ClinVar Miner

Submissions for variant NM_000540.2(RYR1):c.12956G>A (p.Arg4319Gln) (rs539194350)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000721299 SCV000233222 uncertain significance not provided 2014-07-10 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000376367 SCV000412915 likely benign Neuromuscular disease, congenital, with uniform type 1 fiber 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000286783 SCV000412916 likely benign Multiminicore Disease 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000341804 SCV000412917 likely benign Myopathy, Central Core 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000400216 SCV000412918 likely benign Malignant hyperthermia susceptibility 2016-06-14 criteria provided, single submitter clinical testing
GeneDx RCV000180737 SCV000582991 uncertain significance not specified 2017-05-17 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the RYR1 gene. The R4319Q variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The R4319Q variant is observed in 11/1322 (0.83%) alleles from individuals of African background in large population cohorts and in 42/69576 (0.06%) alleles from individuals undergoing testing at GeneDx (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). This substitution occurs at a position where amino acids with similar properties to Arginine are tolerated across species. However, the R4319Q variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV000721299 SCV000659805 likely benign not provided 2019-02-21 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000721299 SCV000852326 uncertain significance not provided 2018-03-13 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000721299 SCV001151896 uncertain significance not provided 2018-02-01 criteria provided, single submitter clinical testing

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