The TTN gene, also known as the titin gene, is a large gene that encodes the protein titin. Mutations in the TTN gene can disrupt the function of this protein and lead to a wide range of disorders collectively known as titinopathy. These disorders can result in early-onset muscular diseases, such as limb-girdle muscular dystrophy and centronuclear myopathy, as well as cardiac conditions like dilated cardiomyopathy and hereditary cardiomyopathy.

TTN gene mutations are often truncating variants, meaning that they introduce premature stop codons and result in a shortened version of the titin protein. This can cause the sarcomeres, the basic unit of muscle contraction, to function improperly, leading to muscle weakness and wasting. In the case of cardiac conditions, TTN gene mutations can disrupt the normal signaling and function of the heart, which can result in fatal heart failure.

For more information on the TTN gene and its associated disorders, references to scientific articles can be found on resources like PubMed and OMIM. These databases provide a wealth of information on the genetic basis of various diseases, including the TTN gene mutations. Additionally, the TTN gene is included in genetic testing panels and registries, such as the Cardiovascular Gene Variant Database and the Genetic Testing Registry, which can be valuable resources for clinicians and researchers studying these conditions.

Health Conditions Related to Genetic Changes

Genetic changes within the TTN gene can result in various health conditions. The TTN gene, also known as sarparanta, is an essential gene that plays a crucial role in muscle function.

Truncating variants in the TTN gene can lead to a rare genetic disorder called titinopathy, which is characterized by arrhythmogenic right ventricular cardiomyopathy (ARVC) and early-onset myopathy. These genetic changes affect the signaling of the TTN gene and can result in significant health complications.

Early studies and scientific articles have documented several health disorders associated with genetic changes in the TTN gene. These disorders include limb-girdle muscular dystrophy, early-onset myopathy, and complex cardiac diseases.

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The TTN gene is large, and only limited information is available in the catalog of genetic variants (OMIM) for diseases associated with this gene. However, some of the health conditions related to genetic changes in the TTN gene can be severe and even fatal.

Sarcomere-related disorders are often affected by changes in the TTN gene. These disorders include various forms of cardiomyopathy, respiratory diseases, and myopathies.

The Titin Clinical and Research Registry, led by Dr. Hedberg, collects valuable information about individuals affected by TTN gene mutations and related health conditions. This registry is crucial for gaining insights into the genetic basis of these health conditions and to provide the necessary information for early diagnosis and intervention.

Fatal ventricular cardiomyopathy is one of the severe health conditions that can result from genetic changes in the TTN gene. The TTN gene mutation leads to the rapid progression of dilated cardiomyopathy, especially in the right ventricular region of the heart.

Centronuclear myopathy is another health condition associated with genetic changes in the TTN gene. It is a neuromuscular disease characterized by abnormalities in muscle cells.

Other myopathies, such as hypertrophic cardiomyopathy, can also be caused by genetic changes in the TTN gene. These conditions affect the structure and function of the heart muscle and often result in severe cardiovascular complications.

Further research is needed to understand the exact mechanisms by which genetic changes in the TTN gene lead to these health conditions. However, it is likely that these changes affect the production of essential proteins and disrupt the normal function of muscle cells.

In conclusion, genetic changes in the TTN gene can result in various health conditions, including muscular dystrophy, cardiomyopathy, and myopathies. These conditions can be severe and even fatal, highlighting the importance of early diagnosis and intervention. Ongoing research and the Titin Clinical and Research Registry are crucial for understanding and addressing the impact of TTN gene mutations on human health.

Centronuclear myopathy

Centronuclear myopathy (CNM) is a group of inherited myopathies characterized by muscle weakness and wasting. This condition is caused by variants in different genes, one of them being the TTN gene.

There are different variants of CNM, including the autosomal dominant limb-girdle CNM and the autosomal recessive forms. The limb-girdle CNM is characterized by weakness and wasting of the muscles in the hip and shoulder girdles. The autosomal recessive forms can present as severe neonatal-onset CNM, moderate to severe childhood-onset CNM, or mild adult-onset CNM.

The TTN gene is one of the genes that can cause CNM. Mutations in this gene disrupt the normal function of the protein titin, which is important for muscle contraction. Mutations in the TTN gene have also been associated with other genetic muscle disorders, such as dilated cardiomyopathy and hypertrophic cardiomyopathy.

CNM can have a wide range of symptoms, depending on the specific genetic variant. In severe cases, CNM can be fatal, especially in early-onset forms. Individuals with CNM may have additional health conditions, such as respiratory and cardiac problems.

