A major influence on the number and pattern of variants detected in a study such as this is the tumor phenotypes occurring in the cohort, which in this case reflect both the population incidence and the patterns of referral for genetic assessment and investigation. Compared with MPT-affected individuals in cancer registries, our series is enriched with combinations such as breast-ovary (4.4% versus 1.9%) and breast-colorectal (5.5% versus 2.8%), most likely reflecting common cancers with a significant hereditary component and for which genetic testing has been routinely available for a number of years. Many of these cancers are sex specific, most likely contributing to the uneven sex distribution in this series. Some combination types making up >1% of MPT combinations, e.g., breast-thyroid (3.6% in MPT data), are not observed frequently (<1%) in the population-based cohort used here, which could be accounted for by referral prompted by suspicion of germline PTEN variants.