Molecular Vision: Kondo, Mol Vis 2013; 19:476-485. Table 2

Table 2. Rare FZD4 variants identified in patients with advanced retinopathy of prematurity

Location	cDNA change	Protein change (score with Blosum62)	Occurrence in patients	Allele frequency in ethnically matched samples	Known polymorphism (rs ID, allele frequency)	Computational analysis score				Patient characteristics: ethnicity; gender; birthweight; gestational age; clinical data	Reference
Location	cDNA change	Protein change (score with Blosum62)	Occurrence in patients	Allele frequency in ethnically matched samples	Known polymorphism (rs ID, allele frequency)	SIFT	Poly- phen2	Muta- tion Taster	Phylop		Reference
Exon 1	c.205C>T	p.H69Y (2)	1/53	2/300	Yes  (rs80358282)	0.02 (D)	0.197 (B)	0.9907 (Dc)	0.9992 (C)	#N5301: Japanese; male; 460 g; 24 gw; APROP/stage4A (OU), Lx at 2 months (OU), Vx at 4 months (OU)	This study
Exon 2	c.380G>A	p.R127H (0)	1/53	0/300	Yes (rs184709254 0.05%)	0.11 (T)	0.984 (PrD)	0.9968 (Dc)	0.9818 (C)	#N3401: Japanese; male; 801 g; 25 gw; APROP/stage 5 (OU), Lx at 1 month, Vx (OU)	This study
Exon 2	c.502C>T	p.P168S (−1)	7/71 [15] 4/60 [37]	12/346 [15] ND [37]	Yes (rs61735303, 1.424%)	0.02 (D)	0.146 (B)	0.9990 (Dc)	0.9997 (C)	ND	[15,37]
Exon 2	c.609G>T	p.K203N (0)	1/71	0/346	No	0.13 (T)	0.415 (B)	0.9913 (Dc)	0.9841 (C)	Caucasian; male; 780 g; 26 gw; Stage 3 (OU), Lx at 78 d	[15]
Exon 2	c.631T>C	p.Y211H (2)	2/53	0/300	No	0.02 (D)	0.003 (B)	0.9983 (Dc)	0.9818 (C)	#N1901: Japanese; female; 1,152 g; 27 gw; Classic/stage 5 (OU), Vx (OD), glaucoma (OS), #N4001: Japanese; male; 566 g; 23 w; APROP/stage 4A (OU), Lx & Vx (OU)	This study
Exon 2	c.766A>G	p.I256V (3)	1/20	0/200	Yes (rs10489423, 0.179%)	0.11 (T)	0.938 (PsD)	0.9900 (Dc)	0.9981 (C)	ND	[36]
Exon 2	c.1109C>G	p.A370G (0)	1/71	0/346	No	1 (T);	0.058 (B)	0.9987 (Dc)	0.9997 (C)	Caucasian; male; 880 g; 28 gw; Stage 3 (OU), Lx at 92 d	[15]
Exon 2	c.1396C>T	p.R466W (−3)	1/71	0/346	No	0.01 (D)	0.999 (PrD)	0.9949 (Dc)	0.9705 (C)	Mixed (Chinese and Caucasian); female; 650 g; 24 gw; Stage 3 (OU), Lx at 68 d	[15]

Allele frequency from ethnically-matched samples was obtained from either random or control individuals. Known polymorphism was based on the dbSNP, and the allele frequency was on the Exome Variant Server, NHLBI Exome Sequencing Project (ESP), Seattle, WA. Computational analyses were performed by 4 programs (SIFT, Polyphen2, Mutation taster, and PhyloP). Pathogenic results were shown by bold characters as “D (damaging)” for SIFT, “PrD (probably damaging)” or “PsD (possibly damaging)” for Polyphen2, “Dc (disease-causing)” for Mutation Taster, and “C (conserved)” for PhyloP. Non-pathogenic results are shown in italics as “T (tolerated)” for SIFT, and “B (benign)” for Polyphen2. Note p.P168S was found as a compound mutation with p.P33S, however, p.P33S was not listed because this study showed it was “non-pathogenic” by SIFT, Polyphen2 and Mutation Taster. d: days after birth, g: gram, gw: gestational weeks, Lx: laser, m: months after birth, ND: not described, Vx: vitrectomy, w: weeks after birth.