In July 2017, the SVI Working Group, representing clinical geneticists, genetic counselors, genomic researchers, and clinical laboratory geneticists, held a two-day in-person meeting in Boston, MA to specifically refine and extend several ACMG/AMP criteria including the PVS1 criterion. During this meeting, the group outlined a detailed framework for evolving the previous PVS1 criterion into the current recommendations in this report. Subsequently, a smaller group within the ClinGen Hearing Loss (HL) Working Group continued further refinement of this rule through weekly conference calls and solicited feedback from the SVI Working group via monthly conference calls.
In October 2017, the SVI Working Group held a second in-person meeting at the American Society of Human Genetics (ASHG) meeting in Orlando, FL. During that meeting, the group finalized a first recommendation draft and provided comments for additional refinements that were addressed through the HL group and later approved by the SVI Working Group.
Throughout the PVS1 criterion refinement process, we used expert opinions, empirical data in the literature, and unpublished observations from participating research and clinical laboratories. In addition, to ensure comprehensive utility of the new rule, seven ClinGen Clinical Domain Working Groups (CDWGs) were asked to use this rule to classify five to ten LoF variants each in their genes of interest (total 56 variants in ten genes). Their feedback was then incorporated into the final PVS1 recommendations.
In October 2017, the SVI Working Group held a second in-person meeting at the American Society of Human Genetics (ASHG) meeting in Orlando, FL. During that meeting, the group finalized a first recommendation draft and provided comments for additional refinements that were addressed through the HL group and later approved by the SVI Working Group.
Throughout the PVS1 criterion refinement process, we used expert opinions, empirical data in the literature, and unpublished observations from participating research and clinical laboratories. In addition, to ensure comprehensive utility of the new rule, seven ClinGen Clinical Domain Working Groups (CDWGs) were asked to use this rule to classify five to ten LoF variants each in their genes of interest (total 56 variants in ten genes). Their feedback was then incorporated into the final PVS1 recommendations.
