We hypothesized that there were several possible reasons for NMI status in TSC patients: 1) mutation detection failure due to technical issues; 2) mosaicism for mutations in TSC1 or TSC2; 3) mutations in introns that affect splicing and are not near exons, or mutations in promoter and enhancer regions of TSC1 and TSC2, regions typically not examined during molecular diagnostic assessment; 4) occurrence of a third TSC gene. This evidence concerns the gene TSC1 and tuberous sclerosis.