SERPINA1 E288V - GET-Evidence

Note: This variant has not been sufficiently evaluated by a GET-Evidence editor.

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Curation:

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Currentness:

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SERPINA1 E288V

(SERPINA1 Glu288Val)


You are viewing an old version of this page that was saved on January 13, 2010 at 11:35am by Abraham Rosenbaum.

Short summary

This variant represents the PiS variant in alpha-1-antitrypsin deficiency where a homozygous individual has 60% enzymatic activity.

Variant evidence
Computational -
Functional -
Case/Control -
Familial -
 
Clinical importance
Severity -
Treatability -
Penetrance -
 

Impact

Insufficiently evaluated pathogenic

(The "insufficiently evaluated" qualifier is assigned automatically based on the above evidence and importance scores.)

Inheritance pattern

recessive

Summary of published research, and additional commentary

E288V and E366K comprise the PiS and PiZ variants of Alpha 1-antitrypsin. An individual heterozygous or homozygous at these two positions is at increased risk for Alpha-1-antitrypsin deficiency.

Allele frequency

  • A @ chr14:94847262: 3.0% (328/10758) in EVS
  • A @ chr14:93917014: 4.7% (6/128) in GET-Evidence
  • Frequency shown in summary reports: 3.0% (328/10758)

Publications
 

Fregonese L, Stolk J. Hereditary alpha-1-antitrypsin deficiency and its clinical consequences. Orphanet J Rare Dis. 2008 Jun 19;3:16. Review. PubMed PMID: 18565211; PubMed Central PMCID: PMC2441617.

This variant represents the PiS variant in alpha-1-antitrypsin deficiency where a homozygous individual has 60% enzymatic activity.

Genomes
 

Edited in this revision:

hu43860C - CGI sample GS00253-DNA_A01_200_37
het A @ chr14:94847262

This individual has the PiSZ genotype, placing him at increased risk for Alpha-1-antitrypsin deficiency. Smoking and alcohol consumption should be limited.

Other external references
 

    dbSNP
  • rs17580
    www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi
    PolyPhen-2
  • Score: 0.995 (probably damaging)
    Web search results (8 hits -- see all)
  • An Improved Approach to Diagnosis of α α 1-Antitrypsin Deficiency
    for glutamic acid at codon 288 (E288V). This change. results in intracellular A1AT ... gene=serpina1;jsessionid=2F91D1EF6AADE481D03 BCC3F3BA8B429 ...
    mayomedicallaboratories.com/.../communique/mc2831-1006.pdf
  • Table 3
    AAT (SERPINA1) dbSNP rs# SNP. amino acid. Control. Lung Disease. Power to detect 2× increase ... E288V. 5/190 (0.03) 4/190 (0.02) 0.1. Exon 4. rs28929474. 1096G/A. E366K. 4 ...
    www.jnrbm.com/content/5/1/5/table/T3
  • Journal of Negative Results in BioMedicine
    individuals of the AAT S allele (E288V) are not at risk for. emphysema but compound ... (SERPINA1) dbSNP rs# SNP. amino acid. Control. Lung Disease. Power to ...
    www.biomedcentral.com/content/pdf/1477-5751-5-5.pdf
  • Genetic polymorphisms and susceptibility to lung disease
    LeeLPaulineplee@scripps.eduWestCarolcwest@scripps.eduCrainKarenkcrain@scripps. ... individuals of the AAT S allele (E288V) are not at risk for emphysema but ...
    www.biomedcentral.com/content/download/xml/1477-5751-5-5.xml
  • Table 3 Text
    member 1" 24 rs1303 SERPINA1 5265 14 93914596 NM_000295 NP_000286 G/T E400D ... rs1303 SERPINA1 5265 14 93914596 NM_000295 NP_000286 G/T E400D plus 16651029 ...
    icr.ac.uk/research/research_sections/.../2842.txt
  • Molekulaargeneetilised uuringud sisekliinikus
    AAT puudulikkuse põhjuseks on SERPINA1 (anti-elastaasi, antitrüpsiini) geeni mutatsioonid; ... PI*S (p.E288V) – kliiniliselt oluline vaid olulise AAT languse ...
    elmy.ee/public/files/T.Kahre - Geneetilised uuringud sise...
  • Type II- 95%
    Gene name SWISS-PROT ID Variant site Phosphorylation site SWISS-PROT ... CK2 (0.555) Polymorphism (dbSNP:rs17655) 8483504 OR5I1 Q13606 F76S 75 VAR_024101 ...
    nih.go.kr/phosphovariant/html/family_whole/TypeII-_95.txt
  • Real time PCR detection of the PI*Z and PI*S mutations ...
    Mutations in the SERPINA1 gene can result in both early onset chronic ... glutamic acid to valine substitution at amino acid 288 (E288V; rs17580) [13, 14] ...
    www.ncbi.nlm.nih.gov/pmc/articles/PMC2780033

Other in silico analyses
 

  • NBLOSUM100 score = 5
  • GET-Evidence autoscore = 5

Edit history
 

Gene search

"GENE" or "GENE A123C":

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