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Table 2 SERPING1 mutations identified in Chinese HAE patients

From: Mutation update of SERPING1 related to hereditary angioedema in the Chinese population

Region

DNA change

Consequences

Predictive algorithm

Laboratory test

SIFTa

Polyphen-2b

MutationTasterc

Clinical classificationd

No. of patients

C1-INH protein (g/L)e

C4 protein (g/L)f

References

Exon 2

c.1A > G

p.(Met1Val)

0.022

0.941

DC(1)

pxathogenic

1

0.04

0.015

[18]

Exon 2

c.44del

p.(Leu15Argfs*64)

   

likely pathogenic

1

0.04

0.01

[9]

Exon 2

c.49G > A

p.(Gly17Arg)

0.003

0.011

DC(1)

likely pathogenic

2

0.05

0.06

[19]

        

0.16

0.043

 

Exon 3

c.74del

p.(Asn25Metfs*54)

   

pathogenic

1

0.09

0.093

This study

Exon 3

c.100C > A

p.(Pro34Thr)

0.136

0.975

P(1)

VUS

1

0.13

0.053

This study

Exon 3

c.120_121del

Increased exon 3 skipping

   

pathogenic

1

0.04

0.015

[20]

Exon 3

c.172_181del

p.(Pro58Argfs*18)

  

DC(1)

pathogenic

1

0.03

0.006

This study

Exon 3

c.197dup

p.(Thr67Aspfs*15)

   

pathogenic

1

0.05

0.218

This study

Exon 3

c.229A > T

p.(Lys77*)

  

DCA(1)

pathogenic

1

0.04

0.024

This study

Exon 3

c.232del

p.(Ile78*)

   

pathogenic

1

0.03

0.005

This study

Exon 3

c.322C > T

p.(Gln108*)

  

DCA(1)

pathogenic

1

0.04

0.033

[21]

Exon 3

c.377del

p.(Pro126Leufs*22)

   

pathogenic

1

0.11

0.06

This study

Exon 3

c.403_404del

p.(His136Phefs*120)

   

pathogenic

1

0.09

0.094

[11]

Exon 3

c.508 T > C

p.(Ser170Pro)

0

1

DC(1)

pathogenic

1

0.04

0.011

[22]

Exon 3

c.509C > T

p.(Ser170Phe)

0

1

DC(1)

likely pathogenic

1

0.06

0.041

[23]

Exon 3

c.538C > T

p.(Gln180*)

  

DCA(1)

likely pathogenic

1

0.06

0.04

This study

Exon 3

c.550G > T

Exon 3 skipping

0

1

DC(1)

pathogenic

2

0.05

0.002

[20]

        

0.08

0.076

 

Exon 3

c.550G > A

Exon 3 skipping

0

1

DC(1)

pathogenic

1

0.04

0.028

[24]

Intron 3

c.550 + 1G > T

Splicing defect

   

pathogenic

1

0.05

0.016

This study

Intron 3

c.550 + 1G > A

Splicing defect

   

pathogenic

1

0.20

0.046

[25]

Exon 4

c.623dup

p.(Ala209Glyfs*48)

   

pathogenic

1

0.15

0.200

This study

Exon 4

c.635dup

p.(Phe213Leufs*44)

   

pathogenic

1

0.07

0.061

This study

Exon 4

c.666_667del

p.(Gln223Aspfs*33)

   

pathogenic

1

0.06

0.111

[12]

Exon 4

c.669_670del

p.(Gln223Hisfs*33)

   

pathogenic

1

0.05

0.003

[26]

Exon 4

c.673_675del

p.(Phe225del)

   

pathogenic

1

0.08

0.054

This study

Intron 4

c.685 + 1G > T

Splicing defect

   

pathogenic

1

0.04

0.018

[12]

Intron 4

c.686-1G > A

Splicing defect

   

pathogenic

2

0.04

0.030

[27]

        

0.07

0.052

 

Exon 5

c.708 T > G

p.(Phe236Leu)

0.007

0.999

DC(0.907)

likely pathogenic

1

0.12

0.329

This study

Exon 5

c.733_736dup

p.(Ser246Lysfs*12)

