Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002010194 | SCV002282878 | uncertain significance | Hermansky-Pudlak syndrome 2 | 2021-05-18 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals with AP3B1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces isoleucine with threonine at codon 775 of the AP3B1 protein (p.Ile775Thr). The isoleucine residue is weakly conserved and there is a moderate physicochemical difference between isoleucine and threonine. 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 threonine 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. |