ClinVar Miner

Submissions for variant NM_000540.2(RYR1):c.14471T>C (p.Leu4824Pro) (rs193922874)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000545453 SCV000659849 pathogenic RYR1-Related Disorders 2017-04-04 criteria provided, single submitter clinical testing This sequence change replaces leucine with proline at codon 4824 of the RYR1 protein (p.Leu4824Pro). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and proline. This variant is not present in population databases (rs193922874, ExAC no frequency). This variant has been reported in several individuals and families affected with malignant hyperthermia (PMID: 14985404, 15448513). ClinVar contains an entry for this variant (Variation ID: 133070). 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: "Unknown"; Align-GVGD: "Class C0"). This missense change is located in a region of the RYR1 protein where a significant number of previously reported RYR1 missense mutations are found (PMID: 16917943, 12565913, 23919265). In summary, this is a rare missense change located in a mutation-rich region of the RYR1 protein. It is absent from the general population but has been reported in several affected individuals. For these reasons, this variant has been classified as Pathogenic.
Leiden Muscular Dystrophy (RYR1) RCV000119517 SCV000154424 not provided not provided no assertion provided not provided
PreventionGenetics RCV000119517 SCV000852417 uncertain significance not provided 2017-10-20 criteria provided, single submitter clinical testing

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