Fig. 1: Comparison of two distinct testing pathways: diagnostic and screening.

The diagnostic pathway (a) is prompted by clinical signs, symptoms, or a positive family history. The screening pathway (b, c) is prompted by a pathogenic or likely pathogenic variant reported on the DNA-based test aimed at identifying those individuals with sufficient risk of a specific disorder to warrant further investigation or direct preventive action. While many of the elements of the two pathways are the same, they are in a different order in the diagnostic versus screening pathways. In (c) it is the absence of diagnostic findings signifying a “nonpenetrant risk” that prompts condition-specific periodic re-evaluation.