Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17051 | 51376;51377;51378 | chr2:178610375;178610374;178610373 | chr2:179475102;179475101;179475100 |
| N2AB | 15410 | 46453;46454;46455 | chr2:178610375;178610374;178610373 | chr2:179475102;179475101;179475100 |
| N2A | 14483 | 43672;43673;43674 | chr2:178610375;178610374;178610373 | chr2:179475102;179475101;179475100 |
| N2B | 7986 | 24181;24182;24183 | chr2:178610375;178610374;178610373 | chr2:179475102;179475101;179475100 |
| Novex-1 | 8111 | 24556;24557;24558 | chr2:178610375;178610374;178610373 | chr2:179475102;179475101;179475100 |
| Novex-2 | 8178 | 24757;24758;24759 | chr2:178610375;178610374;178610373 | chr2:179475102;179475101;179475100 |
| Novex-3 | None | None | chr2:None | chr2:None |
Information
Reported SAVs
| SNV | RS | DUET |
PolyPhen-2 |
Condel |
Rhapsody |
REVEL |
MVP |
Source |
MAF |
Disease |
Zygosity |
Site annotation |
mCSM PPI |
Predicted PPI site |
Comments |
AFR |
AMR |
AMS |
ASJ |
EAS |
EUR |
FIN |
MDE |
NFE |
SAS |
OTH |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| C/R | rs781155992  |
-1.361 | 1.0 | N | 0.901 | 0.616 | 0.733602862534 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| C/R | rs781155992 |
-1.361 | 1.0 | N | 0.901 | 0.616 | 0.733602862534 |
Rees (2021)
| None |
MmD 
|
comp het with Q32711Lfs*22 | None | None | N | Genetic analysis of TTN in 30 CM patients; comp het with truncating; Domain unfolded in vitro | None | None | None | None | None | None | None | None | None | None | None |
| C/R | rs781155992 |
-1.361 | 1.0 | N | 0.901 | 0.616 | 0.733602862534 | gnomAD-4.0.0 | 1.59406E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.4339E-05 | 0 |
Saturation Mutagenesis
SAV |
AlphaMissense (IC) |
AlphaMissense Class (IC) |
AlphaMissense (N2AB) |
AlphaMissense Class (N2AB) |
mCSM |
mCSM class |
PolyPhen-2 |
PolyPhen-2 Class |
Rhapsody |
Rhapsody Class |
Condel |
Condel Score |
Site annotation |
mCSM PPI |
Predicted PPI site |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| C/A | 0.7754 | likely_pathogenic | 0.7742 | pathogenic | -1.784 | Destabilizing | 0.998 | D | 0.513 | neutral | None | None | None | None | N |
| C/D | 0.9983 | likely_pathogenic | 0.9984 | pathogenic | -1.843 | Destabilizing | 1.0 | D | 0.871 | deleterious | None | None | None | None | N |
| C/E | 0.999 | likely_pathogenic | 0.9991 | pathogenic | -1.621 | Destabilizing | 1.0 | D | 0.896 | deleterious | None | None | None | None | N |
| C/F | 0.9694 | likely_pathogenic | 0.9719 | pathogenic | -1.016 | Destabilizing | 1.0 | D | 0.879 | deleterious | N | 0.496400668 | None | None | N |
| C/G | 0.8679 | likely_pathogenic | 0.8629 | pathogenic | -2.133 | Highly Destabilizing | 1.0 | D | 0.812 | deleterious | N | 0.464151275 | None | None | N |
| C/H | 0.9977 | likely_pathogenic | 0.9979 | pathogenic | -2.353 | Highly Destabilizing | 1.0 | D | 0.889 | deleterious | None | None | None | None | N |
| C/I | 0.8012 | likely_pathogenic | 0.8344 | pathogenic | -0.835 | Destabilizing | 1.0 | D | 0.719 | prob.delet. | None | None | None | None | N |
| C/K | 0.9996 | likely_pathogenic | 0.9996 | pathogenic | -1.665 | Destabilizing | 1.0 | D | 0.861 | deleterious | None | None | None | None | N |
| C/L | 0.8745 | likely_pathogenic | 0.8714 | pathogenic | -0.835 | Destabilizing | 0.999 | D | 0.577 | neutral | None | None | None | None | N |
| C/M | 0.9561 | likely_pathogenic | 0.9597 | pathogenic | -0.011 | Destabilizing | 1.0 | D | 0.805 | deleterious | None | None | None | None | N |
| C/N | 0.9877 | likely_pathogenic | 0.9897 | pathogenic | -2.15 | Highly Destabilizing | 1.0 | D | 0.899 | deleterious | None | None | None | None | N |
| C/P | 0.5871 | likely_pathogenic | 0.5673 | pathogenic | -1.13 | Destabilizing | 1.0 | D | 0.895 | deleterious | None | None | None | None | N |
| C/Q | 0.9973 | likely_pathogenic | 0.9974 | pathogenic | -1.71 | Destabilizing | 1.0 | D | 0.893 | deleterious | None | None | None | None | N |
| C/R | 0.9964 | likely_pathogenic | 0.9963 | pathogenic | -1.941 | Destabilizing | 1.0 | D | 0.901 | deleterious | N | 0.496400668 | None | None | N |
| C/S | 0.8895 | likely_pathogenic | 0.8925 | pathogenic | -2.469 | Highly Destabilizing | 1.0 | D | 0.702 | prob.neutral | N | 0.463913805 | None | None | N |
| C/T | 0.8765 | likely_pathogenic | 0.885 | pathogenic | -2.079 | Highly Destabilizing | 1.0 | D | 0.692 | prob.neutral | None | None | None | None | N |
| C/V | 0.5319 | ambiguous | 0.5648 | pathogenic | -1.13 | Destabilizing | 0.999 | D | 0.606 | neutral | None | None | None | None | N |
| C/W | 0.9978 | likely_pathogenic | 0.9979 | pathogenic | -1.449 | Destabilizing | 1.0 | D | 0.864 | deleterious | N | 0.497386252 | None | None | N |
| C/Y | 0.9949 | likely_pathogenic | 0.9954 | pathogenic | -1.279 | Destabilizing | 1.0 | D | 0.884 | deleterious | N | 0.496400668 | None | None | N |
Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.