Frequency and distribution of predicted disruptive variants in the HLH cohort. (A) Schematic of germline variant frequency within cohort among 17 HLH-associated genes sequenced. (B) Frequency of total and predicted disruptive germline variants observed in FHL genes in cohort. (C) Percentage of individuals in HLH and the 1000 Genomes Project (TGP) cohort carrying variants in HLH-associated genes. TGP var indicates the percentage of individuals in the TGP cohort carrying variants identified in the HLH cohort; TGP rule indicates the percentage of individuals in the TGP cohort carrying any variants identified by the same rules as for the HLH cohort. Percentages compared whole data (HLH [n = 88] and TGP [n = 2503]) and white or Caucasian individuals (HLH [n = 68] and TGP [n = 503]). Among white or Caucasian individuals, similar analysis was performed by excluding the PRF1 A91V variant. The percentage of individuals carrying predicted disruptive variants is shown in red. *P < .05; •P ≥ .05. The significance test result for carriers of all variants is indicated in black; the same for carriers of predicted disruptive variants is shown in red. + indicates the SH2D1A R55Q mutation, which is encoded on the X chromosome, was present in a male patient.