Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001236290 | SCV001409007 | uncertain significance | Glycogen storage disease, type IV; Glycogen storage disease IV, classic hepatic | 2019-10-07 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid with asparagine at codon 459 of the GBE1 protein (p.Asp459Asn). The aspartic acid residue is weakly conserved and there is a small physicochemical difference between aspartic acid and asparagine. This variant is present in population databases (rs752100789, ExAC 0.003%). This variant has not been reported in the literature in individuals with GBE1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The asparagine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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. |