ClinVar Miner

Submissions for variant NM_000152.5(GAA):c.701C>T (p.Thr234Met)

gnomAD frequency: 0.00001  dbSNP: rs752054011
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001551208 SCV001771668 uncertain significance not provided 2019-11-11 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect
Labcorp Genetics (formerly Invitae), Labcorp RCV001832749 SCV002152029 pathogenic Glycogen storage disease, type II 2024-01-15 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 234 of the GAA protein (p.Thr234Met). This variant is present in population databases (rs752054011, gnomAD 0.003%). This missense change has been observed in individual(s) with Pompe disease (PMID: 36310651). ClinVar contains an entry for this variant (Variation ID: 1190471). 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 with a positive predictive value of 95%. This variant disrupts the p.Thr234 amino acid residue in GAA. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 22644586, 22676651, 34852371). 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.
Revvity Omics, Revvity RCV001551208 SCV003828463 uncertain significance not provided 2022-12-08 criteria provided, single submitter clinical testing
Natera, Inc. RCV001832749 SCV002091953 uncertain significance Glycogen storage disease, type II 2020-03-19 no assertion criteria provided clinical testing

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