Genomic Testing
What is RNA-Integrated Sequence Evaluation (RISE)?
RISE combines a foundational whole exome sequencing (WES) or whole genome sequencing (WGS) analysis* with simultaneous transcriptomic analysis by RNA sequencing (RNA-seq). This can allow for greater diagnostic yield of complex or undiagnosed cases. Integrating DNA-centric and RNA-centric analysis maximizes clinical utility by assessing the RNA-level impact of coding regions, splice site changes, and variants in noncoding regulatory regions of phenotypically relevant target genes.1, 2
*RISE is also available with select hereditary cancer panels. Contact us for details.
*RISE is also available with select hereditary cancer panels. Contact us for details.
Benefits of RISE
Evidence-Based Yields
Up to 36% diagnostic yield in previously undiagnosed WES/WGS cases3
Clearer Insights
Refines DNA variant classification and reduces VUS rates
Richer Analysis
Detects gene expression impact of coding and noncoding variants
Higher Diagnostic Yields
An RNA-integrated approach is expected to increase the overall diagnostic rate up to 52% through the detection of abnormal gene expression, aberrant splicing, or mono-allelic expression, alterations that would not have been flagged by DNA analysis alone.1-5 The clinical utility behind the RISE concept has been reported across various tissue types and conditions, particularly in complex cases involving mitochondrial, muscular, and neurodevelopmental disorders.
| Test | Diagnostic Rate2 | Diagnostic Rate Uplift with RNA-Seq |
| Whole Exome Sequencing | ~30% | +17% |
| Whole Genome Sequencing | ~35% | +17% |
Whole Exome Sequencing
Whole Genome Sequencing
RNA Sequencing
Adapted Image2
RNA-Seq Provides Richer Analysis Over WES/WGS Alone
Identifies impact on gene expression levels from regulatory regions
Identifies functional consequence of splice site variants
Identifies large insertions/deletions and complex structural changes
Confirms structural variants, including tandem duplications
Provides insight into imprinting disorders, including uniparental disomy (UPD)
Determines status of skewed X-inactivation
Verifies and distinguishes variants from sequencing artifacts and pseudogenes
Test Specifications
TEST DETAILS
Duo/trio preferred (RNA-seq will only be run on the proband); singleton accepted
RISE turnaround time: 5-7 additional days from the TAT of ordered test
SPECIMEN REQUIREMENTS
Requires 1 EDTA tube (4 mL whole blood*) and 1 PAXgene Blood RNA tube (2.5 mL whole blood)
*For patients less than 1 year of age, we can accept 1-2 mL
Contact us to request a kit
References
1. Kernohan, K.D., Boycott, K.M. The expanding diagnostic toolbox for rare genetic diseases. Nat Rev Genet (2024).
2. Peymani F, Farzeen A, Prokisch H. RNA sequencing role and application in clinical diagnostic. Pediatr Investig. 2022;6(1):29-35. Published 2022 Mar 5.
3. Curry, P.D.K., Broda, K.L. & Carroll, C.J. The Role of RNA-Sequencing as a New Genetic Diagnosis Tool. Curr Genet Med Rep 9, 13–21 (2021).
4. Gonorazky HD, Naumenko S, Ramani AK, et al. Expanding the Boundaries of RNA Sequencing as a Diagnostic Tool for Rare Mendelian Disease [published correction appears in Am J Hum Genet. 2019 May 2;104(5):1007]. Am J Hum Genet. 2019;104(3):466-483.
5. Deelen P, van Dam S, Herkert JC, et al. Improving the diagnostic yield of exome- sequencing by predicting gene-phenotype associations using large-scale gene expression analysis. Nat Commun. 2019;10(1):2837. Published 2019 Jun 28.