ClinVar Miner

Submissions for variant NM_000540.3(RYR1):c.14759C>T (p.Thr4920Ile)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001046203 SCV001210097 likely pathogenic RYR1-Related Disorders 2019-03-21 criteria provided, single submitter clinical testing This sequence change replaces threonine with isoleucine at codon 4920 of the RYR1 protein (p.Thr4920Ile). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and isoleucine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in several individuals affected with central core disease or myopathy (PMID: 23919265, 25256590, Invitae). This variant disrupts the p.Thr4920 amino acid residue in RYR1. Other variant(s) that disrupt this residue have been observed in individuals with RYR1-related conditions (PMID: 16621918, 27363342, 29629541), which suggests that this may be a clinically significant amino acid residue. 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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