P687: A master in mimicry: Expanding the renal phenotype of COL4A1-related disorders

SD 13.2, range 2-74).The Mendelian category generated the most VUS, which is expected given that it had the largest gene list; our expanded medically actionable gene list and the ACMG subset generated fewer VUS.Given the broader scope of analysis, variant filtration, variant classification and report preparation were substantially more time consuming in the intervention arm compared to the control arm.Variant filtration took 7.7 times longer per case (95% CI 5.3 to 11.3, p<0.0001; 65.7 vs 8.5 minutes on average per case).Variant classification took 13.3 times longer (95% CI 10.6 to 16.5, p<0.0001; 497.8 minutes vs 37.4 minutes on average per case), and report preparation took 3.3 times longer (95% CI 2.6 to 4.1, p<0.0001; 157.2 minutes vs 47.9 minutes on average per case).SFs related to monogenic disease risk were reported in 35.3% (49/139) of participants, ACMG-recommended SFs in 1.4% (2/139), carrier status in 89.3% (117/131), pharmacogenomic variants in 97.8% (135/138), and risk variants in 89.4% (118/132).Conclusion: While the yield of reportable SFs was high, this was accompanied by many non-reportable VUS, which substantially increased the time required for exome analysis and reporting.Analytic approaches that streamline variant prioritization and classification, such as through greater use of automation, may help promote the feasibility of offering a broad range of clinically relevant SFs.