Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000698467 | SCV000827133 | uncertain significance | Hermansky-Pudlak syndrome 2 | 2018-05-09 | criteria provided, single submitter | clinical testing | This sequence change replaces proline with leucine at codon 583 of the AP3B1 protein (p.Pro583Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is present in population databases (rs148023800, ExAC 0.06%). This variant has not been reported in the literature in individuals with AP3B1-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C15"). 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. |