ClinVar Miner

Submissions for variant NM_000540.2(RYR1):c.14210G>A (p.Arg4737Gln) (rs193922868)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000119503 SCV000567320 pathogenic not provided 2017-06-06 criteria provided, single submitter clinical testing The R4737Q variant has reported previously as R4893Q due to the use of alternate nomenclature. TheR4737Q substitution in the RYR1 gene has been previously reported in association with malignanthyperthermia in multiple unrelated individuals (Monnier et al., 2005; Robinson et al., 2006; Gillies et al.,2008; Carpenter et al., 2009). The R4737Q variant was not observed in approximately 6,500 individualsof European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is nota common benign variant in these populations. The R4737Q variant is a semi-conservative amino acidsubstitution, which may impact secondary protein structure as these residues differ in some properties.This substitution occurs at a position that is conserved across species. In silico analysis is inconsistent in itspredictions as to whether or not the variant is damaging to the protein structure/function. In addition amissense variants at this residue (R4737W) and in nearby residues (Y4733D, G4734E, R4735Q,G4743D) have been reported in the Human Gene Mutation Database in association with RYR1-relateddisorders (Stenson et al., 2014), supporting the functional importance of this region of the protein. Weinterpret R4737Q as a pathogenic variant.
Leiden Muscular Dystrophy (RYR1) RCV000119503 SCV000154410 not provided not provided no assertion provided not provided
PreventionGenetics RCV000119503 SCV000852398 likely pathogenic not provided 2015-11-19 criteria provided, single submitter clinical testing

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