Proband ID
|
Gender
|
Agea [years]
|
Exon/intron
|
Nucleotide change
|
Amino acid change
|
Allele state
|
dbSNP/ClinVar accession number
|
Variant classificationb
|
MAF
|
New or known variants
|
Best’s disease stagec
|
BCVAd
|
---|
LE
|
RE
|
LE
|
RE
|
---|
P1
|
M
|
50
|
ex2
|
c.5C>T
|
p.(Thr2Ile)
|
HET
|
NA
|
Likely pathogenic
|
NA
|
Kinnick (2011)
|
5
|
5
|
0.1
|
0.4
|
P2
|
F
|
42
|
ex2
|
c.11C>T
|
p.(Thr4Ile)
|
HET
|
NA
|
Likely pathogenic
|
NA
|
Tian (2014)
|
2
|
2
|
0
|
0
|
P3*
|
F
|
13
|
ex2
|
c.11C>T
|
p.(Thr4Ile)
|
HET
|
NA
|
Likely pathogenic
|
NA
|
Kinnick (2011)
|
1
|
1
|
0.1
|
0.1
|
P4*
|
M
|
27
|
ex2
|
c.26T>G
|
p.(Val9Gly)
|
HET
|
SCV000599452
|
Likely pathogenic
|
NA
|
NEW
|
2
|
2
|
0
|
0.6
|
P5
|
F
|
34
|
ex2
|
c.44G>A
|
p.(Gly15Asp)
|
HET
|
NA
|
Likely pathogenic
|
NA
|
Querques (2009)
|
NA
|
NA
|
NA
|
NA
|
P6
|
M
|
22
|
ex2
|
c.44G>A
|
p.(Gly15Asp)
|
HET
|
NA
|
Likely pathogenic
|
NA
|
Querques (2009)
|
3
|
4
|
0
|
0.2
|
P7
|
F
|
13
|
ex2
|
c.44G>A
|
p.(Gly15Asp)
|
HET
|
NA
|
Likely pathogenic
|
NA
|
Querques (2009)
|
0
|
3
|
0
|
0.22
|
P8*
|
M
|
56
|
ex2
|
c.47C>T
|
p.(Ser16Phe)
|
HET
|
rs281865210
|
Likely pathogenic
|
NA
|
Marchant (2001)
|
2
|
2
|
0.1
|
0.7
|
P9
|
F
|
23
|
ex2
|
c.74G>A
|
p.(Arg25Gln)
|
HET
|
rs281865215
|
Likely pathogenic
|
A = 0.000008 (Topmed)
|
Marquardt (1998)
|
4
|
2
|
0.5
|
0
|
P10
|
F
|
47
|
ex1
|
c.80G>C
|
p.(Ser27Thr)
|
HET
|
NA
|
Likely pathogenic
|
NA
|
Bernardis (2016)
|
3
|
4
|
0.1
|
0.2
|
P11*
|
F
|
55
|
ex2
|
c.80G>C
|
p.(Ser27Thr)
|
HET
|
NA
|
Likely pathogenic
|
NA
|
Bernardis (2016)
|
2
|
2
|
NA
|
NA
|
P12
|
F
|
52
|
ex2
|
c.80G>C
|
p.(Ser27Thr)
|
HET
|
NA
|
Likely pathogenic
|
NA
|
Bernardis (2016)
|
3
|
3
|
0.7
|
1
|
P13*
|
M
|
10
|
ex2
|
c.86A>G
|
p.(Tyr29Cys)
|
HET
|
NA
|
Likely pathogenic
|
NA
|
Downs (2007)
|
4
|
4
|
0
|
0
|
P14
|
F
|
27
|
ex4
|
c.274C>T
|
p.(Arg92Cys)
|
HOM
|
rs281865224
|
Pathogenic
|
NA
|
Bakall (1999)
|
NA
|
NA
|
NA
|
NA
|
P15
|
M
|
42
|
ex4
|
c.278G>C
|
p.(Trp93Ser)
|
HET
|
NA
|
Likely pathogenic
|
NA
|
Tian (2017)
|
NA
|
NA
|
NA
|
NA
|
P16*
|
M
|
70
|
ex4
|
c.301C>A
|
p.(Pro101Thr)
|
HET
|
rs281865229
|
Likely pathogenic
|
NA
|
Lotery (2000)
|
4
|
3
|
0.5
|
0
|
P17
|
M
|
26
|
ex4
|
c.324C>G
|
p.(Ser108Arg)
|
HET
|
SCV000747137
|
Vus
|
NA
|
NEW
|
2
|
2
|
0.1
|
1
|
P18
|
M
|
46
|
ex5
|
c.535A>G
|
p.(Asn179Asp)
|
HET
|
SCV000599453
|
Likely pathogenic
|
NA
|
NEW
|
1
|
2
|
0.3
|
0.3
|
P19
|
F
|
13
|
ex5
|
c.544T>C
|
p.(Trp182Arg)
|
HET
|
SCV000747139
|
Vus
|
NA
|
NEW
|
4
|
4
|
NA
|
NA
|
P20*
|
M
|
19
|
ex5
|
c.598C>T
|
p.(Arg200*)
|
HET
|
rs121918286
|
Pathogenic
|
T = 0.00002/3 (ExAC)
|
Burgess (2008)
|
NA
|
NA
|
NA
|
NA
|
| | |
ex7
|
c.728C>A
|
p.(Ala243Glu)
|
HET
|
NA
|
Likely pathogenic
|
NA
|
Fung (2014)
|
NA
|
NA
|
NA
|
NA
|
P21*
|
F
|
25
|
ex6
|
c.652C>T
|
p.(Arg218Cys)
|
HET
|
rs281865238
|
