Table 1. Pathogenic or likely pathogenic... | American Society of Hematology

Table 1.

Pathogenic or likely pathogenic variants identified in 197 HLH patients with a definite genetic diagnosis

Patient no.	Sex	Age at testing, y (unless indicated otherwise)	Ethnicity	Gene	Variant	Zygosity	Population frequency (gnomAD*), %	Symptoms/immunology testing/family history†
1	Female	53 d	African American	PRF1	c.50del(p.Leu17fs)	Homozygous	0.033	Symptoms of HLH
2	Male	63 d	Unknown	PRF1	c.50del(p.Leu17fs)	Homozygous	0.033	Symptoms of HLH
3	Male	0.4	Middle Eastern	PRF1	c.50del(p.Leu17fs)	Homozygous	0.033	Symptoms of HLH
4	Female	27 d	Unknown	PRF1	c.50del(p.Leu17fs)	Homozygous	0.033	Absent perforin expression
5	Female	32 d	African American	PRF1	c.50del(p.Leu17fs)	Homozygous	0.033	Absent perforin expression
6	Male	4 d	African American	PRF1	c.50del(p.Leu17fs)	Homozygous	0.033	Absent perforin expression; sibling died of HLH
7	Female	0.4	African American	PRF1	c.50del(p.Leu17fs)	Homozygous	0.033	Symptoms of HLH
8	Male	6 d	African American + European-white	PRF1	c.50del(p.Leu17fs)	Homozygous	0.033	Absent perforin expression
9	Male	59 d	African American	PRF1	c.50del(p.Leu17fs)	Homozygous	0.033	Symptoms of HLH
10	Male	13 d	African	PRF1	c.50del(p.Leu17fs)	Homozygous	0.033	Symptoms of HLH
11	Female	7 d	Unknown	PRF1	c.50del(p.Leu17fs)	Heterozygous	0.033	Absent NK cell function
				PRF1	c.266C>T(p.Pro89Leu)	Heterozygous	ND	Absent NK cell function
12	Female	0.3	African American	PRF1	c.50del(p.Leu17fs)	Heterozygous	0.033	NA
				PRF1	c.350_356delinsATGC (p.Val117_Arg119delinsAspAla)	Heterozygous	ND	NA
13	Male	0.4	Unknown	PRF1	c.50del(p.Leu17fs)	Heterozygous	0.033	NA
				PRF1	c.445G>A(p.Gly149Ser)	Heterozygous	0.014	NA
14	Male	3.3	African American	PRF1	c.50del(p.Leu17fs)	Heterozygous	0.033	Absent perforin expression; brother with HLH
				PRF1	c.527G>A(p.Cys176Tyr)	Heterozygous	ND	Absent perforin expression; brother with HLH
15	Female	0.5	Latino-Hispanic	PRF1	c.50del(p.Leu17fs)	Heterozygous	0.033	Absent perforin expression
				PRF1	c.659G>A(p.Gly220Asp)	Heterozygous	0.0008	Absent perforin expression
16	Female	0.2	African American	PRF1	c.50del(p.Leu17fs)	Heterozygous	0.033	Absent NK cell function
				PRF1	c.853_855del(p.Lys285del)	Heterozygous	0.0056	Absent NK cell function
17	Male	66 d	Unknown	PRF1	c.50del(p.Leu17fs)	Heterozygous	0.033	NA
				PRF1	c.895C>T(p.Arg299Cys)	Heterozygous	0.0012	NA
18	Male	20.6	Latino-Hispanic	PRF1	c.50del(p.Leu17fs)	Heterozygous	0.033	NA
				PRF1	c.902C>T(p.Ser301Leu)	Heterozygous	ND	NA
19	Male	54 d	African American	PRF1	c.50del(p.Leu17fs)	Heterozygous	0.033	Symptoms of HLH
				PRF1	c.916G>T(p.Gly306Cys)	Heterozygous	ND	Symptoms of HLH
20	Female	45 d	African American	PRF1	c.50del(p.Leu17fs)	Heterozygous	0.033	Absent perforin expression
				PRF1	c.916G>T(p.Gly306Cys)	Heterozygous	ND	Absent perforin expression
21	Male	32 d	Latino-Hispanic	PRF1	c.50del(p.Leu17fs)	Heterozygous	0.033	Symptoms of HLH
				PRF1	c.985dup(p.Val329fs)	Heterozygous	ND	Symptoms of HLH
22	Male	0.3	African American	PRF1	c.50del(p.Leu17fs)	Heterozygous	0.033	Absent perforin expression
				PRF1	c.1385C>A(p.Ser462*)	Heterozygous	ND	Absent perforin expression
23	Male	36.1	Unknown	PRF1	c.116C>A(p.Pro39His)	Heterozygous	0.00081	NA
				PRF1	c.445G>A(p.Gly149Ser)	Heterozygous	0.014	NA
24	Female	1.2	Asian-American	PRF1	c.133G>A(p.Gly45Arg)	Homozygous	0.0012	Absent NK cell function
25	Female	37 d	Non-Hispanic white	PRF1	c.150del(p.Thr51fs)	Heterozygous	0.0004	Absent perforin expression
				PRF1	c.227G>A(p.Cys76Tyr)	Heterozygous	0.00071	Absent perforin expression
26	Male	69 d	Latino-Hispanic	PRF1	c.218G>C(p.Cys73Ser)	Homozygous	0.0004	Symptoms of HLH
27	Female	20	European-American	PRF1	c.227G>A(p.Cys76Tyr)	Heterozygous	0.00071	Absent perforin expression
				PRF1	c.626A>C(p.Gln209Pro)	Heterozygous	0.0012	Absent perforin expression
28	Female	21.8	Unknown	PRF1	c.272C>T(p.Ala91Val)‡	Heterozygous	2.92	Absent NK cell function, decreased perforin expression
				PRF1	c.445G>A(p.Gly149Ser)	Heterozygous	0.014	Absent NK cell function, decreased perforin expression
29	Male	17	European-American	PRF1	c.272C>T(p.Ala91Val)‡	Heterozygous	2.92	Absent perforin expression
				PRF1	c.635A>C(p.Tyr212Ser)	Heterozygous	ND	Absent perforin expression
30	Female	41.2	European-American	PRF1	c.272C>T(p.Ala91Val)‡	Heterozygous	2.92	Absent NK cell function, decreased perforin expression
				PRF1	c.666C>A(p.His222Gln)	Heterozygous	0.0039	Absent NK cell function, decreased perforin expression
31	Female	8.3	European-American	PRF1	c.443C>G(p.Ala148Gly)	Heterozygous	0.0004	NA
				PRF1	c.666C>A(p.His222Gln)	Heterozygous	0.0039	NA
32	Male	2.6	Unknown	PRF1	c.445G>A(p.Gly149Ser)	Homozygous	0.014	Absent NK cell function
33	Male	0.8	Latino-Hispanic	PRF1	c.445G>A(p.Gly149Ser)	Homozygous	0.014	Symptoms of HLH
34	Female	6	Latino-Hispanic	PRF1	c.445G>A(p.Gly149Ser)	Homozygous	0.014	NA
35	Female	0.3	European-American	PRF1	c.445G>A(p.Gly149Ser)	Heterozygous	0.014	Family history of HLH
				PRF1	c.614A>G(p.Asn205Ser)	Heterozygous	0.0043	Family history of HLH
36	Male	42 d	Latino-Hispanic	PRF1	c.445G>A(p.Gly149Ser)	Heterozygous	0.014	NA
				PRF1	c.938A>T(p.Asp313Val)	Heterozygous	0.0012	NA
37	Male	4.6	Unknown	PRF1	c.445G>A(p.Gly149Ser)	Heterozygous	0.014	Absent perforin expression
				PRF1	c.1081A>T(p.Arg361Trp)	Heterozygous	0.0011	Absent perforin expression
38	Female	32 d	Middle Eastern	PRF1	c.501C>G(p.Tyr167*)	Homozygous	ND	Symptoms of HLH
39	Female	0.3	Unknown	PRF1	c.512C>A(p.Thr171Asn)	Homozygous	0.0028	Absent perforin expression
40	Male	9.5	European-American	PRF1	c.786_801del(p.Gln263fs)	Heterozygous	ND	Absent NK cell function
				PRF1	c.886T>C(p.Tyr296His)	Heterozygous	0.0012	Absent NK cell function
41	Male	59 d	Unknown	PRF1	c.853_855del(p.Lys285del)	Heterozygous	0.0057	NA
				PRF1	c.921del(p.His308fs)	Heterozygous	0.002	NA
42	Female	0.7	Middle Eastern	PRF1	c.880del(p.Gln294fs)	Homozygous	ND	Symptoms of HLH
43	Female	2	Middle Eastern	PRF1	c.895C>T(p.Arg299Cys)	Homozygous	0.0012	Symptoms of HLH
