ClinVar Miner

Submissions for variant NM_000540.2(RYR1):c.4711A>G (p.Ile1571Val) (rs146429605)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000147429 SCV000194836 uncertain significance not provided 2014-04-29 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000147429 SCV000331484 uncertain significance not provided 2018-02-15 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000375527 SCV000540246 uncertain significance not specified 2016-04-25 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: 2 papers describe as LB; ExAC: 0.5% (3/608) Latino chromosomes; ClinVar: 1 LB, 1 VUS; ML: Frequent for disease. 0.2% Eur
CeGaT Praxis fuer Humangenetik Tuebingen RCV000147429 SCV000575167 uncertain significance not provided 2016-09-30 criteria provided, single submitter clinical testing
Invitae RCV000655534 SCV000777465 uncertain significance RYR1-Related Disorders 2018-11-27 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with valine at codon 1571 of the RYR1 protein (p.Ile1571Val). The isoleucine residue is highly conserved and there is a small physicochemical difference between isoleucine and valine. This variant is present in population databases (rs146429605, ExAC 0.5%). Three missense variants, p.Ile1571Val, p.Arg3366His, and p.Tyr3933Cys, which includes this variant (p.Ile1571Val), have been reported together in multiple individuals and families affected with RYR1-related disorders including malignant hyperthermia (MH) syndrome, congenital myopathy, central core disease (CCD), and multi minicore disease (MmD). In some cases, the phase of the three variants along with additional RYR1 variants was established, while in other cases it could not be determined. It is therefore unclear if one of the three variants or the additive effect of some or all of these mutations are causative for the RYR1-associated diseases in reported individuals (PMID: 25958340, 25735680, 25214167, 24950660, 25960145, 25658027, 22473935, 20681998, 28259615). ClinVar contains an entry for this variant (Variation ID: 159851). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
PreventionGenetics,PreventionGenetics RCV000147429 SCV000852638 uncertain significance not provided 2016-08-15 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000765446 SCV000896737 uncertain significance Myopathy, Central Core; Malignant hyperthermia, susceptibility to, 1; Minicore myopathy; Congenital myopathy with fiber type disproportion 2018-10-31 criteria provided, single submitter clinical testing
CSER_CC_NCGL; University of Washington Medical Center RCV000148793 SCV000190531 likely benign Malignant hyperthermia, susceptibility to, 1 2014-06-01 no assertion criteria provided research

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