ClinVar Miner

Submissions for variant NM_000540.2(RYR1):c.14489C>A (p.Ser4830Tyr) (rs1555803852)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000557858 SCV000659850 uncertain significance RYR1-Related Disorders 2017-05-18 criteria provided, single submitter clinical testing This sequence change replaces serine with tyrosine at codon 4830 of the RYR1 protein (p.Ser4830Tyr). The serine residue is highly conserved and there is a large physicochemical difference between serine and tyrosine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a 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 disruptive, but these predictions have not been confirmed by published functional studies. This missense change is located in the C-terminal mutational hotspot of the RYR1 protein where a significant number of previously reported RYR1 missense mutations have been found (PMID: 16084090). In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance.

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