ClinVar Miner

Submissions for variant NM_000540.2(RYR1):c.14545G>A (p.Val4849Ile) (rs118192168)

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Total submissions: 13
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
PharmGKB RCV000786644 SCV000925466 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 RCV000786685 SCV000925507 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.
PharmGKB RCV000786686 SCV000925508 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 RCV000786687 SCV000925509 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 RCV000786688 SCV000925510 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 RCV000786689 SCV000925511 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 RCV000786690 SCV000925512 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 RCV000786691 SCV000925513 drug response volatile anesthetics 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.
GeneDx RCV000119527 SCV000566861 pathogenic not provided 2017-11-13 criteria provided, single submitter clinical testing The V4849I variant was previously identified in multiple individuals with a clinical diagnosis of central core disease(CCD). It was observed in the homozygous state in an individual with proximal weakness, scoliosis and minicoreson muscle biopsy, and in trans with a pathogenic nonsense variant in an individual with contractures, scoliosis, and feeding difficulties (Jungbluth et al., 2002; Klein et al., 2012). Additionally, it was identified as a single variant in several families with a history of both malignant hyperthermia and CCD (Carpenter et al., 2009), as well as in an individual with scapular winging, limb weakness and a muscle biopsy with increased internal nuclei (Løseth et al., 2013). CCD is typically dominantly inherited, but there are reports of recessive inheritance (Malicdan and Nishino, 2010). Functional studies showed that V4849I did not have an effect on calcium release after channel activation, but it did affect resting calcium concentration, in vitro (Ducreux et al., 2006). V4849I was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. This substitution occurs at a position that is conserved across species and multiple missense variants in nearby residues (A4846V, Y4850C, T4853I) have been reported in the Human Gene Mutation Database (Stenson et al., 2014). V4849I is a pathogenic variant.
PreventionGenetics,PreventionGenetics RCV000119527 SCV000852429 pathogenic not provided 2016-06-08 criteria provided, single submitter clinical testing
OMIM RCV000013855 SCV000034102 pathogenic Central core disease, autosomal recessive 2008-05-01 no assertion criteria provided literature only
OMIM RCV000013856 SCV000034103 pathogenic Minicore myopathy 2008-05-01 no assertion criteria provided literature only
Leiden Muscular Dystrophy (RYR1) RCV000119527 SCV000154434 not provided not provided no assertion provided not provided

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