   

pathogenic

1

0.05

0.046

This study

Exon 5

c.744_745del

p.(Arg249Serfs*7)

   

pathogenic

2

0.03

0.032

[28]

        

0.03

0.028

 

Exon 5

c.779dup

p.(Leu261Alafs*44)

   

pathogenic

1

0.07

0.059

This study

Exon 5

c.785dup

p.(Asn263Glnfs*42)

   

pathogenic

1

0.07

0.054

This study

Exon 5

c.816_818del

p.(Asn272del)

   

pathogenic

1

0.07

0.025

[29]

Exon 6

c.941_942insTC

p.(Phe315Profs*7)

   

pathogenic

1

0.06

0.058

This study

Exon 6

c.951dup

p.(Ser318Leufs*10)

   

pathogenic

1

0.04

0.014

This study

Exon 6

c.983_984delinsC

p.(Lys328Thrfs*13)

   

pathogenic

1

0.04

0.030

This study

Exon 6

c.1019del

p.(Leu340*)

   

pathogenic

1

0.03

0.002

This study

Intron 6

c.1030-2A > G

Splicing defect

   

pathogenic

1

0.04

0.037

[30]

Exon 7

c.1051del

p.(His351Thrfs*3)

   

pathogenic

1

0.06

0.020

This study

Exon 7

c.1094dup

p.(His365Glnfs*4)

   

pathogenic

2

0.05

0.019

This study

        

0.05

0.073

 

Exon 7

c.1100 T > G

p.(Leu367Arg)

0.001

1

DC(1)

likely pathogenic

1

0.07

0.082

This study

Exon 7

c.1121 T > C

p.(Leu374Pro)

0.006

1

DC(1)

VUS

1

0.07

0.054

ClinVar VCV000426682.2

Exon 7

c.1157_1158del

p.(Leu386Argfs*38)

   

pathogenic

1

0.06

0.024

[30]

Exon 7

c.1186del

p.(Leu396*)

   

pathogenic

1

0.08

0.063

This study

Exon 7

c.1192C > G

p.(Leu398Val)

0.141

0.902

P(1)

likely pathogenic

1

0.09

0.101

This study

Exon 7

c.1193 T > G

p.(Leu398Arg)

0.002

1

P(0.915)

likely pathogenic

1

0.05

0.016

This study

Exon 7

c.1223A > G

p.(Asp408Gly)

0.006

0.999

DC(0.987)

pathogenic

1

0.07

0.022

[31]

Intron 7

c.1249 + 2 T > C

Splicing defect

   

pathogenic

1

0.04

0.034

This study

Intron 7

c.1250-2A > G

Splicing defect

   

pathogenic

1

0.25

0.026

[21]

Exon 8

c.1269 T > A

p.(Tyr423*)

  

DC(1)

pathogenic

1

0.03

0.01

This study

Exon 8

c.1289 T > C

p.(Leu430Pro)

0.001

1

DC(1)

pathogenic

1

0.08

0.071

[12]

Exon 8

c.1289 T > G

p.(Leu430Arg)

0.001

0.999

DC(0.999)

likely pathogenic

1

0.05

0.019

This study

Exon 8

c.1312del

p.(Val438Phefs*12)

   

pathogenic

1

0.05

0.060

[11]

Exon 8

c.1340 T > C

p.(Leu447Pro)

0.001

1

DC(1)

pathogenic

1

0.12

0.142

[26]

Exon 8

c.1342G > T

p.(Glu448*)

  

DC(1)

pathogenic

1

0.05

0.049

[14]

Exon 8

c.1351G > A

p.(Glu451Lys)

0.042

1

DC(1)

pathogenic

1

0.05

0.060

[32]

Exon 8

c.1356_1357del

p.(Val454Glyfs*18)

   

pathogenic

1

0.05

0.018

[33]

Exon 8

c.1373C > T

p.(Ala458Val)

0.004

1

P(0.960)

pathogenic

1

0.13

0.053

[34]

Exon 8

c.1379C > G

p.(Ser460Cys)

