ClinVar Miner

Submissions for variant NM_000540.2(RYR1):c.6640G>A (p.Val2214Ile) (rs193922795)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CSER_CC_NCGL; University of Washington Medical Center RCV000148822 SCV000190561 uncertain significance Malignant hyperthermia, susceptibility to, 1 2014-06-01 no assertion criteria provided research
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000119666 SCV000230502 uncertain significance not provided 2014-11-15 criteria provided, single submitter clinical testing
Invitae RCV000528915 SCV000660002 uncertain significance RYR1-Related Disorders 2017-06-05 criteria provided, single submitter clinical testing This sequence change replaces valine with isoleucine at codon 2214 of the RYR1 protein (p.Val2214Ile). The valine residue is highly conserved and there is a small physicochemical difference between valine and isoleucine. This variant is present in population databases (rs193922795, ExAC 0.01%). This variant has been reported in an individual affected with malignant hyperthermia (PMID: 11575529). ClinVar contains an entry for this variant (Variation ID: 133168). 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"). This sequence change is located in the central mutational hotspot of the RYR1 gene, where a significant number of previously reported RYR1 missense mutations are found (PMID: 16084090). In summary, this variant is a rare missense change with uncertain impact on protein function. It has been reported in both the population and an affected individual, but the available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Leiden Muscular Dystrophy (RYR1) RCV000119666 SCV000154573 not provided not provided no assertion provided not provided

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