Around the time of these tumour diagnoses, in 2019, MSH6 c.3226C>T was reclassified as (likely) pathogenic by InSiGHT following its detection in trans with truncating MSH6 variants in patients with a CMMRD phenotype18–22, and as a heterozygous variant in patients with an LS phenotype23–26 (Supplementary Table S1). Here, MSH6 is linked to neoplasm.