44	Female	0.2	Latino-Hispanic	PRF1	c.904G>T(p.Glu302*)	Homozygous	ND	Absent perforin expression
45	Female	1.8	Unknown	PRF1	c.949G>A(p.Gly317Arg)	Homozygous	0.0008	Symptoms of HLH
46	Female	10.3	European-American	PRF1	c.973T>C(p.Tyr325His)	Heterozygous	ND	Absent perforin expression
				PRF1	c.1326_1328del(p.Phe443del)	Heterozygous	ND	Absent perforin expression
47	Male	1.1	Middle Eastern	PRF1	c.1070G>C(p.Arg357Pro)	Homozygous	ND	Symptoms of HLH
48	Male	12.5	Middle Eastern	PRF1	c.1081A>T(p.Arg361Trp)	Homozygous	0.0011	Abnormal brain lesions and seizures
49	Female	2.6	Unknown	PRF1	c.1229_1230delinsCC (p.Arg410Pro)	Homozygous	ND	NA
50	Female	0.2	African American	PRF1	c.1304C>T(p.Thr435Met)	Heterozygous	0.0028	Absent perforin expression
				PRF1	c.1314T>A(p.Tyr438*)	Heterozygous	0.0032	Absent perforin expression
51	Female	2.6	Latino-Hispanic	PRF1	c.1337A>C(p.Gln446Pro)	Homozygous	0.0016	NA
52	Female	2.6	Unknown	PRF1	c.1337A>C(p.Gln446Pro)	Homozygous	0.0016	Symptoms of HLH
53	Female	0.4	Middle Eastern	STXBP2	c.37+2T>C	Heterozygous	ND	Absent NK cell function
				STXBP2	c.1430C>T(p.Pro477Leu)	Heterozygous	0.00074	Absent NK cell function
54	Male	0.6	Unknown	STXBP2	c.37+5G>A	Heterozygous	ND	NA
				STXBP2	c.1057T>C (p.Cys353Arg)	Heterozygous	0.0004	NA
55	Female	63 d	Asian-American	STXBP2	c.193C>T(p.Arg65Trp)	Homozygous	0.00071	Absent NK cell function
56	Female	5.5	Unknown	STXBP2	c.194G>A(p.Arg65Gln)	Heterozygous	0.0028	Absent NK cell function
				STXBP2	c.560C>T (p.Pro187Leu)	Heterozygous	0.00064	Absent NK cell function
57	Male	4.1	European-American	STXBP2	c.194G>A(p.Arg65Gln)	Heterozygous	0.0028	Symptoms of HLH
				STXBP2	c.1621G>A(p.Gly541Ser)	Heterozygous	0.023	Symptoms of HLH
58	Female	4.2	European-American	STXBP2	c.326-30_326-23del	Heterozygous	0.0068	Symptoms of HLH
				STXBP2	c.1621G>A(p.Gly541Ser)	Heterozygous	0.023	Symptoms of HLH
59	Male	0.6	Latino-Hispanic	STXBP2	c.389T>C(p.Leu130Ser)	Homozygous	0.0032	Symptoms of HLH
60	Male	45 d	African American	STXBP2	c.389T>C(p.Leu130Ser)	Heterozygous	0.0032	Symptoms of HLH; family history of HLH
				STXBP2	exon 14-19 deletion	Heterozygous	ND	Symptoms of HLH; family history of HLH
61	Male	0.7	Middle Eastern	STXBP2	c.481del(p.Arg161fs)	Homozygous	ND	Symptoms of HLH
62	Male	0.4	Unknown	STXBP2	c.481del(p.Arg161fs)	Homozygous	ND	Symptoms of HLH
63	Female	11	European-American	STXBP2	c.539_540delinsAA(p.Cys180*)	Heterozygous	ND	Symptoms of HLH
				STXBP2	c.1247-1G>C	Heterozygous	0.02	Symptoms of HLH
64	Male	0.3	Latino-Hispanic	STXBP2	c.703C>G(p.Arg235Gly)	Homozygous	0.00071	Absent NK cell function
65	Female	52.7	European-American	STXBP2	c.752C>T(p.Ala251Val)	Heterozygous	ND	Symptoms of HLH
				STXBP2	c.1621G>A(p.Gly541Ser)	Heterozygous	0.023	Symptoms of HLH
66	Male	0.9	Unknown	STXBP2	c.902+5G>A	Heterozygous	0.0036	NA
				STXBP2	c.1247-1G>C	Heterozygous	0.02	NA
67	Male	3.1	Unknown	STXBP2	c.1247-1G>C	Homozygous	0.02	Symptoms of HLH
68	Female	22.7	Latino-Spanish	STXBP2	c.1247-1G>C	Homozygous	0.02	Decreased NK cell function
69	Male	26.4	European-American	STXBP2	c.1247-1G>C	Homozygous	0.02	Symptoms of HLH
70	Male	25.6	European-American	STXBP2	c.1247-1G>C	Homozygous	0.02	Symptoms of HLH
71	Female	29.7	European-American	STXBP2	c.1247-1G>C	Homozygous	0.02	NA
72	Male	4	European-American	STXBP2	c.1247-1G>C	Heterozygous	0.02	Absent NK cell function
				STXBP2	c.1621G>A(p.Gly541Ser)	Heterozygous	0.023	Absent NK cell function
73	Female	15.8	European-American	STXBP2	c.1247-1G>C	Heterozygous	0.02	Absent NK cell function
				STXBP2	c.1621G>A(p.Gly541Ser)	Heterozygous	0.023	Absent NK cell function
74	Female	19	Unknown	STXBP2	c.1247-1G>C	Heterozygous	0.02	Decreased NK cell function
				STXBP2	c.1621G>A(p.Gly541Ser)	Heterozygous	0.023	Decreased NK cell function
75	Female	26.9	European-American	STXBP2	c.1247-1G>C	Heterozygous	0.02	Symptoms of HLH
				STXBP2	c.1621G>A(p.Gly541Ser)	Heterozygous	0.023	Symptoms of HLH
76	Female	57.8	European-American	STXBP2	c.1247-1G>C	Heterozygous	0.02	Absent NK cell function
				STXBP2	c.1621G>A(p.Gly541Ser)	Heterozygous	0.023	Absent NK cell function
77	Female	0.2	Middle Eastern	STXBP2	c.1430C>T(p.Pro477Leu)	Homozygous	0.00074	Symptoms of HLH
78	Female	0.3	Middle Eastern	STXBP2	c.1430C>T(p.Pro477Leu)	Homozygous	0.00074	NA
79	Female	0.3	Middle Eastern	STXBP2	c.1430C>T(p.Pro477Leu)	Homozygous	0.00074	Symptoms of HLH
80	Female	0.6	Middle Eastern	STXBP2	c.1430C>T(p.Pro477Leu)	Homozygous	0.00074	Symptoms of HLH
81	Male	0.2	Middle Eastern	STXBP2	c.1430C>T(p.Pro477Leu)	Homozygous	0.00074	NA
82	Male	0.7	Middle Eastern	STXBP2	c.1430C>T(p.Pro477Leu)	Homozygous	0.00074	Symptoms of HLH
83	Female	0.8	Middle Eastern	STXBP2	c.1430C>T(p.Pro477Leu)	Homozygous	0.00074	Symptoms of HLH
84	Male	0.8	Unknown	STXBP2	c.1430C>T(p.Pro477Leu)	Homozygous	0.00074	Symptoms of HLH
85	Male	0.6	Unknown	STXBP2	c.1430C>T(p.Pro477Leu)	Homozygous	0.00074	Family history of HLH
86	Male	1.6	Middle Eastern	STXBP2	c.1430C>T(p.Pro477Leu)	Homozygous	0.00074	Symptoms of HLH
87	Male	0.3	Middle Eastern	STXBP2	c.1430C>T(p.Pro477Leu)	Homozygous	0.00074	Symptoms of HLH
88	Female	63 d	Middle Eastern	STXBP2	c.1430C>T(p.Pro477Leu)	Homozygous	0.00074	Family history of HLH
89	Male	0.5	Unknown	STXBP2	c.1430C>T(p.Pro477Leu)	Homozygous	0.00074	Symptoms of HLH
90	Male	0.2	Middle Eastern	STXBP2	c.1430C>T(p.Pro477Leu)	Homozygous	0.00074	Symptoms of HLH
91	Male	11.1	Unknown	STXBP2	c.1430C>T(p.Pro477Leu)	Homozygous	0.00074	Absent NK cell function
92	Female	10.1	Unknown	STXBP2	c.1430C>T(p.Pro477Leu)	Heterozygous	0.00074	Symptoms of HLH
				STXBP2	c.1696+5G>T	Heterozygous	ND	Symptoms of HLH
93	Male	0.5	Middle Eastern	STXBP2	c.1452+1G>A	Homozygous	ND	Symptoms of HLH
94	Male	1	Middle Eastern	STXBP2	c.1452+1G>A	Homozygous	ND	Abnormal NK cell function
95	Female	49 d	European-American	UNC13D	c.118-308C>T	Heterozygous	0.019	Dysmorphic facies, decreased NK cell function
				UNC13D	c.2258_2267delinsTACCTTGTTCGA (p.Gly753fs)	Heterozygous	ND	Dysmorphic facies, decreased NK cell function
