About CeGaT’s VUS Re-Evaluation
Research on human genetics and rare disease genomics is rapidly advancing. Scientific findings can shed new light on unclear cases where a lack of evidence at the point of analysis has rendered impossible the assessment of the variant’s pathogenicity and to consider it in clinical decision-making.
CeGaT now offers a service that aims to clarify such variants of uncertain clinical significance (VUS) in the long term:
Our goal is to offer the best possible diagnostics for all patients. Therefore, we follow the scientific progress concerning the reported VUS, as new findings can change their evaluation. We proactively inform you when the pathogenicity of the variant has been clarified and whether the re-evaluation is relevant for your patient. On request, we will issue a new report on the basis of these findings.
VUS re-evaluation helps you to treat patients optimally: Once the contribution of a VUS to the phenotype of your patient has been clarified, you can consider this information in the treatment. Studies show that re-evaluation of VUS significantly improves diagnostic yield.
Key aspects of CeGaT’s VUS re-evaluation
- Solves cases with identified variants of uncertain clinical significance (VUS)
- Supports physicians in making a valid genetic diagnosis and in clinical decision making
- Procedure:
- Automatic follow-up of scientific progress related to reported VUS for two years after medical report got issued
- Proactive information in case of re-classification and, if desired, reinterpretation of genomic data and reissue of medical report based on newest findings
- Within further three years after the initial two-year period, information on VUS reclassifications can be requested once a year
- Free of charge
- Considering all relevant databases, literature, and in-house findings
- Available for germline diagnostics: Single Gene Testing, Panel Diagnostics, Exome Diagnostics
- Standard for medical reports issued from October 1, 2019, on request also available for previous analyses
Classification of Variants – What is a VUS?
Technological progress allows the identification of plenty of variants in an ever-growing number of known genes and gene regions associated with diverse disorders. For an easier interpretation, sequence variants are categorized by their clinical significance, in the sense of whether they affect gene function and hence could cause the patient’s phenotype. The American College of Medical Genetics and Genomics has defined five classes as a clinical decision-making framework.
- Class 1 – benign: The variant is not causative.
- Class 2 – likely benign: There is a strong indication that the variant is not causative.
- Class 3 – variant of uncertain clinical significance (VUS): There is not enough evidence for an assessment of whether the variant is causative or not.
- Class 4 – likely pathogenic: There is strong evidence that the variant is causative.
- Class 5 – pathogenic: The variant is causative.
For VUS, at the point of analysis, it is still unknown if they are relevant to disease or if they are benign variations. Thus, they cannot be considered either for risk assessment of disease outbreak or for clinical decision-making and challenge counseling and managing patients.
Our Service
CeGaT has established a straightforward re-evaluation process: For two years after the medical report got issued, we will regularly review the current scientific status of the VUS reported for your patients. If new information lead to a better understanding and reclassification of the variant to “benign”, “likely benign”, “likely pathogenic”, or “pathogenic”, we proactively report them to you. If desired, we reanalyze and reinterpret the test results for the variant based on the new findings and issue an updated medical report.
After the initial period, you can request once a year information about the status of your patient’s VUS for further three years.
The VUS re-evaluation is free of charge. It is carried out as a standard for all test results from Single Gene Testing, Panel Diagnostics, and Exome Diagnostics issued after October 1, 2019. If you wish a re-evaluation of medical reports generated before October 1, 2019, please contact our sales team (sales@cegat.de).
