Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000672716 | SCV000797850 | uncertain significance | Glycogen storage disease due to glucose-6-phosphatase deficiency type IA | 2018-02-13 | criteria provided, single submitter | clinical testing | |
Fulgent Genetics, |
RCV000672716 | SCV002786518 | uncertain significance | Glycogen storage disease due to glucose-6-phosphatase deficiency type IA | 2022-02-09 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000672716 | SCV004297780 | likely pathogenic | Glycogen storage disease due to glucose-6-phosphatase deficiency type IA | 2023-08-25 | criteria provided, single submitter | clinical testing | This missense change has been observed in individual(s) with glycogen storage disease type 1a (PMID: 10834516, 10874313). This variant is not present in population databases (gnomAD no frequency). ClinVar contains an entry for this variant (Variation ID: 556681). This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 166 of the G6PC protein (p.Val166Ala). 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.Val166Gly amino acid residue in G6PC. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 7623438). 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. |