All resolved MYHRS cases to date have one of four heterozygous missense variants in the two affected codons (c.1486C>T [p.Arg496Cys], c.1498A>G [p.Ile500Val], c.1499T>C [p.Ile500Thr], or c.1500A>G [p.Ile500Met]) within the MH2 domain of SMAD4. The gene discussed is SMAD4; the disease is Myhre syndrome.