Table 2

Overview of the 21 pathogenic or likely pathogenic variants identified by gene panel targeted sequencing

Sample ID	Affected gene	Types of variants	Chromosome and location (CHROM: Start-End)	Variant (sequence; protein level)	Disease name	References	Allele frequency		Prediction results		ACMG criteria*	ACMG classification
Sample ID	Affected gene	Types of variants	Chromosome and location (CHROM: Start-End)	Variant (sequence; protein level)	Disease name	References	ExAC	Internal controls	MutationTaster	CADD	ACMG criteria*	ACMG classification
NHP0000000889	ARMC5	Stop-gain	16:31473958–31473958	c.1090C>T; p.Arg364	ACTH-independent macronodular adrenal hyperplasia (AIMAH)	Faucz (2014)47	0.00006754	0	Disease causing	39	PVS, PM	LP
D16045354	CYP11B1	Non-synonymous	8:143956411–143956411	c.1360C>T; p.Arg454Cys	11 β-hydroxylase deficiency	Ye (2010)48	0	0	Disease causing	14.84	PM2, PP1, PP4, PM1	P
D16030882	CYP11B1	Splicing	8:143958438–143958438	c.595+1G>A ;-	11 β-hydroxylase deficiency	No report	0	0	Disease causing	18.17	PVS, PM2	P
NHP0000000235	CYP17A1	Non-synonymous	10:104592323–104592323	c.1084C>T; p.Arg362Cys	17α-hydroxylase deficiency	Martin (2003)49; Belgini (2010)50	0	0	Disease causing	25.80	PS3, PP3, PP4, PM	LP
NHP0000001345, NHP0000001347, NHP0000001348	CYP17A1	Stop-gain	10:104592420–104592420	c.985_987 delTACinsAA; p.Tyr329Lysfs*90	17α-hydroxylase deficiency	Wang (2014)51					PVS	LP
D16045355, NHP0000000130, NHP0000000635, NHP0000000855	CYP17A1	Stop-gain	10:104592420–104592420	c.987delC; p.Y329X	17α-hydroxylase deficiency	Biason-Lauber (2000)52	0.00004947	0	–	–	PVS, PM2	P
D16030881	KCNJ5	Non-synonymous	11:128781601–128781601	c.433G>C; p.Glu145Gln	Hyperaldosteronism, familial, type III	No report	0	0	Disease causing	19.08	PP3, PM2, PS2	P
D16045356	MEN1	Frameshift insertion	11:64577393–64577393	c.188_189insCCAGC; p.F63fs	Multiple endocrine neoplasia type 1 (MEN1)	No report	0	0	–	–	PVS, PM2	P
D16030884	RET	Non-synonymous	10:43609948–43609948	c.1900T>C; p.Cys634Arg	Multiple endocrine neoplasia type 2, MEN2	Donis-Keller (1993)53; Birla (2014)54; Borrello (1995)55	0.000008274	0	Disease causing	21.00	PP3, PM6, PM, PS3	P
NHP0000000001, NHP0000000003, NHP0000000004, NHP0000000005	RET	Non-synonymous	10:43617416–43617416	c.2753T>C; p.Met918Thr	Multiple endocrine neoplasia type 2 (MEN2)	Carlson (1994)56; Borrello (1995)57; Choi (2012)	0	0	Disease causing	23.50	PP3, PM6, PM, PS3	LP
ZTD16072123	SCNN1B	Stop-gain	16:23391895–23391895	c.1696C>T; p.Arg566	Liddle syndrome	Shimkets (1994)58	0	0	Disease causing	15.98	PVS, PM2	P
ZTD16071412	SCNN1B	Non-synonymous	16:23392052–23392052	c.1853C>A; p.Pro618His	Liddle syndrome	Freundlich (2005)59; Wang (2006)60	0	0	Disease causing	22.00	PM2, PP3, PP4, PM1	P
D16072556, D16072557, NHP0000000569	SCNN1B	Non-synonymous	16:23392052–23392052	c.1853C>T; p.Pro618Leu	Liddle syndrome	Freundlich (2005)59; Wang (2006)60	0	0	Disease causing	24.20	PM2, PP3, PS3	P
D16040803	SCNN1B	Frameshift insertion	Frameshift insertion	c.1854_1855insC; p.P618fs	Liddle syndrome	Yang (2015)61	0	0	–	–	PM4, PS2, PP4	LP
D16072547	SDHB	Non-synonymous	1:17349179–17349179	c.689G>A; p.Arg230His	Paraganglioma type 4 (PGL4)	Amar (2005)62; Cerecer-Gil (2010)63; Hermsen (2010)64	0	0	Disease causing	33.00	PM2, PP3, PP5, PM1	P
D16030885	SDHB	Splicing	1:17371255–17371255	c.200+1G>C;-	PGL4	Burnichon (2009)65; Xiong (2015)66	0	0	Disease causing	13.94	PVS, PM2	P
D16030888	SDHD	Stop-gain	11:111958640–111958640	c.112C>T; p.Arg38	Paraganglioma type 1 (PGL1)	Baysal (2000)22; Neumann (2002)67; Erlic (2009)68	0	0	Disease causing	19.87	PVS, PM2	P
D16030886	VHL	Frameshift deletion	3:10183716–10183717	c.185_186del; p.62_62del	Von Hippel-Lindau syndrome (VHL syndrome)	Wang (2014)69	0	0	–	–	PVS, PM2	P
ZTD16072119	VHL	Non-synonymous	3:10183781–10183781	c.250G>T; p.Val84Leu	VHL syndrome	Crossey (1995)70; Bangiyeva (2009)71; Hoffman (2001)72	0	0	Disease causing	29.50	PM2, PM, PS3	P
D16072544	VHL	Non-synonymous	3:10191489–10191489	c.482G>A; p.Arg161Gln	VHL syndrome	Chen (1995)73; Couvé (2014)74; Neumann (2002)67	0	0	Disease causing	28.20	PM2, PS3	P
D16030887, NHP0000000722	VHL	Non-synonymous	3:10191506–10191506	c.499C>T; p.Arg167Trp	VHL syndrome	Crossey (1994)75; Bachurska (2014)76; Bangiyeva (2009)71	0.000008257	0	Disease causing	19.54	PM2, PP3, PS3	P
D16072546	VHL	Non-synonymous	3:10191507–10191507	c.500G>A; p.Arg167Gln	VHL syndrome	Crossey (1994)75; Bachurska (2014)76; Bangiyeva (2009)71	0	0	Disease causing	29.80	PM2, PS3, PP3	P

*See ACMG guidelines for further information on classification criteria.
ACMG, American College of Medical Genetics; LP, likely pathogenic; P, pathogenic; PM, pathogenic moderate; PP, pathogenic supporting; PS, pathogenic strong; PVS, pathogenic very strong.