96	Male	0.7	European-American	UNC13D	c.118-308C>T	Heterozygous	0.019	Decreased NK cell function
				UNC13D	c.2346_2349del(p.Arg782fs)	Heterozygous	0.01	Decreased NK cell function
97	Male	0.2	European-American + Latino-Spanish	UNC13D	c.118-308C>T	Heterozygous	0.019	Decreased NK cell function
				UNC13D	c.2346_2349del(p.Arg782fs)	Heterozygous	0.01	Decreased NK cell function
98	Female	1.3	Non-Hispanic white	UNC13D	c.118-308C>T	Heterozygous	0.019	Symptoms of HLH, seizures, normal NK cell function
				UNC13D	c.2867C>T(p.Pro956Leu)	Heterozygous	ND	Symptoms of HLH, seizures, normal NK cell function
99	Female	1	Non-Hispanic white	UNC13D	c.118-308C>T	Heterozygous	0.019	Absent NK cell function
				UNC13D	c.3193C>T(p.Arg1065*)	Heterozygous	0.0011	Absent NK cell function
100	Female	3.2	European-American	UNC13D	c.118-308C>T	Heterozygous	0.019	Absent NK cell function
				UNC13D	253Kb inversion	Heterozygous	ND	Absent NK cell function
101	Male	2.6	Unknown	UNC13D	253Kb inversion	Heterozygous	ND	Decreased NK cell function
				UNC13D	c.154-1G>C	Heterozygous	ND	Decreased NK cell function
102	Male	0.2	Unknown	UNC13D	253Kb inversion	Heterozygous	ND	Symptoms of HLH
				UNC13D	c.551G>A(p.Trp184*)	Heterozygous	0.0011	Symptoms of HLH
103	Female	0.2	European-American	UNC13D	253Kb inversion	Heterozygous	ND	NA
				UNC13D	c.1389+1G>A	Heterozygous	0.0071	NA
104	Female	0.2	European-American	UNC13D	253Kb inversion	Heterozygous	ND	Absent NK cell function
				UNC13D	c.2447+1G>A	Heterozygous	0.00051	Absent NK cell function
105	Female	0.6	Non-Hispanic white	UNC13D	253Kb inversion	Heterozygous	ND	Decreased NK cell function
				UNC13D	c.2695C>T(p.Arg899*)	Heterozygous	0.0018	Decreased NK cell function
106	Male	11.4	Hispanic white	UNC13D	c.182A>G(p.Tyr61Cys)	Heterozygous	ND	Symptoms of HLH
				UNC13D	c.778T>C(p.Trp260Arg)	Heterozygous	ND	Symptoms of HLH
107	Male	0.4	European-American	UNC13D	c.262-1G>A	Heterozygous	ND	Symptoms of HLH, abnormal NK cell function, family history of HLH
				UNC13D	c.766C>T(p.Arg256*)	Heterozygous	0.0025
108	Male	0.4	Unknown	UNC13D	c.321+1_321+2del	Heterozygous	ND	Decreased NK cell function
				UNC13D	c.753+1G>T	Heterozygous	0.0044	Decreased NK cell function
109	Male	0.3	Unknown	UNC13D	c.322-2A>T	Heterozygous	0.0024	Symptoms of HLH, decreased NK cell function
				UNC13D	c.2346_2349del(p.Arg782fs)	Heterozygous	0.01	Symptoms of HLH, decreased NK cell function
110	Male	0.3	Unknown	UNC13D	c.419T>C(p.Ile140Thr)	Heterozygous	0.0004	NA
				UNC13D	c.460C>T(p.Arg154Trp)	Heterozygous	0.011	NA
111	Female	5.4	Middle Eastern	UNC13D	c.424dup(p.Gln142fs)	Homozygous	ND	Symptoms of HLH
112	Male	7.7	Latino-Hispanic	UNC13D	c.518C>T(p.Thr173Met)	Heterozygous	0.0028	NA
				UNC13D	c.1803_1819dup(p.Arg607fs)	Heterozygous	ND	NA
113	Female	39 d	European-American	UNC13D	c.551G>A(p.Trp184*)	Heterozygous	0.0011	Abnormal NK cell function
				UNC13D	c.766C>T(p.Arg256*)	Heterozygous	0.0025	Abnormal NK cell function
114	Male	4.9	European-American	UNC13D	c.570-2A>T	Heterozygous	ND	Absent NK cell function
				UNC13D	c.3049G>A(p.Glu1017Lys)	Heterozygous	0.00044	Absent NK cell function
115	Female	0.2	Middle Eastern	UNC13D	c.753+1G>T	Homozygous	0.0044	Symptoms of HLH
116	Female	0.6	European-American	UNC13D	c.766C>T(p.Arg256*)	Heterozygous	0.0025	Symptoms of HLH, abnormal NK cell function
				UNC13D	c.2447+1G>A	Heterozygous	0.00051	Symptoms of HLH, abnormal NK cell function
117	Female	1.2	Latino-Spanish	UNC13D	c.859del(p.Arg287fs)	Homozygous	ND	Decreased NK cell function
118	Female	1	Non-Hispanic white	UNC13D	c.1055+1G>T	Heterozygous	ND	Decreased NK cell function, family history of HLH
				UNC13D	c.2346_2349del(p.Arg782fs)	Heterozygous	0.01	Decreased NK cell function, family history of HLH
119	Male	0.7	European-American	UNC13D	c.1229_1230dup(p.Arg411fs)	Heterozygous	0.00	Symptoms of HLH, hypertelorism
				UNC13D	c.2298+1G>T	Heterozygous	ND	Symptoms of HLH, hypertelorism
120	Female	0.2	European-American	UNC13D	c.1259_1260del(p.Ser420fs)	Heterozygous	ND	symptoms of HLH, decreased NK cell function
				UNC13D	c.1848+1G>C	Heterozygous	ND	symptoms of HLH, decreased NK cell function
121	Male	18.3	European-American	UNC13D	c.1387C>T(p.Gln463*)	Heterozygous	ND	symptoms of HLH, decreased NK cell function
				UNC13D	c.1820G>C(p.Arg607Pro)	Heterozygous	0.011	symptoms of HLH, decreased NK cell function
122	Female	58 d	European-American + African American	UNC13D	c.1389+1G>A	Heterozygous	0.0071	Symptoms of HLH
				UNC13D	c.1848+1G>C	Heterozygous	ND	Symptoms of HLH
123	Female	0.2	Middle Eastern	UNC13D	c.1423C>T(p.Gln475*)	Homozygous	ND	NA
124	Male	10 d	Pacific Islander	UNC13D	c.2296C>T(p.Gln766*)	Homozygous	ND	Decreased NK cell function
125	Female	13.2	Unknown	UNC13D	c.2346_2349del(p.Arg782fs)	Heterozygous	0.01	NA
				UNC13D	c.2588G>A(p.Gly863Asp)	Heterozygous	0.029	NA
126	Female	2	Unknown	UNC13D	c.2346_2349del(p.Arg782fs)	Heterozygous	0.01	NA
				UNC13D	c.3065T>C(p.Leu1022Pro)	Heterozygous	ND	NA
127	Female	0.2	Middle Eastern	UNC13D	c.2553+1G>T	Homozygous	ND	Symptoms of HLH
128	Female	0.3	Middle Eastern	UNC13D	c.2553+1G>T	Homozygous	ND	Symptoms of HLH
129	Female	1	Asian	UNC13D	c.2588G>A(p.Gly863Asp)	Homozygous	0.029	Decreased NK cell function
130	Female	0.4	African American	UNC13D	c.2695C>T(p.Arg899*)	Homozygous	0.0018	Symptoms of HLH, absent NK cell function, dysmorphic facies
131	Male	0.7	Non-Hispanic white	UNC13D	c.2819del(p.Leu940fs)	Homozygous	ND	symptoms of HLH
132	Female	0.6	Middle Eastern	UNC13D	c.3048dup(p.Glu1017fs)	Homozygous	ND	NA
133	Female	0.7	Unknown	UNC13D	c.3053C>A(p.Ala1018Asp)	Homozygous	0.00088	2 affected siblings
134	Male	13	European-American	RAB27A	c.121A>G(p.Thr41Ala)	Heterozygous	ND	NA
				RAB27A	c.352C>T(p.Gln118*)	Heterozygous	ND	NA
135	Male	9.6	Middle Eastern	RAB27A	c.244C>T(p.Arg82Cys)	Homozygous	0.0016	NA
136	Male	9.9	Middle Eastern	RAB27A	c.244C>T(p.Arg82Cys)	Homozygous	0.0016	NA
137	Female	2	Middle Eastern	RAB27A	c.244C>T(p.Arg82Cys)	Homozygous	0.0016	Failure to thrive, bone marrow failure
