PTPN11 and juvenile myelomonocytic leukemia: This association between NS and JMML reflects the difference in oncogenic strength: NS-associated PTPN11 variants act as relatively weak drivers of proliferation, a hallmark of cancer, whereas the somatic variants seen in JMML have stronger molecular defects and would likely be embryonically lethal if present in the germline (Liu et al., 2023).