Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Eurofins Ntd Llc |
RCV000596844 | SCV000702898 | uncertain significance | not provided | 2016-11-17 | criteria provided, single submitter | clinical testing | |
| Fulgent Genetics, |
RCV002483587 | SCV002780504 | uncertain significance | Glycogen storage disease, type II | 2021-12-28 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV002483587 | SCV004281394 | likely pathogenic | Glycogen storage disease, type II | 2023-09-21 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 154 of the GAA protein (p.Arg154Cys). This variant is present in population databases (rs539841659, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with GAA-related conditions. ClinVar contains an entry for this variant (Variation ID: 498074). 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 GAA protein function. This variant disrupts the p.Arg154 amino acid residue in GAA. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 18285536). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. |