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Risks and Limitations of Exome Testing

Published Date

Like all tests, exome testing has risks and limitations in addition to benefits. There are a number of factors to consider that may affect an individual’s decision whether to pursue exome testing.

  • Exome testing does not detect all types of genomic variants.*
  • Reporting of variants detected depends on clinical presentation.
  • Access to parental samples can aid in interpretation, but parental samples are not always available.
  • Many variants will be identified for which the lab is unable to determine the clinical significance.
  • Interpretation of results may be subject to change. Reanalysis of data can alter the previously reported test results.
  • If a lab does not have a policy on reanalysis, new information may be missed if the patient’s providers do not request reanalysis.
  • Exome testing may reveal unexpected causes of a given patient’s phenotype, with unexpected associated risks.
  • Secondary findings are a possibility, and variants associated with adult-onset conditions may be identified in children.
  • Exome testing does not currently assess for all conditions with a genetic component, such as multifactorial conditions due to multiple low- to moderate-penetrance variants in combination with environmental factors.
  • Exome with parental (trio) testing may incidentally reveal unexpected family relationships (e.g., nonpaternity).
  • Patients, especially those who have experienced a long-term diagnostic odyssey, may be disappointed if exome testing does not return any actionable information.
  • Exome testing may introduce emotional, ethical, legal or social issues, such as genetic discrimination.

See the Talking Points About Exome Testing tool for tips to prepare patients for possible exome testing and the GINA resource for more information about genetic discrimination protections.

*Reasons a variant might not be reported

  • The patient may have a disorder that is not due to a genetic cause.
  • As stated above, there may be a causal genetic variant that the technology is not able to detect.

There may be a causal variant detected by the technology, but not reported for a number of reasons, such as:

  • Due to limitations in current knowledge about many variants and associated disease, a variant that is thought to be benign or a variant of uncertain significance (VUS) may not be reported.
  • Labs use complex interpretation algorithms, and filtering of data will impact what is reported.

See the factsheet on Variant classification and reanalysis in exome testing for more information.