Fig. 2: Germline CHEK2 variants identified in a cohort of patients tested for HHM.

A CHK2 protein schematic showing the locations of the encoded protein variants identified among 69 probands tested for HHMs. CHK2 protein domains are outlined: SQ/TQ (green bar), forkhead-associated (FHA) domain (red bar), and the kinase domain (black bar). Diamonds depict P/LP variants, and circles denote VUS. Red, missense variants; green, intronic and UTR variants; blue, frameshift variants; yellow, nonsense variants; and purple, deletion variants. N gives the number of independent probands/families with a particular allele. B The frequency with which individual alleles were identified amongst probands. Self-reported ethnicities were given by color: Western Europe, red; Polish, blue; Unknown, green; Ashkenazi, purple; Mixed, orange; Eastern Europe, yellow. C Distribution of HMs in those with the CHEK2 p.I157T allele. Color indicates the order of the malignancy for those diagnosed with multiple cancers: first cancer, red; second cancer, blue; third cancer, green. D Cytogenetic and molecular profiles of the myeloid malignancies that developed in those with germline P/LP CHEK2 variants. E–G Representative pedigrees from probands with P/LP germline CHEK2 variants. The proband is indicated by the triangle. The germline CHEK2 variant is indicated for those family members who were genotyped. Cancer diagnoses are given below each pedigree member along with the age at diagnosis (dx.) or death (dc.) when known. Circles indicate women, and squares, men. The generation number is given to the left in Roman numerals. (ns not significant. * P < 0.05, ** P < 0.01, *** P < 0.001).