Validation of RNA Genetic Testing for Use in a Clinical Diagnostic Setting - Ambry Genetics

Explore the validation of RNA genetic testing for clinical diagnostic applications in this 45-minute webinar presented by Ambry Genetics. Delve into the advancements in genetic testing, focusing on the molecular biology of RNA splicing and its role in providing functional information. Learn about a targeted and scalable approach to RNA genetic testing in 18 tumor suppressor genes, and examine the results from a pilot cohort that demonstrated an increase in diagnostic yield. Gain insights through case studies illustrating how RNA contributes to improved diagnostics. Presented by Tyler Landrith, PhD, and moderated by Tara Namey, MS, LCGC, this webinar covers topics such as mRNA processing, alternative splicing, considerations for whole transcriptome sequencing, and the clinical utility of RNA genetic testing. Discover how RNA genetic testing complements DNA-based testing and its potential to identify variants missed by traditional methods.

Intro
Disclosures/ Conflict of Interest
Lecture Outline
Advancements in genetic testing
DNA-based genetic testing may miss patients with hereditary cancer or provide inconclusive results
Morphological and functional diversity of RNA
mRNA processing
RNA alternative splicing (AS)
RNA AS provides functional evidence to support variant reclassification and identification
Background of RNA genetic testing
Considerations for whole transcriptome sequencing
RNA genetic testing and DNA MGPT are performed in parallel
DNA MGPT reporting range is not required for RNA genetic testing
Aberrant splicing is determined based on data quality and comparison to healthy controls
Clinical utility and scalability of RNA genetic testing
Demographics of healthy controls
Selection of 18 tumor suppressor genes
Demographics do not confound splicing profile for 18 TSGS
Number of alternative splicing events vary by gene
Validation of RNA genetic testing with known splicing variants
Orthogonal confirmation with Clone-Seq
Pilot Data
Variants identified only with RNA genetic testing
Case #2: Exon 17 skipping in BRCAL
Case study #3: Exon 56 skipping in ATM