138	Female	9.4	Middle Eastern	RAB27A	c.244C>T(p.Arg82Cys)	Homozygous	0.0016	Symptoms of HLH
139	Male	10.6	Middle Eastern	RAB27A	c.244C>T(p.Arg82Cys)	Homozygous	0.0016	Symptoms of HLH
140	Male	19.5	Middle Eastern	RAB27A	c.244C>T(p.Arg82Cys)	Homozygous	0.0016	Symptoms of HLH
141	Female	0.3	Latino-Hispanic	RAB27A	c.335del(p.Asn112fs)	Homozygous	0.0044	Symptoms of HLH
142	Female	0.4	Middle Eastern	RAB27A	c.400A>C(p.Lys134Gln)	Homozygous	ND	NA
143	Female	53.9	Pacific Islander	RAB27A	c.476A>G(p.Tyr159Cys)	Homozygous	ND	Symptoms of HLH, absent NK cell function
144	Male	1.2	Middle Eastern	RAB27A	c.598C>T(p.Arg200*)	Homozygous	0.0004	NA
145	Female	0.4	European-American	RAB27A	c.638_642del(p.Glu213fs)	Homozygous	0.0008	Symptoms of HLH
146	Female	0.7	African American	LYST	c.925C>T(p.Arg309*)	Heterozygous	ND	Oculocutaneous albinism, neutropenia
				LYST	c.2015dup(p.Tyr672*)	Heterozygous	ND	Oculocutaneous albinism, neutropenia
147	Male	3.4	Unknown	LYST	c.3194del(p.Leu1065*)	Homozygous	0.0004	NA
148	Female	0.3	Middle Eastern	LYST	c.4159dup(p.Thr1387fs)	Homozygous	ND	Premature gray hair, anemia
149	Male	0.9	European-American	LYST	c.5715del(p.Asn1905fs)	Heterozygous	ND	Oculocutaneous albinism, neutropenia, absent NK cell function
				LYST	c.8802-2A>G	Heterozygous	ND
150	Female	6.9	Unknown	LYST	c.5784+1G>T	Homozygous	ND	Oculocutaneous albinism, dysmorphic facies, neutropenia
151	Male	3.2	Non-Hispanic white	LYST	c.6159_6160del(p.Met2053fs)	Homozygous	ND	NA
152	Male	1.8	Middle Eastern	LYST	c.7291del(p.Leu2431fs)	Homozygous	ND	Hypopigmentation, anemia
153	Male	1.2	African American	LYST	c.8770C>T(p.Gln2924*)	Heterozygous	ND	Silver hair, hypopigmented skin lesions, pancytopenia
				LYST	c.9844_9845del(p.Ser3282fs)	Heterozygous	ND	Silver hair, hypopigmented skin lesions, pancytopenia
154	Female	7.1	Middle Eastern	LYST	c.10776C>G(p.Tyr3592*)	Homozygous	ND	Abnormal pigmentation, neutropenia
155	Female	1.2	Unknown	STX11	c.73G>T(p.Glu25*)	Heterozygous	0.0004	Decreased NK cell function
				STX11	c.748C>T(p.Gln250*)	Heterozygous	0.00081	Decreased NK cell function
156	Female	5.6	Middle Eastern	STX11	c.173T>C(p.Leu58Pro)	Homozygous	0.0008	Symptoms of HLH, grayish hair
157	Female	11.6	Middle Eastern	STX11	c.173T>C(p.Leu58Pro)	Homozygous	0.0008	NA
158	Male	2.9	European-American + Latino-Hispanic	STX11	c.462_463delinsA(p.Asp155fs)	Heterozygous	ND	Decreased NK cell function
				STX11	c.784C>T(p.Gln262*)	Heterozygous	ND	Decreased NK cell function
159	Male	1.4	Asian-Indian	STX11	c.687dup(p.Gln230fs)	Homozygous	ND	NA
160	Female	12 d	Middle Eastern	SLC7A7	c.1429+1G>C	Homozygous	ND	Family history of HLH
161	Male	1.2	African American	SLC7A7	c.701del(p.Ser234fs)	Heterozygous	0.0016	NA
				SLC7A7	c.895-1G>A	Heterozygous	ND
162	Female	13.7	European-American	SLC7A7	c.360_361delinsAA (p.Trp121Arg)	Homozygous	ND	NA
163	Male	5.4	African American	XIAP	c.145C>T(p.Arg49*)	Hemizygous	ND	Markedly decreased XIAP expression
164	Male	18.7	European-American	XIAP	c.345C>G(p.Tyr115*)	Hemizygous	ND	Symptoms of HLH
165	Male	30.3	European-American	XIAP	c.608G>T(p.Cys203Phe)	Hemizygous	ND	NA
166	Male	2	European-American	XIAP	c.664C>T(p.Arg222*)	Hemizygous	ND	Symptoms of HLH
167	Male	8.9	European-American	XIAP	c.738del(p.Asp247fs)	Hemizygous	ND	NA
168	Male	16	European-American	XIAP	c.738del(p.Asp247fs)	Hemizygous	ND	Absent XIAP expression
169	Male	3.6	African American	XIAP	c.889A>T(p.Lys297*)	Hemizygous	ND	NA
170	Male	0.4	Unknown	XIAP	c.894_898del(p.Lys299fs)	Hemizygous	ND	NA
171	Male	17.2	European-American	XIAP	c.894_898del(p.Lys299fs)	Hemizygous	ND	Symptoms of HLH
172	Male	19.6	African American	XIAP	c.926_929del(p.Asp309fs)	Hemizygous	ND	Symptoms of HLH
173	Male	17.2	European-American	XIAP	c.969G>A(p.Trp323*)	Hemizygous	ND	Decreased XIAP expression
174	Male	22.6	Unknown	XIAP	c.1021_1022del(p.Asn341fs)	Hemizygous	ND	NA
175	Male	4.5	Unknown	XIAP	c.1056+1G>A	Hemizygous	ND	NA
176	Male	2.7	Latino-Hispanic	XIAP	c.1141C>T(p.Arg381*)	Hemizygous	ND	NA
177	Male	11.8	Unknown	XIAP	c.1141C>T(p.Arg381*)	Hemizygous	ND	Absent XIAP expression
178	Male	1 d	Pacific-Islander	XIAP	c.1239_1242dup(p.Val415fs)	Hemizygous	ND	Markedly decreased XIAP expression
179	Male	1.9	Unknown	XIAP	c.1239_1242dup(p.Val415fs)	Hemizygous	ND	NA
180	Male	1.1	Unknown	XIAP	c.1301-1G>A	Hemizygous	ND	Symptoms of HLH
181	Male	1.5	Unknown	XIAP	c.1445C>G(p.Pro482Arg)	Hemizygous	ND	NA
182	Male	35	European-American	XIAP	c.1456dup(p.Thr486fs)	Hemizygous	ND	Symptoms of HLH
183	Male	4.5	European-American	SH2D1A	c.20A>G(p.Tyr7Cys)	Hemizygous	ND	Absent SAP in CD8⁺ T cells
184	Male	1.8	Unknown	SH2D1A	c.117C>T(p.Gly39Gly)	Hemizygous	ND	NA
185	Male	3.5	Unknown	SH2D1A	c.130T>C(p.Cys44Arg)	Hemizygous	ND	Absent SAP in CD8⁺ T cells
186	Male	27	European-American	SH2D1A	c.163C>T(p.Arg55*)	Hemizygous	ND	History of pneumonia
187	Male	8 d	Unknown	SH2D1A	c.172C>T(p.Gln58*)	Hemizygous	ND	NA
188	Male	6.8	African American	SH2D1A	c.172C>T(p.Gln58*)	Hemizygous	ND	Absent SAP in CD8⁺ T cells
189	Male	4.7	Latino-Hispanic	SH2D1A	c.199_201+19del(p.Glu67del)	Hemizygous	ND	Absent SAP in CD8⁺ T cells
190	Male	1.3	African American	SH2D1A	c.201G>A(p.Glu67Glu)	Hemizygous	ND	Absent SAP in CD8⁺ T cells
191	Male	7 d	European-American	SH2D1A	c.245del(p.Asn82fs)	Hemizygous	ND	Absent SAP in CD8⁺ T cells
192	Male	34 d	European-American + Pacific-Islander	SH2D1A	c.295C>T(p.Gln99*)	Hemizygous	ND	Absent SAP in CD8⁺ T cells
193	Male	5.4	Middle-Eastern	MAGT1	c.154_161delinsC(p.Ile52fs)	Hemizygous	ND	Symptoms of HLH, bone pain in low extremities
194	Male	10.4	European-American	MAGT1	c.223C>T(p.Gln75*)	Hemizygous	ND	NA
195	Male	18.4	African American	MAGT1	c.407G>A(p.Trp136*)	Hemizygous	ND	NA
196	Male	27.6	European-American	MAGT1	c.443_444del(p.Phe148fs)	Hemizygous	ND	Symptoms of HLH
197	Male	17.3	European-American	MAGT1	c.774del(p.Phe258fs)	Hemizygous	ND	NA

Patient no.	Sex	Age at testing, y (unless indicated otherwise)	Ethnicity	Gene	Variant	Zygosity	Population frequency (gnomAD*), %	Symptoms/immunology testing/family history†
