Reporting Incidental Findings in Genomic Scale Clinical Sequencing—A Clinical Laboratory Perspective

Abstract

Advances in sequencing technologies have facilitated concurrent testing for many disorders, and the results generated may provide information about a patient's health that is unrelated to the clinical indication, commonly referred to as incidental findings. This is a paradigm shift from traditional genetic testing in which testing and reporting are tailored to a patient's specific clinical condition. Clinical laboratories and physicians are wrestling with this increased complexity in genomic testing and reporting of the incidental findings to patients. An enormous amount of discussion has taken place since the release of a set of recommendations from the American College of Medical Genetics and Genomics. This discussion has largely focused on the content of the incidental findings, but the laboratory perspective and patient autonomy have been overlooked. This report by the Association of Molecular Pathology workgroup discusses the pros and cons of nextgeneration sequencing technology, potential benefits, and harms for reporting of incidental findings, including the effect on both the laboratory and the patient, and compares those with other areas of medicine. The importance of genetic counseling to preserve patient autonomy is also reviewed. The discussion and recommendations presented by the workgroup underline the need for continued research and discussion among all stakeholders to improve our understanding of the effect of different policies on patients, providers, and laboratories. (J Mol Diagn 2015, 17: 107e117; http://dx

CAGI4 SickKids clinical genomes challenge: A pipeline for identifying pathogenic variants

“…Reporting of predictive secondary variants to the patients is a highly debated subject (Shahmirzadi et al 2014), because of potential false positives (Kohane et al 2006; Biesecker 2013; Hegde et al 2015). Indeed, we found 22 candidate variants in the ACMG approved 56 gene set, and is likely nearly all of these are sequence errors.…”

Standards and Guidelines for the Interpretation and Reporting of Sequence Variants in Cancer

“…107,109 For secondary findings revealed in germline testing, the ACMG recommends disclosure of positive germline results for 53 genes, approximately half of which are associated with cancer predisposition susceptibility genes that will likely be on somatic testing panels. 108 Disclosure is recommended even when the germline is only being evaluated as part of a tumor/normal study.…”

The Continuing Evolution of Ethical Standards for Genomic Sequencing in Clinical Care: Restoring Patient Choice

“…Instead, the AMP group endorsed “opt-in or opt-out…in the precounseling session.” 31 The group elaborated, [P]ersons undergoing WES or WGS should have the opportunity to opt-in or opt-out of receiving a report that documents variants that are not relevant to the initial reason for testing…. Most patients will likely opt-in, given the opportunity to receive additional information that could be used to improve their health.…”