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Indications for Exome Testing

Exome may be used in the prenatal, neonatal, pediatric, or adult setting. Although recommendations for the indications for exome testing are continually evolving, the American College of Medical Genetics and Genomics (ACMG) recommended in its policy statements in 2012 and 2021 that exome testing is indicated when:

  • the patient's clinical signs and symptoms, and possibly the family history, strongly implicate a genetic etiology but the presentation does not correspond with a specific disorder
  • the patient has an atypical presentation of a suspected genetic condition
  • the patient presents with a defined genetic condition that is known to be associated with multiple genes (genetic heterogeneity)

Exome testing may be indicated:

  • as a first- or second-line test for certain patients, such as pediatric patients with one or more congenital anomalies prior to one year of age, or for patients with intellectual disability/developmental delay prior to 18 years of age
  • when there is clinical urgency
  • for patients with a likely genetic disorder when specific genetic tests have failed to arrive at a diagnosis

Other professional societies for specialties such as obstetrics, pediatrics, cardiology, and neurology also have published recommendations about indications and considerations of exome testing.

Please see Tools and Resources for a list of published clinical guidelines.

Possible contraindications for exome testing

Exome testing may not be the best choice for your patients when:

  • a pathogenic variant has already been identified in the family, and targeted testing for this particular variant in relatives is typically most efficient and cost-effective
  • the clinical symptoms align with a known syndrome, and targeted testing of the associated gene or genes may be indicated before exome testing
  • other testing methods may be better at detecting certain types of genetic variants

There are also situations for which evidence is not yet strong enough to recommend exome testing routinely. For example, while fetal exome sequencing may be indicated in certain situations, the American College of Genetics and Genomics and the American College of Obstetricians and Gynecologists recommend against routine exome testing for prenatal screening.

Exome testing is not currently recommended as a screening tool for genetic conditions in healthy individuals. Family history risk assessment is still the best first-line screen for risk of hereditary disease.

Even if exome testing appears to be indicated for your patient, certain patient characteristics may guide the decision whether or not to pursue it, such as:

  • anticipated anxiety over uncertain findings
  • concerns about discrimination and stigma
  • lack of insurance coverage

Each patient or family will weigh factors for and against testing differently. The role of the referring provider is to prepare patients for these conversations with the genetic specialist.