1	Female	53 d	African American	PRF1	c.50del(p.Leu17fs)	Homozygous	0.033	Symptoms of HLH
2	Male	63 d	Unknown	PRF1	c.50del(p.Leu17fs)	Homozygous	0.033	Symptoms of HLH
3	Male	0.4	Middle Eastern	PRF1	c.50del(p.Leu17fs)	Homozygous	0.033	Symptoms of HLH
4	Female	27 d	Unknown	PRF1	c.50del(p.Leu17fs)	Homozygous	0.033	Absent perforin expression
5	Female	32 d	African American	PRF1	c.50del(p.Leu17fs)	Homozygous	0.033	Absent perforin expression
6	Male	4 d	African American	PRF1	c.50del(p.Leu17fs)	Homozygous	0.033	Absent perforin expression; sibling died of HLH
7	Female	0.4	African American	PRF1	c.50del(p.Leu17fs)	Homozygous	0.033	Symptoms of HLH
8	Male	6 d	African American + European-white	PRF1	c.50del(p.Leu17fs)	Homozygous	0.033	Absent perforin expression
9	Male	59 d	African American	PRF1	c.50del(p.Leu17fs)	Homozygous	0.033	Symptoms of HLH
10	Male	13 d	African	PRF1	c.50del(p.Leu17fs)	Homozygous	0.033	Symptoms of HLH
11	Female	7 d	Unknown	PRF1	c.50del(p.Leu17fs)	Heterozygous	0.033	Absent NK cell function
				PRF1	c.266C>T(p.Pro89Leu)	Heterozygous	ND	Absent NK cell function
12	Female	0.3	African American	PRF1	c.50del(p.Leu17fs)	Heterozygous	0.033	NA
				PRF1	c.350_356delinsATGC (p.Val117_Arg119delinsAspAla)	Heterozygous	ND	NA
13	Male	0.4	Unknown	PRF1	c.50del(p.Leu17fs)	Heterozygous	0.033	NA
				PRF1	c.445G>A(p.Gly149Ser)	Heterozygous	0.014	NA
14	Male	3.3	African American	PRF1	c.50del(p.Leu17fs)	Heterozygous	0.033	Absent perforin expression; brother with HLH
				PRF1	c.527G>A(p.Cys176Tyr)	Heterozygous	ND	Absent perforin expression; brother with HLH
15	Female	0.5	Latino-Hispanic	PRF1	c.50del(p.Leu17fs)	Heterozygous	0.033	Absent perforin expression
				PRF1	c.659G>A(p.Gly220Asp)	Heterozygous	0.0008	Absent perforin expression
16	Female	0.2	African American	PRF1	c.50del(p.Leu17fs)	Heterozygous	0.033	Absent NK cell function
				PRF1	c.853_855del(p.Lys285del)	Heterozygous	0.0056	Absent NK cell function
17	Male	66 d	Unknown	PRF1	c.50del(p.Leu17fs)	Heterozygous	0.033	NA
				PRF1	c.895C>T(p.Arg299Cys)	Heterozygous	0.0012	NA
18	Male	20.6	Latino-Hispanic	PRF1	c.50del(p.Leu17fs)	Heterozygous	0.033	NA
				PRF1	c.902C>T(p.Ser301Leu)	Heterozygous	ND	NA
19	Male	54 d	African American	PRF1	c.50del(p.Leu17fs)	Heterozygous	0.033	Symptoms of HLH
				PRF1	c.916G>T(p.Gly306Cys)	Heterozygous	ND	Symptoms of HLH
20	Female	45 d	African American	PRF1	c.50del(p.Leu17fs)	Heterozygous	0.033	Absent perforin expression
				PRF1	c.916G>T(p.Gly306Cys)	Heterozygous	ND	Absent perforin expression
21	Male	32 d	Latino-Hispanic	PRF1	c.50del(p.Leu17fs)	Heterozygous	0.033	Symptoms of HLH
				PRF1	c.985dup(p.Val329fs)	Heterozygous	ND	Symptoms of HLH
22	Male	0.3	African American	PRF1	c.50del(p.Leu17fs)	Heterozygous	0.033	Absent perforin expression
				PRF1	c.1385C>A(p.Ser462*)	Heterozygous	ND	Absent perforin expression
23	Male	36.1	Unknown	PRF1	c.116C>A(p.Pro39His)	Heterozygous	0.00081	NA
				PRF1	c.445G>A(p.Gly149Ser)	Heterozygous	0.014	NA
24	Female	1.2	Asian-American	PRF1	c.133G>A(p.Gly45Arg)	Homozygous	0.0012	Absent NK cell function
25	Female	37 d	Non-Hispanic white	PRF1	c.150del(p.Thr51fs)	Heterozygous	0.0004	Absent perforin expression
				PRF1	c.227G>A(p.Cys76Tyr)	Heterozygous	0.00071	Absent perforin expression
26	Male	69 d	Latino-Hispanic	PRF1	c.218G>C(p.Cys73Ser)	Homozygous	0.0004	Symptoms of HLH
27	Female	20	European-American	PRF1	c.227G>A(p.Cys76Tyr)	Heterozygous	0.00071	Absent perforin expression
				PRF1	c.626A>C(p.Gln209Pro)	Heterozygous	0.0012	Absent perforin expression
28	Female	21.8	Unknown	PRF1	c.272C>T(p.Ala91Val)‡	Heterozygous	2.92	Absent NK cell function, decreased perforin expression
				PRF1	c.445G>A(p.Gly149Ser)	Heterozygous	0.014	Absent NK cell function, decreased perforin expression
29	Male	17	European-American	PRF1	c.272C>T(p.Ala91Val)‡	Heterozygous	2.92	Absent perforin expression
				PRF1	c.635A>C(p.Tyr212Ser)	Heterozygous	ND	Absent perforin expression
30	Female	41.2	European-American	PRF1	c.272C>T(p.Ala91Val)‡	Heterozygous	2.92	Absent NK cell function, decreased perforin expression
				PRF1	c.666C>A(p.His222Gln)	Heterozygous	0.0039	Absent NK cell function, decreased perforin expression
31	Female	8.3	European-American	PRF1	c.443C>G(p.Ala148Gly)	Heterozygous	0.0004	NA
				PRF1	c.666C>A(p.His222Gln)	Heterozygous	0.0039	NA
32	Male	2.6	Unknown	PRF1	c.445G>A(p.Gly149Ser)	Homozygous	0.014	Absent NK cell function
33	Male	0.8	Latino-Hispanic	PRF1	c.445G>A(p.Gly149Ser)	Homozygous	0.014	Symptoms of HLH
34	Female	6	Latino-Hispanic	PRF1	c.445G>A(p.Gly149Ser)	Homozygous	0.014	NA
35	Female	0.3	European-American	PRF1	c.445G>A(p.Gly149Ser)	Heterozygous	0.014	Family history of HLH
				PRF1	c.614A>G(p.Asn205Ser)	Heterozygous	0.0043	Family history of HLH
36	Male	42 d	Latino-Hispanic	PRF1	c.445G>A(p.Gly149Ser)	Heterozygous	0.014	NA
				PRF1	c.938A>T(p.Asp313Val)	Heterozygous	0.0012	NA
37	Male	4.6	Unknown	PRF1	c.445G>A(p.Gly149Ser)	Heterozygous	0.014	Absent perforin expression
				PRF1	c.1081A>T(p.Arg361Trp)	Heterozygous	0.0011	Absent perforin expression
38	Female	32 d	Middle Eastern	PRF1	c.501C>G(p.Tyr167*)	Homozygous	ND	Symptoms of HLH
39	Female	0.3	Unknown	PRF1	c.512C>A(p.Thr171Asn)	Homozygous	0.0028	Absent perforin expression
40	Male	9.5	European-American	PRF1	c.786_801del(p.Gln263fs)	Heterozygous	ND	Absent NK cell function
				PRF1	c.886T>C(p.Tyr296His)	Heterozygous	0.0012	Absent NK cell function
41	Male	59 d	Unknown	PRF1	c.853_855del(p.Lys285del)	Heterozygous	0.0057	NA
				PRF1	c.921del(p.His308fs)	Heterozygous	0.002	NA
42	Female	0.7	Middle Eastern	PRF1	c.880del(p.Gln294fs)	Homozygous	ND	Symptoms of HLH
43	Female	2	Middle Eastern	PRF1	c.895C>T(p.Arg299Cys)	Homozygous	0.0012	Symptoms of HLH
44	Female	0.2	Latino-Hispanic	PRF1	c.904G>T(p.Glu302*)	Homozygous	ND	Absent perforin expression
45	Female	1.8	Unknown	PRF1	c.949G>A(p.Gly317Arg)	Homozygous	0.0008	Symptoms of HLH
46	Female	10.3	European-American	PRF1	c.973T>C(p.Tyr325His)	Heterozygous	ND	Absent perforin expression
