Of 20 HNSCC hallmark variants predicted as deleterious by two of three algorithms used for functional prediction [29–31], 17 variants could be validated by Sanger sequencing (Fig. 1d; Additional file 2: Table S5) including: TP53 (R273H), TP53 (P72R), PTEN (H141Y), EGFR (R521K), HRAS (G12S and R78W), and CASP8 (G328E). The gene discussed is CASP8; the disease is head and neck squamous cell carcinoma.