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Table 3 Non-synonymous SNPs predicted to impact protein function either by Polyphen-2, SIFT or PROVEAN

From: Non-synonymous genetic variation in exonic regions of canine Toll-like receptors

Canine gene

Position

SNP

dbSNP ID

AA Subst

Protein domain a

Polyphen-2 result

SIFT result

Provean result

Variant freq (dog) b

Variant freq (wolf) b

EXTRACELLULAR TLRs

TLR1

3:73542337

G/T

rs23585044

S29I

ncp

Pos. damaging

Tolerated

Neutral

0,36

0,77

 

3:73543092

T/G

new

S281A

ncp

Pos. damaging

Tolerated

Neutral

0,06

0,00

 

3:73543825

C/T

new

A525V

LRRCT2

Pos. damaging

Tolerated

Deleterious

0

0,11

TLR2

15:51463020

C/A

rs22410121

S46Y

ncp

Pos. damaging

Tolerated

Neutral

0,10

0,00

 

15:51464430

C/T

new

S516L

ncp

Prob. damaging

Aff. function

Deleterious

0,14

0

TLR3

16:44623632

C/G

new

E176D

ncp

Pos. damaging

Tolerated

Neutral

0,16

0,12

TLR4

11:71356420

C/T

reference1

A8V

ncp

Prob. damaging

Tolerated

Neutral

0,77

0,57

 

11:71360887

G/A

new

V82M

ncp

Pos. damaging

Tolerated

Neutral

0,09

0,15

 

11:71364581

T/C

rs22145736

L167P

ncp

Prob. damaging

Aff. function

Deleterious

0,15

0

 

11:71364681

A/C

reference1

Q200H

ncp

Pos. damaging

Aff. function

Neutral

0,88

0,23

 

11:71365810

A/G

new

T577A

LRRCT3

Pos. damaging

Aff. function

Neutral

0,01

0

TLR5

38:23702837

C/T

rs9070447

R269C

ncp

Prob. damaging

Aff. function

Neutral

0,19

0,01

 

38:23702918

G/A

new

V296I

ncp

Pos. damaging

Tolerated

Neutral

0,05

0,26

 

38:23703629

G/A

new

G533S

ncp

Prob. damaging

Tolerated

Neutral

0,02

0

 

38:23704331

G/T

new

D767Y

ncp

Prob. damaging

Tolerated

Deleterious

0,04

0

 

38:23704531

C/G

new

N833K

LRRCT

Pos. damaging

Tolerated

Deleterious

0

0,06

 

38:23704562

C/T

new

R844C

LRRCT

Pos. damaging

Tolerated

Neutral

0,04

0,39

 

38:23704581

C/T

reference 1

S850L

LRRCT

Prob. damaging

Aff. function

Deleterious

0,68

0,02

 

38:23704695

T/G

new

F888C

low complexity

Prob. damaging

Aff. function

Deleterious

0,04

0

 

38:23705081

C/T

new

H1017Y

TIR

Benign

Aff. function

Neutral

0,02

0

 

38:23705264

G/A

new

A1078T

TIR4

Pos. damaging

Aff. function

Neutral

0,07

0,00

TLR6

3:73521250

A/G

new

Y182C

ncp

Prob. damaging

Tolerated

Deleterious

0,01

0,09

 

3:73522074

C/T

new

L457F

ncp

Prob. damaging

Aff. function

Deleterious

0,03

0

 

3:73522242

G/A

rs23570247

D513N

ncp

Pos. damaging

Tolerated

Neutral

0,73

1,00

 

3:73522441

C/T

new

P579L

LRRCT

Pos. damaging

Aff. function

Deleterious

0,01

0,07

TLR10

3:73569402

C/T

rs23518574

T361M

ncp

Prob. damaging

Aff. function

Deleterious

0,13

0,12

 

3:73570681

T/A

new

F787L

TIR5

Pos. damaging

Low confidence

Neutral

0,00

0,39

INTRACELLULAR TLRs

TLR8

X:9397240

T/C

new

V157A

ncp

Pos. damaging

Aff. function

Deleterious

0,06

0

TLR9

20:37544129

G/A

new

V87I

ncp

Benign

Aff. function

Neutral

0,02

0

 

20:37546230

C/T

new

P787L

ncp

Pos. damaging

Tolerated

Neutral

0,22

0,24

 

20:37546454

C/T

new

R862W

ncp

Prob. damaging

Tolerated

Neutral

0,2

0

  1. In italics, SNPs that are predicted to have an effect on protein function by the three algorithms. ancp, no confident prediction. bObserved frequency by massive sequencing. 1reference allele tested as the alternative in the SNP. 2Leucine Rich Repeat C-terminal (LRRCT) domain predicted from aminoacid 528 to 582. 3LRRCT domain predicted from aminoacid 579 to 629. 4TIR domain predicted from aminoacid 927 to 1074. 5TIR domain predicted from aminoacid 641 to 784.