Cancer Risk Associated With Pathogenic Variants Identified Using Multigene Hereditary Cancer Panel Testing.

Purpose: -associated clinical syndromes such as Cowden syndrome (CS) increase cancer risk and have historically been diagnosed based upon phenotypic criteria. Because not all patients clinically diagnosed with CS have pathogenic variants (PVs), and not all patients with PVs have been clinically diagnosed with CS, the cancer risk conferred by PVs calculated from cohorts of patients with clinical diagnoses of CS/CS-like phenotypes may be inaccurate.

Methods: We assessed a consecutive cohort of 727,091 individuals tested clinically for hereditary cancer risk, with a multigene panel between September 2013 and February 2022.