This mutation is located at extracellular domain. Patients with mutation of ERBB2 S310F, which is very close to S295 and also an extracellular domain, have been treated successfully with anti-HER agents (Jia et al, 2014; Vornicova et al, 2014). Although mutation at extracellular domain does not elevate HER2 protein level (negative for IHC), it might still activate HER2 protein or it’s downstream signaling.