SLC6A5 A89E - GET-Evidence

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

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Curation:
Currentness:

SLC6A5 A89E

(SLC6A5 Ala89Glu)


Short summary

Reported causative for hyperekplexia in 2006, but later reports find an allelic frequency of 0.02 in controls and in vitro expression indistinguishable from wildtype.

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

Impact

Insufficiently evaluated benign

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

Inheritance pattern

dominant

Summary of published research, and additional commentary

 

Allele frequency

  • A @ chr11:20622937: 2.4% (251/10620) in EVS
  • A @ chr11:20579512: 2.5% (3/118) in GET-Evidence
  • Frequency shown in summary reports: 2.4% (251/10620)

Publications
 

Rees MI, Harvey K, Pearce BR, Chung SK, Duguid IC, Thomas P, Beatty S, Graham GE, Armstrong L, Shiang R, Abbott KJ, Zuberi SM, Stephenson JB, Owen MJ, Tijssen MA, van den Maagdenberg AM, Smart TG, Supplisson S, Harvey RJ. Mutations in the gene encoding GlyT2 (SLC6A5) define a presynaptic component of human startle disease. Nat Genet. 2006 Jul;38(7):801-6. Epub 2006 Jun 4. PubMed PMID: 16751771.

The variant is reported with an allelic frequency of 0.02 in controls.

Eulenburg V, Becker K, Gomeza J, Schmitt B, Becker CM, Betz H. Mutations within the human GLYT2 (SLC6A5) gene associated with hyperekplexia. Biochem Biophys Res Commun. 2006 Sep 22;348(2):400-5. Epub 2006 Jul 26. PubMed PMID: 16884688.

The variant is associated with hyperekplexia.

Harvey RJ, Topf M, Harvey K, Rees MI. The genetics of hyperekplexia: more than startle! Trends Genet. 2008 Sep;24(9):439-47. Epub 2008 Aug 15. Review. PubMed PMID: 18707791.

 

Genomes
 

hu011C57 - CGI sample GS01669-DNA_B05 from PGP sample 86486261
het A @ chr11:20622937

 

hu44DCFF - CGI sample GS01669-DNA_C07 from PGP sample 74521372
het A @ chr11:20622937

 

huD37D14 - CGI sample GS01175-DNA_A04 from PGP sample 13272228
het A @ chr11:20622937

 

huFFAD87 - CGI sample GS01669-DNA_H05 from PGP sample 10971581
het A @ chr11:20622937

 

GS07357 - var-GS07357-1100-36-ASM
het A @ chr11:20579513

 

Other external references
 

    dbSNP
  • rs61736602
    www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi
    PolyPhen-2
  • Score: 0.011 (benign)

Other in silico analyses
 

  • NBLOSUM100 score = 3
  • GET-Evidence autoscore = 2

Edit history
 

Gene search

"GENE" or "GENE A123C":

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