Lack of a complete mutation profile, which we define for simplicity in this manuscript as having an activating oncogenic variant with either biallelic CCM loss-of-function variants or a monoallelic activating MAP3K3 variant, may be driven by additional somatic variants in currently unidentified genes or variants in known disease-causing genes that are currently not being identified using existing sequencing strategies. This evidence concerns the gene MAP3K3 and cerebral cavernous malformation.