|Section of the report ||Action(s) ||Concern(s) |
|Patient identification || |
- Verify the patient identification with at least two independent identifiers.
- Repeat testing if clinically indicated* and the original testing does not have a proper "chain of evidence."
- Individuals may inadvertently provide the wrong name or date of birth on a test sample.
- Testing should be done by a laboratory that can ensure that the identification matches the tested individual.
|Testing laboratory || |
- Verify that testing was done in a CLIA-certified laboratory (or other nationally certified laboratory).
- Repeat testing if clinically indicated and/or if original results are actionable and testing was not performed in a CLIA or other nationally certified laboratory.
- All actionable medical testing (eg, positive finding or negative finding in an individual suspected of having a genetic disorder) should be conducted in a CLIA-certified laboratory (or other nationally certified laboratory) that has met appropriate quality standards for performing the specific test.
- In the United States, most certification is performed by the College of American Pathologists (CAP) and a CAP number for the laboratory is listed.
- Some direct-to-consumer testing in some countries is not performed in certified laboratories and may lack appropriate quality controls.
|Date of testing || |
- Review the testing date.
- Request reinterpretation of the results if the interpretation is inconclusive (eg, a variant of uncertain significance [VUS]).
- Germline variants do not change over time. However, as new data become available, the classification of variant pathogenicity may change, especially for variants classified as variant of uncertain significance (VUS).
- Repeat testing may be considered, as the technologies for exome sequencing may improve and may identify a variant missed on a prior test.
|Gene(s) tested || |
- Verify which genes were tested.
- If testing was performed to evaluate a medical condition or a familial disorder, ensure that the correct gene(s) were included.
- If new research has identified new disease genes, additional testing may be appropriate.
- Not all genetic testing panels are comprehensive for the genes that can cause a particular health condition or for the variants in those genes that the panel evaluates.
- New disease genes or clinically important variants in existing genes may be identified through further research.
|Testing method || |
- Review whether the gene(s) were evaluated using genome sequencing, exome sequencing, panel testing, or other methods such as Sanger sequencing for a specific variant.
- Not all methods will identify all variants.
- In some cases such as HFE testing, only one or two variants are clinically relevant, and sequencing of the entire coding region of the gene is not required, whereas in other conditions, limited testing for one or two variants may miss clinically important findings.
- Gene panels may be especially useful when multiple genes could potentially be responsible for a clinical phenotype.
|Classification of pathogenicity || |
- Review the category of pathogenicity that was assigned to each variant.
- For a variant of uncertain significance (VUS; or any variant for which interpretation is inconclusive), consider requesting reinterpretation annually and/or before making a final decision on interventions.
Interpretation of pathogenicity incorporates many data sources including laboratory research, research databases, population studies, and pedigree analyses.
- In some cases, pathogenicity is well established (eg, the known variant that causes sickle cell disease); in others, it is more subjective and incomplete. The designation of a variant of uncertain significance (VUS) refers to the lack of available information on pathogenicity for the variant; further information may eventually allow pathogenicity to be determined.
- Variants of uncertain significance (VUS), likely benign, or benign are generally not considered actionable and should not impact medical interventions, which would typically be based on personal and family history of disease.
- Consulting a publicly curated database such as ClinVar (or other disease-specific specialty database), discussing the results with an expert in the specific disease, or referral to a clinical geneticist, genetic counselor, or disease expert may be helpful.