ClinVar Miner

Submissions for variant NM_000169.3(GLA):c.1072G>A (p.Glu358Lys)

dbSNP: rs797044774
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000179727 SCV000232021 pathogenic not provided 2014-08-12 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001048991 SCV001213022 pathogenic Fabry disease 2023-09-27 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 358 of the GLA protein (p.Glu358Lys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with classic Fabry disease (PMID: 9452068, 12429061, 26297554). ClinVar contains an entry for this variant (Variation ID: 198399). 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 not expected to disrupt GLA protein function. Experimental studies have shown that this missense change affects GLA function (PMID: 21598360, 26415523). This variant disrupts the p.Glu358 amino acid residue in GLA. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 8807334, 15339079, 15712228, 15713906, 18154965, 26297554). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Genome-Nilou Lab RCV001048991 SCV002054376 pathogenic Fabry disease 2021-07-15 criteria provided, single submitter clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.