Associated disorders

The TTN gene is associated with autosomal dominant dilated cardiomyopathy (DCM) (MedGen UID: 2880). Additionally, the TTN gene is associated with a diverse group of disorders affecting skeletal muscles, including autosomal dominant tibial muscular dystrophy (TMD) (MedGen UID: 333047) and autosomal recessive limb-girdle muscular dystrophy type 2J (LGMD2J) (MedGen UID: 324741), autosomal recessive centronuclear myopathy (PMID: 23975875), and autosomal dominant hereditary myopathy with early respiratory failure (HMERF) (MedGen UID: 350930). Additional TTN-related conditions have also been reported (OMIM: 188840).

TTN is a significant cause of cardiomyopathy; pathogenic variants in TTN have been shown to account for 18%-25% of clinical cases of dilated cardiomyopathy. In addition, pathogenic variants in TTN are the only known cause of tibial muscular dystrophy and hereditary myopathy with early respiratory failure. The percentage of clinical cases of LGMD and centronuclear myopathy attributable to pathogenic TTN variants are unknown, although TTN appears to be a relatively rare cause of these disorders.

TTN encodes the giant sarcomeric protein titin. A single titin molecule spans a distance greater than 1 uM from M-band to Z-band. Titin is involved with sarcomere assembly, I-band flexibility, and force transmission. Numerous other proteins interact with titin, including calpain, myosin, actin, and telethonin.

Assay and technical information

Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).

Our sequence analysis covers clinically important regions of each gene, including coding exons, +/- 10 base pairs of adjacent intronic sequence, and select noncoding variants. Our assay provides a Q30 quality-adjusted mean coverage depth of 350x (50x minimum, or supplemented with additional analysis). Variants classified as pathogenic or likely pathogenic are confirmed with orthogonal methods, except individual variants that have high quality scores and previously validated in at least ten unrelated samples.

Our analysis detects most intragenic deletions and duplications at single exon resolution. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. If you are requesting the detection of a specific single-exon copy number variation, please contact Client Services before placing your order.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
TTN* NM_001267550.2

*TTN: Deletion/duplication and sequencing analysis is not offered for exons 153-155 (NM_133378.4).