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In December 2019, ClinGen published recommendations for application of the functional evidence PS3/BS3 criterion using the ACMG/AMP sequence variant interpretation framework (https://genomemedicine.biomedcentral.com/articles/10.1186/s13073-019-0690-2). This guidance should be incorporated into ClinGen VCEP specifications.
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The SVI functional assay evaluation group has put together this spreadsheet to assist you in presenting your work on PS3/BS3. This spreadsheet attempts to document the steps of the validation requirements that were outlined in the SVI paper on this topic (https://genomemedicine.biomedcentral.com/articles/10.1186/s13073-019-0690-2). This spreadsheet is meant to give your VCEP a way to document the general functional assays that are used in your field, and to evaluate specific instances of those assays.
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Basic instructions:
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Fill out one spreadsheet per gene.
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Each tab should be used for a “general class of assay” (e.g. “Cellular growth assay” or “Radioligand binding assay” etc.)  and each column should represent one “specific instance” (typically a publication) that uses that type of assay.
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You can use multiple columns to document specific examples of assays that do meet your VCEPs criteria for inclusion (and at what strength) as well as those that you evaluated but do not meet your threshold for PS3/BS3.  This will also help the SVI to compare the rigor of the controls that were used in each specific instance and the degree of clinical validation (the “known” controls that were evaluated in the assay).
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