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Table 3 Rare non-synonymous CLU variants identified in Stage II Lille and Toronto AD cohorts.

From: Both common variations and rare non-synonymous substitutions and small insertion/deletions in CLU are associated with increased Alzheimer risk

Stage II: Lille AD cohort

       

Gene locationa

DNAb

Proteinc

dbSNP

Total number

MAF AD

MAF C

Protein location

PolyPhen (PSIC)

SIFT

Exon 5

c.908insA

p.I303NfsX13

 

1

0.0004

 

β-chain

  

Exon 6

c.1012C > T

p.R338W

 

1

0.0004

 

β-chain

probable (2.37)

not tolerated (0.00)

Exon 7

c.1105A > C

p.N369H

rs9331936

6

0.0023

 

β-chain

possible (1.56)

tolerated (0.15)

Exon 8

c.1333_1341del

p.T445_D447del

 

3

0.0011

 

β-chain

  

Exon 8

c.1343C > T

p.S448L

rs13494

1

0.0004

 

β-chain

benign (0.73)

tolerated (0.23)

Exon 8

c.1358G > A

p.G453S

rs34627536

1

0.0004

 

β-chain

benign (0.39)

 

Exon 5

c.965T > C

p.P322L

 

5

0.0015

(4 AD)

0.0008

(1 C)

β-chain

possible (1.96)

tolerated (0.25)

Exon 7

c.1138G > A

p.D380N

rs9331938

5

0.0015

(4 AD)

0.0008

(1 C)

β-chain

benign (0.32)

tolerated (0.36)

Exon 7

c.1310G > A

p.R437Q

 

1

 

0.0008

β-chain

benign (0.700)

 

Stage II: Toronto AD cohort

       

Gene location a

DNA b

Protein c

dbSNP

Total Number

MAF AD

MAF C

Protein location

PolyPhen (PSIC)

SIFT

Exon 7

c.1138G > A

p.D380N

rs9331938

1

0.0016

 

β-chain

benign (0.322)

tolerated (0.36)

Exon 8

c.1333_1341del

p.T445_D447del

 

1

0.0016

 

β-chain

  

Exon 7

c.1105A > C

p.N369H

rs9331936

3

0.0033

(2 AD)

0.0022

(1 C)

β-chain

possibly (1.557)

tolerated (0.15)

Exon 8

c.1343C > T

p.S448L

rs13494

3

0.0033

(2 AD)

0.0022

(1 C)

β-chain

benign (0.73)

tolerated (0.23)

  1. aGene location position according to the longest CLU transcript with 9 coding exons [NM_001831.2], bNumbering according to CLU mRNA sequence starting at the A of the ATG translation initation codon in the reference sequence [GenBank accesion number NM_001831.2], cNumbering according to CLU protein sequence [GenPept accession number NP_001822.2]; MAF = Minor Allele Frequency, calculated upon the minimum number of successful sequences (Lille cohort: 2650 patient and 1214 control alleles; Toronto cohort: 608 patient and 462 control alleles). Prediction of pathogenicity of missense mutations was performed using in silico programs PolyPhen (benign/possibly damaging/probably damaging) and SIFT (tolerated/not tolerated).