Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2024 Mar 4;14(1):5313.
doi: 10.1038/s41598-024-56154-7.

Exploring TTN variants as genetic insights into cardiomyopathy pathogenesis and potential emerging clues to molecular mechanisms in cardiomyopathies

Amir Ghaffari Jolfayi  1 , Erfan Kohansal  1 , Serwa Ghasemi  1 , Niloofar Naderi  2 , Mahshid Hesami  1 , MohammadHossein MozafaryBazargany  1 , Maryam Hosseini Moghadam  2 , Amir Farjam Fazelifar  1 , Majid Maleki  2 , Samira Kalayinia  3
Affiliations
Review

Exploring TTN variants as genetic insights into cardiomyopathy pathogenesis and potential emerging clues to molecular mechanisms in cardiomyopathies

Amir Ghaffari Jolfayi et al. Sci Rep. .

Abstract

The giant protein titin (TTN) is a sarcomeric protein that forms the myofibrillar backbone for the components of the contractile machinery which plays a crucial role in muscle disorders and cardiomyopathies. Diagnosing TTN pathogenic variants has important implications for patient management and genetic counseling. Genetic testing for TTN variants can help identify individuals at risk for developing cardiomyopathies, allowing for early intervention and personalized treatment strategies. Furthermore, identifying TTN variants can inform prognosis and guide therapeutic decisions. Deciphering the intricate genotype-phenotype correlations between TTN variants and their pathologic traits in cardiomyopathies is imperative for gene-based diagnosis, risk assessment, and personalized clinical management. With the increasing use of next-generation sequencing (NGS), a high number of variants in the TTN gene have been detected in patients with cardiomyopathies. However, not all TTN variants detected in cardiomyopathy cohorts can be assumed to be disease-causing. The interpretation of TTN variants remains challenging due to high background population variation. This narrative review aimed to comprehensively summarize current evidence on TTN variants identified in published cardiomyopathy studies and determine which specific variants are likely pathogenic contributors to cardiomyopathy development.

Keywords: TTN; Cardiomyopathy; Genetic; Titin; Variant.

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Molecular structure of sarcomere and the interaction of Titin with thin and thick filaments.
Figure 2
Figure 2
Prevalence of variants in different exons and introns in TTN.
Figure 3
Figure 3
Comparative analysis of TTN variants with their pathogenicity, type of alternation, and conservity.
Figure 4
Figure 4
Illustration of the intricate signaling pathway implicated in the development of cardiomyopathy associated with Titin and other related proteins.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Ormerod, J.O. and A. Yavari, Cardiomyopathies. Medicine, 2022.
    1. Ciarambino T, et al. Cardiomyopathies: An Overview. Int. J. Mol. Sci. 2021;22(14):7722. doi: 10.3390/ijms22147722. - DOI - PMC - PubMed
    1. Maron BJ, et al. Contemporary definitions and classification of the cardiomyopathies: An American heart association scientific statement from the council on clinical cardiology, heart failure and transplantation committee; quality of care and outcomes research and functional genomics and translational biology interdisciplinary working groups; and council on epidemiology and prevention. Circulation. 2006;113(14):1807–1816. doi: 10.1161/CIRCULATIONAHA.106.174287. - DOI - PubMed
    1. Elliott P, et al. Classification of the cardiomyopathies: A position statement from the European society of cardiology working group on myocardial and pericardial diseases. Eur. Heart J. 2008;29(2):270–276. doi: 10.1093/eurheartj/ehm342. - DOI - PubMed
    1. Maurizia Grasso B, Favalli V, Riccardo Bellazzi M. The MOGE (S) classification of cardiomyopathy for clinicians. J. Am. College Cardiol. 2014;64(3):304–318. doi: 10.1016/j.jacc.2014.05.027. - DOI - PubMed