Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000730949 | SCV000858717 | pathogenic | not provided | 2017-12-15 | criteria provided, single submitter | clinical testing | |
Invitae | RCV002535181 | SCV003445174 | pathogenic | Fabry disease | 2023-04-06 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 63 of the GLA protein (p.Cys63Tyr). This missense change has been observed in individual(s) with Fabry disease (PMID: 15776423, 16720462, 22551898, 27585509). For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Cys63 amino acid residue in GLA. Other variant(s) that disrupt this residue have been observed in individuals with GLA-related conditions (PMID: 24830310, 27585509), 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). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt GLA protein function. ClinVar contains an entry for this variant (Variation ID: 595414). |