Assessment of disease-associated missense variants in RYR2 on transcript splicing

  • Damilola Olubando Manchester Centre for Genomic Medicine, Manchester University NHS Foundation Trust, Health Innovation Manchester, Manchester, UK; Division of Evolution and Genomic Sciences, Faculty of Biology, Medicine and Human Sciences, University of Manchester, Manchester, United Kingdom.
  • Huw Thomas Manchester Centre for Genomic Medicine, Manchester University NHS Foundation Trust, Health Innovation Manchester, Manchester, UK; Division of Evolution and Genomic Sciences, Faculty of Biology, Medicine and Human Sciences, University of Manchester, Manchester, United Kingdom.
  • Minoru Horie Department of Cardiovascular and Respiratory Medicine, Shiga University of Medical Sciences, Otsu, Shiga, Japan.
  • Raymond T. O’Keefe Manchester Centre for Genomic Medicine, Manchester University NHS Foundation Trust, Health Innovation Manchester, Manchester, UK; Division of Evolution and Genomic Sciences, Faculty of Biology, Medicine and Human Sciences, University of Manchester, Manchester, United Kingdom.
  • Luigi Venetucci Manchester Heart Centre, Manchester University NHS Foundation Trust, Manchester, UK; Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Human Sciences, University of Manchester, Manchester, United Kingdom.
  • William Newman | william.newman@manchester.ac.uk Manchester Centre for Genomic Medicine, Manchester University NHS Foundation Trust, Health Innovation Manchester, Manchester, UK; Division of Evolution and Genomic Sciences, Faculty of Biology, Medicine and Human Sciences, University of Manchester, Manchester; UK; Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Human Sciences, University of Manchester, Manchester, United Kingdom.

Abstract

Heterozygous RYR2 missense variants cause catecholaminergic polymorphic ventricular tachycardia. Rarely, loss of function variants can result in ventricular arrhythmias. We used splice prediction tools and an ex vivo splicing assay to investigate whether RYR2 missense variants result in altered splicing. Ten RYR2 variants were consistently predicted to disrupt splicing, however none altered splicing in the splicing assay. In summary, missense RYR2 variants are unlikely to cause disease by altered splicing.

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Published
2020-06-01
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Section
Brief Reports
Keywords:
Genetic disease, catecholaminergic ventricular tachycardia, arrhythmia.
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  • Supplementary Tables: 31
How to Cite
Olubando, D., Thomas, H., Horie, M., O’Keefe, R. T., Venetucci, L., & Newman, W. (2020). Assessment of disease-associated missense variants in RYR2 on transcript splicing. Cardiogenetics, 10(1). https://doi.org/10.4081/cardiogenetics.2020.8637