ClinVar Miner

Submissions for variant NM_000152.5(GAA):c.59C>G (p.Ser20Cys)

dbSNP: rs752449306
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000427881 SCV000535010 uncertain significance not provided 2017-01-09 criteria provided, single submitter clinical testing The S20C variant in the GAA gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The S20C variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The S20C variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is not conserved. In silico analysis predicts this variant likely does not alter the protein structure/function. We interpret S20C as a variant of uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV001851081 SCV002165431 uncertain significance Glycogen storage disease, type II 2021-10-28 criteria provided, single submitter clinical testing This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 20 of the GAA protein (p.Ser20Cys). 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: 391853). 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. 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.

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