ClinVar Miner

Submissions for variant NM_000540.2(RYR1):c.13940T>C (p.Leu4647Pro) (rs1555801902)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000655547 SCV000777478 likely pathogenic RYR1-Related Disorders 2017-12-27 criteria provided, single submitter clinical testing This sequence change replaces leucine with proline at codon 4647 of the RYR1 protein (p.Leu4647Pro). 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 (ExAC no frequency). This variant has been reported in several individuals affected with central core disease (PMID: 23183335, 25960145). Experimental studies have shown that this missense change alters RYR1 protein function (PMID: 23183335). 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 currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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