SDHC and gastrointestinal stromal tumor: In addition to sequence variants and copy number changes contributing to the genetic pathogenesis of SDHx variants, disease resulting from epigenetic alteration of SDHC by increased promoter methylation (i.e., epimutation) resulting in decreased expression have also been described, especially in PGLs and gastrointestinal stromal tumors (GISTs) (45, 46).