				PRF1	c.1326_1328del(p.Phe443del)	Heterozygous	ND	Absent perforin expression
47	Male	1.1	Middle Eastern	PRF1	c.1070G>C(p.Arg357Pro)	Homozygous	ND	Symptoms of HLH
48	Male	12.5	Middle Eastern	PRF1	c.1081A>T(p.Arg361Trp)	Homozygous	0.0011	Abnormal brain lesions and seizures
49	Female	2.6	Unknown	PRF1	c.1229_1230delinsCC (p.Arg410Pro)	Homozygous	ND	NA
50	Female	0.2	African American	PRF1	c.1304C>T(p.Thr435Met)	Heterozygous	0.0028	Absent perforin expression
				PRF1	c.1314T>A(p.Tyr438*)	Heterozygous	0.0032	Absent perforin expression
51	Female	2.6	Latino-Hispanic	PRF1	c.1337A>C(p.Gln446Pro)	Homozygous	0.0016	NA
52	Female	2.6	Unknown	PRF1	c.1337A>C(p.Gln446Pro)	Homozygous	0.0016	Symptoms of HLH
53	Female	0.4	Middle Eastern	STXBP2	c.37+2T>C	Heterozygous	ND	Absent NK cell function
				STXBP2	c.1430C>T(p.Pro477Leu)	Heterozygous	0.00074	Absent NK cell function
54	Male	0.6	Unknown	STXBP2	c.37+5G>A	Heterozygous	ND	NA
				STXBP2	c.1057T>C (p.Cys353Arg)	Heterozygous	0.0004	NA
55	Female	63 d	Asian-American	STXBP2	c.193C>T(p.Arg65Trp)	Homozygous	0.00071	Absent NK cell function
56	Female	5.5	Unknown	STXBP2	c.194G>A(p.Arg65Gln)	Heterozygous	0.0028	Absent NK cell function
				STXBP2	c.560C>T (p.Pro187Leu)	Heterozygous	0.00064	Absent NK cell function
57	Male	4.1	European-American	STXBP2	c.194G>A(p.Arg65Gln)	Heterozygous	0.0028	Symptoms of HLH
				STXBP2	c.1621G>A(p.Gly541Ser)	Heterozygous	0.023	Symptoms of HLH
58	Female	4.2	European-American	STXBP2	c.326-30_326-23del	Heterozygous	0.0068	Symptoms of HLH
				STXBP2	c.1621G>A(p.Gly541Ser)	Heterozygous	0.023	Symptoms of HLH
59	Male	0.6	Latino-Hispanic	STXBP2	c.389T>C(p.Leu130Ser)	Homozygous	0.0032	Symptoms of HLH
60	Male	45 d	African American	STXBP2	c.389T>C(p.Leu130Ser)	Heterozygous	0.0032	Symptoms of HLH; family history of HLH
				STXBP2	exon 14-19 deletion	Heterozygous	ND	Symptoms of HLH; family history of HLH
61	Male	0.7	Middle Eastern	STXBP2	c.481del(p.Arg161fs)	Homozygous	ND	Symptoms of HLH
62	Male	0.4	Unknown	STXBP2	c.481del(p.Arg161fs)	Homozygous	ND	Symptoms of HLH
63	Female	11	European-American	STXBP2	c.539_540delinsAA(p.Cys180*)	Heterozygous	ND	Symptoms of HLH
				STXBP2	c.1247-1G>C	Heterozygous	0.02	Symptoms of HLH
64	Male	0.3	Latino-Hispanic	STXBP2	c.703C>G(p.Arg235Gly)	Homozygous	0.00071	Absent NK cell function
65	Female	52.7	European-American	STXBP2	c.752C>T(p.Ala251Val)	Heterozygous	ND	Symptoms of HLH
				STXBP2	c.1621G>A(p.Gly541Ser)	Heterozygous	0.023	Symptoms of HLH
66	Male	0.9	Unknown	STXBP2	c.902+5G>A	Heterozygous	0.0036	NA
				STXBP2	c.1247-1G>C	Heterozygous	0.02	NA
67	Male	3.1	Unknown	STXBP2	c.1247-1G>C	Homozygous	0.02	Symptoms of HLH
68	Female	22.7	Latino-Spanish	STXBP2	c.1247-1G>C	Homozygous	0.02	Decreased NK cell function
69	Male	26.4	European-American	STXBP2	c.1247-1G>C	Homozygous	0.02	Symptoms of HLH
70	Male	25.6	European-American	STXBP2	c.1247-1G>C	Homozygous	0.02	Symptoms of HLH
71	Female	29.7	European-American	STXBP2	c.1247-1G>C	Homozygous	0.02	NA
72	Male	4	European-American	STXBP2	c.1247-1G>C	Heterozygous	0.02	Absent NK cell function
				STXBP2	c.1621G>A(p.Gly541Ser)	Heterozygous	0.023	Absent NK cell function
73	Female	15.8	European-American	STXBP2	c.1247-1G>C	Heterozygous	0.02	Absent NK cell function
				STXBP2	c.1621G>A(p.Gly541Ser)	Heterozygous	0.023	Absent NK cell function
74	Female	19	Unknown	STXBP2	c.1247-1G>C	Heterozygous	0.02	Decreased NK cell function
				STXBP2	c.1621G>A(p.Gly541Ser)	Heterozygous	0.023	Decreased NK cell function
75	Female	26.9	European-American	STXBP2	c.1247-1G>C	Heterozygous	0.02	Symptoms of HLH
				STXBP2	c.1621G>A(p.Gly541Ser)	Heterozygous	0.023	Symptoms of HLH
76	Female	57.8	European-American	STXBP2	c.1247-1G>C	Heterozygous	0.02	Absent NK cell function
				STXBP2	c.1621G>A(p.Gly541Ser)	Heterozygous	0.023	Absent NK cell function
77	Female	0.2	Middle Eastern	STXBP2	c.1430C>T(p.Pro477Leu)	Homozygous	0.00074	Symptoms of HLH
78	Female	0.3	Middle Eastern	STXBP2	c.1430C>T(p.Pro477Leu)	Homozygous	0.00074	NA
79	Female	0.3	Middle Eastern	STXBP2	c.1430C>T(p.Pro477Leu)	Homozygous	0.00074	Symptoms of HLH
80	Female	0.6	Middle Eastern	STXBP2	c.1430C>T(p.Pro477Leu)	Homozygous	0.00074	Symptoms of HLH
81	Male	0.2	Middle Eastern	STXBP2	c.1430C>T(p.Pro477Leu)	Homozygous	0.00074	NA
82	Male	0.7	Middle Eastern	STXBP2	c.1430C>T(p.Pro477Leu)	Homozygous	0.00074	Symptoms of HLH
83	Female	0.8	Middle Eastern	STXBP2	c.1430C>T(p.Pro477Leu)	Homozygous	0.00074	Symptoms of HLH
84	Male	0.8	Unknown	STXBP2	c.1430C>T(p.Pro477Leu)	Homozygous	0.00074	Symptoms of HLH
85	Male	0.6	Unknown	STXBP2	c.1430C>T(p.Pro477Leu)	Homozygous	0.00074	Family history of HLH
86	Male	1.6	Middle Eastern	STXBP2	c.1430C>T(p.Pro477Leu)	Homozygous	0.00074	Symptoms of HLH
87	Male	0.3	Middle Eastern	STXBP2	c.1430C>T(p.Pro477Leu)	Homozygous	0.00074	Symptoms of HLH
88	Female	63 d	Middle Eastern	STXBP2	c.1430C>T(p.Pro477Leu)	Homozygous	0.00074	Family history of HLH
89	Male	0.5	Unknown	STXBP2	c.1430C>T(p.Pro477Leu)	Homozygous	0.00074	Symptoms of HLH
90	Male	0.2	Middle Eastern	STXBP2	c.1430C>T(p.Pro477Leu)	Homozygous	0.00074	Symptoms of HLH
91	Male	11.1	Unknown	STXBP2	c.1430C>T(p.Pro477Leu)	Homozygous	0.00074	Absent NK cell function
92	Female	10.1	Unknown	STXBP2	c.1430C>T(p.Pro477Leu)	Heterozygous	0.00074	Symptoms of HLH
				STXBP2	c.1696+5G>T	Heterozygous	ND	Symptoms of HLH
93	Male	0.5	Middle Eastern	STXBP2	c.1452+1G>A	Homozygous	ND	Symptoms of HLH
94	Male	1	Middle Eastern	STXBP2	c.1452+1G>A	Homozygous	ND	Abnormal NK cell function
95	Female	49 d	European-American	UNC13D	c.118-308C>T	Heterozygous	0.019	Dysmorphic facies, decreased NK cell function
				UNC13D	c.2258_2267delinsTACCTTGTTCGA (p.Gly753fs)	Heterozygous	ND	Dysmorphic facies, decreased NK cell function
96	Male	0.7	European-American	UNC13D	c.118-308C>T	Heterozygous	0.019	Decreased NK cell function
				UNC13D	c.2346_2349del(p.Arg782fs)	Heterozygous	0.01	Decreased NK cell function
97	Male	0.2	European-American + Latino-Spanish	UNC13D	c.118-308C>T	Heterozygous	0.019	Decreased NK cell function
