Although we report the application of WGS to an adult MPT series, other studies have used agnostic NGS strategies in cohorts with single-site cancer. The detection rate of pathogenic variants in these analyses could be influenced by the assay used, the variant filtering and assessment applied, and the nature of the series in terms of both phenotype and ascertainment. The application of a 76-gene panel to ∼1,000 cancer-affected adults referred for germline genetic testing and ACMG-guideline-based assessment of the resulting variants showed a 17.5% rate,37 whereas tumor-normal sequencing of a similarly sized series with advanced cancer from the same center (regardless of genetic testing referral) reported an equivalent figure of 12.6%.38 The genes containing the most frequent pathogenic variants in both studies were similar to those in the current study (BRCA1, BRCA2, CHEK2, and ATM), but the detection rates were lower than our estimate of around a third of newly referred MPT-affected individuals, most likely reflecting a greater likelihood of a germline pathogenic variant in both genetics referrals and in MPT-affected individuals. Studies of WGS and/or WES applied to unselected pediatric cancer series have also shown pathogenic-variant detection rates close to 10% but a contrasting range of affected genes, suggesting that TP53 and genes associated with embryonal tumors play a far greater role.39, 40, 41