Fig 1.
Influence of 1000 genomes project evolution on titin truncation prevalence.
Abbreviations: P1V1 –phase 1 version 1; P1V2 –phase 1 version 2; P1V3 –phase 1 version 3; P3V5 –phase 3 version 5.
Fig 2.
Flowchart for analysis of TTN truncations in publicly available reference populations.
Abbreviations: 1KG– 1000 Genomes project; ESP–Exome Sequencing Project; ExAC—Exome Aggregation Consortium; LV–Left ventricle.
Table 1.
Distribution and burden of TTN truncations in publicly available reference populations.
Fig 3.
Spatial distribution of titin frameshift, nonsense and splice-site mutations in reference populations.
Titin is linearly depicted with its 152 Ig-like domains in green and 132 fibronectin type III domains in purple. TTNtv are shown as lollipops and bars. Depicted are nonsense (red) and frameshift (green) mutations in various phases of the 1000 Genomes project. Dark grey bars represent the complete map of various TTN mutations from ExAC. Variants are shown relative to the titin Uniprot Sequence identifier Q8WZ42. The dashed lines below the protein schematic indicate the location of variants within the sarcomere. Abbreviations: 1KG– 1000 Genomes project; ESP–Exome Sequencing project; ExAC—Exome Aggregation Consortium; V–version.
Fig 4.
Titin population splice site/region allele frequency spectrum.
TTN population non-essential splice-site variants (>2bp) have significantly lower proportion of private variants and higher proportion of low-frequency variants compared to essential splice-site variants (P = 0.01; P = 5.1 × 10−4, respectively). The P-values are shown for comparison between essential splice-site (1-2bp) and non-essential splice-site variants: 3–4bp (red), 5–6bp (green), and (blue) for combined comparison.