ClinVar Miner

Submissions for variant NM_000540.2(RYR1):c.7229C>T (p.Pro2410Leu) (rs145787667)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000655536 SCV000777467 uncertain significance RYR1-Related Disorders 2017-12-21 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 2410 of the RYR1 protein (p.Pro2410Leu). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and leucine. This variant is present in population databases (rs145787667, ExAC 0.04%). This variant has not been reported in the literature in individuals with RYR1-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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 RCV000721645 SCV000852759 uncertain significance not provided 2016-06-06 criteria provided, single submitter clinical testing

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