Because the MPT cohort reported here was mostly ascertained from UK genetics centers (and was similar to the previous retrospective cohort that did not have a known genetic cause), we estimate (by assuming that WGS would detect variants identified by routine targeted sequencing approaches) that comprehensive genetic analysis in a genetics-center-referred series of individuals with MPTs (and no prior genetic testing) would detect a P/LP variant in around a third of individuals (20.7% + 12.1% [estimated under the assumption of a diagnostic yield of 15.2% in the 79.3% of individuals without a variant in routine testing] = 32.8%). The estimated proportion of individuals with a P/LP variant and a typical tumor would be ∼27.5% (20.7% [all of those with variants detected by targeted analysis had a typical tumor] + [79.3% × 8.6% = 6.8%]). Therefore, in individuals seen in a genetic clinic, the presence of MPTs (two tumors before 60 years of age or three before 70 years of age) could be taken as an indication for considering genetic testing.