ClinVar Miner

Submissions for variant NM_000540.2(RYR1):c.10042C>T (p.Arg3348Cys) (rs118204421)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000377005 SCV000412700 uncertain significance Malignant hyperthermia, susceptibility to, 1 2017-04-28 criteria provided, single submitter clinical testing The RYR1 c.10042C>T (p.Arg3348Cys) variant has been reported in one study in which it was found in two individuals from the same family (Kaufmann et al. 2012). The index individual was compound heterozygous for the p.Arg3348Cys variant and a second missense variant and was found to be susceptible to malignant hyperthermia based on an in vitro contracture test. In addition, her mother was heterozygous for the p.Arg3348Cys variant and exhibited malignant hyperthermia equivocal to halothane based on an in vitro contracture test. The index individual's sister was heterozygous for the other missense variant and was also susceptible to malignant hyperthermia. In the presence of halothane, cells that carried the p.Arg3348Cys variant were three times more sensitive than control cells, and in cells that carried both variants, the reaction sensitivity was increased even further. The p.Arg3348Cys variant was absent from 105 controls and is reported at a frequency of 0.00014 in the European (non-Finnish) population of the Exome Aggregation Consortium. Based on the limited evidence, the p.Arg3348Cys variant is classified as a variant of unknown significance but suspicious for pathogenicity for malignant hyperthermia susceptibility. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Illumina Clinical Services Laboratory,Illumina RCV000263630 SCV000412701 uncertain significance Myopathy, Central Core 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000318907 SCV000412702 uncertain significance Neuromuscular disease, congenital, with uniform type 1 fiber 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000373530 SCV000412703 uncertain significance Multiminicore Disease 2016-06-14 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000721186 SCV000852191 uncertain significance not provided 2013-10-28 criteria provided, single submitter clinical testing

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