ClinVar Miner

Submissions for variant NM_000540.2(RYR1):c.14717C>G (p.Ala4906Gly) (rs118192153)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000173935 SCV000225116 uncertain significance not provided 2014-12-17 criteria provided, single submitter clinical testing
Invitae RCV000797894 SCV000937480 uncertain significance RYR1-Related Disorders 2018-11-07 criteria provided, single submitter clinical testing This sequence change replaces alanine with glycine at codon 4906 of the RYR1 protein (p.Ala4906Gly). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and glycine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual with malignant hyperthermia susceptibility (PMID: 23558838). ClinVar contains an entry for this variant (Variation ID: 193772). 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.

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