Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000591773 | SCV000704687 | pathogenic | not provided | 2016-12-19 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV003509575 | SCV004299648 | pathogenic | Fabry disease | 2023-06-21 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 92 of the GLA protein (p.Asp92Asn). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of Fabry disease (PMID: 11322659; Invitae). ClinVar contains an entry for this variant (Variation ID: 499270). 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. For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Asp92 amino acid residue in GLA. Other variant(s) that disrupt this residue have been observed in individuals with GLA-related conditions (PMID: 9100224, 18724168, 20367968), which suggests that this may be a clinically significant amino acid residue. Experimental studies have shown that this missense change affects GLA function (PMID: 21598360). |