Delivering more actionable insights through variant classification utilizing DNA and RNA analysis

Myriad Oncology

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Delivering more actionable insights through variant classification utilizing DNA and RNA analysis

Want clearer answers from the start? Choose the leader.

The MyRisk® Hereditary Cancer Test, combined with Myriad’s industry-leading Variant Classification Program, utilizes RNA testing strategically, along with other proprietary tools, to deliver highly accurate variant interpretations, ensuring precise and actionable results for more patients, without unnecessary testing.1,2

While others leave you guessing, MyRisk delivers clarity, with the industry’s lowest reported VUS rate for BRCA1/2 of 1.0%.1,2 Get more definitive results for more patients—don’t settle for less.

Myriad pioneered the use of RNA analysis in hereditary cancer testing in 2015 and continues to lead the way in variant detection and classification

What sets our testing approach apart from other labs?

RNA analysis works by complementing DNA analysis to show how genetic variants impact splicing, revealing whether a gene produces normal or abnormal transcripts, or a mixture of the two. But not all patients benefit from RNA analysis, and not all labs offer a personalized approach to RNA testing.

Superior baseline DNA analysis: The MyRisk® Test identifies and classifies most variants that could influence splicing via its DNA analysis that includes exons and extends into the introns of each gene. Because of Myriad’s superior variant classification tools, most variants can be classified confidently without the need for RNA analysis.

Targeted RNA analysis for maximum impact: Unlike competitors who apply RNA testing across all cases, the MyRisk Test strategically utilizes RNA analysis to resolve specific VUS cases, helping to avoid unnecessary testing while allowing for precise classifications.

No additional cost for RNA testing: Myriad proactively works with the ordering clinician and the patient when a variant is found that may benefit from RNA analysis. In our process, if RNA testing is appropriate, the additional analysis of the variant is done at no additional cost, often without the need for a re-draw.3 This ensures clinicians receive the most meaningful insights without additional financial burden for the patient.

Superior baseline DNA analysis: What does it mean?

While other labs rely on upfront paired DNA/RNA testing to compensate for weaker variant classification via DNA analysis, The MyRisk Test already classifies most variants through its superior DNA analysis.

This deep baseline analysis helps optimize the use of reflex testing.

of potential splicing variants occur within the DNA regions analyzed on MyRisk4

Targeted and smart RNA analysis delivers maximum impact.

Whenever the MyRisk Test detects a new potential splicing variant through DNA sequencing, Myriad carefully investigates the relevance of further RNA analysis. MyRisk utilizes RNA analysis only on variants where RNA data could be the determining factor in a pathogenic classification. When RNA analysis is performed, our methodology allows us to classify splicing variants with exceptional precision.

Standard RNA sequencing methods used by some labs may produce false-positive classifications by detecting aberrant transcripts while failing to recognize the presence of normal transcripts, mistakenly classifying a variant as pathogenic.5 The MyRisk Test incorporates allele-specific quantification, which identifies whether a variant allele produces both normal and aberrant transcripts—a level of precision that helps avoid false-positive classifications that could mislead clinical decisions.5

In addition, the targeted approach of the MyRisk test optimizes cost efficiency by applying RNA analysis only to VUSs where it can change the classification. This ensures that unnecessary testing does not inflate healthcare expenses while maintaining the highest level of diagnostic accuracy.

The MyRisk test methodology for utilizing RNA analysis in variant classification5


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References:
  1. Gradishar W, Johnson K, Brown K, et al. Clinical Variant Classification: A Comparison of Public Databases and a Commercial Testing Laboratory. Oncologist. 2017;22(7):797-803.
  2. Mundt E, McGreevy K, Nix P, Cummings S. Myriad’s Multidisciplinary Approach and Consistent Investment in Variant Classification for Clinical Decision Making [White paper]. Myriad Genetics. 2025.
  3. Internal data on file at Myriad Genetics, Inc. Abstract submitted at ASCO 2025. 30 residual EDTA blood samples with 29 unique germline DNA variants were analyzed. RNA and cDNA of sufficient quantity and quality were successfully isolated from 28/30 (93%) samples.
  4. Kamps-Hughes N, Carlton VEH, Fresard L, et al. A Systematic Method for Detecting Abnormal mRNA Splicing and Assessing Its Clinical Impact in Individuals Undergoing Genetic Testing for Hereditary Cancer Syndromes. J Mol Diagn. 2023;25(3):156-167.
  5. Nix P, Mundt E, Manley S, Coffee B, Roa B. Functional RNA Studies Are a Useful Tool in Variant Classification but Must Be Used With Caution: A Case Study of One BRCA2 Variant. JCO Precis Oncol. 2020;4:730-735.