One potential interpretation of these atypical tumor phenotypes is that the tumor spectrum associated with some CPGs is wider than currently recognized given that, to date, testing of particular genes has been limited to specific phenotypes. For example, although FH variants were demonstrated to predispose to RCC in 2002, they were shown to predispose to pheochromocytoma and paraganglioma 12 years later.46, 47, 48 We therefore suggest that further “agnostic” research testing of a comprehensive panel of CPGs in MPT-affected individuals could lead to the identification of novel associations between genes and tumor phenotypes. Our observation of a significantly higher rate of loss-of-function variants associated with non-characteristic tumors in our cohort than in the gnomAD dataset suggests that at least some variants identified in individuals with atypical phenotypes are relevant. We would, however, urge caution in automatically linking a pathogenic CPG variant to the observed tumor phenotype without further evidence, such as larger studies of variant carriers or tumor studies that demonstrate a variant’s causative effect.