rs570357965 (MAF: 0.001976) is located on chromosome 9 and results in a S/L amino acid substitution in the protein RAPGEF1. All three carriers share a diagnosis of TS and co-morbid ADHD and are 7th or more distant cousins (separated by at least 16 meiosis), sharing ancestry through FP B. RAPGEF1 has a probability of being loss-of-function intolerant (pLI) score of 1 and an intolerance to missense variation Z-score of 3.13 [37, 47], implying that this gene is extremely intolerant to loss-of-function. This evidence concerns the gene RAPGEF1 and Timothy syndrome.