EM-mosaic detects mosaic point mutations that contribute to congenital heart disease

Table 2 Mosaics detected in individuals with matched cardiovascular tissue and blood

ID	Gene	Variant class	Pipeline	CHD tissue				Blood WES VAF
ID	Gene	Variant class	Pipeline	Location	WES AD	WES VAF	MiSeq VAF	WES AD	WES VAF	MiSeq VAF
1-00543	CTCFL	Bmis	EM-mosaic	AO	138,36	0.21	0.32	29,8	0.22	0.19
1-00984	ZNF16	syn	EM-mosaic	LV	262,1	0.00	0.01	100,7	0.07	0.07
1-01282	GABRA6	Dmis	MosaicHunter	RV	104,1	0.01	0.01	55,12	0.18	0.18
1-01684	CCNC	Bmis	Both	AoValve, RV	36,7	0.16	0.17, 0.19	224,40	0.15	0.14
1-02672	TOR1A	syn	Both	AtrSpt	159,10	0.06	0.10	29,6	0.17	0.19
1-03512	RFX3	LoF	MosaicHunter	RV	156,15	0.09	0.08	39,0	0.00	0.03
1-04652	PCDH10	syn	Both	AtrSpt	154,19	0.11	0.14	15,1	0.06	0.10
1-07004	ANK2	Bmis	MosaicHunter	SubAoMembr	226,13	0.05	0.04	30,0	0.00	0.00
1-07004	MYH14	Bmis	Both	SubAoMembr	124,22	0.15	0.27	33,0	0.00	0.00
1-07004	NRG3	Bmis	EM-mosaic	SubAoMembr	152,30	0.16	0.24	43,0	0.00	0.00
1-07004	NUDT21	Bmis	Both	SubAoMembr	137,22	0.14	0.14	74,0	0.00	0.02
1-07004	TET3	Dmis	MosaicHunter	SubAoMembr	131,1	0.01	0.03	81,16	0.16	0.27
1-07299	RRS1	syn	Both	RV, UNK	160,25	0.14	0.25	22,2	0.08	0.14
1-09869	PIK3C2G	LoF	MosaicHunter	LV	126,9	0.07	0.10	31,0	0.00	0.00
1-11800	TMEM45A	Bmis	MosaicHunter	RV	213,0	0.00	0.00	32,7	0.18	0.06

Characteristics of mosaic variants predicted for individuals with blood and cardiovascular tissue WES data available. Among 15 mosaics, 5 were detected via analysis of blood WES, 8 were detected from cardiovascular tissue WES, and 2 were detected by both approaches. Six of 7 (86%) mosaics detected from analysis of blood were present in both DNA sources with MiSeq VAF ≥ 0.01. Two additional variants previously identified as de novo germline variants in blood WES were absent from CHD tissue WES. Minimum 1023 MiSeq reads used to determine VAF. Note: multiple cardiovascular tissue samples were available for participants 1-01684 and 1-07299. Abbreviations: AD allelic depth (reference, alternate), AO aorta, AtrSpt atrial septum, Bmis benign missense, Dmis deleterious missense, LOF loss of function variant, LV left ventricle, RV right ventricle, VAF variant allele fraction

ISSN: 1756-994X