Western blotting using 2 different antibodies (M10-1 and 11-4-3) against the titin C-terminal M10 domain. A, Patient VIII with a single identified protein truncating variant shows a severe reduction of titin C-terminal fractions of all sizes; patient IV presents a reduced amount of the small (<20 kDa) titin fragments, and additionally the presence of a truncated fragment (arrowheads) resulting from the aberrant splicing due to the splice site mutation in intron 362. B, Patient Xa with missense mutations showed a normal titin C-terminal pattern, while patient IXa with a single protein truncating variant and 2 missense variants showed a reduction of the small (<20 kDa) titin C-terminal fragments in particular. The myosin heavy chain (MyHC) serves as the loading control. Ctrl indicates control; LGMD2J, limb-girdle muscular dystrophy 2J; TMD, tibial muscular dystrophy.