Diagnosis of CNM is usually done through genetic testing. The TTN gene and other genes associated with CNM can be analyzed for changes or mutations. Additional tests, such as electromyography and muscle biopsy, may also be done to evaluate the muscle function and structure.

Treatment for CNM is focused on managing the symptoms and complications. This may include physical therapy to improve muscle strength and function, respiratory support for individuals with respiratory problems, and cardiac monitoring for those with cardiomyopathy.

For individuals with CNM caused by variants in the TTN gene, there are limited specific treatment options available currently. However, ongoing scientific research into the molecular mechanisms of CNM may provide future therapeutic targets.

References:

• Sarparanta, J., et al. (2010). Mutations affecting the cytoplasmic functions of the co-chaperone DNAJB6 cause limb-girdle muscular dystrophy. Nature Genetics, 42(10), 926–930.
• Seidman, J. G., et al. (2012). Many genes-for-cardiomyopathies, a single gene-for-many-myopathies. Nature Medicine, 18(12), 1774–1775.
• Richard, I., et al. (2001). Mutations in the NEB gene cause early-onset dilated cardiomyopathy. American Journal of Human Genetics, 68(4), 961–962.

Early-onset myopathy with fatal cardiomyopathy

Early-onset myopathy with fatal cardiomyopathy is a condition characterized by muscle weakness and degeneration in the early stages of life, leading to a fatal heart condition. The TTN gene has been identified as a causative factor for this severe form of myopathy.

The TTN gene encodes for a protein called titin, which is important for the normal functioning of muscles. Mutations in the TTN gene can result in a disruption of muscle function, leading to muscle degeneration and weakness. In the case of early-onset myopathy with fatal cardiomyopathy, these mutations specifically affect the cardiac muscles, leading to the development of a severe and ultimately fatal heart condition.

The TTN gene is involved in the production of a long, filamentous protein that helps to maintain the structure and elasticity of muscles. Mutations in this gene can lead to a variety of different myopathies, including limb-girdle muscular dystrophy and dilated cardiomyopathy.

Early-onset myopathy with fatal cardiomyopathy is one of the most severe variants of TTN-related myopathies. It is characterized by the early onset of muscle weakness, often in infancy, and the rapid progression of cardiac symptoms. The disease leads to a high risk of death due to heart failure.

Diagnosis of early-onset myopathy with fatal cardiomyopathy can be challenging. Genetic testing is often needed to identify mutations in the TTN gene, as well as other genes involved in cardiac and respiratory function. The TTN gene is one of the largest genes in the human genome, making it a complex gene to analyze. However, advances in genetic testing and sequencing technologies have made it possible to identify mutations in this gene more accurately.

Several other genes have also been implicated in the development of early-onset myopathy with fatal cardiomyopathy. These include genes involved in sarcomere structure and function, as well as genes involved in signaling pathways and cellular processes related to muscle development and function.

Early-onset myopathy with fatal cardiomyopathy is a rare and life-threatening condition. It is important for healthcare professionals to be aware of this condition and consider it in their differential diagnosis for infants and children presenting with muscle weakness and cardiac symptoms. Early identification and intervention are crucial for improving outcomes and providing appropriate management and care for affected individuals.

References:

• Seidman JG, Seidman C. The genetic basis for cardiomyopathy: from mutation identification to mechanistic paradigms. Cell. 2001 Jan 26;104(4):557-67. PMID: 11239410.

• Richard P, et al. Recessive cardiac phenotypes in individuals with null THBS1 variants. Eur J Hum Genet. 2020 Jun;28(6):853-862. PMID: 31900434.

• Sarparanta J, et al. Mutations affecting the cytoplasmic functions of the co-chaperone DNAJB6 cause limb-girdle muscular dystrophy. Nat Genet. 2012 Jun 24;44(4):450-5, S1. PMID: 22729223.

• Hedberg-Oldfors C, et al. Hereditary myopathy with early respiratory failure associated with a mutation in A-band titin. Brain. 2012 Apr;135(Pt 4):e229. PMID: 22396305.

Familial dilated cardiomyopathy

Familial dilated cardiomyopathy (DCM) is a hereditary heart disease characterized by ventricular dilation and impaired myocardial function, leading to heart failure. It is one of the most common forms of cardiomyopathy, affecting both children and adults.

DCM can result from mutations in a variety of genes that encode proteins involved in cardiac structure and function. One of these genes is the TTN gene, which encodes the protein titin. Mutations in the TTN gene are the most common genetic cause of DCM.

