MSH6 and mismatch repair cancer syndrome 1: In addition, MSH6 c.3226C>T (p.Arg1076Cys) variant, initially classified as VUS, was reclassified as probably pathogenic (class 4) because of its co-occurrence in trans with MSH6 pathogenic mutations in patients with constitutional MMR deficiency and loss of MSH6 expression in normal cells [41,42].