ClinVar Miner

Submissions for variant NM_000152.5(GAA):c.1669A>G (p.Ile557Val)

gnomAD frequency: 0.00001  dbSNP: rs747150965
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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 RCV001062538 SCV001227345 uncertain significance Glycogen storage disease, type II 2022-08-15 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 557 of the GAA protein (p.Ile557Val). This variant is present in population databases (rs747150965, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with GAA-related conditions. ClinVar contains an entry for this variant (Variation ID: 856959). 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 not expected to disrupt GAA protein function. This variant disrupts the p.Ile557 amino acid residue in GAA. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 23884227, 25612604). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Natera, Inc. RCV001062538 SCV002092054 uncertain significance Glycogen storage disease, type II 2021-09-09 no assertion criteria provided clinical testing

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