Identification of a deep intronic PTEN pathogenic variant, which was not detected by standard DNA-targeted panel sequencing but was uncovered by targeted PTEN RNA sequencing using CaptureSeq technology, illustrates the added value of concurrent DNA and RNA analyses in risk assessment for PTEN Hamartoma Tumor Syndrome (PHTS) and in patients given the diagnosis of clinical Cowden Syndrome (CS). This evidence concerns the gene PTEN and Cowden disease.