ClinVar Miner

Submissions for variant NM_000540.2(RYR1):c.3127C>T (p.Arg1043Cys) (rs111272095)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CSER_CC_NCGL; University of Washington Medical Center RCV000148799 SCV000190537 likely benign Malignant hyperthermia, susceptibility to, 1 2014-06-01 no assertion criteria provided research
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000119607 SCV000228120 uncertain significance not provided 2014-07-11 criteria provided, single submitter clinical testing
Invitae RCV000546583 SCV000659912 uncertain significance RYR1-Related Disorders 2018-12-28 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 1043 of the RYR1 protein (p.Arg1043Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs111272095, ExAC 0.004%). This variant has been observed in individuals affected with malignant hyperthermia or autosomal recessive RYR1-related myopathy (PMID: 19191329, 23558838, 30155738). However, in some of these individuals pathogenic allele(s) were also identified in RYR1, which suggests that the p.Arg1043Cys variant is not the primary cause of disease. ClinVar contains an entry for this variant (Variation ID: 133124). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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.
Leiden Muscular Dystrophy (RYR1) RCV000119607 SCV000154514 not provided not provided no assertion provided not provided
PreventionGenetics RCV000119607 SCV000852561 uncertain significance not provided 2013-11-19 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.