SCN5A S524Y - GET-Evidence

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

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Curation:
Currentness:

SCN5A S524Y

(SCN5A Ser524Tyr)


Short summary

The rare variant SCN5A-S524Y does not appear to be a risk for cardiac arrhythmia in a case-control study.

Variant evidence
Computational 1

PolyPhen-2 predicts PROBABLY DAMAGING with a score of 0.959 (sensitivity: 0.78; specificity 0.95).

Functional -
Case/Control

In this study, the entire SCN5A coding region is sequenced in 375 subjects with atrial fibrillation or atrial fibrillation associated with heart disease. Controls (n=360) from the same population were then genotyped to identify all variants identified in the study subjects. The frequency of the rare variant SCN5A-S524Y is comparable in study cases (2/752) and controls (3/720). This gives a p value (using the PGP’s Fisher’s Exact Test calculator) of p = 0.6807723109022572.

See Darbar D et al. 2008 (18378609).

Familial -
 
Clinical importance
Severity -
Treatability -
Penetrance -
 

Impact

Insufficiently evaluated not reviewed

(The "insufficiently evaluated" 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 @ chr3:38645522: 1.2% (119/10194) in EVS
  • T @ chr3:38620525: 0.8% (1/128) in GET-Evidence
  • Frequency shown in summary reports: 1.2% (119/10194)

Publications
 

Darbar D, Kannankeril PJ, Donahue BS, Kucera G, Stubblefield T, Haines JL, George AL Jr, Roden DM. Cardiac sodium channel (SCN5A) variants associated with atrial fibrillation. Circulation. 2008 Apr 15;117(15):1927-35. doi: 10.1161/CIRCULATIONAHA.107.757955. Epub 2008 Mar 31. PubMed PMID: 18378609; PubMed Central PMCID: PMC2365761.

In this study, the entire SCN5A coding region is sequenced in 375 subjects with atrial fibrillation or atrial fibrillation associated with heart disease. Controls (n=360) from the same population were then genotyped to identify all variants identified in the study subjects. The frequency of the rare variant SCN5A-S524Y is comparable in study cases (2/752) and controls (3/720).

Genomes
 

 

show discussion

Discussion

PGP89 (heterozygous for SCN5A-S524Y) is a 58 year old male with normal cardiac function assessed by EKG and no history of cardiac incidents.

GS18517 - var-GS18517-1100-36-ASM
het T @ chr3:38620526

 

Other external references
 

    dbSNP
  • rs41313691
    www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi
    GeneTests
  • GeneTests records for the SCN5A gene
    Dilated Cardiomyopathy
    Brugada Syndrome
    Long QT Syndrome 3
    LQT3-Related Romano Ward Syndrome
    Progressive Cardiac Conduction Disease
    Romano-Ward Syndrome
    SCN5A-Associated Dilated Cardiomyopathy
    SCN5A-Related Dilated Cardiomyopathy
    SCN5A-Related Disorders
    www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/SCN5A

Other in silico analyses
 

  • NBLOSUM100 score = 5
  • GET-Evidence autoscore = 3

Edit history
 

Gene search

"GENE" or "GENE A123C":

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