The recommendations 1 and 6 of these guidelines are based on the C4CMMRD guidelines for the clinical indication for CMMRD testing in cancer patients ([15], Table 2) and in children suspected to have sporadic NF1/Legius syndrome without cancer and without an NF1/SPRED1 germline PV after comprehensive genetic analysis ([20], Table 3). The gene discussed is SPRED1; the disease is neurofibromatosis type 1.