Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001390823 | SCV001592674 | pathogenic | Glycogen storage disease due to glucose-6-phosphatase deficiency type IA | 2022-08-23 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 122 of the G6PC protein (p.Gly122Asp). This variant is present in population databases (rs759982943, gnomAD 0.02%). This missense change has been observed in individual(s) with glycogen storage disease type Ia (PMID: 10748407, 11196115, 15151508). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 1076798). 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 G6PC protein function. Experimental studies have shown that this missense change affects G6PC function (PMID: 11739393). For these reasons, this variant has been classified as Pathogenic. |
Natera, |
RCV001390823 | SCV002093303 | pathogenic | Glycogen storage disease due to glucose-6-phosphatase deficiency type IA | 2021-08-18 | no assertion criteria provided | clinical testing |