Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001062884 | SCV001227708 | uncertain significance | Glycogen storage disease, type II | 2021-09-01 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine with isoleucine at codon 439 of the GAA protein (p.Met439Ile). The methionine residue is weakly conserved and there is a small physicochemical difference between methionine and isoleucine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with GAA-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The isoleucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. This variant disrupts the p.Met439 amino acid residue in GAA. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 17092519, 19862843, 20202878, 23884227, 25213570, 29124014). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Natera, |
RCV001062884 | SCV002092013 | uncertain significance | Glycogen storage disease, type II | 2021-04-27 | no assertion criteria provided | clinical testing |