SCN11A L1158P - GET-Evidence

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Currentness:

SCN11A L1158P

(SCN11A Leu1158Pro)


You are viewing the latest version of this page, saved on February 23, 2017 at 7:13am by Madeleine Ball.

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Short summary

Reported by ClinVar to cause familial episodic pain syndrome (https://www.ncbi.nlm.nih.gov/clinvar/variation/157599/). In ClinVar this variant is reported as “pathogenic” (causing this condition) by a single source, OMIM, which cites Huang et al 2014 (https://www.ncbi.nlm.nih.gov/pubmed/24776970). However, it is reported as “uncertain significance” by Emory Genetics Laboratory.

Huang et al found this variant heterozygous in two of 345 patients screened with painful peripheral neuropathy. The authors also report molecular evidence that this variant disrupts the function of the SCN11A protein product. This variant is uncommon but not rare: according to ExAC it is carried by 1 in 600 Europeans (http://exac.broadinstitute.org/variant/5-176048219-G-T).

The frequency of this variant seems at odds with a proposed “rare disease” effect, and the statistical significance of Huang et al’s observation may be weak or absent. They report the variant is also seen in EVS, and a two-tailed Exact Fisher test using their reported numbers produces a p-value of 0.087.

Variant evidence
Computational -
Functional -
Case/Control

Statistical significance seems to be weak or absent, and frequency in controls may be at odds with a rare disease hypothesis.

Familial

No familial evidence provided

 
Clinical importance
Severity 3
Treatability 1
Penetrance 5
 

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

  • None available.

Publications
 

Genomes
 

Other in silico analyses
 

  • NBLOSUM100 score = 7
  • GET-Evidence autoscore = 1

Edit history
 

Gene search

"GENE" or "GENE A123C":

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