In summary, we have demonstrated that the application of comprehensive CPG testing to a cohort of previously investigated MPT-affected individuals resulted in the detection of multiple pathogenic variants with relevance to the management of those individuals and their relatives. The finding that comprehensive genetic analysis of MPT-affected individuals can frequently result in the identification of pathogenic CPG variants that cannot automatically be attributed as causative for the observed MPT clinical phenotype has important implications both for clinical practice and for future research into the phenotypic consequences of germline CPG variants. Summing together variant detection rates from a previous series of MPT-affected individuals ascertained in a similar manner and the present results suggests that first-line application of WGS (or other strategies for comprehensive CPG variant detection) to a clinical-genetics-referral-based cohort of MPT-affected individuals would detect a deleterious mutation in about a third of individuals, a large proportion of whom would not have a family history of cancer in a first-degree relative.