Table 2.

Variants in the ABCC6 gene identified in the 20 patients with angioid streaks.

Exon	Nucleotide	Amino acid	Homozygous	Heterozygous	Total (alleles)	dbSNP ID	HGVD (allele frequency)	ExAC East Asian (allele frequency)	ExAC total (allele frequency)	Polyphen-2 results (HumVar)	SIFT results	PROVEAN results	Pathogenicity	References
9	c.1132C>T	p.Q378X	1	5	7/40	rs72650699	0.002% (2/427)	0.000% (0/8646)	0.000% (1/121188)				Pathogenic	Le Saux et al. [2001], Pulkkinen et al. [2001]
10	c.1256G>A	p.R419Q	0	4	4/40	rs772434460	0.001% (2/1077)	0.001% (10/8204)	0.000% (10/111520)	0.742 (possibly damaging)	0.00 (damaging)	−3.27 (deleterious)	Pathogenic	Iwanaga et al. [2017]
	c.1283A>G	p.N428S	0	1	1/40	rs201880691	0.009% (20/1123)	0.001% (12/8524)	0.000% (13/117386)	0.999 (probably damaging)	0.00 (damaging)	−4.69 (deleterious)	Pathogenic	Sato et al. [2009] (reported in the controls)
15	c.1939C>T	p.H647Y	0	1	1/40	Not reported	Not reported	Not reported	Not reported	0.127 (benign)	0.01 (damaging)	−3.32 (deleterious)	Pathogenic	N/A (novel variant)
19	c.2542delG	p.V848CfsX83	2	10	14/40	rs67867306	Inconclusive	0.003% (27/8654)	0.000% (27/121324)				Pathogenic	Sato et al. [2009]
24	c.3340C>T	p.R1114C	0	1	1/40	rs63749794	Not reported	0.000% (0/8608)	0.000% (12/120184)	0.998 (probably damaging)	0.00 (damaging)	−7.13 (deleterious)	Pathogenic	Gheduzzi et al. [2004]
	c.3374C>T	p.S1125F	0	1	1/40	Not reported	Not reported	Not reported	Not reported	0.992 (probably damaging)	0.00 (damaging)	−4.85 (deleterious)	Pathogenic	N/A (novel variant)
29	c.4069C>T	p.R1357W	0	6	6/40	rs63750428	0.006% (14/1099)	0.001% (5/7944)	0.000% (6/107190)	1.000 (probably damaging)	0.00 (damaging)	−6.56 (deleterious)	Pathogenic	Miksch et al. [2005]

N/A = not applicable; HGVD = Human Genetic Variation database (http://www.hgvd.genome.med.kyoto-u.ac.jp/index.html); ExAC = Exome Aggregation Consortium database (http://exac.broadinstitute.org); Polyphen-2 (http://genetics.bwh.harvard.edu/pph2/); SIFT (http://sift.jcvi.org); PROVEAN (http://provean.jcvi.org).