ClinVar Miner

Submissions for variant NM_024301.5(FKRP):c.563C>T (p.Ala188Val) (rs768762059)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000489382 SCV000577046 uncertain significance not specified 2017-04-12 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the FKRP gene. The A188V variant has not been published as pathogenic or been reported as benign to our knowledge. This variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). Nevertheless, the A188V variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. Additionally, this substitution occurs at a position that is not conserved. Furthermore, in silico analysis predicts this variant likely does not alter the protein structure/function.
Genetic Services Laboratory,University of Chicago RCV000489382 SCV000594780 uncertain significance not specified 2015-12-31 criteria provided, single submitter clinical testing
Invitae RCV001242700 SCV001415803 uncertain significance Walker-Warburg congenital muscular dystrophy 2019-06-04 criteria provided, single submitter clinical testing This sequence change replaces alanine with valine at codon 188 of the FKRP protein (p.Ala188Val). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and valine. This variant is present in population databases (rs768762059, ExAC 0.08%). This variant has not been reported in the literature in individuals with FKRP-related conditions. ClinVar contains an entry for this variant (Variation ID: 426570). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The valine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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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