RB1 and retinoblastoma: Retinoblastoma is a rare intraocular childhood cancer caused by a pathogenic variant (formerly termed a mutation) in both RB1 (OMIM 614041) alleles.1 In patients with heritable retinoblastoma, the patient has a germ-line RB1 pathogenic variant, and a new sporadic pathogenic variant in the other RB1 gene initiates tumorigenesis.2 The RB1 germ-line variant can be inherited from an affected parent, but is most often a de novo variant.3 In RB1 mosaicism, the RB1 variant is present in only a fraction of cells and tissues.4,5