Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001225198 | SCV001397439 | pathogenic | Glycogen storage disease due to glucose-6-phosphatase deficiency type IA | 2023-10-03 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 274 of the G6PC protein (p.Ala274Val). This variant is present in population databases (rs774212157, gnomAD 0.004%). This missense change has been observed in individual(s) with clinical features of glycogen storage disorder type 1a (GSD1a) (PMID: 24980439; Invitae). 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: 952976). 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. This variant disrupts the p.Ala274 amino acid residue in G6PC. Other variant(s) that disrupt this residue have been observed in individuals with G6PC-related conditions (PMID: 29374762), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic. |