Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000597741 | SCV000707656 | likely pathogenic | not provided | 2017-04-10 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV002531083 | SCV003321695 | pathogenic | Fabry disease | 2022-02-27 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Trp236 amino acid residue in GLA. Other variant(s) that disrupt this residue have been observed in individuals with GLA-related conditions (PMID: 10666480, 16595074), which suggests that this may be a clinically significant amino acid residue. Experimental studies have shown that this missense change affects GLA function (PMID: 23935525). 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. ClinVar contains an entry for this variant (Variation ID: 501332). This missense change has been observed in individual(s) with Fabry disease (PMID: 8875188, 16720462, 27431810). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces tryptophan, which is neutral and slightly polar, with cysteine, which is neutral and slightly polar, at codon 236 of the GLA protein (p.Trp236Cys). |