ClinVar Miner

Submissions for variant NM_024301.5(FKRP):c.1363G>T (p.Ala455Ser)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000700840 SCV000829614 uncertain significance Walker-Warburg congenital muscular dystrophy 2018-05-31 criteria provided, single submitter clinical testing This sequence change replaces alanine with serine at codon 455 of the FKRP protein (p.Ala455Ser). The alanine residue is moderately conserved and there is a moderate physicochemical difference between alanine and serine. This variant is present in population databases (rs747785577, ExAC 0.003%). This variant has not been reported in the literature in individuals with FKRP-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). The p.Ala455 amino acid residue in FKRP has been determined to be clinically significant (PMID: 14652796, 15574464, 16368217, 18671187, 23420653, 23894383). This suggests that variants that disrupt this residue are likely to be causative of disease. 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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