On the other end of the classification spectrum, a patient with clinical features of a genetic disorder deserves a diagnosis even if the causative variant(s) cannot be identified using current methodology, for example, > 6 CALs (cafe-au-lait spots), axillary freckling and dermal neurofibromas should be diagnosed as Neurofibromatosis Type 1 even if there is no identifiable mutation in the NF1 gene [62, 63]. This evidence concerns the gene NF1 and neurofibromatosis type 1.