ArticleInternational journal of legal medicine2023
Reevaluation of ambiguous genetic variants in sudden unexplained deaths of a young cohort.
Article in International journal of legal medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 2 of them syntheses that pooled it.
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Who cites it
19 citing papers in PubMed, 2 syntheses or guidelines pooled it, 25 citations in OpenAlex.
- Molecular autopsy in unexplained sudden death: a systematic review and meta-analysis of ACMG-corrected diagnostic yield, genomic architecture, and family translation.International journal of legal medicine · 2026Pooled it
- Diagnosis and management of very rare primary arrhythmia syndromes in children and adults: a Clinical Consensus Statement of the European Heart Rhythm Association of the ESC and the Association of Cardiovascular Nursing & Allied Professions of the ESC, endorsed by the Association for European Paediatric and Congenital Cardiology.Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2026Guideline
- Molecular mechanisms of sudden unexplained death and recent updates on molecular autopsy strategies for forensic investigation.International journal of legal medicine · 2026Review
- Review
- [Molecular autopsy: post-mortem genetic testing following sudden cardiac death].Innere Medizin (Heidelberg, Germany) · 2025Article
- Exploring transcriptomic signatures in sudden unexplained death (SUD) cases.International journal of legal medicine · 2025Article
- Cardiac dysfunction related to cardiac mRNA and protein traffic impairment due to reduced unconventional motor protein myosin-5b expression.European heart journal · 2025Article
- Appropriate time interval to update ambiguous genetic diagnosis in inherited arrhythmogenic syndromes.iScience · 2025Article
- Brugada syndrome in the forensic field: what do we know to date?Frontiers in cardiovascular medicine · 2025Review
- Interpretation of molecular autopsy findings in 45 sudden unexplained death cases: from coding region to untranslated region.International journal of legal medicine · 2025Article
- Sudden cardiac death in the young: single-center study of Bari autopsy cases.Frontiers in cardiovascular medicine · 2025Article
- Interpreting the actionable clinical role of rare variants associated with short QT syndrome.Human genetics · 2024Article
- Actionable Variants of Unknown Significance in Inherited Arrhythmogenic Syndromes: A Further Step Forward in Genetic Diagnosis.Biomedicines · 2024Article
- Cardiac channelopathies in pediatrics: a genetic update.European journal of pediatrics · 2024Review
- Coenzyme Q deficiency may predispose to sudden unexplained death via an increased risk of cardiac arrhythmia.International journal of legal medicine · 2024Article
- New Insights on Molecular Autopsy in Sudden Death: A Systematic Review.Diagnostics (Basel, Switzerland) · 2024Review
- Sudden Cardiac Death in the Young: State-of-the-Art Review in Molecular Autopsy.Current issues in molecular biology · 2024Review
- Implementing a New Algorithm for Reinterpretation of Ambiguous Variants in Genetic Dilated Cardiomyopathy.International journal of molecular sciences · 2024Article
- A narrative review of inherited arrhythmogenic syndromes in young population: role of genetic diagnosis in exercise recommendations.BMJ open sport & exercise medicine · 2024Review
Corrections and comments
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Authors and funding
25 authors at 6 institutions in 3 countries.
Funding
Abstract
Sudden death cases in the young population remain without a conclusive cause of decease in almost 40% of cases. In these situations, cardiac arrhythmia of genetic origin is suspected as the most plausible cause of death. Molecular autopsy may reveal a genetic defect in up to 20% of families. Most than 80% of rare variants remain classified with an ambiguous role, impeding a useful clinical translation. Our aim was to update rare variants originally classified as of unknown significance to clarify their role. Our cohort included fifty-one post-mortem samples of young cases who died suddenly and without a definite cause of death. Five years ago, molecular autopsy identified at least one rare genetic alteration classified then as ambiguous following the American College of Medical Genetics and Genomics' recommendations. We have reclassified the same rare variants including novel data. About 10% of ambiguous variants change to benign/likely benign mainly because of improved population frequencies. Excluding cases who died before one year of age, almost 21% of rare ambiguous variants change to benign/likely benign. This fact makes it important to discard these rare variants as a cause of sudden unexplained death, avoiding anxiety in relatives' carriers. Twenty-five percent of the remaining variants show a tendency to suspicious deleterious role, highlighting clinical follow-up of carriers. Periodical reclassification of rare variants originally classified as ambiguous is crucial, at least updating frequencies every 5 years. This action aids to increase accuracy to enable and conclude a cause of death as well as translation into the clinic.
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