ArticleGenetics in medicine : official journal of the American College of Medical Genetics2021
The role of clinical response to treatment in determining pathogenicity of genomic variants.
Article 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 12 papers.
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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.
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Who cites it
12 citing papers in PubMed.
- An AI-based approach driven by genotypes and phenotypes to uplift the diagnostic yield of genetic diseases.Human genetics · 2025Article
- Beyond genetics: Deciphering the impact of missense variants in CAD deficiency.Journal of inherited metabolic disease · 2023Article
- The clinical utility of rapid exome sequencing in a consanguineous population.Genome medicine · 2023Article
- Review
- Limb girdle muscular disease caused byProceedings of the National Academy of Sciences of the United States of America · 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
- Clinical and biochemical footprints of inherited metabolic disorders. VII. Ocular phenotypes.Molecular genetics and metabolism · 2022Review
- A mild case of sodium-dependent multivitamin transporter (SMVT) deficiency illustrating the importance of treatment response in variant classification.Cold Spring Harbor molecular case studies · 2022Article
- Mitochondrial "dysmorphology" in variant classification.Human genetics · 2022Article
- Treatable inherited metabolic disorders causing intellectual disability: 2021 review and digital app.Orphanet journal of rare diseases · 2021Review
- Response to Biesecker et al.Genetics in medicine : official journal of the American College of Medical Genetics · 2021Article
- Correspondence on "The role of clinical response to treatment in determining pathogenicity of genomic variants" by Shen et al.Genetics in medicine : official journal of the American College of Medical Genetics · 2021Article
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Authors and funding
11 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeThe 2015 American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) guidelines for the interpretation of sequence variants provide a framework to standardize terminology in the classification of variants uncovered through genetic testing. We aimed to assess the validity of utilizing clinical response to therapies specifically targeted to a suspected disease in clarifying variant pathogenicity.
methodsFive families with disparate clinical presentations and different genetic diseases evaluated and treated in multiple diagnostic settings are summarized.
resultsExtended evaluations indicated possible genetic diagnoses and assigned candidate causal variants, but the cumulative clinical, biochemical, and molecular information in each instance was not completely consistent with the identified disease. Initiation of treatment specific to the suspected diagnoses in the affected individuals led to clinical improvement in all five families.
conclusionWe propose that the effect of therapies that are specific and targeted to treatable genetic diseases embodies an in vivo physiological response and could be considered as additional criteria within the 2015 ACMG/AMP guidelines in determining genomic variant pathogenicity.
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