Myriad myRisk® and RNA Analysis

Myriad uses RNA analysis to reduce the rate of uncertain variants and provide the most accurate results for you and your patients

How does RNA analysis relate to hereditary cancer testing?

Variants in DNA can be predicted to impact splicing of RNA, which can in turn affect the function of proteins that are important to hereditary cancer risk. Functional studies using RNA can help determine whether the protein is likely to be significantly impacted by alternative splicing or splice defects and add valuable information about how the variant in DNA should be classified. The application of RNA analysis to hereditary cancer risk is at an early stage and care should be taken when using functional studies to classify or reclassify variants.1,2,3

DNA is transcribed to RNA is translated to protein

RNA Analysis Process

  • myrisk-kit Patient submits saliva or blood sample for myRisk testing
  • gene-question Eligible VUS identified
  • help Myriad contacts ordering healthcare provider and then patient
  • sample Blood kit shipped to patient – Myriad can also help arrange mobile phlebotomy
  • dna RNA data analyzed and reviewed by classification committee
    Criteria for variant reclassification based on RNA analysis

    Suggested workflow for using RNA functional studies in variant classification (adapted from Nix et al, 2020)

    criteria diagram

    SNP, single-nucleotide polymorphism

    Myriad requires data on the extent of the splice defect before using RNA studies to reclassify a variant. If the variant allele produces any normal transcript, additional strong evidence is needed to reclassify

  • results Amended report issued if variant is reclassified
If you have questions about whether your patient could benefit from RNA studies, please call our medical team at 800-469-7423 or email helpmed@myriad.com.

Impact of Myriad’s RNA Analysis Program

50% of variants studied by RNA are reclassified, with 82% upgraded and 18% downgraded

Myriad has performed RNA studies on over 200 variants since 2015, which have impacted over 3,200 patients.

78% of tests are reclassified based on RNA analysis

The majority (78%) of variant reclassifications changed medical management guidelines for patients.

ATM, BRCA1 and BRCA2 have had the most variants analyzed using RNA
All genes in Myriad's myRisk panel are eligible for RNA studies and nearly every gene has had a variant undergo RNA analysis

Publications

Myriad’s unique, allele-specific approach to RNA studies was first described by Warf et al in 2015. Since then, several case studies have been published demonstrating the value of this approach in accurately classifying variants that could impact splicing.
References
  1. Nix P, Mundt E, Manley S, et al: 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 4: 730-735, 2020
  2. Whiley PJ, de la Hoya M, Thomassen M, et al: Comparison of mRNA splicing assay protocols across multiple laboratories: Recommendations for best practice in standardized clinical testing. Clin Chem 60:341-352, 2014
  3. Brnich SE, Abou Tayoun AN, Couch FJ, et al: Recommendations for application of the functional evidence PS3/BS3 criterion using the ACMG/AMP sequence variant interpretation framework. Genome Med 12:3, 2019

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