ReviewAnnals of laboratory medicine2019
Challenges and Considerations in Sequence Variant Interpretation for Mendelian Disorders.
Review in Annals of laboratory medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 34 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
34 citing papers in PubMed.
- Association Study BetweenInternational journal of molecular sciences · 2026Article
- Dual-SVF: a robust knowledge-guided multimodal method for structural variant filtering in long-read sequencing.Briefings in bioinformatics · 2026Article
- AI in variant analysis: fast track to genetic diagnoses.Human genetics · 2026Review
- Revisiting the Genetics of Hypertrophic Cardiomyopathy: From Sarcomeres to Polygenic Modulation and Clinical Translation.Journal of clinical medicine · 2026Review
- MOLGENIS VIP: an end-to-end DNA variant interpretation pipeline for research and diagnostics configurable to support rapid implementation of new methods.NAR genomics and bioinformatics · 2025Article
- SVHunter: long-read-based structural variation detection through the transformer model.Briefings in bioinformatics · 2025Article
- Article
- VarGuideAtlas: a repository of variant interpretation guidelines.Database : the journal of biological databases and curation · 2025Article
- CAGI6 ID panel challenge: assessment of phenotype and variant predictions in 415 children with neurodevelopmental disorders (NDDs).Human genetics · 2025Article
- Taking after a parent: Phenotypic resemblance and the professional familialisation of genomics.Sociology of health & illness · 2024Article
- Specifications of the ACMG/AMP guidelines for ACADVL variant interpretation.Molecular genetics and metabolism · 2023Article
- Article
- The landscape of tolerated genetic variation in humans and primates.Science (New York, N.Y.) · 2023Article
- Reflexive standardization and the resolution of uncertainty in the genomics clinic.Social studies of science · 2023Article
- The landscape of tolerated genetic variation in humans and primates.bioRxiv : the preprint server for biology · 2023Article
- Variant curation and interpretation in hereditary cancer genes: An institutional experience in Latin America.Molecular genetics & genomic medicine · 2023Article
- Exome/Genome Sequencing in Undiagnosed Syndromes.Annual review of medicine · 2023Review
- Systematic errors in annotations of truncations, loss-of-function and synonymous variants.Frontiers in genetics · 2023Article
- Protein domains provide a new layer of information for classifying human variations in rare diseases.Frontiers in bioinformatics · 2023Article
- Clinical Phenotypes and Outcomes in Monogenic Versus Non-monogenic Very Early Onset Inflammatory Bowel Disease.Journal of Crohn's & colitis · 2022Article
Corrections and comments
- Erratum issued
Authors and funding
3 authors.
Funding
Abstract
In 2015, the American College of Medical Genetics and Genomics (ACMG), together with the Association for Molecular Pathology (AMP), published the latest guidelines for the interpretation of sequence variants, which have been widely adopted into clinical practice. Despite these standardized efforts, the degrees of subjectivity and uncertainty allowed by the guidelines can lead to inconsistent variant classification across clinical laboratories, making it difficult to assess the pathogenicity of identified variants. We describe the critical elements of variant interpretation processes and potential pitfalls through practical examples and provide updated information based on a review of recent literature. The variant classification we describe is meant to be applicable to sequence variants for Mendelian disorders, whether identified by single-gene tests, multi-gene panels, exome sequencing, or genome sequencing. Continuing efforts to improve the reproducibility and objectivity of sequence variant interpretation across individuals and laboratories are needed.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.