ERBB2 encodes HER2, an EGFR receptor tyrosine kinase, which activates PI3K-AKT-mTOR and RAS-RAF-MEK-ERK pathways. ERBB2 (HER2) amplification has been implicated in several tumor types. Simple ERBB2 variants are seen in about 1.4% of all tumors, inclusing with 2-3% of lung cancers, skin cancers, breast cancers, and colorectal cancers, and 10% of small intestine cancers. ERBB2 amplification (not detected by this assay) is seen in a number of tumors and selects patients for targeted therapy. In a clinical trial, tumors with ERBB2-activating variants have been shown to be sensitive to HER2 inhibitors.