				UNC13D	c.2346_2349del(p.Arg782fs)	Heterozygous	0.01	Decreased NK cell function
98	Female	1.3	Non-Hispanic white	UNC13D	c.118-308C>T	Heterozygous	0.019	Symptoms of HLH, seizures, normal NK cell function
				UNC13D	c.2867C>T(p.Pro956Leu)	Heterozygous	ND	Symptoms of HLH, seizures, normal NK cell function
99	Female	1	Non-Hispanic white	UNC13D	c.118-308C>T	Heterozygous	0.019	Absent NK cell function
				UNC13D	c.3193C>T(p.Arg1065*)	Heterozygous	0.0011	Absent NK cell function
100	Female	3.2	European-American	UNC13D	c.118-308C>T	Heterozygous	0.019	Absent NK cell function
				UNC13D	253Kb inversion	Heterozygous	ND	Absent NK cell function
101	Male	2.6	Unknown	UNC13D	253Kb inversion	Heterozygous	ND	Decreased NK cell function
				UNC13D	c.154-1G>C	Heterozygous	ND	Decreased NK cell function
102	Male	0.2	Unknown	UNC13D	253Kb inversion	Heterozygous	ND	Symptoms of HLH
				UNC13D	c.551G>A(p.Trp184*)	Heterozygous	0.0011	Symptoms of HLH
103	Female	0.2	European-American	UNC13D	253Kb inversion	Heterozygous	ND	NA
				UNC13D	c.1389+1G>A	Heterozygous	0.0071	NA
104	Female	0.2	European-American	UNC13D	253Kb inversion	Heterozygous	ND	Absent NK cell function
				UNC13D	c.2447+1G>A	Heterozygous	0.00051	Absent NK cell function
105	Female	0.6	Non-Hispanic white	UNC13D	253Kb inversion	Heterozygous	ND	Decreased NK cell function
				UNC13D	c.2695C>T(p.Arg899*)	Heterozygous	0.0018	Decreased NK cell function
106	Male	11.4	Hispanic white	UNC13D	c.182A>G(p.Tyr61Cys)	Heterozygous	ND	Symptoms of HLH
				UNC13D	c.778T>C(p.Trp260Arg)	Heterozygous	ND	Symptoms of HLH
107	Male	0.4	European-American	UNC13D	c.262-1G>A	Heterozygous	ND	Symptoms of HLH, abnormal NK cell function, family history of HLH
				UNC13D	c.766C>T(p.Arg256*)	Heterozygous	0.0025
108	Male	0.4	Unknown	UNC13D	c.321+1_321+2del	Heterozygous	ND	Decreased NK cell function
				UNC13D	c.753+1G>T	Heterozygous	0.0044	Decreased NK cell function
109	Male	0.3	Unknown	UNC13D	c.322-2A>T	Heterozygous	0.0024	Symptoms of HLH, decreased NK cell function
				UNC13D	c.2346_2349del(p.Arg782fs)	Heterozygous	0.01	Symptoms of HLH, decreased NK cell function
110	Male	0.3	Unknown	UNC13D	c.419T>C(p.Ile140Thr)	Heterozygous	0.0004	NA
				UNC13D	c.460C>T(p.Arg154Trp)	Heterozygous	0.011	NA
111	Female	5.4	Middle Eastern	UNC13D	c.424dup(p.Gln142fs)	Homozygous	ND	Symptoms of HLH
112	Male	7.7	Latino-Hispanic	UNC13D	c.518C>T(p.Thr173Met)	Heterozygous	0.0028	NA
				UNC13D	c.1803_1819dup(p.Arg607fs)	Heterozygous	ND	NA
113	Female	39 d	European-American	UNC13D	c.551G>A(p.Trp184*)	Heterozygous	0.0011	Abnormal NK cell function
				UNC13D	c.766C>T(p.Arg256*)	Heterozygous	0.0025	Abnormal NK cell function
114	Male	4.9	European-American	UNC13D	c.570-2A>T	Heterozygous	ND	Absent NK cell function
				UNC13D	c.3049G>A(p.Glu1017Lys)	Heterozygous	0.00044	Absent NK cell function
115	Female	0.2	Middle Eastern	UNC13D	c.753+1G>T	Homozygous	0.0044	Symptoms of HLH
116	Female	0.6	European-American	UNC13D	c.766C>T(p.Arg256*)	Heterozygous	0.0025	Symptoms of HLH, abnormal NK cell function
				UNC13D	c.2447+1G>A	Heterozygous	0.00051	Symptoms of HLH, abnormal NK cell function
117	Female	1.2	Latino-Spanish	UNC13D	c.859del(p.Arg287fs)	Homozygous	ND	Decreased NK cell function
118	Female	1	Non-Hispanic white	UNC13D	c.1055+1G>T	Heterozygous	ND	Decreased NK cell function, family history of HLH
				UNC13D	c.2346_2349del(p.Arg782fs)	Heterozygous	0.01	Decreased NK cell function, family history of HLH
119	Male	0.7	European-American	UNC13D	c.1229_1230dup(p.Arg411fs)	Heterozygous	0.00	Symptoms of HLH, hypertelorism
				UNC13D	c.2298+1G>T	Heterozygous	ND	Symptoms of HLH, hypertelorism
120	Female	0.2	European-American	UNC13D	c.1259_1260del(p.Ser420fs)	Heterozygous	ND	symptoms of HLH, decreased NK cell function
				UNC13D	c.1848+1G>C	Heterozygous	ND	symptoms of HLH, decreased NK cell function
121	Male	18.3	European-American	UNC13D	c.1387C>T(p.Gln463*)	Heterozygous	ND	symptoms of HLH, decreased NK cell function
				UNC13D	c.1820G>C(p.Arg607Pro)	Heterozygous	0.011	symptoms of HLH, decreased NK cell function
122	Female	58 d	European-American + African American	UNC13D	c.1389+1G>A	Heterozygous	0.0071	Symptoms of HLH
				UNC13D	c.1848+1G>C	Heterozygous	ND	Symptoms of HLH
123	Female	0.2	Middle Eastern	UNC13D	c.1423C>T(p.Gln475*)	Homozygous	ND	NA
124	Male	10 d	Pacific Islander	UNC13D	c.2296C>T(p.Gln766*)	Homozygous	ND	Decreased NK cell function
125	Female	13.2	Unknown	UNC13D	c.2346_2349del(p.Arg782fs)	Heterozygous	0.01	NA
				UNC13D	c.2588G>A(p.Gly863Asp)	Heterozygous	0.029	NA
126	Female	2	Unknown	UNC13D	c.2346_2349del(p.Arg782fs)	Heterozygous	0.01	NA
				UNC13D	c.3065T>C(p.Leu1022Pro)	Heterozygous	ND	NA
127	Female	0.2	Middle Eastern	UNC13D	c.2553+1G>T	Homozygous	ND	Symptoms of HLH
128	Female	0.3	Middle Eastern	UNC13D	c.2553+1G>T	Homozygous	ND	Symptoms of HLH
129	Female	1	Asian	UNC13D	c.2588G>A(p.Gly863Asp)	Homozygous	0.029	Decreased NK cell function
130	Female	0.4	African American	UNC13D	c.2695C>T(p.Arg899*)	Homozygous	0.0018	Symptoms of HLH, absent NK cell function, dysmorphic facies
131	Male	0.7	Non-Hispanic white	UNC13D	c.2819del(p.Leu940fs)	Homozygous	ND	symptoms of HLH
132	Female	0.6	Middle Eastern	UNC13D	c.3048dup(p.Glu1017fs)	Homozygous	ND	NA
133	Female	0.7	Unknown	UNC13D	c.3053C>A(p.Ala1018Asp)	Homozygous	0.00088	2 affected siblings
134	Male	13	European-American	RAB27A	c.121A>G(p.Thr41Ala)	Heterozygous	ND	NA
				RAB27A	c.352C>T(p.Gln118*)	Heterozygous	ND	NA
135	Male	9.6	Middle Eastern	RAB27A	c.244C>T(p.Arg82Cys)	Homozygous	0.0016	NA
136	Male	9.9	Middle Eastern	RAB27A	c.244C>T(p.Arg82Cys)	Homozygous	0.0016	NA
137	Female	2	Middle Eastern	RAB27A	c.244C>T(p.Arg82Cys)	Homozygous	0.0016	Failure to thrive, bone marrow failure
138	Female	9.4	Middle Eastern	RAB27A	c.244C>T(p.Arg82Cys)	Homozygous	0.0016	Symptoms of HLH
139	Male	10.6	Middle Eastern	RAB27A	c.244C>T(p.Arg82Cys)	Homozygous	0.0016	Symptoms of HLH
140	Male	19.5	Middle Eastern	RAB27A	c.244C>T(p.Arg82Cys)	Homozygous	0.0016	Symptoms of HLH
141	Female	0.3	Latino-Hispanic	RAB27A	c.335del(p.Asn112fs)	Homozygous	0.0044	Symptoms of HLH
