CACNA1A and Cowden disease: They showed that an alternate allele fraction (AAF) of 13–24% for mosaic variants in MTOR and PIK3CA could lead to Smith-Kingsmore syndrome, Cowden syndrome 5, and/or megalocephaly-capillary malformation-polymicrogyria syndrome, while a comparable AAF of 16–30% for mosaic variants in CACNA1A was found in asymptomatic parents of children affected with epileptic encephalopathies19,20.