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NM_001127701.1(SERPINA1):c.326C>T (p.Thr109Met) AND PI Z(BRISTOL)

Germline classification:
other (1 submission)
Last evaluated:
Jul 15, 2016
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
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:
RCV000019609.3

Allele description [Variation Report for NM_001127701.1(SERPINA1):c.326C>T (p.Thr109Met)]

NM_001127701.1(SERPINA1):c.326C>T (p.Thr109Met)

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.326C>T (p.Thr109Met)
Other names:
T85M; SERPINA1, THR85MET ON M1V
HGVS:
  • NC_000014.9:g.94382912G>A
  • NG_008290.1:g.12781C>T
  • NM_000295.5:c.326C>TMANE SELECT
  • NM_001002235.3:c.326C>T
  • NM_001002236.3:c.326C>T
  • NM_001127700.2:c.326C>T
  • NM_001127701.2:c.326C>T
  • NM_001127702.2:c.326C>T
  • NM_001127703.2:c.326C>T
  • NM_001127704.2:c.326C>T
  • NM_001127705.2:c.326C>T
  • NM_001127706.2:c.326C>T
  • NM_001127707.2:c.326C>T
  • NP_000286.3:p.Thr109Met
  • NP_001002235.1:p.Thr109Met
  • NP_001002236.1:p.Thr109Met
  • NP_001121172.1:p.Thr109Met
  • NP_001121173.1:p.Thr109Met
  • NP_001121174.1:p.Thr109Met
  • NP_001121175.1:p.Thr109Met
  • NP_001121176.1:p.Thr109Met
  • NP_001121177.1:p.Thr109Met
  • NP_001121178.1:p.Thr109Met
  • NP_001121179.1:p.Thr109Met
  • LRG_575t1:c.326C>T
  • LRG_575:g.12781C>T
  • LRG_575p1:p.Thr109Met
  • NC_000014.8:g.94849249G>A
  • NM_000295.4:c.326C>T
  • P01009:p.Thr109Met
Protein change:
T109M; THR85MET
Links:
UniProtKB: P01009#VAR_011620; OMIM: 107400.0040; dbSNP: rs199422213
NCBI 1000 Genomes Browser:
rs199422213
Molecular consequence:
  • NM_000295.5:c.326C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001002235.3:c.326C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001002236.3:c.326C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001127700.2:c.326C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001127701.2:c.326C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001127702.2:c.326C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001127703.2:c.326C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001127704.2:c.326C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001127705.2:c.326C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001127706.2:c.326C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001127707.2:c.326C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
PI Z(BRISTOL)
Identifiers:

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000039907OMIM
no assertion criteria provided
other
(Jul 15, 2016)
germlineliterature only

PubMed (1)
[See all records that cite this PMID]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

A new alpha 1-antitrypsin mutation, Thr-Met 85, (PI Zbristol) associated with novel electrophoretic properties.

Lovegrove JU, Jeremiah S, Gillett GT, Temple IK, Povey S, Whitehouse DB.

Ann Hum Genet. 1997 Sep;61(Pt 5):385-91.

PubMed [citation]
PMID:
9459000

Details of each submission

From OMIM, SCV000039907.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (1)

Description

In a woman with an obstetric history of 3 perinatal deaths from fulminant liver disease and no living offspring, Lovegrove et al. (1997) found that she and her father were both heterozygotes for PI M1Z(Bristol). The Z(Bristol) protein was found to be active as a proteinase inhibitor but appeared to be deficient in the plasma to about the same degree as the S protein in MS heterozygotes. It focused on the basic side of Z and lacked the normal pattern of secondary isoforms associated with the commonly occurring AAT variants and migrated faster than normal on an SDS electrophoresis gel. The Z(Bristol) mutation was found to be a C-to-T transition at codon 85, changing ACG (thr) to ATG (met). This disrupted the N-glycosylation site starting at asn83, preventing glycosylation at residue 83 in the PI Z(Bristol) protein, and explained the protein isoelectric focusing and SDS gel electrophoresis results. An analysis of haplotypes in the propositus and her father indicated that the Z(Bristol) mutation occurred on the common M1(val213) genetic background. Of the 3 offspring with perinatal death from fulminant liver disease, 2 were by the woman's husband and 1 by an artificial insemination donor. Of the 2 offspring who were tested for the mutation, 1 had the variant and the other did not. Thus, the relationship between Z(Bristol) and fulminant liver disease in the offspring was unclear.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot providednot providednot providednot providednot provided

Last Updated: Dec 24, 2023