Figure 4.

RENOVO-M validation in BRCA1/2-related context

(A) Comparison of RENOVO-M and ENIGMA database on the 7,445 variants reviewed by the ENIGMA Consortium. Bubble size represents the percentage of common variants for each RENOVO-M class and ENIGMA class. Colors follow the classification provided by RENOVO: blue shades for HP-B and IP-B classes, red shades for HP-P and IP-P, and gray for LP.

(B) RENOVO-M classification of in vitro functional BRCA1 variants. Dark and light blue represent variants classified as HP and IP benign, red and orange are for HP and IP pathogenic variants, and gray slices for mutations classified as LP.

(C) RENOVO-M classification of LOF in vitro BRCA1 variants; colors used as in (B).

(D) Separate view of RENOVO-M results on functional BRCA1 variants from functional assay: variants that are already present in ClinVar and on novel variants are represented on the left and the right, respectively. Color code is the same used in (B).

(E) Separate view of RENOVO-M results on LOF BRCA1 variants from functional assay: classification of variants that are already present in ClinVar is represented on the left and classification of novel variants on the right. Color code is the same used in (B).

(F) RENOVO-M pathogenicity likelihood score versus functional score defined by Findlay in the different RENOVO classes. Colors follow RENOVO-M classification.

(G) RENOVO-M classification of intermediate BRCA1 variants. Color code is described in (B).