Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000200195 | SCV000251520 | uncertain significance | not provided | 2013-05-20 | criteria provided, single submitter | clinical testing | p.Gly222Ala (GGA>GCA): c.665 G>C in exon 5 of the G6PC gene (NM_000151.2). The G222A missense substitution has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The amino acid change is conservative as both Glycine and Alanine are uncharged, non-polar amino acids. This change occurs at a conserved position in the G6PC protein. Multiple in-silico analysis models predict that G222A is damaging to the G6PC protein. Therefore, based on the currently available information, it is unclear whether G222A is a disease-causing mutation or a rare benign variant. The variant is found in MITONUC-MITOP panel(s). |
Invitae | RCV001271888 | SCV002510611 | likely pathogenic | Glycogen storage disease due to glucose-6-phosphatase deficiency type IA | 2024-01-16 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 222 of the G6PC protein (p.Gly222Ala). This variant is present in population databases (rs515726229, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with G6PC-related conditions. ClinVar contains an entry for this variant (Variation ID: 214459). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on G6PC protein function. This variant disrupts the p.Gly222 amino acid residue in G6PC. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 7744838, 7814621, 9359038, 10070617). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
Fulgent Genetics, |
RCV001271888 | SCV002787237 | uncertain significance | Glycogen storage disease due to glucose-6-phosphatase deficiency type IA | 2022-03-16 | criteria provided, single submitter | clinical testing | |
Natera, |
RCV001271888 | SCV001453361 | uncertain significance | Glycogen storage disease due to glucose-6-phosphatase deficiency type IA | 2020-09-16 | no assertion criteria provided | clinical testing |