VITAL (Variant Interpretation Testing Across Laboratories)
NGS testing laboratories classify many variants routinely. In recognition of the non-uniformity of variant classification, ACMG formed a working group with representation from AMP and CAP to address laboratory practice and recently published a consensus guideline for a variant classification system. While this guidance recommendation is a good step forward to help achieve uniformity in variant classification across laboratories, it requires widespread testing and validation to assess its strengths and weaknesses and fine tune the process. For the greater good of the genetics community, VITAL (Variant Interpretation Testing Across Laboratories) was launched in 2016.
- All VITAL challenges should be completed individually. Individuals who wish to participate will sign up by registering at the link below. If you have any questions about VITAL, please contact us. Registration for the second round of variant challenges will remain open until May 2, 2017. If you signed up as an individual participant for Round 1, you do not need to register again.
- Registered participants will be provided the first set of 5 annotated variants on or before May 10, 2017 with a second set of 5 variants to follow approximately 4 weeks later. Challenges were selected from cases submitted for germline testing. Individual participants are strongly encouraged to complete all 10 challenges in Round 2.
- Information about the gene, RefSeq, sequence change and protein change (using HGVS nomenclature), zygosity, the case scenario for each variant, as well as a spreadsheet of evidences, including population frequencies, in silico algorithm predictions and references as a minimum data set will be provided.
- Participants are encouraged to use other information consistent with their assessment processes.
- Participants will be asked to use the terminology (pathogenic, likely pathogenic, VUS, likely benign, benign) and the ACMG/AMP guidelines to classify these 10 cases using the evidences described in the ACMG/AMP publication and enter their classification and evidences used to reach that classification online.
- Participants will also be asked to rate the level of difficulty in classifying these variants as well as questions to assess their use of ACMG/AMP guidelines in clinical practice of variant classification.
- The participant list will be anonymized so the Working Group will not know the identity of individual submissions.
The Working Group will analyze the data and present the findings in a webinar to which all participants are invited. The areas of the guidelines that show inconsistency across laboratories will be highlighted with a plan to improve. Participants will not receive a personalized report as this project is not structured in a PT challenge format. All participants will receive simultaneous access to all response data in conjunction with final manuscript publication. Participant identities are blinded to both the project team and in any public data presentation.
Feedback received from the variant classification exercise will be utilized to draft recommendations for revision/ improvement of guidelines which will be communicated via AMP-guided educational initiatives. Participants will be acknowledged in the resulting manuscript.
AMP's VITAL Working Group
Dr. Elaine Lyon
Dr. Sherri Bale
Dr. Julie Gastier-Foster
Dr. Madhuri Hegde
Dr. Carolyn Sue Richards