Inactivation of the second allele of tumor suppressor genes would be an early event in this oncogenic pathway.3,50 Protein-truncating variants in five genes (ATM, BRCA1/2, CHEK2, and PALB2) were associated with a risk of breast cancer.6,51 However, above moderate to high penetrance susceptibility gene mutations only account for ~5% of overall breast cancer cases3; attention should be paid to low penetrance susceptibility genetic variation. The gene discussed is CHEK2; the disease is breast cancer.