ArticleHuman mutation2020
An assessment of the role of vinculin loss of function variants in inherited cardiomyopathy.
Article in Human mutation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
9 citing papers in PubMed, 19 citations in OpenAlex.
- Vinculin haploinsufficiency impairs integrin-mediated costamere remodeling on stiffer microenvironments.Journal of molecular and cellular cardiology · 2025Article
- Unveiling the Spectrum of Minor Genes in Cardiomyopathies: A Narrative Review.International journal of molecular sciences · 2024Review
- Heart Failure with Recovered Ejection Fraction in Patients with Vinculin Loss-of-function Variants.Journal of cardiovascular translational research · 2023Article
- Age and Sex Differences in the Genetics of Cardiomyopathy.Journal of cardiovascular translational research · 2023Article
- Ethical issues raised by new genomic technologies: the case study of newborn genome screening.Cambridge prisms. Precision medicine · 2023Review
- Serum SELENBP1 and VCL Are Effective Biomarkers for Clinical and Forensic Diagnosis of Coronary Artery Spasm.International journal of molecular sciences · 2022Article
- The Role of Genetics in Risk Stratification Strategy of Dilated Cardiomyopathy.Reviews in cardiovascular medicine · 2022Review
- Understanding the molecular basis of cardiomyopathy.American journal of physiology. Heart and circulatory physiology · 2022Review
- Considering complexity in the genetic evaluation of dilated cardiomyopathy.Heart (British Cardiac Society) · 2021Review
Corrections and comments
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Authors and funding
22 authors at 12 institutions in 4 countries.
Funding
Abstract
The ACMG/AMP variant classification framework was intended for highly penetrant Mendelian conditions. While it is appreciated that clinically relevant variants exhibit a wide spectrum of penetrance, accurately assessing and expressing the pathogenicity of variants with lower penetrance can be challenging. The vinculin (VCL) gene illustrates these challenges. Model organism data provide evidence that loss of function of VCL may play a role in cardiomyopathy and aggregate case-control studies suggest low penetrance. VCL loss of function variants, however, are rarely identified in affected probands and therefore there is a paucity of family studies clarifying the clinical significance of individual variants. This study, which aggregated data from >18,000 individuals who underwent gene panel or exome testing for inherited cardiomyopathies, identified 32 probands with VCL loss-of-function variants and confirmed enrichment in probands with dilated cardiomyopathy (odds ratio [OR] = 9.01; confidence interval [CI] = 4.93-16.45). Our data revealed that the majority of these individuals (89.5%) had pediatric onset of disease. Family studies demonstrated that heterozygous loss of function of VCL alone is insufficient to cause cardiomyopathy but that these variants do contribute to disease risk. In conclusion, VCL loss-of-function variants should be reported in a diagnostic setting but need to be clearly distinguished as having lower penetrance.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.