Additional file 7: Figure S1. Workflow of the methodology used. Figure S2. Electropherograms obtained by Sanger sequencing, confirming the WES results. Figure S3. Location of the potentially causative variants in the canonical protein forms obtained from the UniProt Platform. The proteins, proportional to size, the positions of the mutations (lollipops), and the coordinates of the domains annotated in Pfam are represented. Variants identified in FREM1, C6, C9, ABCC6, and BSCL2 are contained in the functional domains of their proteins, whereas for the ABCA4 variant, two variants are outside functional domains and one is within it. For POLG, the variant is located outside functional domains. MPO variant was not illustrated, since it is intronic. Figure S4. Highly reliable protein–protein interactions network retrieved from the products of the eight genes studied. The red hexagons represent the genes carrying the variants. The circles represent the interactions obtained through the STRING plugin, with the green circles representing genes already related to the MIS-C phenotype and blue circles representing genes already related to Kawasaki disease. Figure S5. Enrichment analysis through EnrichR tool of the proteins verified in the PPIs network (FDR < 0.05) against the following gene-set libraries: KEGG 2021 (a); Gene Ontology 2021—biological processes (b), molecular function (c), and cellular component (d); Jensen tissues (e); the scRNA-seq database PanglaoDB Augmented 2021 (f); COVID-19-related gene sets 2021 (g). Top ten elements were sorted by adjusted p-value ranking.