ClinVar Miner

Submissions for variant NM_000152.5(GAA):c.1557G>A (p.Met519Ile)

dbSNP: rs1447365901
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001933170 SCV002190744 pathogenic Glycogen storage disease, type II 2022-08-16 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Met519 amino acid residue in GAA. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 14695532, 31193175, 31342611). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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: 1415612). This missense change has been observed in individual(s) with Pompe disease (PMID: 31439017, 31965297). 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 methionine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 519 of the GAA protein (p.Met519Ile).
Baylor Genetics RCV001933170 SCV005058763 pathogenic Glycogen storage disease, type II 2023-12-03 criteria provided, single submitter clinical testing

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