[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-455816-105":3,"detail-sidebar-cat-0-en-105":81,"doc-detail-455816-en":130},{"code":4,"msg":5,"data":6},0,"ok",{"site_id":7,"language":8,"slug":9,"title":10,"keywords":11,"description":12,"schema_data":13,"social_meta":74,"head_meta":76,"extra_data":78,"updated_unix":80},105,"en","defining-an-approach-to-empower-clinical-geneticists-to-do-genomic-reanalysis","Defining an approach to empower clinical geneticists to do genomic reanalysis","","Sequencing reanalysis can improve genetic diagnosis by incorporating newly available patient information and updates from the literature, but routine implementation by clinical geneticists is challenging. This study evaluates practical approaches that integrate clinical follow-up with computational support using SimulConsult to generate pertinence metrics from variant tables and patient findings. 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BMC Medical Genomics (2026) 19:4 BMC Medical Genomics  \n[https://doi.org/10.1186/s12920-025-02293-3](https://doi.org/10.1186/s12920-025-02293-3)  \nRESEARCH Open Access  \nDefining an approach to empower clinical geneticists to do genomic reanalysis  \nMichael M. Segal 1*, Meriel McEntagart2, Alexander T. Deng3, Andrea Haworth4, Brian King4, Anthony Rogers4, John Filby4, John Short2, Mary Grace Hash5, Lynette C. Rives5, Kimberly M. Ezell5, Undiagnosed Diseases Network and John A Phillips III5  \nAbstract  \nBackground Sequencing reanalysis can benefit from the inclusion of new information about the patient and from the literature. We studied approaches needed to make reanalysis part of routine follow-up by clinical geneticists. Methods Reanalysis used the SimulConsult diagnostic decision support software, which generates a pertinence metric for gene zygosities determined from the variant table and the patient’s findings. Twenty patients had routine exome sequencing at St. George’s Hospital (London, UK) . Twenty were admitted to the Undiagnosed Diseases Network at Vanderbilt University Medical Center (VUMC) and had all remained undiagnosed despite previous evaluations and sequencing.  \nResults For St. George’s cases, reanalysis picked 7 of the 7 initial diagnoses plus 2 diagnoses found later, and suggested another diagnosis with a gene absent from the variant table. For VUMC, reanalysis picked 5 of 8 diagnoses that were in the variant tables, and suggested a non-coding variant absent from the variant table.  \nConclusion Rapid reanalysis by clinicians could increase the yield of genetic diagnosis with minimal effort and no new lab expenses. For the routine cases at St. George’s, diagnostic yield increased from 7 to 10 (43%) . Capabilities that could further increase yield include joint variant calling, robust phenotyping, clinical correlation after sequencing, and adding CNV data to variant tables.  \nKeywords Bioinformatics, Clinical exome, Diagnostic yield, Phenotype; reevaluation, NGS-based resequencing, Systematic reanalysis, Clinical genomics, Re-analysis, Sequence analysis  \n*Correspondence:  \nMichael M. Segal [medicalgenomics2025@simulconsult.com](medicalgenomics2025@simulconsult.com)[ ](medicalgenomics2025@simulconsult.com)1SimulConsult Inc, Chestnut Hill, MA, United States  \n2St George’s University NHS Foundation Trust, London, UK 3Guy’s & St Thomas’s NHS Foundation Trust, London, UK 4Congenica, Cambridge, UK  \n5Vanderbilt University Medical Center, Nashville, TN, United States  \n© The Author(s) 2026. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creativecommons.org/licenses/by/4.0/](http://creativecommons.org/licenses/by/4.0/.)[.](http://creativecommons.org/licenses/by/4.0/.)  \nSegal et al. BMC Medical Genomics (2026) 19:4  \nIntroduction  \nMany patients who have undergone genomic sequencing but still lack a diagnosis may be diagnosed in the future as new genetic disorders and phenotypic expansions are published. The best care for such patients is to reassess them for a possible diagnosis periodically, ideally as part of routine follow-up care by clinical geneticists. Such reassessment brings in 4 types of new knowledge:  \n1. Novel gene-disease associations  \n2","cbCaimE7ogrfQm7o","https://ap.wps.com/l/cbCaimE7ogrfQm7o","pdf",1807838,"English","# Abstract\n## Background\n## Methods\n## Results\n## Conclusion\n# Introduction\n## Types of new knowledge\n# Materials and methodology\n## Study cohorts","[{\"question\":\"What was the study trying to enable for clinical geneticists?\",\"answer\":\"To make genomic sequencing reanalysis a practical part of routine follow-up care by clinical geneticists.\"},{\"question\":\"How was reanalysis performed in this study?\",\"answer\":\"Reanalysis used the SimulConsult diagnostic decision support software to generate a pertinence metric based on gene zygosities from the variant table and the patient’s findings.\"},{\"question\":\"What impact did rapid clinician-led reanalysis have on diagnostic yield?\",\"answer\":\"It increased the yield for the routine St. George’s cases from 7 to 10 diagnoses, stated as 43%, with minimal effort and no new lab expenses.\"}]","Defining an approach to empower clinical geneticists to do genomic reanalysis | PDF",1790744393,23]