Table 1 –

Summary of the pilot ClinGen Variant Curation Expert Panels (VCEPs)

	MYH7/Inherited Cardiomyopathies	PTEN	RASopathies	PAH
Group Structure and Process	Core group proposed specifications for full EP review	Subgroups formed by different evidence lines. Full EP proposed and reviewed specifications	Subgroups formed by expertise and gene disease mechanism. Subgroups proposed specifications for full EP review	Core group proposed specifications for full EP review
Initial Guideline Optimization	Proposals refined by iterative rounds of curation and feedback	Subgroups curated literature specific to the evidence line and presented to full EP	General proposals refined by iterative rounds of curation and feedback Subgroups curated gene-specific literature to supplement use of specific rules (e.g. functional data)	Proposals refined by iterative rounds of curation and feedback
Consensus	Majority (66%)	Full (100%)	Majority (80%)	Full (100%)
Timeline	1/2015–4/2017	7/2015–4/2018	5/2015–7/2017	10/2014–4/2018
Curation Pilots	60 Variants: 50 Missense 3 Deletion 7 Others	42 Variants: 15 Benign/Likely Benign 16 Path/Likely Path 11 VUS/Conflicting	~15 Variants per gene for 9 genes: 5 Path 5 Non-conflicting 5 Conflicting	15 Missense Variants: 8 Path 7 VUS
Pilot Curation Method	One curator per variant	Two curators per variant	Two curators per variant	One curator per variant
Reviewers	Blinded double expert review (clinical and laboratory) per variant	Full EP	Triple review (clinical/research subspecialist of the gene(s) and two additional EP members)	Full EP
Conflict resolution	Core team with EP engagement as needed	Full EP discussion and voting	Full EP discussion and voting	Full EP discussion and voting
Key Lessons	Consensus determination	Recycle rule specifications that have already been successful	Subjective criteria; time intensive	Use a majority consensus approach in the future