Table 1.

Molecular, biological and clinical characteristics of the 22 new SERPINA1 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

CRP: C-Reactive Protein

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

^a Normal ranges in serum: A1AT: 0.90–2.00 g/L; SEIC (serum elastase inhibitory capacity): 17,500–31,500 IU/L.

^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

^c ACMG classification: 1 = benign, 2 = likely benign, 3 = uncertain significance, 4 = likely pathogenic, 5 = pathogenic

^d inflammatory electrophoretic profile

*nomenclatura rule for stop codon