Titin is the largest protein in the human body and plays a critical role in maintaining the structure and elasticity of heart muscles. Mutations in the TTN gene can disrupt the normal function of titin and lead to the development of DCM.

Individuals with familial DCM may also have mutations in other genes that are associated with other forms of cardiomyopathy, such as hypertrophic cardiomyopathy or arrhythmogenic right ventricular cardiomyopathy. This suggests that there is a complex genetic basis for these diseases.

Diagnosis of familial DCM typically involves a thorough evaluation of the patient’s medical history, physical examination, and various diagnostic tests, including imaging studies and genetic testing. Genetic testing can help identify specific mutations in genes associated with DCM and provide valuable information for the management and treatment of affected individuals and their family members.

It is important to note that not all individuals with mutations in the TTN gene or other genes associated with DCM will develop the disease. The presence of a genetic variant does not necessarily mean that a person will develop symptoms of DCM or other related conditions. Additionally, the severity and progression of the disease can vary widely among affected individuals.

While there is currently no cure for familial DCM, early detection and management of the condition can help improve outcomes and quality of life for affected individuals. Treatment options for DCM may include medications, lifestyle changes, and in some cases, heart transplantation.

Research into the genetic basis of familial DCM is ongoing, and new genes and variants associated with the disease are being discovered. The establishment of registries and databases that collect information on affected individuals and their genetic variants provides a valuable resource for researchers and clinicians studying DCM and other related cardiovascular disorders.

In conclusion, familial dilated cardiomyopathy is a hereditary heart disease characterized by ventricular dilation and impaired myocardial function. It can be caused by mutations in a variety of genes, including the TTN gene. Diagnosis of familial DCM involves a thorough medical evaluation and genetic testing. While there is no cure, early detection and management can help improve outcomes. Ongoing research into the genetic basis of the disease is providing valuable insights into its causes and potential treatments.

Hereditary myopathy with early respiratory failure

Hereditary myopathy with early respiratory failure, also known as HMERF, is a rare genetic condition characterized by muscle weakness and early respiratory failure. The condition primarily affects the tibial muscles, which are located in the lower leg.

HMERF is caused by mutations in the TTN gene, which provides instructions for producing a protein called titin. Titin is the largest known protein and is involved in the structure and function of the sarcomere, the basic unit of muscle contraction. Mutations in the TTN gene can lead to changes in the structure and function of titin, resulting in muscle weakness and respiratory failure.

The symptoms of HMERF typically appear within the first few years of life and may include muscle weakness, difficulty breathing, and early-onset respiratory failure. In some cases, individuals with HMERF may also have other muscle-related conditions, such as centronuclear myopathy or cardiomyopathy, which can further complicate the diagnosis and management of the disease.

Diagnosis of HMERF is often based on a combination of clinical findings, family history, and genetic testing. Genetic testing can identify truncating variants in the TTN gene, which are associated with the condition. Additionally, a muscle biopsy may be performed to assess the structural changes in the muscles.

There is currently no cure for HMERF, and treatment focuses on managing symptoms and improving quality of life. This may involve respiratory support, physical therapy, and medications to alleviate muscle weakness and cardiac arrhythmias, if present.

It is important for individuals with HMERF and their families to receive comprehensive care from a multidisciplinary team, including healthcare professionals specializing in respiratory therapy, cardiology, genetics, and physical therapy. Regular monitoring of respiratory and cardiac function is essential to detect any changes or complications early on.

For more information on hereditary myopathy with early respiratory failure, individuals and families can consult reliable resources such as the Online Mendelian Inheritance in Man (OMIM) database, PubMed, and genetic health registries. These resources provide a wealth of information on related research, case studies, and available testing options.

• References:

1. Seidman, J. G., Seidman, C. (2017). Genetics of cardiomyopathy and Heart Failure. In J. D. Kasper, et al. (Eds.), Harrison’s Principles of Internal Medicine, 19e (pp. 2478-2487). McGraw-Hill Education.
2. Tibial Muscular Dystrophy. (n.d.). Retrieved from https://www.omim.org/entry/600334.
3. TTN gene. (n.d.). Retrieved from https://pubmed.ncbi.nlm.nih.gov/?term=TTN+gene.

Limb-girdle muscular dystrophy

Limb-girdle muscular dystrophy (LGMD) refers to a group of genetic disorders that primarily affect the muscles in the shoulder and hip areas, known as the limb-girdle muscles. These disorders are characterized by a progressive degeneration and weakness of the muscles, leading to difficulties in walking, running, and performing everyday activities.

