Table 1.

Computational and predicted functional effect of FBN1 variants identified in patients with FTAAD.

Family ID	TAA258	TAA321	TAA345	TAA394	TAA748	TAA289	TAA289	TAA620	TAA662	TAA662	TAA682	TAA698	TAA760
Nucleotide change	c.813 C>G	c.6866 G>T	c.7039_7040 delAT	c.4467 T>A	c.7656 C>A	c.185 G>A	c.6596 G>A	c.2093 C>T	c.8121 C>A	c.3797 A>T	c.3428 G>A	c.4270 C>G	c.2207 A>G
Amino acid substitution	p.C271W	p.C2289F	p.M2347V fs*19	p.N1489K	p.C2552*	p.R62H	p.G2199D	p.P698L	p.D2707E	p.Y1266F	p.G1143D	p.P1424A	p.N736S
Variant type	missense	missense	deletion	missense	nonsense	missense	missense	missense	missense	missense	missense	missense	missense
Exon	7	55	57	36	61	2	53	16	64	30	27	34	18
Domain	EGF-like #4	EGF-like #35	TGFBP 7	EGF-like #26	EGF-like #40	4-cysteine motif	EGF-like #33	TB3	-	EGF-like #20	EGF-like #13	EGF-like #24	EGF-like #7
phyloPa	6.519	7.8	․	0.731	1.67	3.619	7.818	9.869	1.286	1.748	7.275	6.523	7.698
phastConsb	1	1	․	0.997	1	1	1	1	1	1	1	1	1
GERPc	4.48	5.8	․	2.15	3.84	3.26	6.07	6.06	5.38	2.28	5.6	5.81	4.79
CADDd	25.3	35	․	24.5	49	28.8	34	26.3	16.97	16.71	32	23.3	24.6
FATHMMe	D	D	․	D	․	D	D	D	T	D	D	D	D
LRTf	D	D	․	D	D	N	D	D	D	N	D	D	D
Mutation Assessorg	H	H	․	M	․	M	N	L	N	N	M	L	M
Mutation Tasterh	D	D	․	D	A	D	D	D	D	D	D	D	D
Polyphen2i	D	D	․	P	․	D	D	D	B	B	D	P	P
SIFTj	D	D	․	D	․	D	D	T	T	T	D	D	D
ExAC All MAFk	0.0000082	0	0	0	0	0.0000584	0	0.0000082	0	0.0000989	0	0.0001812	0
Variant classification	Pathogenic	Pathogenic	Pathogenic	Pathogenic	Pathogenic	Uncertain significance	Uncertain significance	Likely benign	Uncertain significance	Uncertain significance	Uncertain significance	Uncertain significance	Likely benign

^aPhyloP score: evolutionary conservation score, higher score indicates more conserved site;

^bPhastCons: evolutionary conservation score ranges from 0 to 1, with 1 being most conserved;

^cGERP: evolutionary conservation score, higher score indicates more conserved site (17);

^dCADD: (18);

^eFATHMM: D=damaging, T=tolerated, (17);

^fLRT: D=deleterious, N=neutral, (19);

^gMutation Assessor: H=functional, high, M=functional, medium, L=non-functional, low, N=non-functional, neutral, (20);

^hMutation Taster: A=disease-causing automatic, D=disease-causing, (21);

ⁱPolyPhen-2 HVAR: D=probably damaging, P=possibly damaging, B=benign, (22);

^jSIFT: D=damaging, T=tolerated, (23);

^kMAF: minor allele frequency in all populations in the Exome Aggregation Consortium (ExAC) database.