Mutation Screening of MED27 in a Large Dystonia Cohort

Table 2

In silico pathogenicity predictions for rare variants in MED27 identified in patients with dystonia.

hgvs_c

hgvs_p

GERP++

Variant-effect predictions software (scores)

SIFT

Polyphen2 HDIV

Polyphen2 HVAR

LRT

Mutation taster

Mutation assessor

FATHMM

MetaSVM

MetaLR

CADD

c.G740A

p.R247H

5.3

0.023

0.999

0.984

0

1

2.24

n.a.

-0.131

0.43

35

D

D

D

D

D

M

n.a.

T

T

D

c.C520G

p.P174A

5.33

0.459

0.939

0.556

0

1

1.555

n.a.

-0.755

0.228

12.59

T

P

P

D

D

L

n.a.

T

T

D

c.C367G

p.P123A

-0.251

n.a.

n.a.

n.a.

n.a.

1

n.a.

n.a.

n.a.

n.a.

2.305

n.a.

n.a.

n.a.

n.a.

N

n.a.

n.a.

n.a.

n.a.

T

c.C358T

p.L120F

-1.69

n.a.

n.a.

n.a.

n.a.

1

n.a.

n.a.

n.a.

n.a.

4.718

n.a.

n.a.

n.a.

n.a.

N

n.a.

n.a.

n.a.

n.a.

T

c.T167G

p.F56C

5.07

0.002

0.999

0.987

0

1

1.735

n.a.

-0.273

0.371

28.2

D

D

D

D

D

L

n.a.

T

T

D

T: tolerated; D: damaging or disease-causing; P: probably pathogenic; N: neutral; M: medium; L: low; B: benign; n.a.: not available. GERP: genomic evolutionary rate profiling; SIFT: sorting intolerant from tolerant; PolyPhen2 HDIV: polymorphism phenotyping version 2 human diversity; PolyPhen2 HVAR: polymorphism phenotyping version 2 human variation; LRT: likelihood ratio test; FATHMM: functional analysis through hidden Markov models; SVM: support vector machine; LR: logistic regression; CADD: combined annotation dependent depletion. Pathogenicity prediction was obtained using ANNOVAR.