In this perspective, centers already performing tumor-only target sequencing for the diagnostic workup of MDS/AML patients are optimizing these tests, to detect germline variants of genes associated with familial forms of MDS/AML (e.g., RUNX1, CEBPA, GATA2, TP53), to maximize detection and reorganize patients management [75]. The gene discussed is TP53; the disease is acute myeloid leukemia.