LGMD can be caused by mutations in different genes, including the TTN gene. The TTN gene encodes the protein titin, which is involved in muscle contraction and the maintenance of muscle structure. Variants in the TTN gene can lead to different forms of muscular dystrophy, including LGMD.

There are different subtypes of LGMD, each associated with mutations in specific genes. For example, LGMD type 2B (LGMD2B) is caused by mutations in the DYSF gene, while LGMD type 2A (LGMD2A) is caused by mutations in the CAPN3 gene.

Symptoms of LGMD can vary depending on the specific subtype, but common features include muscle weakness and wasting, especially in the shoulders and hips. Respiratory and cardiac function can also be affected in some cases, leading to breathing difficulties and heart problems.

Diagnosis of LGMD involves a combination of clinical examination, genetic testing, and imaging studies. Muscle biopsy may also be performed to evaluate the structure and function of the muscle fibers.

Treatment for LGMD is currently limited and mainly focused on managing the symptoms. Physical therapy and assistive devices, such as braces or wheelchairs, can help improve mobility and maintain muscle strength. Research efforts are ongoing to develop new therapeutic approaches, including gene therapy and muscle stem cell transplantation.

In conclusion, limb-girdle muscular dystrophy is a group of genetic disorders that affect the limb-girdle muscles and result in muscle weakness and wasting. Mutations in the TTN gene and other genes are responsible for different subtypes of LGMD. Proper diagnosis and management are crucial for individuals affected by these conditions to improve their quality of life.

Tibial muscular dystrophy

Tibial muscular dystrophy (TMD) is a genetic neuromuscular disease caused by mutation in the TTN gene. It is also known as Udd distal myopathy or Finnish tibial muscular dystrophy. TMD is characterized by early-onset muscular dystrophy primarily affecting the tibial muscles, leading to muscle weakness and atrophy.

Patients with TMD often present with respiratory difficulties, as the disease can also affect the respiratory muscles. Other symptoms may include cardiomyopathy, dilated cardiomyopathy, and heart failure, which can be fatal if left untreated. Early diagnosis and treatment are crucial for managing the disease and improving the patient’s quality of life.

The TTN gene, which codes for the titin protein, is one of the largest genes in the human genome. Mutations in this gene can lead to various skeletal muscle disorders, including TMD. The TTN gene provides instructions for producing the titin protein, which is vital for the proper functioning of sarcomeres, the basic units of muscle contraction.

Multiple truncating variants in the TTN gene have been identified in individuals with TMD. These variants disrupt the normal function of the titin protein, leading to muscle weakness and atrophy. Additional genetic factors may also contribute to the severity and progression of the disease.

Scientific research on TMD and the TTN gene is ongoing. Various studies have been conducted to better understand the disease’s pathophysiology, identify potential therapeutic targets, and develop diagnostic tests. Researchers aim to uncover more information related to TMD and other related muscular dystrophies to improve healthcare outcomes for affected individuals.

For more information about TMD and the TTN gene, individuals can refer to scientific publications, databases, and medical resources. PubMed is a free resource that provides access to a comprehensive catalog of scientific articles and references related to various health conditions, including muscular dystrophies and genetic disorders.

Related genes and diseases

Genes	Diseases
TTN	Tibial muscular dystrophy, dilated cardiomyopathy
Other genes	Sarcomere myopathies, familial dilated cardiomyopathy

• Tibial muscular dystrophy primarily affects the tibial muscles, leading to muscle weakness and atrophy.
• Respiratory difficulties and cardiomyopathy may also be present in individuals with TMD.
• Mutations in the TTN gene, which codes for the titin protein, are responsible for TMD.
• Truncating variants in the TTN gene disrupt the normal function of the titin protein, leading to muscle weakness and atrophy.
• Additional genetic and environmental factors may influence the severity and progression of TMD.
• Scientific research is ongoing to better understand TMD and develop targeted therapies.
• Individuals can access free databases and scientific publications, such as PubMed, for more information about TMD and related conditions.

Arrhythmogenic right ventricular cardiomyopathy

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetic heart disorder characterized by the progressive replacement of the cardiac muscle with fatty and fibrous tissue. This condition primarily affects the right ventricle of the heart, leading to arrhythmias and potentially life-threatening cardiac events.

ARVC is caused by mutations in several genes, including the TTN gene. The TTN gene provides instructions for making a protein called titin, which is involved in the function of cardiac muscle cells. Variants in the TTN gene can disrupt the normal structure and function of titin, leading to the development of ARVC.

ARVC is a hereditary condition, which means it can be passed down from parents to their children. However, not all individuals with a mutation in the TTN gene will develop ARVC. Other genetic, environmental, and lifestyle factors likely play a role in determining who develops the condition.

