagine, which is neutral and polar, with lysine, which is basic and polar, at codon 899 of the RYR1 protein (p.Asn899Lys). This variant is present in population databases (rs201401814, gnomAD 0.04%). This missense change has been observed in individual(s) with idiopathic hyperCKemia and equivocal in vitro contracture test result with halothane and a negative personal and family history for malignant hyperthermia (PMID: 20681998, 24195946). ClinVar contains an entry for this variant (Variation ID: 224375). 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) performed at Invitae indicates that this missense variant is not expected to disrupt 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.
Fulgent Genetics, Fulgent Genetics RCV002478756 SCV002792182 uncertain significance Central core myopathy; Malignant hyperthermia, susceptibility to, 1; Congenital multicore myopathy with external ophthalmoplegia; Congenital myopathy with fiber type disproportion; King Denborough syndrome 2021-07-12 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV003129811 SCV003810537 uncertain significance not provided 2021-05-24 criteria provided, single submitter clinical testing

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.