ArticlePNAS nexus2023
Mechanisms of pathogenicity in the hypertrophic cardiomyopathy-associated TPM1 variant S215L.
Article in PNAS nexus, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
What it found
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Who cites it
8 citing papers in PubMed, 13 citations in OpenAlex.
- Evaluating Pathogenicity ofJournal of precision medicine (Amsterdam, Netherlands) · 2025Article
- Screening single nucleotide changes to tropomyosin to identify novel cardiomyopathy mutants.Journal of molecular and cellular cardiology · 2025Article
- Pathogenic genes and clinical prognosis in hypertrophic cardiomyopathy.World journal of cardiology · 2025Review
- Distinct mechanisms drive divergent phenotypes in hypertrophic and dilated cardiomyopathy-associated TPM1 variants.The Journal of clinical investigation · 2024Article
- Identification of a novel likely pathogenic TPM1 variant linked to hypertrophic cardiomyopathy in a family with sudden cardiac death.ESC heart failure · 2024Article
- Multi-omics association study of DNA methylation and gene expression levels and diagnoses of cardiovascular diseases in Danish Twins.Clinical epigenetics · 2024Article
- Engineered heart tissue: Design considerations and the state of the art.Biophysics reviews · 2024Review
- Basic science methods for the characterization of variants of uncertain significance in hypertrophic cardiomyopathy.Frontiers in cardiovascular medicine · 2023Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Hypertrophic cardiomyopathy (HCM) is an inherited disorder often caused by mutations to sarcomeric genes. Many different HCM-associated TPM1 mutations have been identified but they vary in their degrees of severity, prevalence, and rate of disease progression. The pathogenicity of many TPM1 variants detected in the clinical population remains unknown. Our objective was to employ a computational modeling pipeline to assess pathogenicity of one such variant of unknown significance, TPM1 S215L, and validate predictions using experimental methods. Molecular dynamic simulations of tropomyosin on actin suggest that the S215L significantly destabilizes the blocked regulatory state while increasing flexibility of the tropomyosin chain. These changes were quantitatively represented in a Markov model of thin-filament activation to infer the impacts of S215L on myofilament function. Simulations of in vitro motility and isometric twitch force predicted that the mutation would increase Ca
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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.