In P1144, a male with neonatal seizures characteristic of tuberous sclerosis (TSC) who responded well to vigabatrin and is progressing toward normality, we detected a missense variant in TSC2. The very high GERP and CONDEL scores for this gene indicate a high degree of sensitivity to variation (this gene had the second lowest z-score of all genes studied). Here, TSC2 is linked to tuberous sclerosis.