Figure 1: Inverse relationship risk, severity and frequency of a genetic mutation. The highly penetrant cancer syndromes are represented as the left arrow. The low-penetrance variants identified through GWAS are characterized by the right arrow. The gap in our knowledge is represented as the arrow between the two. The width of the arrows represents the clinically observed proportion of each diagnostic group. The red, blue, green sliders represent the lifetime relative risk of cancer, the theoretical severity, and the population frequency associated with the different classes of genetic variants respectively.