Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24498 | 73717;73718;73719 | chr2:178572640;178572639;178572638 | chr2:179437367;179437366;179437365 |
| N2AB | 22857 | 68794;68795;68796 | chr2:178572640;178572639;178572638 | chr2:179437367;179437366;179437365 |
| N2A | 21930 | 66013;66014;66015 | chr2:178572640;178572639;178572638 | chr2:179437367;179437366;179437365 |
| N2B | 15433 | 46522;46523;46524 | chr2:178572640;178572639;178572638 | chr2:179437367;179437366;179437365 |
| Novex-1 | 15558 | 46897;46898;46899 | chr2:178572640;178572639;178572638 | chr2:179437367;179437366;179437365 |
| Novex-2 | 15625 | 47098;47099;47100 | chr2:178572640;178572639;178572638 | chr2:179437367;179437366;179437365 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/T | rs999356680  |
-1.605 | 0.324 | N | 0.483 | 0.23 | 0.444305618086 | gnomAD-2.1.1 | 8.06E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.91E-06 | 1.665E-04 |
| I/T | rs999356680 |
-1.605 | 0.324 | N | 0.483 | 0.23 | 0.444305618086 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| I/T | rs999356680 |
-1.605 | 0.324 | N | 0.483 | 0.23 | 0.444305618086 | gnomAD-4.0.0 | 3.71943E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.69562E-06 | 3.29533E-05 | 1.60185E-05 |
| I/V | None | None | 0.041 | N | 0.311 | 0.074 | 0.286848849266 | gnomAD-4.0.0 | 1.59265E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43394E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.2416 | likely_benign | 0.2993 | benign | -2.172 | Highly Destabilizing | 0.116 | N | 0.456 | neutral | None | None | None | None | I |
| I/C | 0.4557 | ambiguous | 0.4833 | ambiguous | -1.416 | Destabilizing | 0.981 | D | 0.513 | neutral | None | None | None | None | I |
| I/D | 0.6123 | likely_pathogenic | 0.6793 | pathogenic | -2.155 | Highly Destabilizing | 0.241 | N | 0.606 | neutral | None | None | None | None | I |
| I/E | 0.4841 | ambiguous | 0.5453 | ambiguous | -1.966 | Destabilizing | 0.388 | N | 0.599 | neutral | None | None | None | None | I |
| I/F | 0.135 | likely_benign | 0.1538 | benign | -1.235 | Destabilizing | 0.69 | D | 0.466 | neutral | None | None | None | None | I |
| I/G | 0.5582 | ambiguous | 0.6245 | pathogenic | -2.682 | Highly Destabilizing | 0.388 | N | 0.559 | neutral | None | None | None | None | I |
| I/H | 0.2668 | likely_benign | 0.3122 | benign | -2.144 | Highly Destabilizing | 0.818 | D | 0.612 | neutral | None | None | None | None | I |
| I/K | 0.2928 | likely_benign | 0.3439 | ambiguous | -1.515 | Destabilizing | 0.324 | N | 0.599 | neutral | N | 0.445375405 | None | None | I |
| I/L | 0.0981 | likely_benign | 0.1013 | benign | -0.728 | Destabilizing | 0.015 | N | 0.315 | neutral | N | 0.47194593 | None | None | I |
| I/M | 0.08 | likely_benign | 0.0876 | benign | -0.7 | Destabilizing | 0.003 | N | 0.119 | neutral | N | 0.440316302 | None | None | I |
| I/N | 0.1547 | likely_benign | 0.1919 | benign | -1.72 | Destabilizing | 0.008 | N | 0.476 | neutral | None | None | None | None | I |
| I/P | 0.9453 | likely_pathogenic | 0.9561 | pathogenic | -1.187 | Destabilizing | 0.932 | D | 0.619 | neutral | None | None | None | None | I |
| I/Q | 0.2815 | likely_benign | 0.3311 | benign | -1.626 | Destabilizing | 0.69 | D | 0.61 | neutral | None | None | None | None | I |
| I/R | 0.2186 | likely_benign | 0.2628 | benign | -1.256 | Destabilizing | 0.627 | D | 0.612 | neutral | N | 0.44485533 | None | None | I |
| I/S | 0.1611 | likely_benign | 0.2002 | benign | -2.432 | Highly Destabilizing | 0.388 | N | 0.54 | neutral | None | None | None | None | I |
| I/T | 0.1117 | likely_benign | 0.1409 | benign | -2.104 | Highly Destabilizing | 0.324 | N | 0.483 | neutral | N | 0.366045043 | None | None | I |
| I/V | 0.0613 | likely_benign | 0.0662 | benign | -1.187 | Destabilizing | 0.041 | N | 0.311 | neutral | N | 0.385308381 | None | None | I |
| I/W | 0.7107 | likely_pathogenic | 0.7446 | pathogenic | -1.591 | Destabilizing | 0.981 | D | 0.633 | neutral | None | None | None | None | I |
| I/Y | 0.3582 | ambiguous | 0.3925 | ambiguous | -1.276 | Destabilizing | 0.818 | D | 0.543 | neutral | None | None | None | None | I |
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.