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Interpreting the Results of a Genetic or Genomic Test

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When interpreting the results of a genetic test, it is important to keep in mind the original purpose of the test. A positive result on a diagnostic test means something different than a positive result on a screening test. Test results are best interpreted within the context of the individual’s family and medical history. The table that follows provides an overview of the interpretation of positive results for different types of genetic tests. More details can be found in the text after the table.

If the test purpose was... The interpretation is... And follow-up includes genetic counseling and...
Diagnostic genetic testing Clinical diagnosis is confirmed Medical management and treatment; counseling for life planning
Predictive genetic testing The likelihood of showing disease symptoms is very high Counseling for life planning; Medical management if available
Susceptibility genetic testing Provides information about the likelihood of an outcome (e.g., disease, drug reaction) Counseling about risk reduction; increased screening and management, if available
Carrier genetic testing The patient is a carrier Testing offered to partner; prenatal testing offered if indicated
Prenatal genetic testing A fetus is diagnosed with a specific condition Pregnancy treatment/management or termination
Prenatal screening Chance for a disorder in a fetus is increased Additional, diagnostic testing offered

Newborn screening

Disease in a newborn is suggested Confirmatory testing; if positive, medical management and treatment
Carrier status in a newborn may be identified Carrier testing offered to parents

Diagnostic Tests

Positive test results
The laboratory found a change in a particular gene, chromosome, or protein of interest. A positive test may confirm a diagnosis, but generally cannot be used to predict the course or severity of a condition. In addition, our understanding of the health consequences of having a certain gene change may change over time as we learn more about how genes interact with other genes as well as with environmental factors. Positive results have implications for the risk of disease in certain blood relatives of the person undergoing testing.

Negative Test Results
The laboratory did not find a change in the gene, chromosome, or protein of interest. Interpreting a negative genetic test result depends upon several conditions of the test itself, including:

  • the accuracy of the test; that is, many genetic tests only detect a certain percentage of the mutations in any given gene
  • whether a mutation has been found in an affected family member; identifying a mutation in an affected relative (and not finding it in the person tested) improves the clinical utility of the negative result
  • whether the correct gene was tested; many phenotypes have more than one causative gene

Keeping these points in mind, a negative test result virtually rules out a particular disorder assuming the test is highly accurate and the individual’s symptoms can be attributed to other causes, or that an individual does not have a causative mutation that is in the family.

Ambiguous Test Results
The laboratory found a variation in the DNA that is not normal, but has not been associated with a disorder in other people. This type of result is difficult to evaluate because everyone has common natural variations in their DNA called polymorphisms that do not affect health, and sometimes it is difficult to tell whether a gene change is a polymorphism or a disease-causing mutation. Ambiguous results occur most often in diagnostic testing, and do not give any useful information (i.e., cannot confirm or rule out a specific diagnosis). In some cases, testing other affected and unaffected family members can help clarify this type of result.

Screening Tests

Positive test results
The laboratory found a level of protein or metabolite suggesting an increased risk for a specific condition. Newborns who have a positive screening test are offered additional diagnostic testing to confirm or rule out a particular disorder. Pregnant couples with a positive screening test are offered additional invasive prenatal testing to diagnose a condition in their fetus.

Negative test results
For newborn screening, a negative result means there is a very low chance that the baby has a specific condition. For prenatal/antenatal screening, a negative result is interpreted the same way; the fetus has a very low (although not 0) chance of having a serious genetic condition. Typically, no additional testing is suggested.

Predictive Tests

Positive test results
The laboratory found a mutation in the gene(s) of interest. In this case the individual is at high or certain risk for developing the condition; for example, a patient with a gene mutation that causes Huntington disease gene will develop the disease sometime in his/her adulthood, unless he or she dies of something else before the disorder develops. A female with a mutation in a gene for hereditary breast cancer has up to an 80% chance of developing breast cancer in her lifetime.

Negative test results
The laboratory did not find a mutation in the gene of interest. Interpreting a negative test result may depend on the accuracy of the test, whether a mutation has been found in an affected individual and whether the correct gene is being tested. For predictive testing, a negative test result typically means that the individual is at low or average risk of developing the condition.

Ambiguous test results
The laboratory found a variation in the DNA that is not normal, but has not been associated with a disorder in other people. This type of result is difficult to evaluate because everyone has common natural variations in their DNA called polymorphisms that do not affect health, and sometimes it is difficult to tell whether a gene change is a polymorphism or a disease-causing mutation. Ambiguous results occur most often in diagnostic testing, but also occur in predictive testing for genes of major effect. Such results do not give any useful information (i.e., cannot confirm or rule out a specific diagnosis). In some cases, testing other affected and unaffected family members can help clarify this type of result.

Susceptibility tests

Positive test results
The laboratory detected genetic variations that indicate that an individual is at increased risk for some outcome (e.g., disease, diet interaction, drug reaction). The overall risk assessment after a positive susceptibility test may depend on other factors such as family and medical history, exposures, diet, and lifestyle. Individuals determined to be at increased risk could be managed and followed more aggressively than those found to be at average or low risk. Interpreting the results of many susceptibility tests, including nutritional genomic testing, is complex because these tests generally evaluate for variations in multiple genes, and the results must be interpreted as a whole. Interpretation depends on which genes have been tested and the strength of the association between the genetic variants and the outcome in question.

Negative test results
The laboratory did not find genetic variations associated with increased risk for a specific outcome, or the laboratory found variants associated with decreased risk for a specific outcome. The interpretation of this test result may depend on other factors such as family and medical history, exposures, diet, and lifestyle. Interpreting the results of many susceptibility tests, including nutritional genomic testing, is complex because these tests generally evaluate for variations in multiple genes, and the results must be interpreted as a whole. Interpretation depends on which genes have been tested and the strength of the association between the genetic variants and the outcome in question.

Getting more help

  • Lab reports will typically provide an interpretation of the results and contact information. This can be a valuable resource if you need further information or clarification about the test results.
  • Contact a genetics professional if you have questions about test results; you can find a local contact at www.nsgc.org or www.ashg.org.