NM_001127701.1(SERPINA1):c.1096G>A (p.Glu366Lys) AND Chronic obstructive pulmonary disease

Germline classification:: risk factor (1 submission)
Last evaluated:: Mar 4, 2020
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001195107.13

Allele description [Variation Report for NM_001127701.1(SERPINA1):c.1096G>A (p.Glu366Lys)]

NM_001127701.1(SERPINA1):c.1096G>A (p.Glu366Lys)

Gene:

SERPINA1:serpin family A member 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

14q32.13

Genomic location:

Preferred name:

NM_001127701.1(SERPINA1):c.1096G>A (p.Glu366Lys)

Other names:

E342K; Z allele; PI Z(AUGSBURG); PI Z(TUN); PI*Z; SERPINA1, GLU342LYS ON M1A; SERPINA1, GLU342LYS ON M2; Z; p.E366K

HGVS:

NC_000014.9:g.94378610C>T
NG_008290.1:g.17083G>A
NM_000295.5:c.1096G>AMANE SELECT
NM_001002235.3:c.1096G>A
NM_001002236.3:c.1096G>A
NM_001127700.2:c.1096G>A
NM_001127701.2:c.1096G>A
NM_001127702.2:c.1096G>A
NM_001127703.2:c.1096G>A
NM_001127704.2:c.1096G>A
NM_001127705.2:c.1096G>A
NM_001127706.2:c.1096G>A
NM_001127707.2:c.1096G>A
NP_000286.3:p.Glu366Lys
NP_000286.3:p.Glu366Lys
NP_001002235.1:p.Glu366Lys
NP_001002236.1:p.Glu366Lys
NP_001121172.1:p.Glu366Lys
NP_001121173.1:p.Glu366Lys
NP_001121173.1:p.Glu366Lys
NP_001121174.1:p.Glu366Lys
NP_001121175.1:p.Glu366Lys
NP_001121176.1:p.Glu366Lys
NP_001121177.1:p.Glu366Lys
NP_001121178.1:p.Glu366Lys
NP_001121179.1:p.Glu366Lys
LRG_575t1:c.1096G>A
LRG_575:g.17083G>A
LRG_575p1:p.Glu366Lys
NC_000014.8:g.94844947C>T
NM_000295.4:c.1096G>A
NM_000295.5:c.1096G>A
NM_001002235.2:c.1096G>A
NM_001127701.1:c.1096G>A
P01009:p.Glu366Lys

Protein change:

E366K; Glu342Lys

Links:

Genetic Testing Registry (GTR): GTR000006840; UniProtKB: P01009#VAR_007004; OMIM: 107400.0011; OMIM: 107400.0028; dbSNP: rs28929474

NCBI 1000 Genomes Browser:

rs28929474

Molecular consequence:

NM_000295.5:c.1096G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001002235.3:c.1096G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001002236.3:c.1096G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001127700.2:c.1096G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001127701.2:c.1096G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001127702.2:c.1096G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001127703.2:c.1096G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001127704.2:c.1096G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001127705.2:c.1096G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001127706.2:c.1096G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001127707.2:c.1096G>A - missense variant - [Sequence Ontology: SO:0001583]

Functional consequence:

effect on catalytic protein function [Variation Ontology: 0008]

Observations:

Condition(s)

Name:: Chronic obstructive pulmonary disease
Synonyms:: Chronic pulmonary obstruction
Identifiers:: MONDO: MONDO:0005002; MedGen: C0024117; OMIM: 606963; Human Phenotype Ontology: HP:0006510

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000200303	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	risk factor (Mar 4, 2020)	germline	clinical testing	PubMed (15) [See all records that cite these PMIDs] 9195389, 21960536, 26987331, 26831755, 14522813, 26672964, 26304913, 15454649, 22912729, 26243289, 24518491, 22971141, 24428606, 21637600, 24033266

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000200303

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(LMM Criteria)

risk factor
(Mar 4, 2020)

germline

clinical testing

PubMed (15)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	13	13	not provided	not provided	not provided	clinical testing

Citations

PubMed

Review: alpha 1-antitrypsin deficiency associated liver disease.

Qu D, Teckman JH, Perlmutter DH.

J Gastroenterol Hepatol. 1997 May;12(5):404-16. Review.

PubMed [citation]

PMID:: 9195389

A review of α1-antitrypsin deficiency.

Stoller JK, Aboussouan LS.

Am J Respir Crit Care Med. 2012 Feb 1;185(3):246-59. doi: 10.1164/rccm.201108-1428CI. Epub 2011 Sep 29. Review.

PubMed [citation]

PMID:: 21960536

See all PubMed Citations (15)

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000200303.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	13	not provided	not provided	clinical testing	PubMed (15)

Description

SERPINA1 c.1096G>A (p.Glu366Lys, commonly known as Z allele or PiMZ) has been associated with increased risk for chronic obstructive pulmonary disease (COPD). This variant has been observed in multiple ethnic backgrounds with highest frequencies in individuals of European non-Finnish ancestry (1.8%, Genome Aggregation Database (gnomAD); rs28929474) and is present in ClinVar (ID: 17967). Large meta-analyses have reported odds ratios of 2.31-3.54 (OR= 2.31 95% CI [1.60-3.35], Hersh 2004, OR=3.54 95% CI [2.14-5.85] Topic 2012) developing COPD in individuals who are heterozygous for this variant. In vitro functional studies provide some evidence that the p.Glu366Lys variant may impact protein function (Fregonese 2008). In summary, this variant is an established risk factor for COPD. SERPINA1 c.1096G>A (p.Glu366Lys, commonly known as Z allele or PiZZ and historically reported as p.Glu342Lys) has been associated with increased risk for chronic obstructive pulmonary disease (COPD). This variant has been observed in multiple ethnic backgrounds with highest frequencies in individuals of European non-Finnish ancestry (1.8%, Genome Aggregation Database (gnomAD); rs28929474) and is present in ClinVar (ID: 17967). A large meta-analysis has reported an odds ratio of 42.42 [95% CI 4.41â€“332.55] (Topic 2012) for developing COPD in individuals who are homozygous for this variant. In vitro functional studies provide some evidence that the p.Glu366Lys variant may impact protein function (Fregonese 2008). In summary, this variant is an established risk factor for COPD.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		13	not provided	13	not provided

Last Updated: Dec 14, 2024

ClinVar

Relating variation to medicine