ClinVar Miner

Submissions for variant NM_024301.5(FKRP):c.628C>G (p.Leu210Val) (rs778472624)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000519238 SCV000620982 uncertain significance not provided 2018-08-30 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the FKRP gene. The L210V variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The L210V variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). The L210V variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. In-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function. Based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV000697869 SCV000826502 uncertain significance Walker-Warburg congenital muscular dystrophy 2019-06-05 criteria provided, single submitter clinical testing This sequence change replaces leucine with valine at codon 210 of the FKRP protein (p.Leu210Val). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and valine. This variant is present in population databases (rs778472624, ExAC 0.008%). This variant has not been reported in the literature in individuals with FKRP-related disease. ClinVar contains an entry for this variant (Variation ID: 452196). 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"). 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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