NM_000295.5(SERPINA1):c.1097A>G (p.Glu366Gly) AND Alpha-1-antitrypsin deficiency

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: May 10, 2022
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:: RCV002786692.3

Allele description [Variation Report for NM_000295.5(SERPINA1):c.1097A>G (p.Glu366Gly)]

NM_000295.5(SERPINA1):c.1097A>G (p.Glu366Gly)

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

14q32.13

Genomic location:

Preferred name:

NM_000295.5(SERPINA1):c.1097A>G (p.Glu366Gly)

HGVS:

NC_000014.9:g.94378609T>C
NG_008290.1:g.17084A>G
NM_000295.5:c.1097A>GMANE SELECT
NM_001002235.3:c.1097A>G
NM_001002236.3:c.1097A>G
NM_001127700.2:c.1097A>G
NM_001127701.2:c.1097A>G
NM_001127702.2:c.1097A>G
NM_001127703.2:c.1097A>G
NM_001127704.2:c.1097A>G
NM_001127705.2:c.1097A>G
NM_001127706.2:c.1097A>G
NM_001127707.2:c.1097A>G
NP_000286.3:p.Glu366Gly
NP_001002235.1:p.Glu366Gly
NP_001002236.1:p.Glu366Gly
NP_001121172.1:p.Glu366Gly
NP_001121173.1:p.Glu366Gly
NP_001121174.1:p.Glu366Gly
NP_001121175.1:p.Glu366Gly
NP_001121176.1:p.Glu366Gly
NP_001121177.1:p.Glu366Gly
NP_001121178.1:p.Glu366Gly
NP_001121179.1:p.Glu366Gly
LRG_575t1:c.1097A>G
LRG_575:g.17084A>G
LRG_575p1:p.Glu366Gly
NC_000014.8:g.94844946T>C

Protein change:

E366G

Molecular consequence:

NM_000295.5:c.1097A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001002235.3:c.1097A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001002236.3:c.1097A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001127700.2:c.1097A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001127701.2:c.1097A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001127702.2:c.1097A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001127703.2:c.1097A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001127704.2:c.1097A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001127705.2:c.1097A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001127706.2:c.1097A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001127707.2:c.1097A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Alpha-1-antitrypsin deficiency (A1ATD)
Synonyms:: AAT deficiency; A1AT deficiency; Alpha1-Antitrypsin Deficiency
Identifiers:: MONDO: MONDO:0013282; MedGen: C0221757; Orphanet: 60; OMIM: 613490

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Homo sapiens solute carrier family 30 member 8 (SLC30A8), transcript variant 1, ...
Homo sapiens solute carrier family 30 member 8 (SLC30A8), transcript variant 1, mRNA
gi|64762488|ref|NM_173851.2|

Nucleotide
Leviprora inops
Leviprora inops
Leviprora inops (Longhead Flathead), fLevIno1, sequence data

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003033987	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (May 10, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 15978931, 22426792, 23632999, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003033987

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(May 10, 2022)

germline

clinical testing

PubMed (4)
[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	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Alpha1-antitrypsin deficiency.

Stoller JK, Aboussouan LS.

Lancet. 2005 Jun 25-Jul 1;365(9478):2225-36. Review.

PubMed [citation]

PMID:: 15978931

Serum levels and genotype distribution of α1-antitrypsin in the general population.

Ferrarotti I, Thun GA, Zorzetto M, Ottaviani S, Imboden M, Schindler C, von Eckardstein A, Rohrer L, Rochat T, Russi EW, Probst-Hensch NM, Luisetti M.

Thorax. 2012 Aug;67(8):669-74. doi: 10.1136/thoraxjnl-2011-201321. Epub 2012 Mar 16.

PubMed [citation]

PMID:: 22426792

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003033987.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt SERPINA1 protein function. This sequence change replaces glutamic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 366 of the SERPINA1 protein (p.Glu366Gly). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SERPINA1-related conditions. This variant disrupts the p.Glu366 amino acid residue in SERPINA1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 15978931, 22426792, 23632999). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

#	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		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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