Diagnostic accuracy of NK cytotoxicity for detecting biallelic HLH gene mutations. (A) Sensitivity/specificity/PPV/NPV of low NK lytic units to distinguish patients with any biallelic HLH gene mutations (PRF1, UNC13D, STX11, STXBP2, RAB27A, LYST, or AP3B1) from patients with all other sequencing results. (B) Sensitivity/specificity/PPV/NPV of low NK lytic units to distinguish patients with any biallelic HLH mutation from those with normal sequencing results. (C) Distribution of NK lytic unit results among patients with no mutations, 1 or more VUCS, carriers (with or without additional VUCS), and biallelic mutations. (D) ROC curve showing diagnostic accuracy of NK lytic units to distinguish patients with biallelic mutations from patients with all other sequencing results; sensitivity and specificity are shown at the optimal diagnostic cutoff of LU ≤ 0.1.