ClinVar Miner

Submissions for variant NM_000540.2(RYR1):c.9713A>G (p.Glu3238Gly) (rs200950673)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000725266 SCV000234972 uncertain significance not provided 2018-04-03 criteria provided, single submitter clinical testing p.Glu3238Gly (GAG>GGG): c.9713 A>G in exon 66 in the RYR1 gene (NM_000540.2). The E3238G variant in the RYR1 gene has been reported previously in one individual with axial myopathy and has been described as a variant of unknown significance in relation to susceptibility for malignant hyperthermia (Loseth et al., 2013; Brandom et al., 2013). This variant is a non-conservative amino acid substitution of a negatively charged Glutamic acid with a non-polar Glycine at a residue that is conserved across species. In silico analysis was inconsistent with regard to the effect this variant may have on the protein structure/function. The E3238G variant was not observed at any significant frequency in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project. We interpret E3238G as a variant of unknown significance. This variant has been observed to be maternally inherited. The variant is found in RYR1 panel(s).
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000725266 SCV000335493 uncertain significance not provided 2015-09-21 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000382036 SCV000412680 likely benign Neuromuscular disease, congenital, with uniform type 1 fiber 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000287628 SCV000412681 likely benign Malignant hyperthermia susceptibility 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000323995 SCV000412682 likely benign Myopathy, Central Core 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000378617 SCV000412683 likely benign Multiminicore Disease 2016-06-14 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000281816 SCV000540244 uncertain significance not specified 2017-01-25 criteria provided, single submitter clinical testing Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: This variant has been reported in one patient with axial myopathy and one who is malignant hyperthermia susceptible as determined by the Caffeine contracture test. The variant has a Max MAF of 0.1% in ExAC (19 South Asian alleles) and 0.1% in gnomAD (35 South Asian alleles). Frequency is too high for disease. It is classified with 1 star in ClinVar as VUS by GeneDx and as Likely benign by CSER_CC_NCGL.
Invitae RCV000725266 SCV000660097 likely benign not provided 2019-01-30 criteria provided, single submitter clinical testing
Mendelics RCV000990203 SCV001141067 benign Malignant hyperthermia, susceptibility to, 1 2019-05-28 criteria provided, single submitter clinical testing
CSER _CC_NCGL, University of Washington RCV000148800 SCV000190538 likely benign Axial myopathy, late-onset 2014-06-01 no assertion criteria provided research

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