Table 3.

Patients with pathogenic or likely pathogenic genetic variants

Patient	Sex	Age (year)	SCT	Outcome	Functional defect	pHLH	Gene	Transcript	Genotype	Inheritance	Change	DNA HGVS	Protein HGVS	ACMG classification	dbSNP	GnomAD AF	References
Patients with biallelic defects
1	M	0.03	No	Death	Nd	FHL3	UNC13D	NM_199242.2	hmz	Both	Frameshift	c.2346_2349del	p.Arg782Serfs*12	Pathogenic	rs764196809	1.03e−4	zur Stadt et al. (2006)
2	F	0.02	Yes	Alive	not detected	FHL3	UNC13D	NM_199242.2	hmz	Both	Frameshift	c.2346_2349del	p.Arg782Serfs*12	Pathogenic	rs764196809	1.03e−4	zur Stadt et al. (2006)
3	M	0.01	Yes	Death	low NK activity, abnormal degranulation	FHL3	UNC13D	NM_199242.2	hmz	Both	Splice-site	c.753 + 1G > T	p.Ile229Thrfs*35	Pathogenic	rs201908137	4.38e−5	Alsina et al. (2014)
4	M	0.82	Yes	Death	low NK activity	FHL3	UNC13D	NM_199242.2	Compound	Paternal	Nonsense	c.640C > T	p.Arg214*	Pathogenic	rs769243366	3.98e−6	Yamamoto et al. (2004)
					abnormal degranulation				htz	Maternal	Frameshift	c.2346_2349del	p.Arg782Serfs*12	Pathogenic	rs764196809	1.03e−4	zur Stadt et al. (2006)
5	M	0.39	Yes	Alive	low NK activity, abnormal degranulation	FHL3	UNC13D	NM_199242.2	hmz	Both	Splice-site	c.753 + 1G > T	p.Ile229Thrfs*35	Pathogenic	rs201908137	4.38e−5	Alsina et al. (2014)
6	M	0.31	Yes	Alive	low NK activity	FHL3	UNC13D	NM_199242.2	Compound	Maternal	Nonsense	c.551G > A	p.Trp184*	Pathogenic	rs754292065	1.07e−5	Murphy et al. (2010)
					abnormal degranulation				htz	Paternal	Missense	c.3049G > A	p.Glu1017Lys	Likely pathogenic	rs776737156	4.35e−6	Sieni et al. (2011)
7	F	0.22	No	Death	not detected	FHL3	UNC13D	NM_199242.2	compound htz	Paternal	Nonsense	c.247C > T	p.Arg83*	Pathogenic	rs1274685768	4.01e−6	Rudd et al. (2008)
										Maternal	Splice-site	2710-1G > A	p.?	Pathogenic	Novel	nd	nd
8	F	0.08	Yes	Alive	low NK activity, abnormal degranulation	FHL3	UNC13D	NM_199242.2	hmz	Both	Frameshift	c.2346_2349del	p.Arg782Serfs*12	Pathogenic	rs764196809	1.03e−4	zur Stadt et al. (2006)
9	M	0.16	Yes	Alive	not detected	FHL3	UNC13D	NM_199242.2	Compound htz	Paternal	Splice-site	c.569 + 1G > A	p.?	Pathogenic	rs1400391434	4.02e−6	nd
										Maternal	Frameshift	c.2346_2349del	p.Arg782Serfs*12	Pathogenic	rs764196809	1.03e−4	zur Stadt et al. (2006)
10	F	0.2	Yes	Death	absent perforin, low NK activity	FHL2	PRF1	NM_005041.2	Compound htz	Paternal	Frameshift,	c.808_812del	p.Gly270Hisfs*9	Pathogenic	Novel	nd	Maxwell et al. (2016) and Pronicka et al. (2016)
										Maternal	Missense	c.938A > T	p.Asp313Val	Likely pathogenic	rs755737064	1.19e−5	nd
11	F	0.2	Yes	Alive	Absent perforin, low NK activity	FHL2	PRF1	NM_005041.2	Compound htz	Paternal	Frameshift,	c.284G > T	p.Trp95Leu	Likely pathogenic	Novel	nd	nd
										Maternal	Missense	c.808_812del	p.Gly270Hisfs*9	Pathogenic	Novel	nd	Maxwell et al. (2016) and Pronicka et al. (2016)
12	M	4.93	Yes	Alive	nd	XLP2	XIAP	NM_001204401.1	hemi	Maternal	Frameshift	c.898delT	p.Cys300Alafs*8	Pathogenic	Novel	nd	Nd
13	M	4.35	Yes	Alive	Not detected	XLP1	SH2D1A	NM_002351.4	hemi	Maternal	Nonsense	c.163C > T	p.Arg55*	Pathogenic	rs111033623	nd	Coffey et al. (1998)
14	M	3.14	Yes	Alive	not detected	XLP2	XIAP	NM_001204401.1	hemi	Maternal	Missense	c.655G > A	p.Glu219Lys	VUS PM2 PP3	Novel	nd	nd
15	M	1.25	No	Death	nd	XLP1	SH2D1A	NM_002351.4	hemi	Maternal	Splice-site	c.137 + 1_137 + 4del	p.?	VUS PM2 PP3	Novel	nd	nd
16	M	17	No	Alive	nd	XMEN	MAGT1	NM_032121.5	hemi	Maternal	Frameshift	c.247delA	p.Arg83Aspfs*3	Pathogenic	Novel	nd	nd
17	F	0	Yes	Alive	Low NK activity	MKD	MVK	NM_001114185.3	hmz	Both	Nonsense	c.1162C > T	p.Arg388*	Pathogenic	rs104895360	2.65e−05	Prasad et al. (2012)
Patients with monoallelic defects
1	F	0.04	No	Death	nd	FHL3	UNC13D	NM_199242.2	htz	Not determined	Splice-site	c.753 + 1G > T	p.Ile229Thrfs*35	PATHOGENIC	rs201908137	4.38e−5	Alsina et al. (2014)
2	M	0.03	Yes	Alive	Low NK activity, abnormal degranulation	FHL3	UNC13D	NM_199242.2	htz	Paternal or maternal	Frameshift	c.2346_2349del	p.Arg782Serfs*12	Pathogenic	rs764196809	1.03e−4	zur Stadt et al. (2006)

hmz homozygous, htz heterozygous, hemi hemizygous, nd not determined