0.005

1

P(1)

likely pathogenic

1

0.14

0.044

This study

Exon 8

c.1396C > T

p.(Arg466Cys)

0.003

0.969

DC(1)

pathogenic

1

0.56

0.007

[35]

Exon 8

c.1396C > A

p.(Arg466Cys)

0.013

0.255

DC(1)

pathogenic

1

0.64

0.027

[36]

Exon 8

c.1397G > T

p.(Arg466Leu)

0.007

0.067

DC(1)

pathogenic

1

0.35

0.016

[37]

Exon 8

c.1397G > A

p.(Arg466His)

0.005

0.666

DCA(1)

pathogenic

3

0.37

0.021

[35]

        

0.36

0.043

 
        

0.37

0.015

 

Exon 8

c.1420C > T

p.(Gln474*)

  

DC(1)

pathogenic

1

0.04

0.008

[38]

Exon 8

c.1422G > C

p.(Gln474His)

0.2

0.996

P(0.725)

likely pathogenic

1

0.05

0.009

This study

Exon 8

c.1423C > T

p.(Gln475*)

  

DC(1)

pathogenic

1

0.06

0.109

[38]

Exon 8

c.1424A > C

p.(Gln475Pro)

0.006

0.998

DC(0.961)

likely pathogenic

1

0.09

0.101

This study

Exon 8

c.1425G > T

p.(Gln475His)

0.074

0.174

DC(0.865)

likely pathogenic

1

0.05

0.003

This study

Exon 8

c.1480C > T

p.(Arg494*)

  

DC(1)

pathogenic

7

0.05

0.050

[24]

        

0.06

0.056

 
        

0.05

0.048

 
        

0.07

0.084

 
        

0.08

0.066

 
        

0.05

0.101

 
        

0.05

0.054

 

Exon 8

c.1481G > T

p.(Arg494Leu)

0.004

0.999

DC(0.994)

pathogenic

2

0.05

0.128

[12]

        

0.05

0.011

 

Exon 8

c.1492C > T

p.(Pro498Ser)

0

1

DC(1)

pathogenic

1

0.05

0.031

[24]

Exon 1–2

 

Deletion of exon 1–2

   

pathogenic

1

0.04

0.031

[26]

Exon 3–4

 

Duplication of exon 3–4

   

pathogenic

1

0.05

0.100

This study

Exon 4

 

Deletion of exon 4

   

pathogenic

3

0.04

0.049

[21]

        

0.07

0.045

 
        

0.04

0.018

 

Exon 1–4

 

Deletion of exon 1–4

   

pathogenic

1

0.04

0.058

[39]

Exon 2–4

 

Deletion of exon 2–4

   

pathogenic

1

0.06

0.041

This study

  1. a SIFT® (Sorting Intolerant From Tolerant) is a program that predicts whether an amino acid substitution affects protein function. SIFT scores range from 0.0 (harmful) to 1.0 (tolerable). This score can be interpreted as follows: variants with scores in the range of 0.0 to 0.05 are considered to be harmful
  2. b PolyPhen-2® (Polymorphism Phenotyping v2) is a tool which predicts possible impact of an amino acid substitution on the structure and function of a human protein using straightforward physical and comparative considerations. The score can be interpreted as follows: 0.0 to 0.15 – Variants with scores in this range are predicted to be benign; 0.15 to 1.0 – Variants with scores in this range are possibly damaging; 0.85 to 1.0 – Variants with scores in this range are more confidently predicted to be damaging
  3. c Mutation Taster® is a free web-based application to evaluate DNA sequence variants for their disease-causing potential. In order to predict the potential pathogenicity of an alteration, each variant is distributed between Disease Causing (DC), according to NCBI ClinVar, and Polymorphism (P), according to the 1000 Genomes Project, with corresponding probability in brackets
  4. d Clinical classification is based on the ACMG-AMP criteria for variant classification supporting pathogenicity
  5. eThe normal range of C1-INH protein is 0.21–0.39 g/L
  6. fThe normal range of C4 protein is 0.100–0.400 g/L
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