ClinVar Miner

Submissions for variant NM_000540.2(RYR1):c.14928C>G (p.Phe4976Leu) (rs368874586)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000210545 SCV000262905 likely pathogenic Inborn genetic diseases 2013-09-13 criteria provided, single submitter clinical testing
CSER_CC_NCGL; University of Washington Medical Center RCV000590883 SCV000700143 uncertain significance Malignant hyperthermia 2016-10-01 criteria provided, single submitter research Found in patient having exome sequencing for an unrelated indication. No known history of malignant hyperthermia. This interpretation considers GERP score and allele frequency data, in addition to published reports of the variant in the literature, available at the time of review.
Invitae RCV000793270 SCV000932617 pathogenic RYR1-Related Disorders 2018-10-17 criteria provided, single submitter clinical testing This sequence change replaces phenylalanine with leucine at codon 4976 of the RYR1 protein (p.Phe4976Leu). The phenylalanine residue is highly conserved and there is a small physicochemical difference between phenylalanine and leucine. This variant is present in population databases (rs368874586, ExAC 0.002%). This variant has been observed to segregate with autosomal recessive congenital myopathy in several families (PMID: 25882082, 30155320) and has also been observed in combination with another RYR1 variant in additional, unrelated affected individuals (PMID: 24706162, 25356970). ClinVar contains an entry for this variant (Variation ID: 201154). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0"). For these reasons, this variant has been classified as Pathogenic.
PreventionGenetics RCV000721408 SCV000852470 pathogenic not provided 2018-03-27 criteria provided, single submitter clinical testing

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