. 2017 Sep 8;8(60):101325–101332. doi: 10.18632/oncotarget.20722

Table 1. Germline and somatic pathogenic BRCA1/2 mutations identified in ctDNA from 121 patients with ovarian cancer.

Gene	Mutation in corresponding ctDNA	Predicted effect	Type	Case no	FIGO stage	Origin	RS number	Classification ^A	% reads
*BRCA1*	c.181T>G	p.Cys61Gly	M	#71	IIIC	Somatic	rs28897672	Pathogenic [class 5]	7
				#115	IIIC	Germline			51
	c.1793T>A	p.Leu598Ter	N	#85	IA	Germline	rs80357118	Pathogenic [class 5]	51
	c.3296delC	p.Pro1099Leufs^*10	FS	#397	IIIC	Germline	rs80357815	Pathogenic [class 5]	38
	c.3700_3704del	p.Val1234Glnfs^*8	FS	#22	IIIB	Germline	rs80357609	Pathogenic [class 5]	54
				#38	IIIC				50
				#66	IIIC				70
	c.3756_3759del	p.Ser1253Argfs^*10	FS	#100	IIIC	Somatic	rs80357868	Pathogenic [class 5]	17
	c.5177_5180del	p.Arg1726Lysfs^*3	FS	#162	IIIC	Germline	rs80357975	Pathogenic [class 5]	60
	c.5266dupC	p.Gln1756Profs^*74	FS	#50	IIIC	Germline	rs397507247	Pathogenic [class 5]	43
				#108	NR				69
				#314	IIIC				49
				#323	IIIC				44
				#368	IV				46
				#374	IIIC				52
				#378	IIIB				52
	c.4357+2T>G	r.[=,4186_4357del] p.Arg1377Tyrfs^*2	S	#95	IIIC	Germline	rs80358152	Pathogenic [NS]	49
	c.4484+1G>A	r.[=,4358_4484del] p.Glu1462Ter	S	#395	IIIC	Germline	rs80358063	Pathogenic [NS]	49
*BRCA2*	c.2806_2809del	p.Ala938Profs^*21	FS	#164	IIIC	Germline	rs80359351	Pathogenic [NR]	50
	c.5042_5043del	p.Val1681Glufs^*7	FS	#178	IIIC	Germline	rs80359478	Pathogenic [class 5]	49
	c.9097delA	p.Thr3033Leufs^*29	FS	#168	IIIC	Somatic	rs762120301	Pathogenic [class 5]	16.5
	c.9976A>T	p.Lys3326Ter	N	#398	IV	Germline	rs11571833	? ^B [class 2]	44
				#411	IIIC				48
*BRCA1 (2 variants)*	c.[594-2A>C; 641A>G]	r.[=,594_670del] p.Gly183_Lys223del	S	#78	NR	Germline	rs80358033rs55680408	Low riskvariant [NS]	5252
	c.3756_3759del	p.Ser1253Argfs^*10	FS	#169	IIIC	Somatic	rs80357868	Pathogenic [class 5]	10
	c.4484+1G>A	r.[=,4358_4484del]p.Glu1462Ter	S				rs80358063	Pathogenic [NS]	12
	c.1693G>T	p.Glu565Ter	N	#170	IIIC	Somatic	rs886039963	Pathogenic [class 5]	14
	c.3756_3759del	p.Ser1253Argfs^*10	FS				rs80357868	Pathogenic [class 5]	20
	c.181T>G	p.Cys61Gly	M	#171	IIIC	Somatic	rs28897672	Pathogenic [class 5]	10
	c.3756_3759del	p.Ser1253Argfs^*10	FS				rs80357868	Pathogenic [class 5]	10
*BRCA1 (3 variants)*	c.181T>G	p.Cys61Gly	M	#175	IIIC	Somatic	rs28897672	Pathogenic [class 5]	7
	c.3756_3759del	p.Ser1253Argfs^*10	FS				rs80357868	Pathogenic [class 5]	4
	c.4484+1G>A	r.[=,4358_4484del] p.Glu1462Ter	S				rs80358063	Pathogenic [NS]	5
*BRCA1 & BRCA2 (2 variants)*	c.181T>G	p.Cys61Gly	M	#8	IV	Somatic	rs28897672	Pathogenic [class 5]	21
	c.3974_3975insTGCT	p.Thr1325Serfs^*4	FS			Germline	-	Absent ^C [NR]	47
	c.4357+2T>G	r.[=,4186_4357del] p.Arg1377Tyrfs^*2	S	#92	IIIC	Germline	rs80358152	Pathogenic [NS]	48
	c.9976A>T	p.Lys3326Ter	N			Germline	rs11571833	? ^B [class 2]	50

^A Variants’ classification reported in the publicly available databases, including the BIC database, BRCA Share^™ database, ClinVar and/or the HGMD; variants’ classification reported in the BRCA Exchange database curated by the ENIGMA consortium was presented in square brackets; ^B this variant should be re-classified in the publicly available databases from prior benign/little clinical significance to likely pathogenic based on the recent findings [18]; ^C reported as novel pathogenic variant in 1/144 female patient with hereditary breast cancer, but no co-segregation study provided [30]; however, this variant fulfilled the followings ACMG recommendations [29]: PVS1, PM2, PM4, PP3 and PP4, thus it can be clearly classified as pathogenic. FS: frameshift; N: nonsense; M: missense; S: splice; NR: not reported; NS: presence of the variant in the database, but its clinical significance has not yet been specified.