Incidental Findings and Return of Results

Incidental findings (often termed secondary findings when deliberately sought) are genetic results unrelated to the original reason for testing — for example, a cancer-predisposition variant discovered during sequencing for an unrelated condition. Genome-scale sequencing makes such findings common, raising the question of what, if anything, should be looked for and returned to patients and research participants.

Definition

An incidental finding is a result that has potential health importance but is unrelated to the indication for which a test was ordered; a secondary finding is one that a laboratory deliberately analyses and may report alongside the primary result. Return of results refers to the policies governing whether and how such findings are communicated to patients or research participants.

Scope

This entry covers the distinction between incidental and secondary findings, the ethical arguments for and against returning them, the major professional recommendations that shaped clinical practice, and the parallel debate in research settings. It is a reference overview and does not advise on whether any specific result should be sought or disclosed in an individual case.

Core questions

• What is the difference between incidental and secondary findings?
• Should laboratories actively look for findings beyond the test indication?
• Which findings are important enough to warrant return, and who decides?
• How do the duties to return results differ between clinical care and research?

Key concepts

• Incidental versus secondary findings
• Actionability and medical utility
• Opt-out and patient choice
• Minimum gene list for reporting
• Duty to return results
• Reanalysis and recontact

Mechanisms

When an exome or genome is sequenced, the data contain far more medically relevant variants than the test indication requires, so a policy is needed for which to examine and report. The influential clinical approach proposed a defined minimum list of genes considered both clinically significant and actionable, to be analysed whenever genome-scale sequencing is performed, with subsequent updates refining the list and incorporating patient choice about whether to receive such findings. In research, where there is no clinician of record, recommendations focus on planning in advance how potentially important findings will be evaluated and offered to participants.

Clinical relevance

Decisions about seeking and returning secondary findings affect informed consent, the scope of testing, and follow-up care. This entry summarises the major recommendations and debates for educational orientation; it is not a protocol, and which findings are analysed or returned depends on laboratory policy, professional guidance, and patient preferences.

Evidence & guidelines

Clinical practice was strongly shaped by professional recommendations: an initial list of genes recommended for analysis and reporting in clinical exome and genome sequencing, a policy update adding the option for patients to decline such findings, and a 2016 revision (SF v2.0) updating the gene list. In the research context, an interdisciplinary consensus set out how investigators should anticipate and manage incidental findings and offer them to participants. These are professional guidance documents, not individualised advice.

History

The issue rose to prominence as clinical exome and genome sequencing entered practice around 2011-2013, when it became clear that comprehensive sequencing would routinely uncover findings beyond the test indication. Professional recommendations from 2013 onward, with subsequent updates, defined which findings to seek and report, while parallel work addressed the distinct duties owed to research participants.

Debates

Should secondary findings be sought, and can patients decline them?

Early recommendations to analyse a defined gene list whenever genome sequencing was performed prompted debate about patient autonomy, leading to a policy update that allowed patients to opt out of receiving secondary findings.

Key figures

• Robert C. Green
• Leslie G. Biesecker
• David T. Miller
• Susan M. Wolf

Seminal works

• green-2013
• kalia-2017
• wolf-2008

Frequently asked questions

What is the difference between an incidental and a secondary finding?

An incidental finding is discovered unexpectedly, unrelated to the test's purpose, whereas a secondary finding is one a laboratory deliberately analyses and may report alongside the primary result. The terms are sometimes used loosely, but professional guidance increasingly favours 'secondary findings' for those that are actively sought.

Do patients have to receive secondary findings?

Not necessarily. After initial recommendations to analyse a defined gene list, professional guidance was updated to let patients opt out of receiving secondary findings, reflecting respect for individual choice. The specifics depend on laboratory policy and the applicable guidance.