ClinVar Miner

Submissions for variant NM_000152.5(GAA):c.2238G>T (p.Trp746Cys)

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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 RCV002745939 SCV003015113 pathogenic Glycogen storage disease, type II 2022-05-08 criteria provided, single submitter clinical testing This sequence change replaces tryptophan, which is neutral and slightly polar, with cysteine, which is neutral and slightly polar, at codon 746 of the GAA protein (p.Trp746Cys). This variant is not present in population databases (gnomAD no frequency). A different variant (c.2238G>C) giving rise to the same protein effect has been determined to be pathogenic (PMID: 18458862, 21232767, 21757382, 23430493, 25093132, 25526786, 27099502). This suggests that this variant is also likely to be causative of disease. 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. For these reasons, this variant has been classified as Pathogenic.

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