Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000539689 | SCV000641798 | likely pathogenic | Baraitser-Winter syndrome 1 | 2017-03-27 | criteria provided, single submitter | clinical testing | In summary, this variant is a rare missense change that is absent from the population and has been observed de novo in an affected individual. This evidence indicates that the variant is pathogenic, but additional data is needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. 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 disruptive, but these predictions have not been confirmed by published functional studies. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a ACTB-related disease. However, family studies have indicated that this variant was not present in the parents of an individual with clinical features of ACTB-related disease, which suggests that it was de novo in that affected individual (Invitae). This sequence change replaces proline with leucine at codon 38 of the ACTB protein (p.Pro38Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. |