Trial reportGenetics in medicine : official journal of the American College of Medical Genetics2021
Randomized prospective evaluation of genome sequencing versus standard-of-care as a first molecular diagnostic test.
Trial report in Genetics in medicine : official journal of the American College of Medical Genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
16 citing papers in PubMed.
- A nationwide prospective randomized trial for diagnosing developmental disorders demonstrates genome sequencing outperforms standard of care.Genome medicine · 2026Trial
- Genome sequencing for the diagnosis of intellectual disability as a paradigm for rare diseases in the French healthcare setting: the prospective DEFIDIAG study.Genome medicine · 2025Trial
- Exome sequencing early in outpatient evaluation in NCGENES 2: Changing the course of the diagnostic odyssey?HGG advances · 2026Article
- Article
- Considerations for reporting variants in novel candidate genes identified during clinical genomic testing.Genetics in medicine : official journal of the American College of Medical Genetics · 2024Article
- Considerations for reporting variants in novel candidate genes identified during clinical genomic testing.bioRxiv : the preprint server for biology · 2024Article
- Exome and genome sequencing in a heterogeneous population of patients with rare disease: Identifying predictors of a diagnosis.Genetics in medicine : official journal of the American College of Medical Genetics · 2024Article
- Genome sequencing as a generic diagnostic strategy for rare disease.Genome medicine · 2024Article
- Molecular diagnostic yield of genome sequencing versus targeted gene panel testing in racially and ethnically diverse pediatric patients.Genetics in medicine : official journal of the American College of Medical Genetics · 2023Article
- Integrated multi-omics for rapid rare disease diagnosis on a national scale.Nature medicine · 2023Article
- Molecular diagnostic yield of genome sequencing versus targeted gene panel testing in racially and ethnically diverse pediatric patients.medRxiv : the preprint server for health sciences · 2023Article
- 2022 Curt Stern Award: Advancing genomic medicine through collaboration and data sharing.American journal of human genetics · 2023Article
- Predictors of the utility of clinical exome sequencing as a first-tier genetic test in patients with Mendelian phenotypes: results from a referral center study on 603 consecutive cases.Human genomics · 2023Article
- The performance of genome sequencing as a first-tier test for neurodevelopmental disorders.European journal of human genetics : EJHG · 2023Article
- How to proceed after "negative" exome: A review on genetic diagnostics, limitations, challenges, and emerging new multiomics techniques.Journal of inherited metabolic disease · 2022Review
- Computational and experimental methods for classifying variants of unknown clinical significance.Cold Spring Harbor molecular case studies · 2022Article
Corrections and comments
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Authors and funding
17 authors.
Funding
Abstract
purposeTo evaluate the diagnostic yield and clinical relevance of clinical genome sequencing (cGS) as a first genetic test for patients with suspected monogenic disorders.
methodsWe conducted a prospective randomized study with pediatric and adult patients recruited from genetics clinics at Massachusetts General Hospital who were undergoing planned genetic testing. Participants were randomized into two groups: standard-of-care genetic testing (SOC) only or SOC and cGS.
resultsTwo hundred four participants were enrolled, 202 were randomized to one of the intervention arms, and 99 received cGS. In total, cGS returned 16 molecular diagnoses that fully or partially explained the indication for testing in 16 individuals (16.2% of the cohort, 95% confidence interval [CI] 8.9-23.4%), which was not significantly different from SOC (18.2%, 95% CI 10.6-25.8%, P = 0.71). An additional eight molecular diagnoses reported by cGS had uncertain relevance to the participant's phenotype. Nevertheless, referring providers considered 20/24 total cGS molecular diagnoses (83%) to be explanatory for clinical features or worthy of additional workup.
conclusioncGS is technically suitable as a first genetic test. In our cohort, diagnostic yield was not significantly different from SOC. Further studies addressing other variant types and implementation challenges are needed to support feasibility and utility of broad-scale cGS adoption.
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