Genotype-phenotype correlations in <i>PMS2</i>-associated constitutional mismatch repair deficiency: a systematic literature review.

Constitutional mismatch repair deficiency (CMMRD) is a rare pediatric cancer predisposition syndrome primarily characterised by central nervous system (CNS), gastro-intestinal (GI) tumours and hematological malignancies, along with NF1-like cutaneous features. The PMS2-related subtype (PMS2-CMMRD) is the most common molecular form of CMMRD, exhibiting variable severity and both early and late-onset clinical presentations. Although pathogenic and likely pathogenic PMS2 heterozygous variants are relatively frequent in healthy population, CMMRD incidence is generally rare in humans and genotype-phenotype correlations are still limited. To better characterise PMS2-CMMRD group, we collected clinical cases described in literature, using three alternative methods (VarChat, VarSome and LitVar2), starting from 102 pathogenic/likely pathogenic PMS2 variants (