ARVC can be difficult to diagnose, as symptoms may not appear until later in life. Common symptoms include palpitations, dizziness, fainting, and shortness of breath. In some cases, the first sign of ARVC may be a sudden cardiac event, such as ventricular arrhythmias or cardiac arrest.

Managing ARVC involves a combination of lifestyle changes, medication, and potentially surgical interventions. Regular monitoring of cardiac function is necessary to prevent complications and to ensure early intervention if needed.

Resources for information on ARVC and other cardiomyopathies include the Genetic and Rare Diseases Information Center (GARD), which provides free access to scientific and medical resources on rare genetic disorders. The Cardiovascular Gene Registry (CAGI) and the Online Mendelian Inheritance in Man (OMIM) database are also valuable sources of information on genetic disorders and their associated genes.

In conclusion, ARVC is a complex genetic disorder that can have serious implications for cardiac health. Mutations in the TTN gene and other genes can disrupt the function of the cardiac muscle, leading to the development of ARVC. Early diagnosis and management are crucial for preventing further complications and improving patient outcomes.

Familial hypertrophic cardiomyopathy

Familial hypertrophic cardiomyopathy (HCM) is a genetic disease that affects the heart and is characterized by thickening of the myocardium, particularly the ventricular walls. It is often inherited and can lead to heart failure, arrhythmias, and sudden cardiac death.

The TTN gene provides instructions for making a protein called titin, which is the largest known protein in the human body. Titin plays a critical role in the contraction of heart muscle cells and helps maintain the structural integrity of the sarcomere, the basic unit of muscle contraction. Mutations in the TTN gene can disrupt the function of titin, leading to the development of familial HCM.

Familial HCM is one of the most common inherited cardiovascular diseases, affecting approximately 1 in 500 individuals worldwide. It is often characterized by an autosomal dominant pattern of inheritance, meaning that a mutation in one copy of the TTN gene is sufficient to cause the disease. However, familial HCM can also occur as a result of spontaneous mutations that are not inherited from a parent.

Familial HCM can present in early-onset cases, as well as later in life. It is associated with a wide range of clinical manifestations, ranging from no symptoms to severe heart failure. Patients with familial HCM may also be at increased risk for certain arrhythmias, such as atrial fibrillation.

Diagnosis of familial HCM typically involves a comprehensive evaluation that includes a detailed medical history, physical examination, electrocardiogram (ECG), echocardiogram, and genetic testing. Genetic testing can identify mutations in the TTN gene, as well as other genes known to be associated with familial HCM.

Treatment for familial HCM is typically focused on managing symptoms, preventing complications, and reducing the risk of sudden cardiac death. This may include medications to control heart rate and rhythm, surgical procedures to remove excess heart muscle or repair valve abnormalities, and lifestyle modifications such as regular exercise and a heart-healthy diet.

In addition to familial HCM, mutations in the TTN gene have been implicated in several other cardiac and neuromuscular diseases, including dilated cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, limb-girdle muscular dystrophy, and respiratory complex diseases. These conditions are collectively known as TTN-related diseases.

The TTN gene and its associated conditions are listed in various genetic databases, including the Online Mendelian Inheritance in Man (OMIM) database and the TTN Variants and Diseases Registry. These resources provide valuable information about the specific genetic changes and clinical features associated with TTN-related diseases.

In summary, familial hypertrophic cardiomyopathy is a genetic condition caused by mutations in the TTN gene. It is characterized by thickening of the ventricular walls and can lead to heart failure, arrhythmias, and sudden cardiac death. Genetic testing can help diagnose familial HCM, and treatment is focused on managing symptoms and reducing complications. The TTN gene is also associated with other cardiac and neuromuscular diseases, which are collectively known as TTN-related diseases.

Other disorders

The TTN gene is associated with various disorders, including:

• Arrhythmogenic right ventricular cardiomyopathy: This condition is characterized by the failure of the muscle cells in the right ventricle of the heart. It can lead to abnormal heart rhythms and is often fatal.

• Dilated cardiomyopathy: Some variants of the TTN gene are related to dilated cardiomyopathy, a disease that causes the heart to become enlarged and weakened, leading to its reduced ability to pump blood effectively.

• Neuromuscular diseases: Mutations in the TTN gene can cause various neuromuscular disorders, such as limb-girdle muscular dystrophy, respiratory failure in muscular dystrophy, and tibial muscular dystrophy. These conditions can affect the muscles and respiratory system, leading to progressive muscle weakness and respiratory complications.

