Variant Interpretation Discrepancy Resolution Module
A module for clinical laboratory geneticists who are involved in the interpretation of genomic variants and are actively submitting variants to the ClinVar database. This module is available for Part IV Practice Improvement Credit through the American Board of Medical Genetics and Genomics (ABMGG).
Currently, a number of variants in ClinVar have been submitted by multiple submitters. In some instances, interpretations from different sources, including operating clinical laboratories, have different clinical significance assertions for the same variant. Although updated standards for interpreting genomic variants have allowed laboratories to resolve some differences, discrepancies remain due to differing interpretation methods, time points of interpretation, access to non-public evidence, and subjectivity in evidence evaluation. Collaboration to potentially resolve discrepant assertions, when possible, could lead to a more accurate reference database and to better health care for patients who harbor these variants.
Completing the Module:
- The module PDF that must be completed for each variant can be found here. Please note that Adobe Acrobat is needed to complete the module.
- To receive ABMGG Part IV credit, laboratory geneticists must complete this module for three variants where the laboratory geneticist’s submitting laboratory and at least one currently operating laboratory or expert consortium have a difference between the three major variant classification levels: “pathogenic (P) / likely pathogenic (LP)”, “uncertain significance (VUS)”, and “likely benign (LB) / benign (B).”
- To complete the activity, the laboratory geneticist should review their interpretation and, if needed, work with one or more of the other laboratories to attempt to resolve interpretation discrepancies.
- Once the module has been completed for three variants, the module can be submitted by emailing the three completed PDF documents to firstname.lastname@example.org. ClinGen staff will then review the module for completeness. If the module is completed at a satisfactory level, a certificate will be sent to the laboratory geneticist's email address. The certificate can then be submitted by the laboratory geneticist to ABMGG via the ABMGG portal for Part IV credit.
Questions? - Contact email@example.com
Resources to view variant classification discrepancies:
Developed by Danielle Azzariti, Steven Harrison, Heidi Rehm, Christa L. Martin, Juliann Savatt, Erin Riggs, with review by the ClinGen Education, Coordination and Training Working Group.