biostudies-literatureWright CFMedical Research CouncilNational Institute for Health Research (NIHR)Wellcome Trust571-575https://www.ebi.ac.uk/biostudies/studies/S-EPMC7935711biostudies-literatureUnknown23(3)<h4>Purpose</h4>Automated variant filtering is an essential part of diagnostic genome-wide sequencing but may generate false negative results. We sought to investigate whether some previously identified pathogenic variants may be being routinely excluded by standard variant filtering pipelines.<h4>Methods</h4>We evaluated variants that were previously classified as pathogenic or likely pathogenic in ClinVar in known developmental disorder genes using exome sequence data from the Deciphering Developmental Disorders (DDD) study.<h4>Results</h4>Of these ClinVar pathogenic variants, 3.6% were identified among 13,462 DDD probands, and 1134/1352 (83.9%) had already been independently communicated to clinicians using DDD variant filtering pipelines as plausibly pathogenic. The remaining 218 variaGenetics in medicine : official journal of the American College of Medical GeneticsEvaluating variants classified as pathogenic in ClinVar in the DDD Study.PMC7935711HICF-1009-003MC_UU_00007/3098051Firth HVFitzPatrick DRDDD StudyWright CFConstantinou PHurles MEEberhardt RYfalseEvaluating variants classified as pathogenic in ClinVar in the DDD Study.<h4>Purpose</h4>Automated variant filtering is an essential part of diagnostic genome-wide sequencing but may generate false negative results. We sought to investigate whether some previously identified pathogenic variants may be being routinely excluded by standard variant filtering pipelines.<h4>Methods</h4>We evaluated variants that were previously classified as pathogenic or likely pathogenic in ClinVar in known developmental disorder genes using exome sequence data from the Deciphering Developmental Disorders (DDD) study.<h4>Results</h4>Of these ClinVar pathogenic variants, 3.6% were identified among 13,462 DDD probands, and 1134/1352 (83.9%) had already been independently communicated to clinicians using DDD variant filtering pipelines as plausibly pathogenic. The remaining 218 varia2021-01-01T00:00:00Z2021 Mar2025-04-05T14:34:20.41Z2025-04-05T14:34:20.41ZS-EPMC79357113314927610.1038/s41436-020-01021-9