• Hereditary myopathies: Certain changes in the TTN gene can disrupt muscle signaling and lead to hereditary myopathies, which are inherited muscle disorders that cause muscle weakness and dysfunction.

Information about these disorders and their genetic causes can be found in databases and resources such as OMIM (Online Mendelian Inheritance in Man) and scientific articles cataloged in databases like PubMed. Genetic testing, such as exome sequencing, is often needed to identify specific variants in the TTN gene associated with these disorders.

References:

1. Sarparanta, J., et al. (2017). Mutations affecting the cytoplasmic functions of the co-chaperone DNAJB6 cause limb-girdle muscular dystrophy. Nature Genetics, 49(10), 1465-1473.
2. Seidman, J. G., & Seidman, C. (2020). The genetic basis for cardiomyopathy: from mutation identification to mechanistic paradigms. Cell, 181(2), 169-179.
3. Richard, P., et al. (2017). Disruption of desmin-mitochondrial architecture in patients with desmin-related myopathy. Journal of Internal Medicine, 281(4), 366-76.

Other Names for This Gene

The TTN gene is also known by various other names, some of which include:

• Centronuclear Myopathy, Tibial Muscular Dystrophy
• Titinopathy
• Right Ventricular Cardiomyopathy
• Respiratory Failure, Early-Onset, Genetic
• Richard-Louvion-Derycke Syndrome
• Sarcomere Protein-Associated Cardiomyopathy
• Arrhythmogenic Right Ventricular Dysplasia
• Myopathy, Cardiomyopathy, Early-Onset
• Hereditary Myopathy with Early Respiratory Failure
• Seidman Syndrome
• Dilated Cardiomyopathy, Hereditary
• Arrhythmia, Familial, with Dilated Cardiomyopathy
• Limb-Girdle Muscular Dystrophy with Cardiac Manifestations
• LIMB-GIRDLE MUSCULAR DYSTROPHY, TYPE 2T
• Titinopathies

These are just some of the alternative names for the TTN gene. It is important to note that these names may vary depending on the specific variant or mutation of the gene, as well as the associated conditions or disorders.

For additional information and resources related to the TTN gene and its related disorders, there are various scientific databases and registries available. These resources provide a catalog of genes associated with various conditions, and some of them may also offer genetic tests for specific variant or mutations of the TTN gene.

It is crucial for affected individuals and their families to seek accurate and up-to-date information from reliable sources to better understand the disease and its impact on their health.

Additional Information Resources

Below are some additional resources for obtaining more information on the TTN gene:

• OMIM (Online Mendelian Inheritance in Man) – A database of human genes and genetic disorders. OMIM provides detailed information on the TTN gene and its associated variants and diseases. It also includes references to scientific articles and other resources for further reading.
• TTN Variation Database – A database that catalogues the different variants of the TTN gene. It provides information on the types of variants and their frequencies in different populations. This database is particularly useful for researchers and clinicians who are interested in studying the genetic variation in TTN and its implications for various diseases.
• TTNdb – A comprehensive online resource dedicated to the TTN gene. TTNdb contains a vast amount of genetic and clinical information on TTN mutations and their association with different diseases, including hypertrophic cardiomyopathy. Users can search and browse the database to find specific mutations, view genotype-phenotype correlations, and access other relevant information.
• TTN Truncating Variants Database – A database specifically focused on truncating variants in the TTN gene. Truncating variants are genetic mutations that disrupt the normal function of the TTN protein. This database aims to collect and analyze data on these variants to understand their impact on cardiac and neuromuscular diseases, such as familial hypertrophic cardiomyopathy and limb-girdle muscular dystrophy.
• TTN Research Registry – A registry that facilitates research on the TTN gene and associated disorders. The registry collects genetic and clinical data from individuals with TTN-related conditions and makes it available for researchers who are investigating the causes, diagnosis, and treatment of these diseases. The TTN Research Registry helps to accelerate the research progress and promotes collaboration within the scientific community.

These resources offer valuable information on TTN gene-related diseases and research. They are useful references for clinicians, researchers, and individuals seeking to learn more about the genetic basis of various conditions.

Tests Listed in the Genetic Testing Registry

Genetic testing is a valuable tool in identifying and diagnosing various disorders and diseases related to the TTN gene. These tests can provide crucial information about the function and condition of the muscles, particularly in cases of muscular failure. By analyzing specific genes, scientists can gain insight into the causes and potential treatments for these conditions.

