ClinVar Miner

Submissions for variant NM_000540.2(RYR1):c.122T>C (p.Phe41Ser) (rs766407858)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000544009 SCV000659786 uncertain significance RYR1-Related Disorders 2018-08-11 criteria provided, single submitter clinical testing This sequence change replaces phenylalanine with serine at codon 41 of the RYR1 protein (p.Phe41Ser). The phenylalanine residue is moderately conserved and there is a large physicochemical difference between phenylalanine and serine. This variant is present in population databases (rs766407858, ExAC 0.03%). This variant has been reported in 2 individuals affected with autosomal recessive congenital myopathy (PMID: 21911697, 23553484). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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 RCV000721268 SCV000852290 likely pathogenic not provided 2016-11-21 criteria provided, single submitter clinical testing

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