Fig. 2: Clinical impact of secondary finding of PPGVs on tumor CGP.

a PPGVs detected across cancer types via combined tissue and liquid CGP. The prevalence and count of total PPGV+ cases for each cancer type are shown. The cancer types with broad recommendations for germline testing in the NCCN guidelines regardless of family and personal history are colored red, i.e., germline testing is recommended universally in ovarian and pancreatic cancer, universal BRCA1/2 testing is recommended in metastatic HER2-negative breast cancer, and testing is recommended for all patients with metastatic/advanced/high-risk localized prostate cancer. b Distribution of cancer types in which select founder mutation PPGVs were detected in BRCA1 (E23fs*17, C61G, Q1756fs*74), BRCA2 (1308*, S1982fs*2), ATM (V2424G), CHEK2 (T367fs*15), and MUTYH (biallelic involving Y165C and/or G382D). c PPGVs identified in BRCA-associated cancers (Breast/Ovarian/Pancreatic/Prostate). HRR Other Genes include ATM, BAP1, BRIP1, CHEK2, PALB2, RAD51C, RAD51D. Non-HRR Genes include FH, FLCN, MLH1, MSH2, MSH6, MUTYH, PMS2, POLE, RET, SDHA, SDHB, SDHC, SDHD, TSC2, VHL. The total number of cases (N) for each cancer type is indicated above the bar. d PPGVs identified in Lynch Syndrome-associated cancers (Uterine/Colorectal). MMR Genes include MLH1, MSH2, MSH6, PMS2. Non-MMR Genes include ATM, BAP1, BRCA1, BRCA2, BRIP1, CHEK2, FH, FLCN, MUTYH, PALB2, POLE, RAD51C, RAD51D, RET, SDHA, SDHB, SDHC, SDHD, TSC2, VHL. C2, VHL. The total number of cases (N) for each cancer type is indicated above the bar. CSG Cancer Susceptibility Gene, HRR Homologous Recombination Repair, MMR Mismatch Repair, NCCN National Comprehensive Cancer Network, PPGV Potential Pathogenic Germline Variant.