In carriers of high-penetrance CSGs with deleterious germline variants, lineage-dependent selective pressure for biallelic inactivation in associated cancer types (e.g., BRCA1/2 in hereditary breast cancer) demonstrated earlier age of cancer onset, fewer somatic drivers, and characteristic somatic features suggestive of dependence on the germline allele for tumor development. The gene discussed is BRCA1; the disease is cancer.