Titin Myopathy (TTN)

This information is for families with variant(s) in the Titin gene (TTN). Changes in a gene are called mutations or variants. These changes may cause muscle weakness as well as heart problems. You will need to discuss with your medical team to see if and how your Titin variant affects your own health.

What is Titin?

Titin is a very large protein. It’s huge! In fact, Titin is the largest protein in the human body. The Titin protein is located in muscle cells in our bodies. It is also found in the heart, which is a specialized muscle. Muscles need Titin in order to work and move. You can learn more about Titin here http://titinmyopathy.com.

Titin variants often cause problems with the heart’s pumping ability (dilated cardiomyopathy) and can also cause abnormalities of the heart rhythm, such as atrial fibrillation. There are many different types of titin variants, and heart disorders are usually associated with a specific subset of variants that shorten the titin protein. These are called “truncating” variants. Other types of titin variants, such as missense variants (that change a single “letter” in the titin gene) are common and are less likely to be harmful. If a person is born with two truncating titin variants, they may develop muscle weakness and heart problems from an early age. More frequently, however, people carry only a single truncating variant. It is a good idea for everyone who carries a titin truncating variant to have a checkup from a heart doctor, even if they feel well.

Titin abnormalities can cause a wide spectrum of muscle disorders called “Titinopathy”. These disorders may be also called a “myopathy” or a “dystrophy” including limb-girdle muscular dystrophy (LGMD) and tibial muscular dystrophy. Some forms of titin-related myopathies may include centronuclear myopathy, multi-minicore myopathy, hereditary myopathy with early respiratory failure, Salih myopathy, core myopathy with heart disease, Emery-Dreifuss-like phenotype without cardiomyopathy and likely more. Muscle weakness may start in childhood or come on later as an adult. Weakness can range from mild to severe.

How to make sense of your Genetic Test Results for Titin

Some variants in a gene may lead to health problems, while others may not. Not all variants are equally problematic. Many truncating titin variants are clearly associated with a high risk of heart or muscle disease, and these are often classified as “pathogenic” or “likely-pathogenic” in the clinical genetic test report. On the other hand some variants are clearly not harmful and are classified as “benign” or “likely-benign”. Often however, there is insufficient information about variants to tell if they are harmful and these are classified as “variants of uncertain significance” (VUS or VOUS). These variants need follow up by experts (see resources).

Please download the PDF which contains more comprehensive information and resources below, created by Diane Fatkin, MD, Renee Johnson, PhD, MGC and Sarah Foye, (Titin Family Advocate) May 2021. Contact: Sarah Foye, Titin Family Advocate (USA) FoyeSarah@gmail.com for more information.