This information is especially important for carriers of the most common LoF variant in NTHL1 (p.(Gln90*); NM_002528.5), which is heterozygous in approximately 0.28% of the general population.6 Identification of monoallelic NTHL1 LoF variants currently presents a clinical conundrum regarding how best to counsel carriers with respect to their cancer risk because of the lack of published evidence. The gene discussed is NTHL1; the disease is cancer.