Beyond DNA: How RNAseq Resolves VUS and Shortens the Diagnostic Odyssey

Beyond DNA: How RNAseq Resolves VUS and Shortens the Diagnostic Odyssey

by DNA Today (Kira Dineen, MS, LCGC, CG(ASCP)CM) with Dr. Christine Eng

Life & Natural Systems Medicine & Health MFPre-clinical medicine: basic sciencesMFNMedical genetics
🎙 DNA Today (Kira Dineen, MS, LCGC, CG(ASCP)CM) with Dr. Christine Eng 👥 4K 📅 March 6, 2026 ⏱ 24 min 👁 186 📄 expert opinion 🧭 2026-08-16
Available in: English (current) Français

Keywords

RNAseqVUSsplicingdiagnostic yieldmulti-omics

Summary

In this episode of DNA Today, host Kira Dineen interviews Dr. Christine Eng, Chief Medical Officer at Baylor Genetics, about the role of RNA sequencing (RNAseq) in resolving variants of uncertain significance (VUS) and shortening the diagnostic odyssey for patients with rare diseases. Dr. Eng explains that RNAseq provides functional evidence by examining splicing abnormalities and gene expression, complementing DNA sequencing. She discusses the targeted RNAseq approach used at Baylor Genetics, where variants suspected to affect splicing are reflexed to RNAseq. A clinical case is presented: a 2-year-old with status epilepticus and developmental delay, where RNAseq reclassified a VUS and led to a diagnosis of Jervell and Lange-Nielsen syndrome, enabling monitoring for prolonged QT interval. Dr. Eng notes that about 4-5% of genome sequencing cases qualify for RNAseq, and of those, approximately 40% are reclassified. Challenges include RNA stability, sample type (blood preferred over buccal), and added turnaround time (21 days). The discussion also covers the integration of multi-omics, including whole transcriptomics and metabolomics, into clinical workflows, and the importance of integrated reporting. Dr. Eng advises clinicians to utilize educational resources and webinars, and predicts that comprehensive testing will become first-tier in certain conditions, as evidenced by recent AAP recommendations.

200 words

Critical Evaluation

Value of the Information & Strength of the Argument

The value of the information is high, as it provides practical insights into the clinical implementation of RNAseq, including diagnostic yield, workflow considerations, and real-world case examples. The argumentation is solid, grounded in Dr. Eng’s extensive experience and the data from Baylor Genetics. The discussion is balanced, acknowledging limitations and challenges. However, the episode is primarily an expert opinion piece without detailed statistical evidence or peer-reviewed citations, which slightly reduces its scientific rigor.

Scientific Rigor, Source Quality, Title Accuracy

The scientific rigor is moderate; the content is based on expert opinion and clinical experience, but lacks explicit references to published studies. The quality of sources is limited to the guest’s expertise and the podcast’s general resources (DNAtoday.com). The title accurately reflects the content, focusing on RNAseq’s role in resolving VUS and shortening diagnostic odyssey. No comments were provided, so no analysis of public trends is included.

155 words

Title / Content Match

The title accurately reflects the content, focusing on RNA sequencing's role in resolving VUS and shortening diagnostic odyssey.

Quality & Reliability

7/10

The content is based on expert opinion from a leading clinical geneticist with extensive experience. The discussion is informative and grounded in clinical practice, but lacks detailed citations or peer-reviewed references. The information is presented clearly and aligns with current knowledge in the field.

Key Moments

Markers derived by PSI from the transcript: the creator did not define chapters.

Cited Sources

Concurring Sources

Contribution & Novelties

This episode provides a clear, expert-led overview of the current clinical utility of RNAseq in resolving VUS, with practical insights into workflow and diagnostic yield. It highlights the potential of multi-omics integration and the importance of functional evidence in genetic diagnostics. The discussion is particularly valuable for clinicians and genetic counselors seeking to understand when and how to utilize RNAseq.

Pour aller plus loin :

  • RNA sequencing in clinical practice — Overview of RNA sequencing technology.
  • ACMG guidelines for variant interpretation — Standards for variant classification.
  • Undiagnosed Diseases Network — Research network integrating multi-omics approaches.

95 words

Radar Profile

The radar profile shows balanced scores across information quantity, quality, technical level, and reliability, with a slight emphasis on quality and reliability. This indicates a well-rounded, expert-driven discussion with practical relevance, though not deeply technical or heavily cited.

Reliability 7/10