Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000526226 | SCV000626774 | likely pathogenic | Glycogen storage disease, type IV; Glycogen storage disease IV, classic hepatic | 2022-02-17 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with GBE1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 524 of the GBE1 protein (p.Arg524Gly). ClinVar contains an entry for this variant (Variation ID: 456517). 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.Arg524 amino acid residue in GBE1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 10545044, 10762170, 12874416, 15452297, 20479904). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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 GBE1 protein function. |
| Fulgent Genetics, |
RCV002483363 | SCV002793685 | uncertain significance | Adult polyglucosan body disease; Glycogen storage disease, type IV | 2021-07-25 | criteria provided, single submitter | clinical testing |