Back to Search
Start Over
Integration of 60,000 exomes and ACMG guidelines question the role of Catecholaminergic Polymorphic Ventricular Tachycardia-associated variants.
- Source :
-
Clinical Genetics . Jan2017, Vol. 91 Issue 1, p63-72. 11p. - Publication Year :
- 2017
-
Abstract
- Catecholaminergic Polymorphic Ventricular Tachycardia ( CPVT) is a highly lethal cardiac arrhythmia disease occurring during exercise or psychological stress. CPVT has an estimated prevalence of 1:10,000 and has mainly been associated with variants in calcium-regulating genes. Identification of potential false-positive pathogenic variants was conducted by searching the Exome Aggregation Consortium ( ExAC) database ( n = 60,706) for variants reported to be associated with CPVT. The pathogenicity of the interrogated variants was assessed using guidelines from the American College of Medical Genetics and Genomics ( ACMG) and in silico prediction tools. Of 246 variants 38 (15%) variants previously associated with CPVT were identified in the ExAC database. We predicted the CPVT prevalence to be 1:132. The ACMG standards classified 29% of ExAC variants as pathogenic or likely pathogenic. The in silico predictions showed a reduced probability of disease-causing effect for the variants identified in the exome database (p < 0.001). We have observed a large overrepresentation of previously CPVT-associated variants in a large exome database. Based on the frequency of CPVT in the general population, it is less likely that the previously proposed variants are associated with a highly penetrant monogenic form of the disease. [ABSTRACT FROM AUTHOR]
- Subjects :
- *TACHYCARDIA
*EXERCISE
*PHYSIOLOGICAL stress
*EXOMES
*MEDICAL genetics
Subjects
Details
- Language :
- English
- ISSN :
- 00099163
- Volume :
- 91
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- Clinical Genetics
- Publication Type :
- Academic Journal
- Accession number :
- 120326009
- Full Text :
- https://doi.org/10.1111/cge.12847