Fig. 1. Overview of pooled variant-to-function mapping in RAD51D.

a ClinVar classifications of RAD51D missense variants each year. P/LP = Pathogenic/Likely Pathogenic, B/LB = Benign/Likely Benign, VUS/CON = uncertain significance/conflicting reports. b, c RAD51D forms an obligate heterodimer with XRCC2 to form the (b) BCDX2 (PDB: 8GBJ) or (c) XRCC3 (X3CDX2) complexes (PDB: 9SVX) through its interaction with RAD51C. d Schematic of pooled RAD51D variant function assay. RAD51D mutant library cell population is treated with 250 nM olaparib over several passages, selecting for cells with normal RAD51D function. RAD51D variants are quantified within the starting (P0) and final (P2) cell populations by sequencing and scored by their relative enrichment in P2 versus P0.