Presentation at the American Society of Human Genetics Annual Meeting also highlights use of virtual panels to identify clinically important secondary findings
Invitae Corporation (NYSE: NVTA), one of the fastest growing genetic information companies, is presenting data showing genetic sequencing and copy number variant (CNV) detection performed together using expert-curated panels offers better diagnosis rates over sequencing alone in patients with neuromuscular disorders and childhood epilepsy. The studies are among the company’s 15 posters and presentations at the 2017 American Society of Human Genetics (ASHG) Annual Meeting in Orlando.
“These data highlight the utility of evaluating both genetic variants and copy number variants on a single testing platform to help clinicians more quickly diagnose patients. Our data also highlight the ability of expertly curated, disease-specific panels to be a more rapid, cost-effective first step for diagnosis that can be used before exome testing when diagnosing epilepsy and neuromuscular disorders,” said Robert Nussbaum, MD, chief medical officer of Invitae. “Well-designed testing and innovative techniques can help shorten the often lengthy process of elimination that can accompany diagnosing genetic disease.”
Using high-depth next generation sequencing with custom bioinformatics that enables simultaneous copy number variant analysis, the epilepsy study evaluated 2,267 patients and showed panel testing provided a molecular diagnosis in up to 24% of patients overall and had treatment implications for 21% of patients with positive results. Using the same underlying methodology, a similar study designated as a Reviewer’s Choice abstract evaluated more than 4,358 patients referred to Invitae for neurological and neuromuscular genetic testing and showed panel testing provided molecular diagnosis rates that ranged from 12% for dystonia to a high of 64% for spinal muscular atrophy. Importantly, copy number variant analysis enabled by Invitae’s custom approach accounted for a significant portion of the positive findings in both studies (up to 40%).
Use of virtual panels to evaluate secondary findings yields actionable information
In another platform presentation at the meeting, researchers from the company are presenting an analysis of the frequency of actionable variants in hereditary cancer genes found in more than 3,000 patients referred for testing for hereditary cardiovascular disorders. Under an IRB-approved protocol that allowed review of de-identified test data, the researchers analyzed a “virtual panel” of hereditary cancer genes in this set of patients. Because these patients had no known indication for hereditary cancer gene testing, the study was designed to model the results that would be seen if the patients were screened for actionable secondary variants. The researchers found that six percent of patients had pathogenic or likely pathogenic variants in hereditary cancer genes with commonly accepted clinical management guidelines, a prevalence rate higher than seen in previously published studies.
“Current ACMG guidelines on secondary findings indicate that such information can be useful regardless of the original indication for testing,” said Dr. Nussbaum, one of the authors of the study. “Our virtual study indicates that one in 16 individuals could learn of actionable information from hereditary cancer gene testing in the absence of the usual indication for such testing based on personal or family history. Our pilot implementation of a screening panel in real health care settings for both hereditary cancer and cardiovascular disease indicates useful information may be obtained for as many as 1 in 7 individuals undergoing such testing. The data support the need for further studies of the utility and impact of genetic screening for actionable variants as part of a health maintenance program. As this approach to genetic screening is still in its infancy, we are actively educating providers and collecting follow-up information from both patients and providers as to the utility of this information on health care. “
Full research presentation schedule
The full schedule of the Invitae researchers’ presentations at the meeting is as follows:
Wednesday, October 18:
- Poster #445: Validation of a novel copy number variant detection algorithm for CFTR from targeted next-generation sequencing data | Presented by Katya Kosheleva, PhD, Good Start Genetics | 2:00 pm ET
- Poster #601: Improving variant classification by incorporating pre-curated gene-specific knowledge into hereditary cancer multi-gene panel testing | Presented by Hio Chung Kang, PhD, Invitae | 2:00 pm ET
- Reviewer’s Choice Abstract | Poster #2371: Paperwork matters! The importance of clinical phenotype information in variant interpretation | Presented by Michael Anderson, PhD, Invitae | 2:00 pm ET
