ClinVar Miner

Submissions for variant NM_000540.2(RYR1):c.7007G>A (p.Arg2336His) (rs112563513)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 10
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000554523 SCV000660010 pathogenic RYR1-Related Disorders 2016-10-21 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 2336 of the RYR1 protein (p.Arg2336His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant is not present in population databases (rs112563513, ExAC no frequency). This variant has been reported in many individuals affected with malignant hyperthermia susceptibility (MHS) and has also been observed to segregate with MHS in several families (PMID: 19191329, 19648156, 21455645, 23476141, 23558838, 24433488). ClinVar contains an entry for this variant (Variation ID: 133174). Experimental studies have shown that this missense change increases RYR1 protein sensitivity to calcium, caffeine and 4-chloro-m-cresol (PMID: 19191329, 23736090). This missense change is located in the central mutational hotspot of the RYR1 protein where a significant number of previously reported RYR1 missense mutations are found (PMID: 16084090). For these reasons, this variant has been classified as Pathogenic.
Leiden Muscular Dystrophy (RYR1) RCV000119673 SCV000154580 not provided not provided no assertion provided not provided
PharmGKB RCV000786419 SCV000925241 drug response halothane response - Toxicity/ADR reviewed by expert panel curation PharmGKB Level of Evidence 1A: Annotation for a variant-drug combination in a CPIC or medical society-endorsed PGx guideline, or implemented at a PGRN site or in another major health system.
PharmGKB RCV000786420 SCV000925242 drug response isoflurane response - Toxicity/ADR reviewed by expert panel curation PharmGKB Level of Evidence 1A: Annotation for a variant-drug combination in a CPIC or medical society-endorsed PGx guideline, or implemented at a PGRN site or in another major health system.
PharmGKB RCV000786421 SCV000925243 drug response methoxyflurane response - Toxicity/ADR reviewed by expert panel curation PharmGKB Level of Evidence 1A: Annotation for a variant-drug combination in a CPIC or medical society-endorsed PGx guideline, or implemented at a PGRN site or in another major health system.
PharmGKB RCV000786422 SCV000925244 drug response sevoflurane response - Toxicity/ADR reviewed by expert panel curation PharmGKB Level of Evidence 1A: Annotation for a variant-drug combination in a CPIC or medical society-endorsed PGx guideline, or implemented at a PGRN site or in another major health system.
PharmGKB RCV000786423 SCV000925245 drug response succinylcholine response - Toxicity/ADR reviewed by expert panel curation PharmGKB Level of Evidence 1A: Annotation for a variant-drug combination in a CPIC or medical society-endorsed PGx guideline, or implemented at a PGRN site or in another major health system.
PharmGKB RCV000786547 SCV000925369 drug response desflurane response - Toxicity/ADR reviewed by expert panel curation PharmGKB Level of Evidence 1A: Annotation for a variant-drug combination in a CPIC or medical society-endorsed PGx guideline, or implemented at a PGRN site or in another major health system.
PharmGKB RCV000786548 SCV000925370 drug response enflurane response - Toxicity/ADR reviewed by expert panel curation PharmGKB Level of Evidence 1A: Annotation for a variant-drug combination in a CPIC or medical society-endorsed PGx guideline, or implemented at a PGRN site or in another major health system.
PreventionGenetics RCV000119673 SCV000852736 pathogenic not provided 2018-02-27 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.