ClinVar Miner

Submissions for variant NM_000152.5(GAA):c.2237G>T (p.Trp746Leu)

dbSNP: rs752921215
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000313359 SCV000337526 uncertain significance not provided 2018-05-16 criteria provided, single submitter clinical testing
Counsyl RCV000671751 SCV000796767 uncertain significance Glycogen storage disease, type II 2017-12-28 criteria provided, single submitter clinical testing
Invitae RCV000671751 SCV001233298 likely pathogenic Glycogen storage disease, type II 2024-01-31 criteria provided, single submitter clinical testing This sequence change replaces tryptophan, which is neutral and slightly polar, with leucine, which is neutral and non-polar, at codon 746 of the GAA protein (p.Trp746Leu). This variant is present in population databases (rs752921215, gnomAD 0.01%). This missense change has been observed in individual(s) with a positive newborn screening result for GAA-related disease (PMID: 23430949). ClinVar contains an entry for this variant (Variation ID: 284776). 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.Trp746 amino acid residue in GAA. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 7981676, 9535769, 21232767, 21757382, 25093132, 27099502). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Genome-Nilou Lab RCV000671751 SCV002027299 uncertain significance Glycogen storage disease, type II 2021-09-05 criteria provided, single submitter clinical testing
Revvity Omics, Revvity Omics RCV000313359 SCV003816215 uncertain significance not provided 2023-02-28 criteria provided, single submitter clinical testing
Natera, Inc. RCV000671751 SCV002092117 uncertain significance Glycogen storage disease, type II 2020-10-07 no assertion criteria provided clinical testing

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