ArticleJournal of clinical oncology : official journal of the American Society of Clinical Oncology2016
Conflicting Interpretation of Genetic Variants and Cancer Risk by Commercial Laboratories as Assessed by the Prospective Registry of Multiplex Testing.
Article in Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 97 papers, 3 of them syntheses that pooled it.
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
97 citing papers in PubMed, 3 syntheses or guidelines pooled it, 175 citations in OpenAlex.
- Management of individuals with heterozygous germline pathogenic variants in RAD51C, RAD51D, and BRIP1: A clinical practice resource of the American College of Medical Genetics and Genomics (ACMG).Genetics in medicine : official journal of the American College of Medical Genetics · 2025Guideline
- Management of individuals with germline pathogenic/likely pathogenic variants in CHEK2: A clinical practice resource of the American College of Medical Genetics and Genomics (ACMG).Genetics in medicine : official journal of the American College of Medical Genetics · 2023Guideline
- Collaborative Group of the Americas on Inherited Gastrointestinal Cancer Position statement on multigene panel testing for patients with colorectal cancer and/or polyposis.Familial cancer · 2020Guideline
- Advancing genetic pathogenicity prediction with three-dimensional proteoform-phenotype analysis.medRxiv : the preprint server for health sciences · 2026Article
- AI in variant analysis: fast track to genetic diagnoses.Human genetics · 2026Review
- Genetic variant interpretation in tumours in the French national ring trials Gen&Tiss - main criteria of improvement.Virchows Archiv : an international journal of pathology · 2026Article
- Review
- Phenotype-first patient matching with SimPheny identifies diagnostic candidates beyond curated gene associations.medRxiv : the preprint server for health sciences · 2026Article
- Germline genomic profiling of patients with early-onset colorectal cancer.ESMO gastrointestinal oncology · 2025Article
- Developing the MyCancerGene Digital Health Portal to Improve Patients' Understanding of Germline Cancer Genetic Test Results: Development, User, and Usability Testing Study.JMIR formative research · 2025Article
- Meta-EA: a gene-specific combination of available computational tools for predicting missense variant effects.Nature communications · 2025Article
- Germinal pathogenic CHEK2, novel APC and somatic JAK2V617F variants in a young patient with colorectal cancer, atypical leukemia, cerebral tumour and aggressive course.Ecancermedicalscience · 2025Article
- Breast cancer screening for transgender individuals with breast cancer susceptibility genes.Translational breast cancer research : a journal focusing on translational research in breast cancer · 2025Review
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- Genetics healthcare providers' experiences counseling patients with results from consumer genomic testing.Molecular genetics & genomic medicine · 2024Article
- Protein-folding chaperones predict structure-function relationships and cancer risk in BRCA1 mutation carriers.Cell reports · 2024Article
- Article
- Uptake of Genetic Research Results and Patient-Reported Outcomes With Return of Results Incorporating Web-Based Predisclosure Education.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2023Article
- Ethical, legal, and social implications (ELSI) and challenges in the design of a randomized controlled trial to test the online return of cancer genetic research results to U.S. Black women.Contemporary clinical trials · 2023Article
37 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
Abstract
Purpose Massively parallel sequencing allows simultaneous testing of multiple genes associated with cancer susceptibility. Guidelines are available for variant classification; however, interpretation of these guidelines by laboratories and providers may differ and lead to conflicting reporting and, potentially, to inappropriate medical management. We describe conflicting variant interpretations between Clinical Laboratory Improvement Amendments-approved commercial clinical laboratories, as reported to the Prospective Registry of Multiplex Testing (PROMPT), an online genetic registry. Methods Clinical data and genetic testing results were gathered from 1,191 individuals tested for inherited cancer susceptibility and self-enrolled in PROMPT between September 2014 and October 2015. Overall, 518 participants (603 genetic variants) had a result interpreted by more than one laboratory, including at least one submitted to ClinVar, and these were used as the final cohort for the current analysis. Results Of the 603 variants, 221 (37%) were classified as a variant of uncertain significance (VUS), 191 (32%) as pathogenic, and 34 (6%) as benign. The interpretation differed among reporting laboratories for 155 (26%). Conflicting interpretations were most frequently reported for CHEK2 and ATM, followed by RAD51C, PALB2, BARD1, NBN, and BRIP1. Among all participants, 56 of 518 (11%) had a variant with conflicting interpretations ranging from pathogenic/likely pathogenic to VUS, a discrepancy that may alter medical management. Conclusions Conflicting interpretation of genetic findings from multiplex panel testing used in clinical practice is frequent and may have implications for medical management decisions.
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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.