ClinVar Miner

Submissions for variant NM_000152.5(GAA):c.1594G>A (p.Gly532Ser)

gnomAD frequency: 0.00001  dbSNP: rs773576381
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000817631 SCV000958200 uncertain significance Glycogen storage disease, type II 2022-03-22 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 532 of the GAA protein (p.Gly532Ser). This variant is present in population databases (rs773576381, gnomAD 0.01%). This missense change has been observed in individual(s) with clinical features of GAA-related conditions (PMID: 31392188, 33202836). ClinVar contains an entry for this variant (Variation ID: 660436). 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 GAA protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Fulgent Genetics, Fulgent Genetics RCV000817631 SCV002778686 likely pathogenic Glycogen storage disease, type II 2024-05-21 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV003141841 SCV003828425 uncertain significance not provided 2019-11-11 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003323733 SCV004030049 uncertain significance not specified 2024-09-17 criteria provided, single submitter clinical testing Variant summary: GAA c.1594G>A (p.Gly532Ser) results in a non-conservative amino acid change located in the Glycoside hydrolase family 31, TIM barrel domain (IPR017853) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 8e-06 in 251158 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1594G>A has been reported in the literature in compound heterozygous individuals either affected with Glycogen Storage Disease, Type 2 (Pompe Disease), with a second variant of unclassified pathogenicity (example: Alandy-dy_2019) or with late-onset Pompe Disease (example: Ficicioglu_2020, Bhatnagar_2022). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 31392188, 33202836, 35365393). ClinVar contains an entry for this variant (Variation ID: 660436). Based on the evidence outlined above, the variant was classified as uncertain significance.
Baylor Genetics RCV000817631 SCV004195468 likely pathogenic Glycogen storage disease, type II 2024-02-27 criteria provided, single submitter clinical testing
Natera, Inc. RCV000817631 SCV001459730 uncertain significance Glycogen storage disease, type II 2020-09-16 no assertion criteria provided clinical testing

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