LPL N318S - GET-Evidence

Curation:
Currentness:

LPL N318S

(LPL Asn318Ser)


Short summary

Also called N291S, this variant has been associated with high hypertriglyceridemia. According to data from Wright et al., carriers of this variant may be two to three times more likely to have very high triglyceride levels, although it is unknown what effect this may have on coronary heart disease.

Variant evidence
Computational -1

Polyphen 2 predicts benign effect

Functional -
Case/Control 4

p = 0.00039

See Wright WT et al. 2008 (18068174).

Familial -
 
Clinical importance
Severity 3

May be associated with coronary artery disease

Treatability 4

May be treatable with dietary and drug interventions

Penetrance 3

Data from Wright et al. implies 5-10% increased risk of very high triglycerides

See Wright WT et al. 2008 (18068174).

 

Impact

Moderate clinical importance, Uncertain pathogenic

(The "moderate clinical importance, uncertain" qualifier is assigned automatically based on the above evidence and importance scores.)

Inheritance pattern

dominant

Summary of published research, and additional commentary

 

Allele frequency

  • G @ chr8:19813529: 1.3% (145/10758) in EVS
  • G @ chr8:19857808: 1.6% (2/128) in GET-Evidence
  • Frequency shown in summary reports: 1.3% (145/10758)

Publications
 

Wright WT, Young IS, Nicholls DP, Graham CA. Genetic screening of the LPL gene in hypertriglyceridaemic patients. Atherosclerosis. 2008 Jul;199(1):187-92. Epub 2008 Feb 20. PubMed PMID: 18068174.

This variant was found in a screen for mutations in eight patients with extreme hypertriglyceridemia, along with three other substitution variants. To follow up on this, the authors tested a set of controls and patients with severe hypertriglyceridemia. They found 28 out of 218 patients were carriers of this variant, and 13 out of 314 controls were carriers (none were homozygous in either group). Two-tailed Fisher’s Exact has p = 0.00039.

Assuming extreme hypertriglyceridemia has a prevalence of 3-5%, these numbers imply carriers of this variant have a 5-10% increased attributable risk.

Genomes
 

hu0D879F - CGI sample GS00253-DNA_G01_200_37
het G @ chr8:19813529

 

 

 

GS20509 - var-GS20509-1100-36-ASM
het G @ chr8:19857809

 

Other external references
 

    dbSNP
  • rs268
    www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi
    PolyPhen-2
  • Score: 0.005 (benign)
    Web search results (8 hits -- see all)
  • Genetic screening of the LPL gene in hypertriglyceridaemic ...
    The complete sequence analysis of the LPL gene was carried out on 19 individuals with extreme ... p.N318S, p.V340I) that alter amino acids at 11 of the 16 LPL alleles. ...
    www.ncbi.nlm.nih.gov/pubmed/18068174
  • AceView: Gene:LPL, a comprehensive annotation of human, mouse ...
    AceView offers a comprehensive annotation of human, mouse and nematode genes reconstructed by co-alignment and clustering of all publicly available mRNAs and ESTs on ...
    ncbi.nlm.nih.gov/IEB/Research/Acembly/...&a=clones&l=LPL
  • Supplemental Table: Primers, probes and assay-on-demand ID# for ...
    Description: Gene variant name, location, function, reference number and the ... primer, probe or assay-on-demand ID for 101 SNPs genotyped in Puerto Rican and ...
    biomedcentral.com/.../supplementary/1471-2156-10-45-S1.doc
  • Download file
    LPL. D9N (D36N) rs1801177. 0.02. 0.0291 -0.162. 0.505. 0.093. N291S (N318S) ... P-value shown for chi-square test of the differences between the predicted MAF ...
    biomedcentral.com/.../supplementary/1471-2156-10-45-s3.doc
  • untitled
    W październiku tego roku upływa piętnaście lat od powołania Polskiego ... [LPL-H (In8T->G ), LPL-P (In6C->T )], scaven- ger receptor klasy B typ ...
    www.ptbnm.pl/pdf/CzR3.pdf
  • International Chair on Cardiometabolic Risk - Documentation ...
    Lipoprotein lipase (LPL) is one of the most important rate-limiting enzymes of ... larger case-control population, the p.N318S variant was found to be closely ...
    cardiometabolic-risk.org/documentation-centre/index.html?...
  • LPL - lipoprotein lipase
    LPL mRNA was also relatively abundant in germ cells, Sertoli cells, CIS cells ... of LPL and its surrounding area and identified p.N318S as a major predisposing factor to ...
    www.ihop-net.org/UniPub/iHOP/bng/89878.html
  • PolyPhen: results for P06858 N318S
    LIPOPROTEIN LIPASE PRECURSOR (EC 3.1.1.34) (LPL). LENGTH: 475 AA. Prediction. This variant ... Mapping of the substitution site to known protein 3D structures ...
    tux.embl-heidelberg.de/ramensky/data/html/SNP000002519.html

Other in silico analyses
 

  • NBLOSUM100 score = 0
  • GET-Evidence autoscore = 3

Edit history
 

Gene search

"GENE" or "GENE A123C":

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