Titin Myopathy

All about Titin Protein, Titin Myopathy, Titinopathy, Titinopathies

Titin Myopathy - All about Titin Protein, Titin Myopathy, Titinopathy, Titinopathies

Genetics

How to make sense of your

Variant of Unknown Significance

Results for Titin

 Changes found in a gene are sometimes called mutations or variants.  Some variants in a gene may lead to health problems, while others may not.

Sometimes a genetic testing laboratory will find a variant in a gene that they have not seen before, and they do not know if it causes disease or not.  When a lab comes across a variant, but it has not yet been reported to cause disease, they call it a “Variant of Unknown Significance” or VOUS or VUS.

There are many great doctors, researchers and clinicians working to discover which VOUSs cause disease and which do not.  This is one reason why it’s really helpful for people like you to register in our patient registry the Congenital Muscle Disease International Registry www.cmdir.org and enroll in research.

Interpreting Titin genetic testing results can be tricky.  One reason for this is that Titin is such a huge gene. Titin’s size matters for several reasons: one is that until recently, scientists did not have the technology to tackle such a giant gene.  New tools have allowed researchers to learn more about Titin, and doctors are beginning to reveal what kind of changes in Titin are disease-causing and which are not.  The second reason is that because Titin is so large and has so many parts (known as exomes), there are many chances for variation.

Let’s think about tires on a car for a moment.  Most cars have four tires.  If I went out into my garage and measured the pressure in 4 tires of my car, it’s likely that all of them are properly filled.  Now, imagine if I had a car that had the same number of tires as Titin has exons: 363!  If I checked the tire pressure of 363 tires, it would be much more likely to find one that was low on air.  The larger the sample size, the more likely I am to find some variation in tire pressure.  Some cars run just fine with a tire low on air, just like some genes work just fine with some variants.  However, some tires are low on air because they are functionally flawed like with a tire with nail puncture.  It’s the same with genes.  Some variants in the gene cause it to not function properly.

VOUS, now what?

So, if you have been diagnosed with a VOUS, how do you figure out if it is the cause of your condition or not?  Here are a few recommendations:

Additional testing options:

-        If one or two disease causing variants were identified in the same gene, testing is recommended for other relatives who might be at risk to be affected or a carrier.  People who have single variants in the Titin gene may be at risk for heart problems.

-        If two disease causing variants are identified in the same gene, testing of parents may be recommended to determine whether each parent carries one of the identified variants.

-        For variants of unknown significance, other kinds of testing might be necessary. These tests may provide additional information to aid in the reclassification of a VOUS and/or help support or refute the diagnosis of a specific disorder. For Titin, this might include medical tests such as:

  • Heart function tests such as EKG and echocardiogram
  • CPK blood levels
  • Neurological examination
  • Muscle ultrasound or MRI, etc.
  • Breathing tests (including a sleep study and pulmonary function test that measures breathing capacity and cough strength)

Genetic Counseling

-        If you participated in the LGMD-diagnosis.org program, a 30 minute telephone session with an Emory Genetics  counselor is available at no additional charge. This genetic counseling session is  designed to help participants better understand what the report says and provide guidance about further testing options for themselves and family members. To schedule a telephone appointment, please contact Alonda Sims, Emory Genetics Laboratory, at 404-727-3875.

-        Schedule a formal genetic counseling session near you.  You can use the “find a genetic counselor” tool on the National Society of Genetic Counselors website, www.nsgc.org, to contact a genetic counselor in your area.  It is ideal to find a genetic counselor that specializes in neuromuscular disorders.

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