ArticleGenetics in medicine : official journal of the American College of Medical Genetics2017
Systematic reanalysis of clinical exome data yields additional diagnoses: implications for providers.
Article in Genetics in medicine : official journal of the American College of Medical Genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 187 papers, 3 of them syntheses that pooled it.
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Who cites it
187 citing papers in PubMed, 3 syntheses or guidelines pooled it.
- Measuring the health benefits of genome and exome sequencing: a systematic review of economic evaluations.Frontiers in public health · 2025Pooled it
- Clinical sequencing yield in epilepsy, autism spectrum disorder, and intellectual disability: A systematic review and meta-analysis.Epilepsia · 2021Pooled it
- Meta-analysis and multidisciplinary consensus statement: exome sequencing is a first-tier clinical diagnostic test for individuals with neurodevelopmental disorders.Genetics in medicine : official journal of the American College of Medical Genetics · 2019Pooled it
- Diagnostic yield and variant spectrum of whole-exome sequencing in Iranian probands with congenital and early-onset ocular disorders.Molecular genetics and metabolism reports · 2026Article
- RankVar: machine learning-based variant ranking and reinterpretation for rare genetic diseases.Genome medicine · 2026Article
- Wiedemann-Steiner Syndrome (WSS): A Neonatal Case Report Expanding the Phenotypic Spectrum of a Previously Reported Missense Variant.International journal of molecular sciences · 2026Review
- Diagnostic Yield After Postnatal Reanalysis of Prenatal Exome Sequencing Results.Prenatal diagnosis · 2026Article
- Article
- Picking Up the Phone: Clinical Perspectives on Recontacting Patients and Their Families.Journal of paediatrics and child health · 2026Review
- Skipping the Biopsy: Real-World Experience of Whole-Exome Sequencing as First-Tier Testing in Pediatric Muscular Disorders.International journal of molecular sciences · 2026Article
- Artificial intelligence-assisted clinical exome sequencing: Insights and outcomes from 822 pediatric diagnoses.Genetics in medicine open · 2026Article
- Comparative Profiles of Pediatric Mendeliome: A Single-Center 572-Whole-Exome Sequencing Study in Xinjiang.Human heredity · 2026Article
- Uncovering the Molecular Signatures of Rare Genetic Diseases in the Punjabi Population.International journal of molecular sciences · 2025Observational
- GREGoR: accelerating genomics for rare diseases.Nature · 2025Article
- Evaluating genome sequencing strategies: trio, singleton, and standard testing in rare disease diagnosis.Genome medicine · 2025Article
- Reclassification of variants of uncertain significance in neonatal genetic diseases: implications from a clinician's perspective.Journal of human genetics · 2025Article
- HMG-CoA Synthase-2 Deficiency: Neonatal Hyperammonemic Coma and Abnormal Metabolic Screening Resembling Maple Syrup Urine Disease.JIMD reports · 2025Article
- Long-term follow-up of children who received rapid genomic sequencing.Genetics in medicine : official journal of the American College of Medical Genetics · 2025Article
- Framework for standardized genetic testing recommendations for chronic kidney disease in Ontario.Genetics in medicine open · 2025Article
- Whole Genome Sequencing Improves the Identification of Pathogenic and Novel Variation in Nonsyndromic Hearing Loss.Human mutation · 2025Article
127 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors.
Funding
Abstract
purposeClinical exome sequencing is nondiagnostic for about 75% of patients evaluated for a possible Mendelian disorder. We examined the ability of systematic reevaluation of exome data to establish additional diagnoses.
methodsThe exome and phenotypic data of 40 individuals with previously nondiagnostic clinical exomes were reanalyzed with current software and literature.
resultsA definitive diagnosis was identified for 4 of 40 participants (10%). In these cases the causative variant is de novo and in a relevant autosomal-dominant disease gene. The literature to tie the causative genes to the participants' phenotypes was weak, nonexistent, or not readily located at the time of the initial clinical exome reports. At the time of diagnosis by reanalysis, the supporting literature was 1 to 3 years old.
conclusionApproximately 250 gene-disease and 9,200 variant-disease associations are reported annually. This increase in information necessitates regular reevaluation of nondiagnostic exomes. To be practical, systematic reanalysis requires further automation and more up-to-date variant databases. To maximize the diagnostic yield of exome sequencing, providers should periodically request reanalysis of nondiagnostic exomes. Accordingly, policies regarding reanalysis should be weighed in combination with factors such as cost and turnaround time when selecting a clinical exome laboratory.Genet Med 19 2, 209-214.
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