ArticleMolecular genetics & genomic medicine2020
Reclassification of genetic variants in children with long QT syndrome.
Article in Molecular genetics & genomic medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 37 citations in OpenAlex.
- Systematic reassessment of reported variants in individuals with suspicion of Alport spectrum disorder reveals a high rate of ambiguous results.European journal of human genetics : EJHG · 2026Article
- Appropriate time interval to update ambiguous genetic diagnosis in inherited arrhythmogenic syndromes.iScience · 2025Article
- The Prenatal Diagnosis and Perinatal Management of Congenital Long QT Syndrome: A Comprehensive Literature Review and Recent Updates.Journal of cardiovascular development and disease · 2025Review
- Canadian College of Medical Geneticists: clinical practice advisory document - responsibility to recontact for reinterpretation of clinical genetic testing.Journal of medical genetics · 2024Article
- Exploring the impact of a KCNH2 missense variant on Long QT syndrome: insights into a novel gender-selective, incomplete penetrance inheritance mode.Frontiers in genetics · 2024Article
- Variant reclassification and recontact research: A scoping review.Genetics in medicine open · 2024Article
- Genetic characterization of dilated cardiomyopathy patients undergoing heart transplantation in the Chinese population by whole-exome sequencing.Journal of translational medicine · 2023Article
- KCNH2 mutation c.3099_3112del causes congenital long QT syndrome type 2 with gender differences.Clinics (Sao Paulo, Brazil) · 2023Article
- Eosinophilic Infiltration of the Sino-Atrial Node in Sudden Cardiac Death Caused by Long QT Syndrome.International journal of molecular sciences · 2022Article
- From diagnostic testing to precision medicine: the evolving role of genomics in cardiac channelopathies and cardiomyopathies in children.Current opinion in genetics & development · 2022Review
- Alanyl-tRNA Synthetase 1 Gene Variants in Hereditary Neuropathy: Genotype and Phenotype Overview.Neurology. Genetics · 2022Article
- Clinical impact of rare variants associated with inherited channelopathies: a 5-year update.Human genetics · 2022Article
- Reanalysis of eMERGE phase III sequence variants in 10,500 participants and infrastructure to support the automated return of knowledge updates.Genetics in medicine : official journal of the American College of Medical Genetics · 2022Article
- It Is Not Carved in Stone-The Need for a Genetic Reevaluation of Variants in Pediatric Cardiomyopathies.Journal of cardiovascular development and disease · 2022Article
- The Complex and Diverse Genetic Architecture of Dilated Cardiomyopathy.Circulation research · 2021Review
- Reclassification of genetic variants in children with long QT syndrome.Molecular genetics & genomic medicine · 2020Article
- The Efficacy of Beta-Blockers in Patients With Long QT Syndrome 1-3 According to Individuals' Gender, Age, and QTc Intervals: A Network Meta-analysis.Frontiers in pharmacology · 2020Review
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundGenes encoding cardiac ion channels or regulating proteins have been associated with the inherited form of long QT syndrome (LQTS). Complex pathophysiology and missing functional studies, however, often bedevil variant interpretation and classification. We aimed to evaluate the rate of change in variant classification based on current interpretation standards and dependent on clinical findings.
methodsMedical charts of children with a molecular genetic diagnosis of LQTS presenting at our centers were retrospectively reviewed. Reinterpretation of originally reported variants in genes associated with LQTS was performed based on current knowledge (March 2019) and according to the "Standards and Guidelines for the Interpretation of Sequence Variants" by the ACMG 2015.
resultsAbout 84 distinct (likely) pathogenic variants identified in 127 patients were reinterpreted. In 12 variants (12/84, 14.3%), classification changed from (likely) pathogenic to variant of unknown significance (VUS). One of these variants was a hypomorphic allele escaping the standard variant classification. Individuals with variants that downgraded to VUS after reevaluation showed significantly lower Schwartz scores and QTc intervals compared to individuals with unchanged variant characterization.
conclusionThis finding confirms genetic variant interpretation as a dynamic process and underlines the importance of ongoing genetic counseling, especially in LQTS patients with minor clinical criteria.
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