ArticleGenetics in medicine : official journal of the American College of Medical Genetics2019
Outcomes of 92 patient-driven family studies for reclassification of variants of uncertain significance.
Article in Genetics in medicine : official journal of the American College of Medical Genetics, 2019. 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.
- The Tyrolean FounderBiomolecules · 2026Article
- Not Forgotten: Patient Experiences with Genetic Variant Reclassifications.medRxiv : the preprint server for health sciences · 2026Article
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- A scalable approach to resolving variants of uncertain significance.bioRxiv : the preprint server for biology · 2026Article
- Reclassification of variants of uncertain significance in neonatal genetic diseases: implications from a clinician's perspective.Journal of human genetics · 2025Article
- Application of clinical exome sequencing in sperm donor screening in China.Journal of assisted reproduction and genetics · 2025Article
- Harnessing genotype and phenotype data for population-scale variant classification using large language models and bayesian inference.Human genetics · 2025Article
- Prevalence of BRCA1 and BRCA2 mutations in ovarian cancer patients from Yunnan Province in southwest China.European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP) · 2025Article
- Germline Testing in Breast Cancer: A Single-Center Analysis Comparing Strengths and Challenges of Different Approaches.Cancers · 2025Article
- Sudden Cardiac Death: The Role of Molecular Autopsy with Next-Generation Sequencing.Diagnostics (Basel, Switzerland) · 2025Review
- Revealing Monogenic Diabetes: Clinical and Genetic Features of Pediatric MODY Cases in Türkiye: Single Center Experience.Pediatric diabetes · 2025Article
- Unrecognised actionability for breast cancer risk variants identified in a national-level review of Australian familial cancer centres.European journal of human genetics : EJHG · 2024Article
- CFAP47 is Implicated in X-Linked Polycystic Kidney Disease.Kidney international reports · 2024Article
- Canadian College of Medical Geneticists: clinical practice advisory document - responsibility to recontact for reinterpretation of clinical genetic testing.Journal of medical genetics · 2024Article
- Observational
- Article
- Classification of MLH1 Missense VUS Using Protein Structure-Based Deep Learning-Ramachandran Plot-Molecular Dynamics Simulations Method.International journal of molecular sciences · 2024Article
- Variant reclassification and recontact research: A scoping review.Genetics in medicine open · 2024Article
- Tracking updates in clinical databases increases efficiency for variant reanalysis.Genetics in medicine open · 2024Article
- Impact of High-to-Moderate Penetrance Genes on Genetic Testing: Looking over Breast Cancer.Genes · 2023Article
Corrections and comments
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Authors and funding
8 authors.
Funding
Abstract
purposeFamily studies are an important but underreported source of information for reclassification of variants of uncertain significance (VUS). We evaluated outcomes of a patient-driven framework that offered familial VUS reclassification analysis to any adult with any clinically ascertained VUS from any laboratory in the United States.
methodsWith guidance from FindMyVariant.org, participants recruited their own relatives for study participation. We genotyped relatives, calculated quantitative cosegregation likelihood ratios, and evaluated variant classifications using Tavtigian's unified framework for Bayesian analysis with American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) criteria. We report participation and VUS reclassification rates from the 50 families enrolled for at least one year and reclassification results for 112 variants from the larger 92-family cohort.
resultsFor the 50-family cohort, 6.7 relatives per family were invited to participate and 67% of relatives returned samples for genotyping. Sixty-one percent of VUS were reclassified, 84% of which were classified as benign or likely benign. Genotyping relatives identified a de novo variant, phase variants, and relatives with phenotypes highly specific for or incompatible with specific classifications.
conclusionsMotivated families can contribute to successful VUS reclassification at substantially higher rates than those previously published. Clinical laboratories could consider offering family studies to all patients with VUS.
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