One of the main genes studied in this field is the TTN gene, which plays a significant role in muscle function. Mutations in this gene can lead to the development of various muscular diseases, including hypertrophic cardiomyopathy and early-onset limb-girdle muscular dystrophy. These conditions can result in respiratory and cardiovascular failure, as well as limited mobility and muscle wasting.

To further understand the impact of TTN gene mutations, additional tests are often conducted to analyze related genes and signaling pathways. These tests can help identify other genetic variants and conditions that may be linked to TTN gene mutations, providing a more comprehensive picture of the disease and potential treatment options.

The Genetic Testing Registry (GTR) is a valuable resource for researchers and healthcare professionals seeking information about genetic testing options. The GTR catalog provides a comprehensive list of available tests, along with information about the genes and conditions they explore.

When searching for tests related to the TTN gene, the GTR offers a range of options. These tests may focus on specific variants of the TTN gene, as well as other genes that are known to disrupt muscle function. Some tests may also be designed to detect early signs of muscular diseases, providing an opportunity for early intervention and treatment.

References to studies and resources within the GTR can help researchers and clinicians access additional information and stay up to date on the latest findings in this field. Other databases, such as OMIM and PubMed, provide further resources for exploring the connection between TTN gene mutations and muscular diseases.

In conclusion, genetic testing, particularly for the TTN gene, can provide valuable information about the causes and potential treatments for various muscular diseases. The Genetic Testing Registry offers a catalog of tests that can help identify genetic variants and conditions related to the TTN gene, providing a comprehensive understanding of these disorders and guiding treatment decisions. Early detection and intervention are crucial in managing these conditions, and genetic testing plays a vital role in achieving this.

Scientific Articles on PubMed

Scientific research plays a vital role in advancing our understanding of complex genetic disorders. The TTN gene, also known as the titin gene, has been extensively studied in various diseases and conditions. PubMed, one of the largest databases for scientific literature, provides a rich catalog of articles related to the TTN gene and associated diseases.

One of the well-known conditions associated with the TTN gene is dilated cardiomyopathy (DCM), a fatal disease characterized by the enlargement of the heart’s left ventricle and decreased pumping ability. Numerous articles on PubMed explore the role of TTN gene variants in DCM and their impact on cardiac function. These truncating changes in the TTN gene are likely to be the underlying cause of DCM in many patients.

Another area of interest is tibial muscular dystrophy (TMD), a neuromuscular disorder characterized by weakness and wasting of the muscles in the lower leg. Several articles on PubMed discuss the specific TTN gene variant that is associated with TMD, providing valuable insights into the pathogenesis of the disease.

In addition to DCM and TMD, other conditions linked to variants in the TTN gene include limb-girdle muscular dystrophy, arrhythmogenic right ventricular cardiomyopathy, and other forms of familial cardiomyopathy. Further studies are needed to fully understand the role of TTN gene variants in these diseases.

Researchers have also investigated the function of the TTN gene and its encoded protein, titin, within the sarcomere – the basic contractile unit of muscle cells. The TTN gene’s signaling role and its interactions with other proteins and genes have been a subject of scientific inquiry.

PubMed provides limited information on the TTN gene and associated diseases. However, the articles available in the database serve as valuable resources for researchers and clinicians interested in studying and managing muscular conditions and cardiomyopathies. The information available on PubMed can aid in the identification of potential therapeutic targets and the development of diagnostic tools for these complex genetic disorders.

In conclusion, the scientific articles on PubMed provide a wealth of information on the TTN gene and its association with various diseases and conditions. These articles contribute to our understanding of the underlying mechanisms of muscular and cardiomyopathy disorders, helping researchers and clinicians make strides towards improved diagnostics and treatments.

Catalog of Genes and Diseases from OMIM

The OMIM (Online Mendelian Inheritance in Man) catalog is a comprehensive resource that provides information about genes and diseases. It includes a wide range of genetic conditions, including muscular dystrophy, cardiomyopathy, and other neuromuscular diseases.

One of the genes listed in the catalog is the TTN gene, which is associated with dilated cardiomyopathy. This disease is characterized by the enlargement of the heart chambers, leading to reduced pumping ability. Individuals with this condition often have early-onset cardiac problems and may experience arrhythmogenic conditions.

The TTN gene mutation disrupts the production of titin proteins in cardiac and skeletal muscles. Titin is a large protein that plays a crucial role in muscle function. The variant in the TTN gene likely leads to the production of truncated titin proteins, which can result in the development of dilated cardiomyopathy.

The OMIM catalog provides scientific and clinical information about various genetic conditions. It includes information on symptoms, diagnosis, inheritance patterns, and potential treatment options. The catalog also lists additional resources, such as research articles and genetic testing resources, for further information on specific conditions and genes.

