Your Exome Test Found a Disease You Weren’t Looking For? | SF Series Part 1

📍 Key Takeaways

1. What are secondary findings? They are genetic results unrelated to the original reason for testing, but knowing about them in advance can help with prevention or treatment.
2. Not every chance finding qualifies. Only a select group of genes associated with clinically actionable conditions is intentionally analyzed and reported.
3. Knowing early means you can act. Earlier screening, preventive treatment, and avoidance of specific medications are all steps that can genuinely change a health outcome.

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You had exome sequencing done to find the cause of a rare disease.

But what if the results reveal a risk of hereditary cancer or heart disease that has nothing to do with the current symptoms?

When genetic information unrelated to the original purpose of testing—but important for future health—is identified, it is referred to as a secondary finding.

What are secondary findings?

Put simply:

A genetic result that is unrelated to the condition currently under investigation, but that can be used for prevention or treatment if identified in advance.

For example, imagine exome sequencing is performed to find the cause of a developmental delay, and a pathogenic variant associated with hereditary arrhythmia or hereditary cancer may also be identified. This result does not explain the developmental delay itself. What it can do, however, is help detect or prevent a serious condition that might otherwise arise later on.

Why are unrelated conditions detected?

Exome sequencing does not look at just a single gene. It analyzes the protein-coding regions of thousands of genes simultaneously.

As a result, it can reveal not only variants related to the condition originally suspected, but also variants associated with entirely different conditions.

That said, secondary findings are not simply every result that happens to appear during analysis. They are closer to results confirmed by intentionally examining a select group of medically important genes.

Is this the same as an incidental finding?

The two terms are often used in similar ways, but there is a meaningful distinction.

Secondary findings are results obtained by intentionally examining specific genes—genes that have no direct connection to the current symptoms, but that may help with prevention or treatment.

Incidental findings are results discovered unexpectedly in the course of analyzing the original purpose of the test.

In other words, the secondary findings defined by the ACMG are not about reporting every unexpected result to a patient. They are a curated set of conditions that carry significant medical meaning and for which real, actionable steps exist once the result is known.

Why are these results shared?

The most important reason is a simple one: knowing early can change a health outcome.

Knowing about a genetic risk in advance makes it possible to begin steps such as:

• Routine screening earlier than the general population
• Cardiac evaluation or cancer screening
• Preventive medication
• Avoidance of certain anesthetics or drugs
• Genetic testing for family members

A secondary finding is not merely information about the possibility of future disease. It is information that offers an opportunity to intervene before disease develops.

Not every condition is reported

Exome sequencing uncovers a great many genetic variants. Most of them, however, are simply normal differences between individuals, or variants whose significance cannot be determined with current medical knowledge.

To be reported as a secondary finding, a variant generally needs to meet the following conditions:

• The relationship between the gene and the disease is well established
• The variant is known to be associated with disease risk
• Options exist for early screening, prevention, or treatment

This quality—the ability to translate a result into concrete medical action—is known as clinical actionability.

In a single sentence

Secondary findings are genetic results that fall outside the original purpose of a test, but that are examined separately because identifying them early can support the prevention, early diagnosis, or treatment of serious conditions.

So, among the countless genetic conditions that exist, which ones are selected to be reported?

In the next post(Coming August 10), we’ll take a closer look at the ACMG Secondary Findings list and the key conditions it covers.

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Received an unexpected secondary finding? Get clear, gene- and condition-specific clinical action guidance drawn from trusted sources—including the ACMG ACT Sheets, GeneReviews®, and the NCCN Guidelines. Find your next steps on the page below.