RUNX1 variant curation codes and isoform schematic. (A) The updated RUNX1 curation codes improve the curation process and increase the accuracy of variant classification. The first version of RUNX1-specific ACMG/AMP codes is shown on the left. The updated RUNX1-specific codes (version 2) are displayed on the right. Only revised codes are highlighted with blue fill. (B) Alternative splicing creates 3 protein isoforms that are shown schematically: A (top), B (middle), and C (bottom, isoform used for variant curation). The exons encoding isoform C are shown at the bottom of the figure. A red arrow indicates the extension of the critical region for variant curation defined by the updated curation rules. The green dotted lines indicate the extension of the amino acid range considered for PM1 and PM4. c, nucleotide numbering; p, amino acid numbering; RHD, RUNT homology domain; TAD, transactivation domain. Nucleotide numbering is according to NM_001754.5.