Fig. 1

Identification of cancer-predisposing variants from the proband’s family. A, The pedigree of the proband. The proband is indicated by the arrow. Deceased individuals are marked with a cross. Shape symbols indicated sex: square for males and circle for females. B, The workflow for identifying germline cancer predisposition variants is composed of candidate variant selection, validation with cancer patient cohort, and functional studies. C, The germline and somatic mutational pattern of CGN c.3560C > T, RASAL2 c.2423A > G, and TTLL4 c.1532C > T in 16 patients from the validation cohort. D, The functional prediction of CGN c.3560C > T, RASAL2 c.2423A > G, and TTLL4 c.1532C > T based on SIFT and PolyPhen-2. E, The allele frequency of CGN c.3560C > T was compared across multiple cohorts, including the cancer patient cohort, normal Taiwanese population, and various ethnic groups enlisted in the Genome Aggregation Database (gnomAD). MAF, minor allelic frequency; Ca, cancer; Het, heterozygous; N/A, non-available; WT, wild-type; T, tolerated; D, damaging; B, benign