Key result
Large NGS panels frequently identify VUS and incidental findings that complicate genetic heart disease care.
Why the study?
Next-generation sequencing gene panels can detect multiple variants, variants of uncertain significance, and incidental findings, creating challenges for counselling and clinical decision-making.
What are the clinical challenges associated with using large next-generation sequencing gene panels in genetic heart disease?
Case Report (n=3)
No
What are the clinical challenges associated with using large next-generation sequencing gene panels in genetic heart disease?
Large gene panels for inherited cardiac diseases increase the detection of variants of uncertain significance and incidental findings, necessitating careful pre- and post-test counseling and multidisciplinary evaluation.
Answers are grounded in this paper and cite their sources.
Complicates variant interpretation in practice; leaves open optimal panel size and counseling protocols.
BACKGROUND: Next-generation sequencing gene panels are increasingly used for genetic diagnosis in inherited cardiac diseases. Besides pathogenic variants, multiple variants, variants of uncertain significance (VUS) and incidental findings can be detected. Such test results can be challenging for counselling and clinical decision making. METHODS: We present patient cases to illustrate the challenges that can arise when unclear genetic test results are detected in cardiogenetic gene panels. results: 1) one or more VUS in combination with a pathogenic variant, 2) variants associated with another genetic heart disease, and 3) variants associated with a syndrome involving cardiac features. CONCLUSION: Large gene panels not only increase the detection rates of pathogenic variants but also of variants with uncertain pathogenicity, multiple variants and incidental findings. Gene panel results can be challenging for genetic counselling and require proper pre-test and post-test counselling. We advise evaluation of challenging cases by a multidisciplinary team.
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Christiaans et al. (2019) conducted a case report in Genetic heart disease (cardiomyopathies and primary arrhythmia syndromes) (n=3). Large next-generation sequencing (NGS) gene panels was evaluated on Types of challenging gene panel results identified. Large next-generation sequencing gene panels in genetic heart disease frequently identify variants of uncertain significance, multiple variants, and incidental findings that complicate clinical care.
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