142	Female	0.4	Middle Eastern	RAB27A	c.400A>C(p.Lys134Gln)	Homozygous	ND	NA
143	Female	53.9	Pacific Islander	RAB27A	c.476A>G(p.Tyr159Cys)	Homozygous	ND	Symptoms of HLH, absent NK cell function
144	Male	1.2	Middle Eastern	RAB27A	c.598C>T(p.Arg200*)	Homozygous	0.0004	NA
145	Female	0.4	European-American	RAB27A	c.638_642del(p.Glu213fs)	Homozygous	0.0008	Symptoms of HLH
146	Female	0.7	African American	LYST	c.925C>T(p.Arg309*)	Heterozygous	ND	Oculocutaneous albinism, neutropenia
				LYST	c.2015dup(p.Tyr672*)	Heterozygous	ND	Oculocutaneous albinism, neutropenia
147	Male	3.4	Unknown	LYST	c.3194del(p.Leu1065*)	Homozygous	0.0004	NA
148	Female	0.3	Middle Eastern	LYST	c.4159dup(p.Thr1387fs)	Homozygous	ND	Premature gray hair, anemia
149	Male	0.9	European-American	LYST	c.5715del(p.Asn1905fs)	Heterozygous	ND	Oculocutaneous albinism, neutropenia, absent NK cell function
				LYST	c.8802-2A>G	Heterozygous	ND
150	Female	6.9	Unknown	LYST	c.5784+1G>T	Homozygous	ND	Oculocutaneous albinism, dysmorphic facies, neutropenia
151	Male	3.2	Non-Hispanic white	LYST	c.6159_6160del(p.Met2053fs)	Homozygous	ND	NA
152	Male	1.8	Middle Eastern	LYST	c.7291del(p.Leu2431fs)	Homozygous	ND	Hypopigmentation, anemia
153	Male	1.2	African American	LYST	c.8770C>T(p.Gln2924*)	Heterozygous	ND	Silver hair, hypopigmented skin lesions, pancytopenia
				LYST	c.9844_9845del(p.Ser3282fs)	Heterozygous	ND	Silver hair, hypopigmented skin lesions, pancytopenia
154	Female	7.1	Middle Eastern	LYST	c.10776C>G(p.Tyr3592*)	Homozygous	ND	Abnormal pigmentation, neutropenia
155	Female	1.2	Unknown	STX11	c.73G>T(p.Glu25*)	Heterozygous	0.0004	Decreased NK cell function
				STX11	c.748C>T(p.Gln250*)	Heterozygous	0.00081	Decreased NK cell function
156	Female	5.6	Middle Eastern	STX11	c.173T>C(p.Leu58Pro)	Homozygous	0.0008	Symptoms of HLH, grayish hair
157	Female	11.6	Middle Eastern	STX11	c.173T>C(p.Leu58Pro)	Homozygous	0.0008	NA
158	Male	2.9	European-American + Latino-Hispanic	STX11	c.462_463delinsA(p.Asp155fs)	Heterozygous	ND	Decreased NK cell function
				STX11	c.784C>T(p.Gln262*)	Heterozygous	ND	Decreased NK cell function
159	Male	1.4	Asian-Indian	STX11	c.687dup(p.Gln230fs)	Homozygous	ND	NA
160	Female	12 d	Middle Eastern	SLC7A7	c.1429+1G>C	Homozygous	ND	Family history of HLH
161	Male	1.2	African American	SLC7A7	c.701del(p.Ser234fs)	Heterozygous	0.0016	NA
				SLC7A7	c.895-1G>A	Heterozygous	ND
162	Female	13.7	European-American	SLC7A7	c.360_361delinsAA (p.Trp121Arg)	Homozygous	ND	NA
163	Male	5.4	African American	XIAP	c.145C>T(p.Arg49*)	Hemizygous	ND	Markedly decreased XIAP expression
164	Male	18.7	European-American	XIAP	c.345C>G(p.Tyr115*)	Hemizygous	ND	Symptoms of HLH
165	Male	30.3	European-American	XIAP	c.608G>T(p.Cys203Phe)	Hemizygous	ND	NA
166	Male	2	European-American	XIAP	c.664C>T(p.Arg222*)	Hemizygous	ND	Symptoms of HLH
167	Male	8.9	European-American	XIAP	c.738del(p.Asp247fs)	Hemizygous	ND	NA
168	Male	16	European-American	XIAP	c.738del(p.Asp247fs)	Hemizygous	ND	Absent XIAP expression
169	Male	3.6	African American	XIAP	c.889A>T(p.Lys297*)	Hemizygous	ND	NA
170	Male	0.4	Unknown	XIAP	c.894_898del(p.Lys299fs)	Hemizygous	ND	NA
171	Male	17.2	European-American	XIAP	c.894_898del(p.Lys299fs)	Hemizygous	ND	Symptoms of HLH
172	Male	19.6	African American	XIAP	c.926_929del(p.Asp309fs)	Hemizygous	ND	Symptoms of HLH
173	Male	17.2	European-American	XIAP	c.969G>A(p.Trp323*)	Hemizygous	ND	Decreased XIAP expression
174	Male	22.6	Unknown	XIAP	c.1021_1022del(p.Asn341fs)	Hemizygous	ND	NA
175	Male	4.5	Unknown	XIAP	c.1056+1G>A	Hemizygous	ND	NA
176	Male	2.7	Latino-Hispanic	XIAP	c.1141C>T(p.Arg381*)	Hemizygous	ND	NA
177	Male	11.8	Unknown	XIAP	c.1141C>T(p.Arg381*)	Hemizygous	ND	Absent XIAP expression
178	Male	1 d	Pacific-Islander	XIAP	c.1239_1242dup(p.Val415fs)	Hemizygous	ND	Markedly decreased XIAP expression
179	Male	1.9	Unknown	XIAP	c.1239_1242dup(p.Val415fs)	Hemizygous	ND	NA
180	Male	1.1	Unknown	XIAP	c.1301-1G>A	Hemizygous	ND	Symptoms of HLH
181	Male	1.5	Unknown	XIAP	c.1445C>G(p.Pro482Arg)	Hemizygous	ND	NA
182	Male	35	European-American	XIAP	c.1456dup(p.Thr486fs)	Hemizygous	ND	Symptoms of HLH
183	Male	4.5	European-American	SH2D1A	c.20A>G(p.Tyr7Cys)	Hemizygous	ND	Absent SAP in CD8⁺ T cells
184	Male	1.8	Unknown	SH2D1A	c.117C>T(p.Gly39Gly)	Hemizygous	ND	NA
185	Male	3.5	Unknown	SH2D1A	c.130T>C(p.Cys44Arg)	Hemizygous	ND	Absent SAP in CD8⁺ T cells
186	Male	27	European-American	SH2D1A	c.163C>T(p.Arg55*)	Hemizygous	ND	History of pneumonia
187	Male	8 d	Unknown	SH2D1A	c.172C>T(p.Gln58*)	Hemizygous	ND	NA
188	Male	6.8	African American	SH2D1A	c.172C>T(p.Gln58*)	Hemizygous	ND	Absent SAP in CD8⁺ T cells
189	Male	4.7	Latino-Hispanic	SH2D1A	c.199_201+19del(p.Glu67del)	Hemizygous	ND	Absent SAP in CD8⁺ T cells
190	Male	1.3	African American	SH2D1A	c.201G>A(p.Glu67Glu)	Hemizygous	ND	Absent SAP in CD8⁺ T cells
191	Male	7 d	European-American	SH2D1A	c.245del(p.Asn82fs)	Hemizygous	ND	Absent SAP in CD8⁺ T cells
192	Male	34 d	European-American + Pacific-Islander	SH2D1A	c.295C>T(p.Gln99*)	Hemizygous	ND	Absent SAP in CD8⁺ T cells
193	Male	5.4	Middle-Eastern	MAGT1	c.154_161delinsC(p.Ile52fs)	Hemizygous	ND	Symptoms of HLH, bone pain in low extremities
194	Male	10.4	European-American	MAGT1	c.223C>T(p.Gln75*)	Hemizygous	ND	NA
195	Male	18.4	African American	MAGT1	c.407G>A(p.Trp136*)	Hemizygous	ND	NA
196	Male	27.6	European-American	MAGT1	c.443_444del(p.Phe148fs)	Hemizygous	ND	Symptoms of HLH
197	Male	17.3	European-American	MAGT1	c.774del(p.Phe258fs)	Hemizygous	ND	NA

NA, no data; ND, no data; NK, natural killer.

gnomAD v2.1.1 total population frequency.

†

HLH hemophagocytic lymphohistiocytosis, symptoms of HLH reported included any or all of the following “fever, hepatosplenomegaly, anemia/cytopenias, neutropenia/leukopenia, elevated ferritin/triglycerides, and/or decreased fibrinogen.”

‡

According to the ACMG guideline, c.272C>T(p.Ala91Val) in PRF1 was classified as a variant of unknown significance.

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