ClinVar Miner

Submissions for variant NM_000152.5(GAA):c.1645G>A (p.Gly549Arg)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002629939 SCV003524347 pathogenic Glycogen storage disease, type II 2023-08-25 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. Experimental studies have shown that this missense change affects GAA function (PMID: 14695532, 16917947, 17213836, 19862843, 22990675, 25036864). 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. ClinVar contains an entry for this variant (Variation ID: 2202283). This missense change has been observed in individual(s) with Pompe disease (PMID: 14695532, 16917947). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 549 of the GAA protein (p.Gly549Arg).

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