Computational Classifications of 36 BRCA1 BRCT Variants Functionally Characterized by the Transactivation Assay

For each variant, the local protein structure environment is represented by secondary structure type and whether the amino acid residue is buried (normalized solvent accessibility < 0.2) or exposed (normalized solvent accessibility ≥ 0.2). Labels (“1655 S->F”) are colored according to whether the variant was functional in the assays (blue) or nonfunctional (red). Computational classifications in agreement with the assay are indicated by filled circles. Computational classifications not in agreement with the assay are indicated by outlined circles. Computational classifications yielding “unclassified” are indicated by an outlined black circle. The variant D1692N is fully functional as a transcriptional activator but results in incorrect splicing in vivo. Results from variant M1775K are unpublished (Foulkes et al.).

A, Ancestral Sequence; B, Rule-based decision tree; D, Decision Tree; F, SIFT; MCC, Matthews correlation coefficient; N, Naïve Bayes; R, Random Forest; S, Support Vector Machine; T, Align-GVGD Tnig; U, Align-GVGD Spur.