Variant "SNTA1:rs572545726"
Search result: 1 record
Variant information
Gene:
SNTA1 
Variant:
SNTA1:rs572545726 
dbSNP ID:
rs572545726  
GWAS trait:
no data 
Modifier statisitcs
Record:
1 
Disorder:
1 
Reference:
1 
Effect type:
Expressivity(1)  
Modifier effect:
Risk factor(1)  
Detail：
  • Target disease:
    Long QT Syndrome (DOID_2843)
    Effect type:
    Expressivity 
    Modifier effect:
    Risk factor 
    Evidence:
    P<0.05 
    Effect:
    p.P74L-SNTA1 functionally modify the pathogenic phenotype of p.A257G-SNTA1
    Reference:
    PMID24319568
    Title:
    LQTS-associated mutation A257G in α1-syntrophin interacts with the intragenic variant P74L to modify its biophysical phenotype.
    Species studied:
    Human
    Abstract:
    The SNTA1-encoded α1-syntrophin (SNTA1) missense mutation, p.A257G, causes long QT syndrome (LQTS) by pathogenic accentuation of Nav1.5's sodium current (INa). Subsequently, we found p.A257G in combination with the SNTA1 polymorphism, p.P74L in 4 victims of sudden infant death syndrome (SIDS) as well as in 3 adult controls. We hypothesized that p.P74L-SNTA1 could functionally modify the pathogenic phenotype of p.A257G-SNTA1, thus explaining its occurrence in non-LQTS populations. The SNTA1 variants p.P74L, p.A257G, and the combination variant p.P74L/p.A257G were engineered using PCR-based overlap-extension and were co-expressed heterologously with SCN5A in HEK293 cells. INa was recorded using the whole-cell method. Compared to wild-type (WT), the significant increase in peak INa and window current found with p.A257G was reversed by the intragenic variant p.P74L (p.P74L/p.A257G). These results report for the first time the intragenic rescue of an LQT-associated SNTA1 mutation when found in combination with the SNTA1 polymorphism p.P74L, suggesting an ever-increasing picture of complexity in terms of genetic risk stratification for arrhythmia.