Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001582383 | SCV001821379 | likely pathogenic | Glycogen storage disease due to glucose-6-phosphatase deficiency type IA | 2021-08-24 | criteria provided, single submitter | clinical testing | Variant summary: G6PC c.808G>C (p.Gly270Arg) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 8e-06 in 251358 control chromosomes (gnomAD). c.808G>C (also described as c.887G>C by old nomenclature in the literature) has been reported in the literature in at least an individual affected with Glycogen Storage Disease Type Ia (Trioche_2000). In in vitro functional studies, the variant resulted in reduced phosphohydrolase activity compared to wild-type (Shieh_2002). Another variant affecting the same codon (p.Gly270Val) has been reported as pathogenic in ClinVar, suggesting this residue may be clinically important. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Invitae | RCV001582383 | SCV002510606 | likely pathogenic | Glycogen storage disease due to glucose-6-phosphatase deficiency type IA | 2023-03-10 | criteria provided, single submitter | clinical testing | This variant is present in population databases (no rsID available, gnomAD 0.003%). 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. This variant disrupts the p.Gly270 amino acid residue in G6PC. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 7573034, 8733042, 10234610, 28397058, 28659124). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Experimental studies have shown that this missense change affects G6PC function (PMID: 11739393). 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. ClinVar contains an entry for this variant (Variation ID: 1217274). This missense change has been observed in individual(s) with glycogen storage disease type Ia (PMID: 11058903). This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 270 of the G6PC protein (p.Gly270Arg). |