ClinVar Miner

Submissions for variant NM_000540.2(RYR1):c.14555A>G (p.Tyr4852Cys) (rs886042826)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000721382 SCV000336785 uncertain significance not provided 2015-11-09 criteria provided, single submitter clinical testing
Invitae RCV000655579 SCV000777510 pathogenic RYR1-Related Disorders 2018-01-26 criteria provided, single submitter clinical testing This sequence change replaces tyrosine with cysteine at codon 4852 of the RYR1 protein (p.Tyr4852Cys). The tyrosine residue is highly conserved and there is a large physicochemical difference between tyrosine and cysteine. This variant is not present in population databases (ExAC no frequency). This variant has been reported to be de novo in an individual affected with central core myopathy (Invitae). ClinVar contains an entry for this variant (Variation ID: 284245). 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 missense change is located in a region of the RYR1 protein where a significant number of previously reported RYR1 missense mutations are found (PMID: 16084090). These observations suggest that a previously unreported missense substitution within this region may affect protein function, but experiments have not been done to test this possibility. For these reasons, this variant has been classified as Pathogenic.
PreventionGenetics,PreventionGenetics RCV000721382 SCV000852430 uncertain significance not provided 2016-08-18 criteria provided, single submitter clinical testing

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