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. ERBB2 (HER2) G776V lies within the protein kinase domain of the ERBB2 protein. G776V has been identified in sequencing studies, but has not been biochemically characterized and therefore, its effect on ERBB2 protein function is unknown. ERBB2 kinase domain mutations are seen in up to 4.3% of breast cancers. In a preclinical study, AP32788 (EGFR and ERBB2 TKI) inhibited growth of transformed cell lines over expressing ERBB2 G776V in culture. The clinicopathologic significance of this variant remains to be further elucidated.