biostudies-literatureUnknown17(1)Yaldiz BExome and genome sequencing are the predominant techniques in the diagnosis and research of genetic disorders. Sufficient, uniform and reproducible/consistent sequence coverage is a main determinant for the sensitivity to detect single-nucleotide (SNVs) and copy number variants (CNVs). Here we compared the ability to obtain comprehensive exome coverage for recent exome capture kits and genome sequencing techniques. We compared three different widely used enrichment kits (Agilent SureSelect Human All Exon V5, Agilent SureSelect Human All Exon V7 and Twist Bioscience) as well as short-read and long-read WGS. We show that the Twist exome capture significantly improves complete coverage and coverage uniformity across coding regions compared to other exome capture kits. Twist performance is comHuman genomics39https://www.ebi.ac.uk/biostudies/studies/S-EPMC10155375biostudies-literatureTwist exome capture allows for lower average sequence coverage in clinical exome sequencing.PMC10155375Yaldiz BKucuk EYntema HGHoischen AGilissen CSolve-RD consortiumHofste TCorominas Galbany JNelen MPfundt RHampstead JRinne TfalseTwist exome capture allows for lower average sequence coverage in clinical exome sequencing.Exome and genome sequencing are the predominant techniques in the diagnosis and research of genetic disorders. Sufficient, uniform and reproducible/consistent sequence coverage is a main determinant for the sensitivity to detect single-nucleotide (SNVs) and copy number variants (CNVs). Here we compared the ability to obtain comprehensive exome coverage for recent exome capture kits and genome sequencing techniques. We compared three different widely used enrichment kits (Agilent SureSelect Human All Exon V5, Agilent SureSelect Human All Exon V7 and Twist Bioscience) as well as short-read and long-read WGS. We show that the Twist exome capture significantly improves complete coverage and coverage uniformity across coding regions compared to other exome capture kits. Twist performance is com2023-01-01T00:00:00Z2023 May2025-04-21T22:45:32.93Z2025-04-05T18:55:07.221ZS-EPMC101553753713834310.1186/s40246-023-00485-5