Despite these caveats, our work shows the benefit of detailed analysis of the TSC1 and TSC2 genomic loci for TSC molecular diagnostics and indicates that targeted genomic NGS with high-quality reads and high read depth is an appropriate molecular screening method for individuals where there is a clinical suspicion of TSC, allowing reliable detection of both deep intronic variants that affect pre-mRNA splicing and low-frequency post-zygotic changes. Here, TSC1 is linked to tuberous sclerosis.