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Table 1 Molecular, biological and clinical characteristics of the 22 new SERPINA1 variants

From: Description of 22 new alpha-1 antitrypsin genetic variants

Variant name

NM_000295.4 (24 amino-acids signal peptide included)

Genetic back-ground

Clinical data

Biological data

ACMG scorec

dbSNP or Clinvar ID

Exon (II-V)

c.DNA

AA change

Sex

Age (years)

Circumstance of discovery

Pulmonary/hepatic status

AATa (g/L)

SEICa (IEU/L)

Rb

IEF (PI)

CRP (mg/L)

Genotype

GSaint-sorlin

/

Exon V

1252A > T

Lys418*

M2

34

IgA nephropathy

No

2.06

37,164

1.28

GM3

19

GSaint-sorlin M3

3

M1Brest

rs774775536

Exon IV

962A > G

Tyr321Cys

M1

19

Familial screening

No

0.66

11,020

1.07

MZ

na

M1Brest Z

2

M1Bruxelles

/

Exon II

116A > T

His39Leu

M1

49

Elevated plasma GGT

Cholestasis

0.83

12,423

1.00

Heterogeneous pattern

na

M1Bruxelles ZAugsburg

2

M1Cremeaux

/

Exon V

1074 T > A

His358Gln

M1

39

Abnormal serum protein electrophoretic pattern

No

0.23

na

na

na

na

M1Cremeaux Z

5

19

Familial screening

No

1.01

na

na

na

na

M1Cremeaux M1

37

Familial screening

No

0.88

11,120

0.83

na

na

M1Cremeaux M2

15

Familial screening

No

na

na

na

na

na

M1Cremeaux M1

M1Lille

rs141095970

Exon III

879C > A

His293Gln

M1

33

Hepatic cytolysis Cholestasis, SLE

Cirrhosis

1.45

21,625

1.06

M

<  3

M1Lille M1

2

M1Lyon

rs141620200

Exon IV

922G > T

Ala308Ser

M1

10

Cystic fibrosis

Liver transplant

1.66

na

na

na

na

M1Lyon Z

2

40

Familial screening

No

1.15

16,165

0.96

M1S

na

M1Lyon S

7

Familial screening

No

1.14

14,172

0.85

M1 M2

na

M1Lyon M2

15

Immune deficiency

No

1.38

19,240

0.99

M

na

M1Lyon M1

79

na

Emphysema

2.35

32,937

1.03

M

na

M1Lyon M1

79

na

Bronchiectasis

2.20

28,510

0.95

M

na

M1Lyon M1

36

Fertility tests

No

0.70

9556

0.88

MZ

na

M1Lyon Z

46

Familial screening

No

0.82

11,190

0.90

MZ

na

M1Lyon Z

MRouen

rs764726147

Exon II

188G > A

Arg63His

M1/M2

45

Familial screening

No

na

na

na

na

na

MRouen M1 or MRouen M2

3

M1Saint-rambert

/

Exon II

356G > T

Gly119Val

M1

73

Solitary bone plasmocytoma

No

1.63

21,879

0.94

M1

17

M1Saint-rambert M1

2

M1

37

na

No

na

na

na

ni

na

M1Saint-rambert M2

OThonon-les-bains

rs759578830

Exon II

547G > A

Asp183Asn

M1

43

Irritable Bowel syndrome

No

1.30

15,521

0.82

M2O

5

M2 OThonon-les-bains

2

PLoyettes

rs766260108

Exon III

734 T > C

Met245Thr

M1

71

CLL and type 2 diabetes

No

1.26

11,347

0.62

PS

23

PLoyettes S

4

PSolaize

RCV000206568.1

Exon III

735G > A

Met245Ile

M2

18

Crohn’s disease

No

1.26

14,318

0.79

M3Pfast

d

M3 PSolaize

4

SRoubaix

rs11575873

Exon II

211A > C

Ser71Arg

M1

69

Cholestasis

HCV Cirrhosis

1.29

18,314

1.00

MS

60

M2 SRoubaix

2

WSaint-Avre

rs537285845

Exon II

436G > A

Glu146Lys

M1

34

Abnormal serum protein electrophoretic pattern

No

0.82

9871

0.80

ni

na

WSaint-Avre Z

3

M1

8

Biliary atresia

Pre-liver transplant data, probably on inflammatory status

1.47

na

na

M1W

na

M1 WSaint-Avre

WVernaison

/

Exon II

449 T > G

Leu150Arg

M1

80

MALT lymphoma

Sjogren’s syndrome

Systemic necrotizing vasculitis

No

1.10

12,376

0.79

SW

35

S WVernaison

4

XCuris

rs755851961

Exon III

811A > G

Asn271Asp

M1

21

Cystic fibrosis

No

1.34

24,121

1.24

M2X

2

M2 XCuris

2

Q0Achicourt

rs750779440

Intron 3

917 + 1G > A

/

S

59

Dyspnea

Emphysema

< 0.10

2045

ns

No band

<  3

Q0Achicourt Q0Clayton

5

Q0Amiens

rs781591420

Intron 4

1065 + 1G > A

/

M1

81

Abnormal serum protein electrophoretic pattern

No

1.18

17,419

1.03

M

na

M1 Q0Amiens

5

35

Neutropenia

No

0.76

11,741

1.01

M

<  3

M3 Q0Amiens

Q0Casablanca

RCV000408906.1

Exon II

288_291del

His97Metfs*7

M2

21

Neutropenia

Bronchiectasis

< 0.10

3747

ns

No band

15

Q0Casablanca homozygous

5

Q0Lille

Z

36

Pneumothorax

Recurrent pneumothorax

1.40

19,317

0.98

M

231

M1 Q0Lille

5

Q0Montluel

rs760849035

Exon V

1237_1239del

Val413*

M1

51

Thrombophilia screening

No

0.66

7547

0.72

M1

5

M1 Q0Montluel

5

Q0Saint-Avold

/

Intron 3

918 – 1G > A

/

M1

63

na

Emphysema

0.21

5898

1.30

Z

na

Q0Saint-Avold Z

5

Q0Saint-Etienne

/

Exon II

559A > T

Lys187*

M4

25

AATD familial screening

No

0.74

6647

0.58

M3

na

M3 Q0Saint-Etienne

5

  1. CRP: C-Reactive Protein
  2. na not available, ni not interpretable (unusual IEF pattern), ns not significant, CLL chronic lymphocytic leukemia, GGT gamma-glutamyl transpeptidase, HCV hepatitis C virus, MALT mucosa-associated lymphoid tissue, SLE Systemic lupus erythematosus
  3. a Normal ranges in serum: A1AT: 0.90–2.00 g/L; SEIC (serum elastase inhibitory capacity): 17,500–31,500 IU/L.
  4. b R = measured SEIC / expected SEIC; expected SEIC is based on the correlation between the measured SEIC and the corresponding AAT level according to the following linear relationship established from 10,863 individuals: SEIC (IU/L) = 12,784 x A1AT (g/L) + 1855. Measured SEIC< 17,500 IEU/L and/or R < 0.8 may result from A1AT functional deficiency
  5. c ACMG classification: 1 = benign, 2 = likely benign, 3 = uncertain significance, 4 = likely pathogenic, 5 = pathogenic
  6. d inflammatory electrophoretic profile
  7. *nomenclatura rule for stop codon