Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000020494 | SCV003525066 | pathogenic | Glycogen storage disease, type VI | 2022-02-20 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Arg491 amino acid residue in PYGL. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 33763395). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. ClinVar contains an entry for this variant (Variation ID: 21329). This missense change has been observed in individuals with clinical features of glycogen storage disease (PMID: 17705025; Invitae). This variant is present in population databases (rs113993980, gnomAD 0.007%). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 491 of the PYGL protein (p.Arg491Cys). |
| Gene |
RCV000020494 | SCV000040942 | not provided | Glycogen storage disease, type VI | no assertion provided | literature only |