Protein modeling to assess the pathogenicity of rare variants of SERPINA1 in patients suspected of having Alpha 1 Antitrypsin Deficiency

Kueppers, Friedrich; Andrake, Mark D.; Xu, Qifang; Dunbrack, Roland L.; Kim, Joannah; Sanders, Christopher L.

doi:10.1186/s12881-019-0852-5

Table 1 Overview of patient characteristics and rare/novel sequence variants identified by next-generation sequencing

From: Protein modeling to assess the pathogenicity of rare variants of SERPINA1 in patients suspected of having Alpha 1 Antitrypsin Deficiency

Patient ID	AAT serum level (mg/dL)	CRP (mg/dL)	Previous phenotypes	Age (yrs)	Sex	NGS DNA analysis
Patient ID	AAT serum level (mg/dL)	CRP (mg/dL)	Previous phenotypes	Age (yrs)	Sex	Novel mutant nucleotide changes	Consequence	Genotype
Splice variants
2250	70	5.9	–	65	F	Novel splice variant: G > C at position +1 of intron 1C		E376D – M3 allele
24023	62.8	–		71	M	917 + 1G > A	Affects the normal mRNA splicing.	E376D – M3 allele
Deletions
10724	52	7.3	M3	49	M	A347fs: Novel 1 bp deletion (1112delC) at position 347	Frameshift that extends the protein by 5 amino acids	E376D – M3 allele
Stop codons
6326^e	2	0	Z/M1	57	F	Q156X: C > T at Chr14:94849037 (GRCh.37.p13) c.538C > T	Insertion of stop codon at position 156	Q156X E342K – Z allele V213A – M1 allele
6376^e	98	7	I	54	M	Q156X: C > T at Chr14:94849037 (GRCh.37.p13) c.538C > T	Insertion of stop codon at position 156	Q156X R39C – I allele
19771	91.4	–	M	57		G192Fs: 1 bp deletion at Chr14:94847477 (GRCh37.p13) c.647_647delG	Predicted to produce a premature stop codon at amino acid 214, leading to a premature termination on exon III
Single-nucleotide variations
CA97	112	–	M3 M2/4	65	F	GAG > AAG		E204K – rare^a E376D – M3 allele R101H – M2/M4 allele
1144	72	–	M1	61	M	CCC > TCC		P289S – rare^a V213A – M1 allele
2343	86	3.6	M1	60	F	ATC > AAC		I9N [includes precursor] – rare^a V213A – M1 allele
4293^d	66	0.5	M1	54	M	CCC > CTC	Q_0Bellingham – insertion of stop codon at position 156	P28L – rare^a K217X – Q0_Bellingham V213A – M1 allele
5564^d	67	1.6	M1	51	F	CCC > CTC	Q_0Bellingham – insertion of stop codon at position 156	P28L – rare^a K217X – Q0_Bellingham V213A – M1 allele
4668	78	2.2	M3	62	M	ATC > AAC		I50N (Pi_Tijarafe) – rare E376D – M3 allele
9533	73	0.9	–	60	M	ATG > ACG		M385 T – rare^c M allele
10889	–	12.5	M3	34	F	CAG > CGG		Q40R – rare^a E376D – M3 allele
12642	89	0.6	M3	66	F	GAC > CTC		D341V – rare^b E376D – M3 allele P = L118 – no amino acid change
14271	47	0.6	Z/M1	61	F	ATG > ACG		M221 T – rare^a V213A – M1 allele E342K – Z allele
15230	34	1	Z/M1	72	M	GTG > GAG		V210E (N_cambodia/Pierre-bénite) – rare^a V213A – M1 allele E342K – Z allele
17,657	160	1.5	M3/M4	87	M	AAG > GAG		K174E – NOVEL^a E376D – M3 allele R101H – M2/M4 allele
21034	121.2	–	–	47	F	CCC > CAC		P369H – rare E264V – S allele
21636	88.4	–	–	58	M	GTG > ATG		V333 M – rare^c E376D – M3 allele R101H – M4 allele
23523	118.6	–	–	48	F	GCA > CCA		A325P (Nvestenanova) – rare^a R223C – F allele E376D – M3 allele R101H – M4 allele
24319	79.3	–	–	57	F	GCC > GAC		A142D – rare^c E264V – S allele V213A – M1 allele
76430	74.8	–	–	59	M	CAC > TAC		H262Y – rare^c M allele

All SNVs are reported without the 24 amino acid precursor unless otherwise stated
^aSNVs have been previously reported in dbSNP (E204K – rs199422208; P289S – rs779938258; Q40R – rs763483402; M221 T – rs766260108; K174E – rs766034720; I9N [includes precursor] – rs1296175763; P28L – rs944607375)
^bSNVs have been previously reported in dbSNP and linked to AATD (D314V – rs864622046)
^cSNV previously reported in the literature (20–26) (H262Y – rs149537225; V333 M – 373,630,097; A142D – rs142942004; V210E – rs746197812; M385 T – rs1488213352; A325P – rs376024688; I50N – rs1275309068)
^dFamilial samples from brother (4293) and sister (5564)
^eFamilial samples from brother (6376) and sister (6326)
bp Base pair, dbSNP Database of single nucleotide polymorphisms, SNV Single nucleotide variation

Back to article page

ISSN: 1471-2350

Contact us

General enquiries: ORSupport@springernature.com

BMC Medical Genetics

Contact us