In 81 Finnish patients with TMD (600334) from 12 unrelated families, Hackman et al. (2002) found a heterozygous 11-bp deletion/insertion mutation located at position 293269-293279 in the TTN sequence. The mutation changed 4 amino acids close to the C-terminal end of the titin protein but did not cause a frameshift or a stop codon. Each of the 4 amino acids was changed to an amino acid of another charge, and the overall charge was changed from acidic to basic. The mutation was not found in 216 Finnish control samples.
In 3 patients with limb-girdle muscular dystrophy type 2J (608807) from a large consanguineous Finnish family, Hackman et al. (2002) identified homozygosity for the TTN 11-bp deletion/insertion. Other members in the same family who were heterozygous for the 11-bp deletion/insertion manifested the less severe TMD phenotype.
Using yeast 2-hybrid analysis, Sarparanta et al. (2010) found that titin containing this mutation failed to interact with myospryn (CMYA5; 612193).