The effects of missense changes and small in-frame deletions and insertions on 
protein function are not easy to predict, and the identification of such 
variants in individuals at risk of a genetic disease can complicate genetic 
counselling. One option is to perform functional tests to assess whether the 
variants affect protein function. We have used this strategy to characterize 
variants identified in the TSC1 and TSC2 genes in individuals with, or suspected 
of having, Tuberous Sclerosis Complex (TSC). Here we present an overview of our 
functional studies on 45 TSC1 and 107 TSC2 variants. Using a standardized 
protocol we classified 16 TSC1 variants and 70 TSC2 variants as pathogenic. In 
addition we identified eight putative splice site mutations (five TSC1 and three 
TSC2). The remaining 24 TSC1 and 34 TSC2 variants were classified as probably 
neutral.