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+RNAinsight™

Expanded gene coverage for RNA analysis to achieve better variant classification.

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Why +RNAinsight™ Matters

+RNAinsight helps classify and clarify DNA variants associated with breast, ovarian, prostate, colon, pancreatic, uterine, and other cancers—finding the answers for more patients and families needing hereditary cancer risk information. +RNAinsight can be paired with Ambry’s hereditary cancer panels[*] to provide functional RNA evidence. This helps to identify and interpret DNA variants, including deep intronic variants that a DNA-only approach would miss.

Paired DNA and RNA Genetic Testing

+RNAinsight™: Paired DNA and RNA Testing

+RNAinsight improves the sensitivity and clarity of hereditary cancer genetic testing. It works in tandem with Ambry’s DNA testing to identify patients who might otherwise be missed with a DNA-only approach. Paired DNA and RNA testing decreases variants of unknown significance (VUS) in real-time and provides more accurate results to inform patient care. [1][2]

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Limitations of DNA-Only Hereditary Cancer Testing

Many patients suspected to have hereditary cancer receive negative or inconclusive results due to limitations of DNA-only genetic testing. While there have been several advancements in genetic testing since the days of Sanger sequencing, there is still a need to enhance variant detection and interpretation. Adding simultaneous RNA genetic testing to DNA-only tests with +RNAinsight is the next step to more accurate, actionable results for patients and their families.

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Clinician Experiences with +RNAinsight™

“Ambiguity in genetic test results is challenging for health care providers and for our patients. The fact that supplemental RNA testing has the potential to offer clarity for an additional 1 in 50 patients is a game changer. Ambry Genetics is setting a new bar for genetic testing.”

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Meagan Farmer, MS, MBA, LCGC
Genetic Counselor, formerly of University of Alabama at Birmingham
“I have a family whose diagnosis has been eluding me for years. I just knew they had Lynch syndrome, but I couldn’t prove it until I was able to order RNA testing. RNA has forever changed the lives of every single member of this family, and it has changed the way I want to practice moving forward. I now firmly believe that RNA should be a part of first-line genetic testing for all patients.”
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Rebekah Krukenberg, MS, LCGC
Genetic Counselor, formerly of Community Health Network
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Finding Missed Hereditary Cancer Patients

Clinical diagnostic labs typically apply a reporting range limit to their DNA genetic testing panels. Variants outside these ranges have a much lower probability of being pathogenic (disease-causing) and would most often be classified as a variant of unknown significance (VUS). Looking beyond these ranges would only increase the VUS rate without increasing the diagnostic yield. However, using +RNAinsight expands the reporting range of DNA-based testing, which in turn enables Ambry to provide a clear diagnosis to more patients who may otherwise be missed. [1]

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Minimizing VUS Results In Real Time

Patients undergoing hereditary cancer testing may receive a VUS result, which can cause uncertainty and confusion for ordering healthcare providers and patients. A VUS result does not provide actionable information to inform medical management, since it doesn’t clarify if the patient is at an increased risk for cancer. +RNAinsight provides an additional line of functional evidence that can tip the scale towards pathogenic or benign. [1] [2] [3] In some cases, this can turn a VUS into an actionable positive or clear, negative result.

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Clarifying Results to Inform Patient Care

A negative report or a VUS result can be unsettling, especially in the context of a strong cancer history. Patients may worry that a mutation was missed by the technology, or that there may be a mutation in another gene. A VUS could be benign or it could be pathogenic. +RNAinsight analyzes functional RNA data to help classify DNA variants. As a result, patients receive more sensitive and specific testing, which leads to lowered rates of inconclusive outcomes.

Medical professionals analyzing and sharing DNA data.
+RNAinsight™ Product Overview

* +RNAinsight is not available with BRCAplus® test. CustomNext-Cancer® can be used for single syndrome/single gene testing orders.
** Orders including +RNAinsight are not eligible for STAT testing.

Reference Note
+RNAinsight is not available with BRCAplus® test. CustomNext-Cancer® can be used for single syndrome/single gene testing orders.

AIP ALK APC ATM ATRIP AXIN2 BAP1 BARD1 BMPR1A BRCA1 BRCA2 BRIP1 CDC73 CDH1 CDK4 CDKN1B CDKN2A CEBPA CFTR CHEK2 CPA1 CTNNA1 CTRC DDX41 DICER1 EGFR EGLN1 EPCAM ETV6 FH FLCN GATA2 GREM1 HOXB13 KIF1B KIT LZTR1 MAX MBD4 MEN1 MET MITF MLH1 MLH3 MSH2 MSH3 MSH6 MUTYH NF1 NF2 NTHL1 PALB2 PALLD PDGFRA PHOX2B PMS2 POLD1 POLE POT1 PRKAR1A PRSS1 PTCH1 PTEN RAD51B RAD51C RAD51D RB1 RET RNF43 RPS20 RUNX1 SDHA SDHAF2 SDHB SDHC SDHD SMAD4 SMARCA4 SMARCB1 SMARCE1 SPINK1 STK11 SUFU TERT TMEM127 TP53 TSC1 TSC2 VHL WT1

Reference Note
Orders including +RNAinsight are not eligible for STAT testing.

One kit that includes 1 EDTA tube (DNA) and 1 PAXgene® tube (RNA)

Ribonucleic acid (RNA) is isolated from the patient’s specimen using standardized methodology and quantified. RNA is converted to complementary DNA (cDNA) by reverse transcriptase polymerase chain reaction (RT-PCR). Sequence enrichment of the targeted coding exons and adjacent intronic nucleotides is carried out by a bait-capture methodology using long biotinylated oligonucleotide probes followed by polymerase chain reaction (PCR) and Next-Generation sequencing. +RNAinsight analyzes transcripts for up to 90 genes depending which Ambry Genetics DNA based Hereditary Cancer Panel it is paired with and depending on the absence or presence of RNA transcripts expressed in the blood. Any transcripts found are compared to a human reference pool. The absence or presence of RNA transcripts meeting quality thresholds is incorporated as evidence towards assessment and classification of DNA variants. Any regions not meeting RNA quality thresholds are excluded from analysis. The results from +RNAinsight are used to provide functional RNA information to further support classification of DNA variants. It is not intended to be used as a stand-alone diagnostic test.

References

  1. Ambry Genetics, internal data on file
  2. Karam R. et al. RNA Genetic Testing in Hereditary Cancer Improves Variant Classification and Patient Management. ACMG 2019.
  3. Richards S. et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015 May;17(5):405-24