Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000215480 | SCV000271504 | uncertain significance | not specified | 2015-08-12 | criteria provided, single submitter | clinical testing | The p.Ile858Val variant in AP3B1 has not been previously reported in individuals with pulmonary disease, but has been identified in 3/65412 European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSN P rs150765181). Computational prediction tools and conservation analysis do no t provide strong support for or against an impact to the protein. In summary, th e clinical significance of the p.Ile858Val variant is uncertain. |
Labcorp Genetics |
RCV001062212 | SCV001226994 | uncertain significance | Hermansky-Pudlak syndrome 2 | 2021-09-02 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine with valine at codon 858 of the AP3B1 protein (p.Ile858Val). The isoleucine residue is moderately conserved and there is a small physicochemical difference between isoleucine and valine. This variant is present in population databases (rs150765181, ExAC 0.005%). This variant has not been reported in the literature in individuals affected with AP3B1-related conditions. ClinVar contains an entry for this variant (Variation ID: 228441). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. |