However, in those families where complement laboratory studies suggest the diagnosis of C1-INH-HAE but no SERPING1 mutation can be identified by the conventional methods used in a diagnostic laboratory, or in case the detected missense SERPING1 variation is supposed to be benign according to previous publications, databases or in silico prediction tools, further unique techniques should be applied in order to explore the pathogenic alteration in the background of the disease. This evidence concerns the gene SERPING1 and hereditary angioedema.