Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001963157 | SCV002242190 | pathogenic | Fabry disease | 2021-08-30 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Phe113 amino acid residue in GLA. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 16773563, 17555407, 32099817). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Experimental studies have shown that this missense change affects GLA function (PMID: 21598360). 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. This missense change has been observed in individual(s) with clinical features of Fabry disease (PMID: 11668641, 12428061, 30386727). This variant is not present in population databases (ExAC no frequency). This sequence change replaces phenylalanine with serine at codon 113 of the GLA protein (p.Phe113Ser). The phenylalanine residue is highly conserved and there is a large physicochemical difference between phenylalanine and serine. |