ClinVar Miner

Submissions for variant NM_000169.3(GLA):c.983G>C (p.Gly328Ala)

dbSNP: rs28935492
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000723545 SCV000110147 pathogenic not provided 2012-08-15 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000011488 SCV002158551 pathogenic Fabry disease 2024-03-07 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 328 of the GLA protein (p.Gly328Ala). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with Fabry disease (PMID: 7504405, 16595074, 27834756). ClinVar contains an entry for this variant (Variation ID: 10740). 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 with a negative predictive value of 80%. Experimental studies have shown that this missense change affects GLA function (PMID: 21598360, 23935525). This variant disrupts the p.Gly328 amino acid residue in GLA. Other variant(s) that disrupt this residue have been observed in individuals with GLA-related conditions (PMID: 1315715, 15712228, 16595074), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000011488 SCV000031720 pathogenic Fabry disease 1993-12-01 no assertion criteria provided literature only

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