- Poster #2461: Copy number analysis using next-generation sequencing: Comprehensive genetic testing and its application to neuromuscular and epilepsy panels | Presented by Ali Entezam, PhD, Invitae | 2:00 pm ET
- Reviewer’s Choice Abstract | Poster #2440: Novel pathogenic variants are routinely detected even in extensively-sequenced genes, such as CFTR | Presented by Nicole Faulkner, PhD, FACMG, Good Start Genetics | 3:00 pm ET
- Poster #2584: New systematic rubric for clinical interpretation of copy number variants (CNVs) improves interpretation consistency across laboratories | Presented by Daniel Pineda-Alvarez, MD, FACMG, Invitae | 3:00 pm ET
- Poster #1540 | Streamlined, efficient, and uniform molecular inversion probe capture for targeted sequencing | Presented by Eric Boyden, PhD, Good Start Genetics | 3:00 pm ET
Thursday, October 19:
- Presentation #130: Secondary findings after virtual panels: A new frontier in incidental findings | Presented by Edward Esplin, MD, PhD, FACMG, FACP, Invitae | 10:15 am ET
- Poster #491: Targeted next generation sequencing-based preimplantation genetic screening can enable detection of uniparental isodisomy, familial relationships, and polyploidy | Presented by Mark Umbarger, PhD, Good Start Genetics | 2:00 pm ET
- Poster #2870: Tracing the dark matter: Prevalence of copy number variants across Mendelian disorders | Presented by Rebecca Truty, Invitae | 3:00 pm ET
Friday, October 20:
- Presentation #222: Genetic screening for healthy individuals: Preliminary results from a medically actionable genetic screening panel | Presented by Eden Haverfield, PhD, FACMG, Invitae | 9:15 am ET
- Presentation #230: An interlaboratory study of complex variant detection in clinical testing | Presented by Stephen Lincoln, Invitae | 9:15 am ET
- Reviewer’s Choice Abstract | Poster #2463: Diagnostic yield for neurological and neuromuscular disorder testing via high-depth multi-gene panel analysis with integrated sequence and copy number detection | Presented by Tom Winder, PhD, FACMG, Invitae | 11:30 am ET
- Poster #978: High-depth multi-gene panel analysis with integrated sequence and copy number detection is a useful first-tier test with a high diagnostic yield and broad mutation spectrum detection in childhood epilepsy | Presented by Nila Patil, PhD, Invitae | 12:30 pm ET
- Poster #2617: Predisposition genetic screening for actionable cardiovascular conditions in patients undergoing heritable cancer syndrome testing: Prevalence of pathogenic variants in 10,812 individuals | Presented by Shan Yang, PhD, Invitae | 2:00 pm ET
Additional information on the ASHG Annual Meeting is available at www.ashg.org/2017meeting.
Invitae Corporation (NYSE: NVTA) is one of the fastest growing genetic information companies in the United States. Invitae Corporation's mission is to bring comprehensive genetic information into mainstream medical practice to improve the quality of healthcare for billions of people. Invitae's goal is to aggregate the world's genetic tests into a single service with higher quality, faster turnaround time, and lower prices. For more information, visit our website at invitae.com.
Safe Harbor Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, including statements relating to research that highlights the utility of evaluating both genetic variants and copy number variants on a single testing platform to help clinicians more quickly diagnose patients; and the ability of expertly curated, disease-specific panels to be a more rapid, cost-effective first step for diagnosis that can be used before exome testing when diagnosing epilepsy and neuromuscular disorders; that well-designed testing and innovative techniques can help shorten the often lengthy process of elimination that can accompany diagnosing genetic disease; and that genetic screening may yield actionable information in the absence of the usual indication for such testing based on personal or family history. Forward-looking statements are subject to risks and uncertainties that could cause actual results to differ materially, and reported results should not be considered as an indication of future performance. These risks and uncertainties include, but are not limited to: risks associated with the company’s ability to use rapidly changing genetic data to interpret test results accurately and consistently; laws and regulations applicable to the company’s business; the company’s history of losses; the company’s ability to compete; and the other risks set forth in the company’s filings with the Securities and Exchange Commission, including the risks set forth in the company’s Quarterly Report on Form 10-Q for the quarter ended June 30, 2017. These forward-looking statements speak only as of the date hereof, and Invitae Corporation disclaims any obligation to update these forward-looking statements.
NOTE: Invitae and the Invitae logo are trademarks of Invitae Corporation. All other trademarks and service marks are the property of their respective owners.
Source: Invitae Corporation