NF1 and neoplasm: Many tumor suppressor genes are associated with characteristic phenotypes that minimally overlap with other clinical presentations, such as NF1 and FH. When a VUS is found in one of these genes and the phenotypes are highly consistent, such as an NF1 VUS detected in a patient with multiple café-au-lait spots and extensive neurofibromatosis, the VUS is highly suspected to be the actual cause of the disease, although rigorous application of the ACMG/AMP guidelines may fail to classify this variant as likely pathogenic.