Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000020504 | SCV000952766 | pathogenic | Glycogen storage disease, type VI | 2023-12-20 | 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 233 of the PYGL protein (p.Gly233Asp). This variant is present in population databases (rs113993975, gnomAD 0.02%). This missense change has been observed in individuals with clinical features of PYGL-related conditions (PMID: 12809646; Invitae). ClinVar contains an entry for this variant (Variation ID: 21339). 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 PYGL protein function with a positive predictive value of 80%. This variant disrupts the p.Gly233 amino acid residue in PYGL. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 31508908; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |
| Gene |
RCV000020504 | SCV000040955 | not provided | Glycogen storage disease, type VI | no assertion provided | literature only |