ClinSeq - Clinical and Behavioral Aspects

Biesecker, Leslie

Abstract

In FY2016 we have substantially advanced the goals and objectives for the ClinSeq clinical and behavioral project by performing the following ongoing substudies. Incidental findings. We are aggressively pushing into the area of malignant hyperthermia by convening an expert panel under the ClinGen umbrella to develop standards and evaluate variants for this important disease. I have also been appointed chair of the Clinical Pharmacogenetic Implementation Consortium working group on malignant hyperthermia. Randomized controlled trial of return of results As sequencing technology is new, it is important to understand how the medical system can take up this technology. As an important foundation for understanding many related questions, we have developed an extensive survey of baseline attitudes towards this sequencing technology. This survey has been completed, analyzed, and a draft publication will be submitted this fall. Our major effort in this domain is that we have completed recruitment for a large (n=400), controlled experiment with experimental arms that vary the mode of return of results to compare the classical model of direct clinician interaction with a new mode of web-based results return. This experiment will be key to discovering efficient modes of return of results. We are currently analyzing data for this study. We are also exploring participant reactions to variants of uncertain clinical significance. This is a major challenge in genomics and we have designed a trial where we will return variants of unknown significance either above or below the 50% threshold of likelihood of pathogenicity to gauge participant reactions to such variants, and measure their intentions to implement medical care based on these results.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Human Genome Research Institute (NHGRI)
• Type: Investigator-Initiated Intramural Research Projects (ZIA)
• Project #: 1ZIAHG200387-04
• Application #: 9358526
• Support Year: 4
• Fiscal Year: 2016

Institution

• Name: Human Genome Research

Publications

Biesecker, Leslie G (2018) Secondary findings in exome slices, virtual panels, and anticipatory sequencing. Genet Med :

Biesecker, B B; Woolford, S W; Klein, W M P et al. (2018) Correction to: PUGS: A novel scale to assess perceptions of uncertainties in genome sequencing. Clin Genet 93:1119

Porter, Kathryn M; Kauffman, Tia L; Koenig, Barbara A et al. (2018) Approaches to carrier testing and results disclosure in translational genomics research: The clinical sequencing exploratory research consortium experience. Mol Genet Genomic Med 6:898-909

Reid, Allecia E; Taber, Jennifer M; Ferrer, Rebecca A et al. (2018) Associations of perceived norms with intentions to learn genomic sequencing results: Roles for attitudes and ambivalence. Health Psychol 37:553-561

Hellwig, Lydia D; Biesecker, Barbara B; Lewis, Katie L et al. (2018) Ability of Patients to Distinguish Among Cardiac Genomic Variant Subclassifications. Circ Genom Precis Med 11:e001975

Biesecker, Leslie G (2018) Response to Mendelsohn and Sabbadini. Genet Med :

Bush, Lynn W; Beck, Anita E; Biesecker, Leslie G et al. (2018) Professional responsibilities regarding the provision, publication, and dissemination of patient phenotypes in the context of clinical genetic and genomic testing: points to consider-a statement of the American College of Medical Genetics and Genomics (AC Genet Med 20:169-171

Amendola, Laura M; Berg, Jonathan S; Horowitz, Carol R et al. (2018) The Clinical Sequencing Evidence-Generating Research Consortium: Integrating Genomic Sequencing in Diverse and Medically Underserved Populations. Am J Hum Genet 103:319-327

Miller, Ilana M; Lewis, Katie L; Lawal, Tokunbor A et al. (2018) Health behaviors among unaffected participants following receipt of variants of uncertain significance in cardiomyopathy-associated genes. Genet Med :

Tavtigian, Sean V; Greenblatt, Marc S; Harrison, Steven M et al. (2018) Modeling the ACMG/AMP variant classification guidelines as a Bayesian classification framework. Genet Med 20:1054-1060