Identification of eight novel SDHB, SDHC, SDHD germline variants in Danish pheochromocytoma/paraganglioma patients

Table 1 SDHB, SDHC, and SDHD variants identified in Danish patients with neuroendocrine cancer. PCC pheochromocytoma, PGL paraganglioma, LGR large genomic rearrangement; ^a identified in homozygote state; N/A not accessible. Results from In silico data analyses from A-GVGD, SIFT, and PolyPhen-2 are listed in the corresponding columns. Each variant is classed according to the five-tiered scheme

Family ID	Disease	Age (yr)	Gene	Exon	Nucleotide	Protein	Mutation type	A-GVGD	SIFT	PolyPhen-2	Frequency (ExAC)	Class	References
1	PGL	51	SDHB	1	c.-1-?_72+?del	-	LGR	-	-	-	-	5	[21, 22]
2	PGL	36	SDHB	1–7	c.-1-?_765+?del	-	LGR	-	-	-	-	5	Novel
3	PGL	29	SDHB	1	c.3G > A	p.Met1?	Start loss	-	-	-	-	4	[24, 32, 43]
4	PGL	34	SDHB	3	c.203G > A	p.Cys68Tyr	Missense	C65	Deleterious	Possibly damaging	-	4	[30, 43]
5	PGL	16	SDHB	4–5	c.287-?_540+?del	-	LGR	-	-	-	-	5	Novel
6	PCC	51	SDHB	4	c.300T > C	p.Ser100Ser	Synonymous	-	-	-	0.15 %	3	[30]
7	PCC	29	SDHB	4	c.416T > C	p.Leu139Pro	Missense	C65	Deleterious	Possibly damaging	-	4	Novel
8	PGL	12	SDHB	6	c.566G > A	p.Cys189Tyr	Missense	C65	Deleterious	Possibly damaging	-	3	Novel
9	PGL	39	SDHB	7	c.653G > A	p.Trp218Ter	Nonsense	-	-	-	-	5	[30]
10	PGL	41	SDHC	2	c.43C > T	p.Arg15Ter	Nonsense	-	-	-	0.00082 %	5	[31–33]
11	PGL	75	SDHC	-	c.78-19C > T	-	-	-	-	-	0.021 %	3	Novel
12	PGL	N/A	SDHC	3	c.148C > T	p.Arg50Cys	Missense	C25	Deleterious	Probably damaging	-	4	[32, 43]
13	PGL	64	SDHC	4	c.191_207del17	p.Pro64LeufsTer28	Frameshift	-	-	-	-	5	Novel
14	PCC	31	SDHC	5	c.242G > T^a	p.Gly81Val	Missense	C0	Deleterious	Probably damaging	0.00082 %	3	Novel
15	PCC	74	SDHC	6	c.496C > G	p.Leu166Val	Missense	C0	Tolerated	Benign	-	3	Novel
16	PGL	41	SDHD	2	c.149A > G	p.His50Arg	Missense	C0	Tolerated	Probably damaging	0.65 %	2	[22, 30, 43–48]
17	PCC	37	SDHD	3	c.274G > T	p.Asp92Tyr	Missense	C65	Deleterious	Probably damaging	-	5	[4, 36, 38–43]
18	PGL	41	SDHD	4	c.341A > G	p.Tyr114Cys	Missense	C65	Deleterious	Probably damaging	-	5	[24, 37, 42, 49–53]

ISSN: 1897-4287