ArticleGenetics in medicine : official journal of the American College of Medical Genetics2016
The challenge of comprehensive and consistent sequence variant interpretation between clinical laboratories.
Article in Genetics in medicine : official journal of the American College of Medical Genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed.
- Phenotype-first patient matching with SimPheny identifies diagnostic candidates beyond curated gene associations.medRxiv : the preprint server for health sciences · 2026Article
- CardioVar: a machine learning framework for pathogenicity prediction of cardiomyopathy genetic variants.Bioinformatics advances · 2026Article
- Rapid Whole-Genome Sequencing in Critically Ill Infants and Children with Suspected, Undiagnosed Genetic Diseases: Evolution to a First-Tier Clinical Laboratory Test in the Era of Precision Medicine.Children (Basel, Switzerland) · 2025Review
- Modular and cloud-based bioinformatics pipelines for high-confidence biomarker detection in cancer immunotherapy clinical trials.PloS one · 2025Article
- Re-evaluation of a Fibrillin-1 Gene Variant of Uncertain Significance Using the ClinGen Guidelines.Annals of laboratory medicine · 2024Article
- Quantitative thresholds for variant enrichment in 13,845 cases: improving pathogenicity classification in genetic hearing loss.Genome medicine · 2023Article
- Clinical implications of conflicting variant interpretations in the cancer genetics clinic.Genetics in medicine : official journal of the American College of Medical Genetics · 2023Article
- Evaluating use of changing technologies for rapid next-generation sequencing in pediatrics.Pediatric research · 2022Article
- Genotype and Cardiac Outcomes in Pediatric Dilated Cardiomyopathy.Journal of the American Heart Association · 2022Article
- Article
- Cross-Site Concordance Evaluation of Tumor DNA and RNA Sequencing Platforms for the CIMAC-CIDC Network.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021Article
- Complex Modes of Inheritance in Hereditary Red Blood Cell Disorders: A Case Series Study of 155 Patients.Genes · 2021Article
- Novel Variant Findings and Challenges Associated With the Clinical Integration of Genomic Testing: An Interim Report of the Genomic Medicine for Ill Neonates and Infants (GEMINI) Study.JAMA pediatrics · 2021Article
- Quantification of Discordant Variant Interpretations in a Large Family-Based Study of Li-Fraumeni Syndrome.JCO precision oncology · 2021Article
- Article
- Clinical Interpretation of Sequence Variants.Current protocols in human genetics · 2020Article
- Improvement of MEFV gene variants classification to aid treatment decision making in familial Mediterranean fever.Rheumatology (Oxford, England) · 2020Article
- In-silico Analysis ofInternational journal of molecular sciences · 2020Article
- An Initial Survey of the Performances of Exome Variant Analysis and Clinical Reporting Among Diagnostic Laboratories in China.Frontiers in genetics · 2020Article
- ClinGen Myeloid Malignancy Variant Curation Expert Panel recommendations for germline RUNX1 variants.Blood advances · 2019Article
Corrections and comments
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Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeGenetic testing has shifted from academic laboratories with expertise in specific genes to commercial laboratories that offer tests of a diverse array of genes. The purpose of this comparative study was to determine whether one academic laboratory's model of variant interpretation is similar to that of several commercial laboratories.
methodsThe Collagen Diagnostic Laboratory (CDL) received, over a 14-month period, 38 requests to interpret variants originally identified by an outside laboratory (OL). The interpretations by the OL and CDL were compared and discrepancies were assessed.
resultsInterpretations from the OL and CDL were concordant in 11 inquiries (29%); discrepancies were moderate in 11 instances (29%) and significant in 16 (42%). Factors that caused discrepancies included the following: (i) private data were not shared in a public database (n = 9); (ii) publicly available allele frequency data were not referenced and used as evidence (n = 5); and (iii) important aspects of protein structure and function were not taken into account (n = 13).
conclusionComprehensive interpretation of sequence variants depends on good functional tests and well-curated variant databases. Provision of clinical information to the clinical laboratory, mandatory submission of identified variants with phenotype data to common resources, and collaboration between clinical laboratories and recognized experts is likely to improve consistency in variant interpretation among clinical laboratories.Genet Med 18 1, 20-24.
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