ClinVar Miner

Submissions for variant NM_000540.2(RYR1):c.443C>T (p.Thr148Ile) (rs151325948)

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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 RCV000623845 SCV000741932 uncertain significance Inborn genetic diseases 2016-11-10 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: UNCERTAIN: Alteration(s) of Uncertain Clinical Significance Detected
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000721535 SCV000705066 uncertain significance not provided 2017-01-09 criteria provided, single submitter clinical testing
Invitae RCV000818782 SCV000959414 uncertain significance RYR1-Related Disorders 2018-12-04 criteria provided, single submitter clinical testing This sequence change replaces threonine with isoleucine at codon 148 of the RYR1 protein (p.Thr148Ile). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and isoleucine. This variant is present in population databases (rs151325948, ExAC 0.2%). This variant has not been reported in the literature in individuals with RYR1-related disease. ClinVar contains an entry for this variant (Variation ID: 499535). 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: "Probably Damaging"; 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. 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 RCV000721535 SCV000852621 uncertain significance not provided 2016-03-08 criteria provided, single submitter clinical testing

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