Table 1. Number of TTNtv in DCM patients and controls.

Numbers of subjects with a TTNtv are shown for each group. TTNtv are classified by type, the affected transcript, and expression level of the variant-encoding exon. Comparisons between groups were assessed by Fisher’s exact test. Cohort ethnicity: Caucasian: healthy volunteer, 75%; FHS, 100%; JHS, 0%; unselected DCM, 88%; end-stage, DCM 85%; African American: healthy volunteer, 2%; FHS, 0%; JHS, 100%; unselected DCM, 4%; end-stage DCM, 6%.

Discovery cohortsReplication cohorts
Healthy
volunteers
(n = 308)
FHS
(n = 1623)
JHS
(n = 1980)
Unselected
DCM
(n = 371)*
End-stage
DCM
(n = 155)
P value DCM
versus controls
WHI
(n = 667)
Familial DCM
(n = 163)
P value DCM
versus
controls
Unselected
DCM
All DCM
Transcript affected by truncation
N2BA and N2B4112042341.7 × 10−255.5 × 10−462313.8 × 10−21
N2BA only428700.00140.0083201
Neither N2BA or
N2B (novex-3
terminal exon
only)
1 (0)8 (5)4 (1)1 (1)1 (1)10.75 (4)0 (0)1
  Totals921325035931
Sarcomere domain
A-band (18,235
amino acids)
271232290.0110.000141250.015
Non–A-band
(17,756
amino acids)
791918846
  Totals916314934531
Usage§ of exon containing truncation
Low (PSI <0.15) 144200.250.38101
Intermediate
(PSI 0.15 to 0.9)
417500.0120.042201
High (PSI >0.9) 4112042341.7 × 10−255.5 × 10−462313.8 × 10−21
  Totals916314934531
Variant type
Frameshift
variant
23722154.9 × 10−164.0 × 10−251151.9 × 10−10
Stop gained37615127.3 × 10−092.3 × 10−152162.8 × 10−10
Canonical splice
sites
237952.9 × 10−052.3 × 10−07101
Splice
variant
predictions||
2311450.0890.0015101
  Totals9163149341.4 × 10−252.8 × 10−435311.6 × 10−18

*Three of 374 subjects were excluded from these analyses due to relatedness to other subjects.

†Variants that only affect the alternative terminal exon of novex-3 are excluded elsewhere.

‡Total number of individuals with TTNtv; four individuals with DCM (one unselected, three end-stage) carry a second TTNtv, which is a splice variant prediction in three cases.

§Exon usage levels are displayed categorically on the basis of PSI.

¶Canonical splice sites refer to the two intronic base pairs at the 5′ and 3′ splice junctions.

||Variants close to canonical splice sites that are predicted in silico to alter splicing.