Table 2.

List of 30 patients in whom only 1 heterozygous pathogenic or likely pathogenic variant was identified

Patient no.	Sex	Age at testing, y (unless indicated otherwise)	Ethnicity	Gene	Variant	Zygosity	Population frequency (gnomAD*), %	Symptoms/immunology testing/family history†
S01	Female	28.3	Unknown	PRF1	c.35_46del(p.Leu12_Leu15del)	Heterozygous	ND	NA
S02	Male	20 d	Unknown	PRF1	c.50del(p.Leu17fs)	Heterozygous	0.033	Decreased NK cell function and perforin expression
S03	Female	0.4	Unknown	PRF1	c.50del(p.Leu17fs)	Heterozygous	0.033	Symptoms of HLH
S04	Male	7.8	African American	PRF1	c.50del(p.Leu17fs)	Heterozygous	0.033	Decreased perforin expression
S05	Female	11.2	African American	PRF1	c.50del(p.Leu17fs)	Heterozygous	0.033	Absent NK cell function
S06	Male	52	African American	PRF1	c.50del(p.Leu17fs)	Heterozygous	0.033	HLH, lymphoma
S07	Male	13.3	Native American	PRF1	c.112G>A(p.Val38Met)	Heterozygous	0.0073	Symptoms of HLH
S08	Male	16.6	Latino-Hispanic	PRF1	c.445G>A(p.Gly149Ser)	Heterozygous	0.014	Symptoms of HLH
S09	Female	9.9	Unknown	PRF1	c.563C>T(p.Pro188Leu)	Heterozygous	0.013	Symptoms of HLH
S10	Male	17.8	Unknown	PRF1	c.853_855del(p.Lys285del)	Heterozygous	0.0057	Thrombocytopenia, absent NK cell function
S11	Female	3.1	European-American	PRF1	c.1066C>T(p.Arg356Trp)	Heterozygous	0.0014	NA
S12	Female	3	Unknown	PRF1	c.1117C>T(p.Arg373Cys)	Heterozygous	0.0051	Symptoms of HLH; normal NK cell function
S13	Female	16.7	Unknown	PRF1	c.1117C>T(p.Arg373Cys)	Heterozygous	0.0051	Absent NK cell function
S14	Female	12 d	Middle Eastern	PRF1	c.1122G>A(p.Trp374*)	Heterozygous	0.0016	NA
S15	Female	9.7	Malaysian-Chinese	PRF1	c.1349C>T(p.Thr450Met)	Heterozygous	0.0028	History of HLH
S16	Female	0.5	Middle Eastern	STXBP2	c.1430C>T(p.Pro477Leu)	Heterozygous	0.00074	Symptoms of HLH
S17	Female	0.5	Latino-Hispanic	STXBP2	c.1717C>T(p.Pro573Ser)	Heterozygous	ND	NA
S18	Male	37 d	European-American	STXBP2	c.1717C>T(p.Pro573Ser)	Heterozygous	ND	Absent NK cell function
				PRF1	c.272C>T(p.Ala91Val)‡	Heterozygous	2.92
S19	Male	14.9	Asian-American	UNC13D	c.118-307G>A	Heterozygous	ND	Absent NK cell function
S20	Male	20.3	Unknown	UNC13D	c.247C>T(p.Arg83*)	Heterozygous	0.0004	NA
S21	Female	62.9	European-American	UNC13D	c.1759C>T(p.Arg587Cys)	Heterozygous	0.019	Symptoms of HLH
S22	Female	13.1	European-American	UNC13D	c.2037_2038insG(p.Arg680fs)	Heterozygous	ND	Symptoms of HLH, one sibling deceased due to HLH
S23	Male	0.8	Middle Eastern	RAB27A	c.148_149delinsC(p.Arg50fs)	Heterozygous	ND	Gray hair, suspected for GS, consanguinity
				PRF1	c.272C>T(p.Ala91Val)‡	Heterozygous	2.92
S24	Male	3	European-American	RAB27A	c.240-47_240delins20	Heterozygous	ND	Rash, neutropenia
S25	Male	11.1	Indian	RAB27A	c.244C>T(p.Arg82Cys)	Heterozygous	0.0016	Symptoms of HLH
S26	Female	24.9	Latino-Hispanic	RAB27A	c.335del(p.Asn112fs)	Heterozygous	0.0044	Symptoms of HLH
S27	Male	2.1	Unknown	RAB27A	c.400_401del(p.Lys134fs)	Heterozygous	0.0004	Abnormal brain MRI, decreased NK cell function
S28	Male	29	European-American	LYST	c.465_466del(p.Asp157fs)	Heterozygous	ND	Pancytopenia, increased ferritin level
S29	Male	6.4	Middle Eastern	LYST	c.4159dup(p.Thr1387fs)	Heterozygous	ND	Gray hair
S30	Female	23.2	Unknown	STX11	c.650T>A(p.Leu217Gln)	Heterozygous	0.0004	NA
				PRF1	c.272C>T(p.Ala91Val)‡	Heterozygous	2.92

^*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.