Some of the remaining ∼10% of TSC individuals are classified as having “no mutation identified” (NMI) despite thorough conventional molecular diagnostic assessment such as exon-based sequencing and analysis for large genomic deletions in TSC1 and TSC2. Several possible factors contribute to NMI status in TSC patients, including mutation detection failure due to technical issues, unknown epigenetic modifications that may affect TSC gene expression, mosaicism and the occurrence of pathogenic variants deep within introns. Here, TSC1 is linked to tuberous sclerosis.