Rare variants in alpha 1 antitrypsin deficiency: a systematic literature review

Table 2 Summary of rare AATD variants by geographic region

	Africa		Asia		Europe		North America		South America		Oceania		Worldwide
Total number of rare variants identified¹	264		338		3419		3481		11		118		7631
Total number of rare variant types	22		39		133		95		6		11		216
Number of countries	17		18		35		5		3		2		80
Number of articles²	39		95		525		228		15		22		864³
Variant, number of reports⁴
Top 20 most common rare variants⁵	*Q0/rare	120	S_Iiyama	72	*Q0/rare	744	F	729	I	5	*Q0/rare	38	*Q0/rare	1492
	St. Albans	24	F	69	F	435	*Q0/rare	569	*Q0/rare	2	F	33	F	1281
	V	22	E_Tokyo	55	M_N^†	377	C^†	441	AN^†	1	I	15	I	699
	F	14	M_Nichinan	20	I	293	E^†	420	F	1	G^†	11	E^†	446
	W_San^†	12	*Q0/rare	19	M_Malton	251	I	374	M_Nichinan	1	W^†	9	C^†	442
	L^†	10	X	15	P_Lowell	132	P^†	158	P_Lowell	1	Q0_Bellingham	4	M_N^†	377
	M_Malton	10	I	11	Q0_Ourém	110	G^†	125			N_Adelaide^†	3	M_Malton	355
	P^†	10	V	11	M_Heerlen	92	M_Malton	91			P_Lowell	2	P^†	221
	S_Berber^†	10	Q0_Clayton	7	M_Procida	74	L^†	62			Christchurch	1	P_Lowell	157
	Q0_Cairo	8	N_Nagato	6	V	74	V	41			E_Franklin^†	1	V	148
	M_Würzburg	5	P_Lowell	4	M_Palermo	71	X	30			N^†	1	G^†	118
	T	5	P_Weishi^†	4	M_Würzburg	55	D^†	28					Q0_Ourém	121
	W^†	3	X_Christchurch	4	P^†	52	M_Heerlen	26					M_Heerlen	118
	E_Johannesburg	2	M_Malton	3	M_Whitstable	49	Q0_Bellingham	24					M_Procida	87
	R^†	2	M_Toyoura^†	3	X	39	Z_Pratt^†	21					X	84
	Christchurch	1	N^†	3	Q0_Bellingham	28	P_Lowell	17					L^†	83
	E_Tripoli^†	1	Pittsburgh	3	E^†	25	Q0_Cardiff	17					S_Iiyama	74
	I	1	P_Oki^†	3	P_Brescia	25	M_Lamb^†	16					M_Palermo	73
	M_Gam^†	1	S_Hangzhou	3	I1^†	23	Q0_{Granite Falls}	15					M_Würzburg	64
	N^†	1	M_Hailin^†	2	M_Cagliari	23	T	15					E_Tokyo	56

¹The total number of rare variants identified is comparable to the number of individuals in which the rare variants were identified, as most individuals were reported as heterozygous for rare variants
²A total of 983 articles met the inclusion criteria and 864 articles contained useful information on AAT/AATD variants (shown in Additional file 1: Table S1). Several articles contained useful information from more than one study population/geographical region; the number of articles identified in each country is shown in Additional file 1: Table S2
³A total of 864 articles contained useful information on AATD variants, including normal M and Z/S variants. However, only 402 articles contained information on rare pathogenic variants
⁴Reported variants listed by worldwide variant numbers are shown in Additional file 1: Table S3
⁵A full list of all rare variants reported by geographical region is shown in Additional file 1: Table S4; these variants are listed by variant numbers in Additional file 1: Table S5 and listed by individual countries in Additional file 1: Table S6
*Q0/rare = unidentified Null or rare variant at the time of source article publication
^†Protein variants identified by IEF; all other variants were genetically identified

ISSN: 1750-1172