Types of germ line test results with communication tips and follow-up recommendations for cascade testing
| Classification . | Implications . | How to convey to a patient . | Cascade testing recommended . |
|---|---|---|---|
| Pathogenic/likely pathogenic (causal) | Diagnostic, explains phenotype, and potentially guides treatment/management | We have found a genetic variant, often referred to as a mutation. This result explains why you developed your disease and is helpful for understanding your treatment options and how we can best care for you now and in the future. | Yes |
| Pathogenic/likely pathogenic (incidental) | Does not explain phenotype but can still be important for personalized care and long-term management/surveillance | We have found a genetic variant, often referred to as a mutation. This result provides important health information for you, but it is not related to the reason we did the testing, and it does not explain why you developed your disease. | Yes |
| Pathogenic/likely pathogenic (carrier) | Does not affect patient’s health and provides reproductive information | We have found a genetic change, often referred to as a mutation. This result does not affect your health but could be important for you and/or your family members who are planning on having children. | Yes |
| Variant of uncertain significance | Not enough data to support pathogenic or benign classification, so generally should not be used to guide medical management (with exceptions as detailed in the row below) | We have found a genetic change that has not been seen in enough people to know if it increases the risk of having a disease or if it is simply a normal variation. This is a very common result; we all have differences in our genes, and most do not cause disease. We do not recommend any changes to your care based on this result. | Typically, no, but should be considered if segregation data will help to reclassify the variant as pathogenic |
| Suspicious variant of uncertain significance | Curation according to ACMG guidelines meets the VUS criteria; however, some features render the variant suspicious enough to potentially inform management. This particularly applies to variants in genes recently identified as disease-causing. The genetic report should indicate when concerning or suspicious features are present in a novel variant, but the provider must think critically about the evidence in light of the patient’s phenotype. The report should also indicate the possibility of variant reclassification in the future. | We have found a genetic change that we believe may be causative of your condition, which by traditional classification tools is considered of uncertain significance. This can often be the case when new genes are associated with a disease. Despite the laboratory's classification as uncertain, we believe that there is enough evidence for us to factor this genetic change into our decision-making for your care. It is possible that the report may be updated when more information about the gene or condition becomes available in the future. | Yes, if it will aide in interpretation or reclassification of the variant, or if despite the inherent uncertainty the provider is recommending following up more closely with family members who have the VUS. Depending on the particular situation cascade testing may be more appropriate to perform on a research basis rather than a clinical basis. |
| Negative∗ | No variants identified in the genes that were analyzed with the technology that was used. Does not completely rule out an underlying genetic condition | We did not find any genetic changes in the genes included on your testing. This can be reassuring, but genetic testing is not perfect, and more testing may be available in the future. | N/A |
| Classification . | Implications . | How to convey to a patient . | Cascade testing recommended . |
|---|---|---|---|
| Pathogenic/likely pathogenic (causal) | Diagnostic, explains phenotype, and potentially guides treatment/management | We have found a genetic variant, often referred to as a mutation. This result explains why you developed your disease and is helpful for understanding your treatment options and how we can best care for you now and in the future. | Yes |
| Pathogenic/likely pathogenic (incidental) | Does not explain phenotype but can still be important for personalized care and long-term management/surveillance | We have found a genetic variant, often referred to as a mutation. This result provides important health information for you, but it is not related to the reason we did the testing, and it does not explain why you developed your disease. | Yes |
| Pathogenic/likely pathogenic (carrier) | Does not affect patient’s health and provides reproductive information | We have found a genetic change, often referred to as a mutation. This result does not affect your health but could be important for you and/or your family members who are planning on having children. | Yes |
| Variant of uncertain significance | Not enough data to support pathogenic or benign classification, so generally should not be used to guide medical management (with exceptions as detailed in the row below) | We have found a genetic change that has not been seen in enough people to know if it increases the risk of having a disease or if it is simply a normal variation. This is a very common result; we all have differences in our genes, and most do not cause disease. We do not recommend any changes to your care based on this result. | Typically, no, but should be considered if segregation data will help to reclassify the variant as pathogenic |
| Suspicious variant of uncertain significance | Curation according to ACMG guidelines meets the VUS criteria; however, some features render the variant suspicious enough to potentially inform management. This particularly applies to variants in genes recently identified as disease-causing. The genetic report should indicate when concerning or suspicious features are present in a novel variant, but the provider must think critically about the evidence in light of the patient’s phenotype. The report should also indicate the possibility of variant reclassification in the future. | We have found a genetic change that we believe may be causative of your condition, which by traditional classification tools is considered of uncertain significance. This can often be the case when new genes are associated with a disease. Despite the laboratory's classification as uncertain, we believe that there is enough evidence for us to factor this genetic change into our decision-making for your care. It is possible that the report may be updated when more information about the gene or condition becomes available in the future. | Yes, if it will aide in interpretation or reclassification of the variant, or if despite the inherent uncertainty the provider is recommending following up more closely with family members who have the VUS. Depending on the particular situation cascade testing may be more appropriate to perform on a research basis rather than a clinical basis. |
| Negative∗ | No variants identified in the genes that were analyzed with the technology that was used. Does not completely rule out an underlying genetic condition | We did not find any genetic changes in the genes included on your testing. This can be reassuring, but genetic testing is not perfect, and more testing may be available in the future. | N/A |
ACMG, American College of Medical Genetics and Genomics; N/A, not applicable.
A negative result indicates that no pathogenic variants, likely pathogenic variants, or VUSs were reported. The patient may have benign and likely benign variants, but these variants are not typically included on the test report.