KCNE1 D85N - GET-Evidence

Curation:
Currentness:

KCNE1 D85N

(KCNE1 Asp85Asn)


Short summary

Proposed to cause drug-induced long QT syndrome by one group. Another group suggests an association with noise-induced hearing loss. Neither study found a statistical significant association for this variant after multiple hypotheses are corrected for.

Variant evidence
Computational -1

Polyphen 2 predicts benign

Functional -
Case/Control

No significance after correction for multiple hypotheses

See Paulussen AD et al. 2004 (14760488), Van Laer L et al. 2006 (16823764).

Familial -
 
Clinical importance
Severity 3

Acquired Long QT syndrome and/or noise-associated hearing loss?

See Paulussen AD et al. 2004 (14760488), Van Laer L et al. 2006 (16823764).

Treatability 4

If true, circumstances could be avoided

Penetrance 4

If hypothesized pathogenic effects are true, penetrance is unclear. Both reports found no cases of carriers in controls, but variant is rare enough that this could have occurred by chance.

See Paulussen AD et al. 2004 (14760488), Van Laer L et al. 2006 (16823764).

 

Impact

High clinical importance, Uncertain pathogenic

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

Inheritance pattern

unknown

Summary of published research, and additional commentary

 

Allele frequency

  • T @ chr21:35821680: 0.9% (94/10758) in EVS
  • T @ chr21:34743549: 0.8% (1/128) in GET-Evidence
  • Frequency shown in summary reports: 0.9% (94/10758)

Publications
 

Paulussen AD, Gilissen RA, Armstrong M, Doevendans PA, Verhasselt P, Smeets HJ, Schulze-Bahr E, Haverkamp W, Breithardt G, Cohen N, Aerssens J. Genetic variations of KCNQ1, KCNH2, SCN5A, KCNE1, and KCNE2 in drug-induced long QT syndrome patients. J Mol Med (Berl). 2004 Mar;82(3):182-8. Epub 2004 Feb 4. PubMed PMID: 14760488.

32 patients with acquired long QT syndrome (in response to drugs) were scanned for variants in five genes implicated in congenital long QT syndrome. Two of the 32 carried this variant, none of 32 controls did. (This not a statistically significant difference.)

Van Laer L, Carlsson PI, Ottschytsch N, Bondeson ML, Konings A, Vandevelde A, Dieltjens N, Fransen E, Snyders D, Borg E, Raes A, Van Camp G. The contribution of genes involved in potassium-recycling in the inner ear to noise-induced hearing loss. Hum Mutat. 2006 Aug;27(8):786-95. PubMed PMID: 16823764.

35 SNPs in 10 genes were studied for association with noise-associated hearing loss. This variant was found in 5 out of 104 cases of noise-associated hearing loss, and not seen at all in 114 noised-exposed individuals without hearing loss.

The authors report this to have a significance of p = 0.023, which is the p-value obtained by using a two-tailed Fisher’s Exact test. However, they do not correct for the fact that multiple hypotheses were being tested. Bonferroni correction would require p < 0.0014 for a significance equivalent to p = 0.05 when 35 hypotheses are being tested.

Genomes
 

Other external references
 

    PolyPhen-2
  • Score: 0.066 (benign)

Other in silico analyses
 

  • NBLOSUM100 score = –1
  • GET-Evidence autoscore = 4

Edit history
 

Gene search

"GENE" or "GENE A123C":

Log in