The mutant allele was observed heterozygous twice in unrelated unaffecteds in our in-house exome database of collectively over 2000 independent exomes (including about 1000 Turkish individuals), and not reported in any public database, suggesting a carrier frequency of 1:1000. In all families, we confirmed that the mutation occurred within a homozygous haplotype block (Figure S1A), suggesting a founder mutation. The mutated amino acid residue was highly conserved in all multicellular organisms (Figure 1C), and predicted to be damaging (Adzhubei et al., 2010). No other potentially deleterious rare homozygous CLP1 variants were present in the database. Comparison of exome allele calls between families suggested a minimal shared haplotype between chr11:57317640-57461472, or 143,832 bp (Figure S1B), dated to a common ancestor approximately 16.2 generations in the past (+/− 8.7 generations, see methods), during the height of the Ottoman expansion.
