Table 3.

Rare nonsynonymous de novo variants in 7 AVSD-associated genes

Fetus ID	AVSD type	Associated cardiac defects	Candidate gene	Nucleotide changes	Amino acid changes	dbsnp147	Damaging predict*	GERP++
23	Partial	None	COL11A1	652-5->TT	Splicing	rs749687230	-	-
40	Complete	TGA	COL11A1	3266C>T	P1089L	rs373734529	Yes	Conserved
13	Complete	CAT	COL6A2	499G>A	G167S	rs115957676	Yes	Conserved
3	Partial	None	COL6A2	679G>A	D227N	rs35881321	No	Conserved
43	Intermediate	TGA, PS, AS	COL6A2	2798G>A	R933H	rs374384263	Yes	Nonconserved
20	Partial	TGA, PA	C5ORF42	8746G>A	A2916T	rs369585190	Yes	Conserved
25	Partial	None	C5ORF42	6443A>G	N2148S	rs150999024	No	Nonconserved
28	Complete	TGA, PS	C5ORF42	608A>G	Y203C	rs144969169	Yes	Conserved
3	Partial	None	GLI3	169G>A	A57T	rs775586921	No	Conserved
3	Partial	None	GLI3	164G>A	R55K	rs764332121	Yes	Conserved
20	Partial	TGA, PA	GLI3	169G>A	A57T	rs775586921	No	Conserved
20	Partial	TGA, PA	GLI3	164G>A	R55K	rs764332121	Yes	Conserved
7	Complete	TGA, PS	LRP2	9937G>A	D3313N	-	Yes	Conserved
41	Complete	TGA	LRP2	9914G>A	R3305H	rs3213760	Yes	Conserved
10	Intermediate	None	GATA6	43G>C	G15R	rs116262672	Yes	Conserved
44	Intermediate	DORV, TAPVC	GATA6	551G>A	S184N	rs387906816	No	Nonconserved
14	Partial	TGA, IAA	HSPG2	2008G>A	V670I	rs147810145	No	Conserved
27	Intermediate	None	HSPG2	10589G>A	R3530Q	rs200062985	Yes	Conserved
44	Intermediate	DORV, TAPVC	HSPG2	2057T>C	L686P	-	Yes	Conserved

Abbreviations: AVSD, atrioventricular septal defect; TGA, transposition of the great arteries; PA, pulmonary valve atresia; PS, pulmonary stenosis; CAT, common arterial trunk; AS, aortic valve stenosis; DORV, double outlet right ventricle; TAPVC, total anomalous pulmonary venous connection.

^*Yes: at least 2 bioinformatics tools suggest damaging or probably damaging or possibly damaging (SIFT, PolyPhen-2, Mutation Taster); No: 2 or 3 bioinformatics tools suggest benign (SIFT, PolyPhen-2, Mutation Taster).