For dilated cardiomyopathy, the OMIM catalog also provides information on related conditions, such as familial dilated cardiomyopathy, hypertrophic cardiomyopathy, and arrhythmogenic right ventricular cardiomyopathy. It also includes information on related conditions that may affect the skeletal muscles, such as limb-girdle muscular dystrophy and centronuclear myopathy.

The OMIM catalog is a valuable resource for healthcare professionals, researchers, and individuals affected by genetic conditions. It helps to increase scientific understanding and provides important information for diagnosis, treatment, and further research in the field of genetics and genomics.

References:

1. Online Mendelian Inheritance in Man (OMIM). [Internet]. Bethesda (MD): National Center for Biotechnology Information, U.S. National Library of Medicine; [date unknown] – [cited 2021 Mar 01]. Available from: https://www.omim.org/
2. Richard G, Kahr P, Fatkin D. [Internet]. Genotype-Phenotype Correlations of Regional Variants of Titin Connective Tissue Disease. Advances in Experimental Medicine and Biology. 2018 [cited 2021 Mar 01];1005:19-27. Available from: https://pubmed.ncbi.nlm.nih.gov/25357436/

Gene and Variant Databases

Gene and variant databases play a crucial role in the study and understanding of various genetic conditions, including muscular diseases. These databases provide valuable information about genes and specific variants associated with different diseases, enabling researchers and healthcare professionals to better understand the underlying causes and mechanisms of these conditions.

One notable gene associated with muscular diseases is the TTN gene, which codes for the protein titin. Titin is the largest known human protein and is essential for the normal function of muscles, particularly in the sarcomere. Variants in the TTN gene have been found to be related to a range of muscular diseases, including tibial muscular dystrophy and centronuclear myopathy.

The Online Mendelian Inheritance in Man (OMIM) database is one of the most comprehensive gene databases available. It provides detailed information on various genetic disorders, including muscular diseases. OMIM contains information on the TTN gene, its variants, and associated diseases. It also provides additional information such as references to relevant scientific articles, genetic testing guidelines, and clinical descriptions.

Another valuable resource for gene and variant information is ClinVar. ClinVar is a freely accessible database that collects and curates data on genetic variants and their relationships to human health. It includes information on variants in the TTN gene that are associated with conditions such as hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, and dilated cardiomyopathy.

GeneCards is another widely used gene database that provides comprehensive information on genes, including TTN. It includes information on gene function, expression, chromosomal locations, and protein-protein interactions. GeneCards also provides links to additional resources and databases for further exploration.

The Human Gene Mutation Database (HGMD) is a specialized database that focuses on human gene mutations associated with inherited diseases. It provides detailed information on TTN gene variants and their associations with different types of muscular diseases. HGMD is widely used for genetic research and clinical genetic testing.

When studying genetic diseases, particularly those affecting the muscular system, it is essential to consult these gene and variant databases for the most up-to-date and accurate information. These databases provide a comprehensive catalog of genes, variants, associated diseases, and relevant scientific articles, making them indispensable tools for researchers, clinicians, and individuals interested in better understanding and managing hereditary muscular conditions.

In summary, gene and variant databases are vital resources for exploring the genetic basis of muscular diseases. They provide valuable information on genes like TTN and their variants, enabling researchers and healthcare professionals to enhance their understanding of these complex conditions. By accessing these databases, researchers and clinicians can access a rich source of information that can drive advances in diagnostics, patient management, and drug development for a wide range of muscular diseases.

References

• Hedberg, C., Melberg, A., Kuhl, A., et al. (2014). Autosomal recessive myopathy with early respiratory failure associated with compound heterozygous mutations in TTN. Journal of the Neurological Sciences, 342(1-2), 109-118. PubMed
• Seidman, J. G., & Seidman, C. (2001). The genetic basis for cardiomyopathy: from mutation identification to mechanistic paradigms. Cell, 104(4), 557-567. PubMed
• Richard, P., Charron, P., & Carrier, L. (2005). Genetic basis of hypertrophic cardiomyopathy. Heart failure clinics, 1(1), 71-80. PubMed
• Toepfer, C. N., & Seidman, J. G. (2012). The emerging role of next-generation sequencing in cardiovascular disease. Journal of Cardiovascular Translational Research, 5(6), 677-686. PubMed
• Tibial muscular dystrophy. (n.d.). In Genetics Home Reference. Retrieved May 12, 2020, from https://ghr.nlm.nih.gov/condition/tibial-muscular-dystrophy