Pathogenic PTPN11 variants involving the poly‐glutamine Gln ²⁵⁵ ‐Gln ²⁵⁶ ‐Gln ²⁵⁷ stretch highlight the relevance of helix B in SHP2's functional regulation

Germline PTPN11 mutations cause Noonan syndrome (NS), the most common disorder among RASopathies. PTPN11 encodes SHP2, a protein tyrosine-phosphatase controlling signaling through the RAS-MAPK and PI3K-AKT pathways. Generally, NS-causing PTPN11 mutations are missense changes destabilizing the inactive conformation of the protein or enhancing its binding to signaling partners. Here, we report on two PTPN11 variants resulting in the deletion or...