ClinVar Miner

Submissions for variant NM_000540.2(RYR1):c.9310G>A (p.Glu3104Lys) (rs193922832)

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Total submissions: 12
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000119768 SCV000617750 likely pathogenic not provided 2017-08-31 criteria provided, single submitter clinical testing The E3104K variant in the RYR1 gene has been reported previously in association with malignant hyperthermia (Robinson et al., 2006; Merritt et al., 2017). The E3104K variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The E3104K variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. Functional assays demonstrate an increased sensitivity of RYR1 channels containing E3104K compared with wild type (Merritt et al., 2017). We interpret E3104K as a likely pathogenic variant.
Invitae RCV000691233 SCV000818982 likely pathogenic RYR1-Related Disorders 2018-11-16 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with lysine at codon 3104 of the RYR1 protein (p.Glu3104Lys). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is present in population databases (rs193922832, ExAC 0.006%). This variant has been observed in individuals and families affected with malignant hyperthermia (PMID: 16917943, 19648156). ClinVar contains an entry for this variant (Variation ID: 133240). Experimental studies have shown that this missense change affects the function of the RYR1 protein (PMID: 28403410). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Leiden Muscular Dystrophy (RYR1) RCV000119768 SCV000154675 not provided not provided no assertion provided not provided
PharmGKB RCV000786507 SCV000925329 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 RCV000786508 SCV000925330 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 RCV000786509 SCV000925331 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 RCV000786510 SCV000925332 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 RCV000786511 SCV000925333 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 RCV000786512 SCV000925334 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.
PharmGKB RCV000786724 SCV000925546 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 RCV000786725 SCV000925547 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 RCV000119768 SCV000852864 likely pathogenic not provided 2015-12-28 criteria provided, single submitter clinical testing

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