Pathogenic
|
NA
|
Johnson (2013)
|
2
|
2
|
0.1
|
0
|
P22
|
F
|
13
|
ex6
|
c.652C>T
|
p.(Arg218Cys)
|
HET
|
rs281865238
|
Pathogenic
|
NA
|
Johnson (2013)
|
0
|
3
|
0
|
0.17
|
P23
|
M
|
14
|
ex6
|
c.652C>T
|
p.(Arg218Cys)
|
HET
|
rs281865238
|
Pathogenic
|
NA
|
Johnson (2013)
|
2
|
2
|
0.4
|
0
|
P24
|
M
|
42
|
ex6
|
c.652C>A
|
p.(Arg218Ser)
|
HET
|
rs281865238
|
Likely pathogenic
|
NA
|
Bakall (1999)
|
3
|
3
|
0.5
|
0.4
|
P25
|
M
|
54
|
ex5
|
c.695T>A
|
p.(Ile232Asn)
|
HET
|
NA
|
Likely pathogenic
|
NA
|
Wabbels (2006)
|
3
|
3
|
0.6
|
0.8
|
P26
|
M
|
17
|
ex6
|
c.703G>T
|
p.(Val235Leu)
|
HET
|
NA
|
Likely pathogenic
|
NA
|
Marchant (2001)
|
3
|
3
|
0.1
|
0.1
|
P27*
|
F
|
51
|
ex7
|
c.727G>A
|
p.(Ala243Thr)
|
HET
|
rs137853905
|
Pathogenic
|
NA
|
Lotery (2000)
|
2
|
2
|
1
|
1
|
P28
|
M
|
49
|
ex7
|
c.728C>T
|
p.(Ala243Val)
|
HET
|
rs28940570
|
Pathogenic
|
T = 0.000008/1 (ExAC)
|
White (2000)
|
3
|
3
|
0.1
|
0
|
P29*
|
F
|
43
|
ex7
|
c.728C>T
|
p.(Ala243Val)
|
HET
|
rs28940570
|
Pathogenic
|
T = 0.000008/1 (ExAC)
|
White (2000)
|
3
|
2
|
0.2
|
0.2
|
P30*
|
F
|
50
|
ex7
|
c.728C>T
|
p.(Ala243Val)
|
HET
|
rs28940570
|
Pathogenic
|
T = 0.000008/1 (ExAC)
|
White (2000)
|
NA
|
NA
|
NA
|
NA
|
P31*
|
M
|
9
|
ex8
|
c.874G>C
|
p.(Glu292Gln)
|
HET
|
SCV000747140
|
Likely pathogenic
|
NA
|
NEW
|
2
|
2
|
1
|
1
|
P32
|
M
|
39
|
ex8
|
c.888C>G
|
p.(Asn296Lys)
|
HET
|
SCV000802932
|
Pathogenic
|
NA
|
NEW
|
3
|
3
|
0.1
|
0.3
|
P33
|
F
|
41
|
ex8
|
c.888C>A
|
p.(Asn296Lys)
|
HET
|
NA
|
Pathogenic
|
NA
|
Boon (2007)
|
2
|
2
|
0.3
|
0.3
|
P34
|
M
|
10
|
ex8
|
c.893T>G
|
p.(Phe298Cys)
|
HET
|
NA
|
Likely pathogenic
|
NA
|
Meunier (2011)
|
NA
|
NA
|
NA
|
NA
|
P35
|
M
|
53
|
ex8
|
c.893T>G
|
p.(Phe298Cys)
|
HET
|
NA
|
Likely pathogenic
|
NA
|
Meunier (2011)
|
NA
|
NA
|
NA
|
NA
|
P36*
|
M
|
21
|
ex8
|
c.903T>G
|
p.(Asp301Glu)
|
HET
|
rs281865261
|
Pathogenic
|
NA
|
Caldwell (1999)
|
NA
|
NA
|
0
|
0.6
|
- HET heterozygous, HOM homozygous, rs# single nucleotide polymorphisms identifier as recorded in the Single Nucleotide Polymorphism Database (dbSNP), SCV# novel variants have been registered in the database of genotype–phenotype associations ClinVar, MAF minor allele frequency, New new variant detected in this study, NA not available
- aAge of proband at last clinical evaluation
- bIn italics, classified in this study according to ACMG Standards and Guidelines; normal, ClinVar last evaluation; VUS, variant of uncertain significance
- cBest’s disease stages of left (LE) and right eye (RE) as diagnosed in probands at the age of last clinical evaluation (stages 1 to 5)
- dBCVA (best-corrected visual acuity) in logMAR scale (logarithm of Minimum Angle of Resolution), logMAR 0/0 (LE/RE) indicates standard vision, logMAR > 0.5/0.5 indicates low vision, logMAR > 1.3/1.3 m indicates blindness
- * Family segregation analysis