TP53 and breast cancer: For example, the new evidence towards pathogenicity is much greater for a rare TP53 variant detected in a context with high phenotypical specificity (for example, testing of only one gene, TP53, in an adolescent with rhabdomyosarcoma and a family history of young-onset cancers) compared with a context with low phenotypical specificity (for example, testing of a 40-gene panel in a 68-year-old woman with breast cancer and no family history).19 20, 21 Without data on the tested gene panel and phenotype, the two instances of the variant would not be distinguishable.