Fig. 1

Germline false positives in tumor-only clinical sequencing. Sensitivity and positive predictive value (PPV) curves for multiple germline filtering strategies identifies optimal approaches for unmatched large targeted panel testing (a) and whole-exome sequencing (b). For 91 patients, germline exome data were used to identify false positives post-filtering. Subsequent molecular pathologist review of variants was performed on individual cases to further classify putative germline variants. With molecular pathology review, 50/54 false positive variants were correctly classified as unknown (“tier 4”), with the remaining variants classified as having uncertain (n = 3; “tier 3”) or potential (n = 1; “tier 2”) clinical utility (c, d). Please see “Methods” for detailed descriptions of the four-tier classification schema