Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17870 | 53833;53834;53835 | chr2:178605687;178605686;178605685 | chr2:179470414;179470413;179470412 |
| N2AB | 16229 | 48910;48911;48912 | chr2:178605687;178605686;178605685 | chr2:179470414;179470413;179470412 |
| N2A | 15302 | 46129;46130;46131 | chr2:178605687;178605686;178605685 | chr2:179470414;179470413;179470412 |
| N2B | 8805 | 26638;26639;26640 | chr2:178605687;178605686;178605685 | chr2:179470414;179470413;179470412 |
| Novex-1 | 8930 | 27013;27014;27015 | chr2:178605687;178605686;178605685 | chr2:179470414;179470413;179470412 |
| Novex-2 | 8997 | 27214;27215;27216 | chr2:178605687;178605686;178605685 | chr2:179470414;179470413;179470412 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | rs758041223  |
-0.728 | 0.022 | N | 0.168 | 0.109 | 0.126345400529 | gnomAD-2.1.1 | 1.71E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.29331E-04 | None | 0 | None | 0 | 0 | 0 |
| T/A | rs758041223 |
-0.728 | 0.022 | N | 0.168 | 0.109 | 0.126345400529 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 1.94704E-04 | None | 0 | 0 | 0 | 0 | 0 |
| T/A | rs758041223 |
-0.728 | 0.022 | N | 0.168 | 0.109 | 0.126345400529 | gnomAD-4.0.0 | 4.4229E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.5835E-04 | None | 0 | 0 | 0 | 0 | 0 |
| T/I | rs1553683359 |
None | 0.669 | N | 0.511 | 0.186 | 0.339793275041 | gnomAD-4.0.0 | 6.98284E-07 | None | None | None | None | N | None | 3.06843E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| T/P | None | None | 0.966 | N | 0.585 | 0.305 | 0.397540356873 | gnomAD-4.0.0 | 6.98982E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.14246E-07 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.1616 | likely_benign | 0.1193 | benign | -0.851 | Destabilizing | 0.022 | N | 0.168 | neutral | N | 0.477963118 | None | None | N |
| T/C | 0.4706 | ambiguous | 0.4037 | ambiguous | -0.53 | Destabilizing | 0.998 | D | 0.55 | neutral | None | None | None | None | N |
| T/D | 0.7789 | likely_pathogenic | 0.7205 | pathogenic | 0.155 | Stabilizing | 0.915 | D | 0.517 | neutral | None | None | None | None | N |
| T/E | 0.6626 | likely_pathogenic | 0.5814 | pathogenic | 0.23 | Stabilizing | 0.842 | D | 0.454 | neutral | None | None | None | None | N |
| T/F | 0.3836 | ambiguous | 0.302 | benign | -0.896 | Destabilizing | 0.949 | D | 0.617 | neutral | None | None | None | None | N |
| T/G | 0.343 | ambiguous | 0.2876 | benign | -1.157 | Destabilizing | 0.842 | D | 0.502 | neutral | None | None | None | None | N |
| T/H | 0.3481 | ambiguous | 0.277 | benign | -1.285 | Destabilizing | 0.016 | N | 0.413 | neutral | None | None | None | None | N |
| T/I | 0.3348 | likely_benign | 0.2483 | benign | -0.11 | Destabilizing | 0.669 | D | 0.511 | neutral | N | 0.485755882 | None | None | N |
| T/K | 0.5228 | ambiguous | 0.4228 | ambiguous | -0.356 | Destabilizing | 0.801 | D | 0.461 | neutral | N | 0.448773574 | None | None | N |
| T/L | 0.1702 | likely_benign | 0.1155 | benign | -0.11 | Destabilizing | 0.275 | N | 0.391 | neutral | None | None | None | None | N |
| T/M | 0.133 | likely_benign | 0.0915 | benign | -0.1 | Destabilizing | 0.325 | N | 0.301 | neutral | None | None | None | None | N |
| T/N | 0.2044 | likely_benign | 0.1667 | benign | -0.579 | Destabilizing | 0.842 | D | 0.463 | neutral | None | None | None | None | N |
| T/P | 0.8332 | likely_pathogenic | 0.6893 | pathogenic | -0.324 | Destabilizing | 0.966 | D | 0.585 | neutral | N | 0.49252814 | None | None | N |
| T/Q | 0.3419 | ambiguous | 0.2677 | benign | -0.53 | Destabilizing | 0.974 | D | 0.589 | neutral | None | None | None | None | N |
| T/R | 0.4501 | ambiguous | 0.3516 | ambiguous | -0.337 | Destabilizing | 0.801 | D | 0.556 | neutral | N | 0.424051275 | None | None | N |
| T/S | 0.1629 | likely_benign | 0.1264 | benign | -0.938 | Destabilizing | 0.454 | N | 0.443 | neutral | N | 0.47132236 | None | None | N |
| T/V | 0.2255 | likely_benign | 0.1677 | benign | -0.324 | Destabilizing | 0.525 | D | 0.428 | neutral | None | None | None | None | N |
| T/W | 0.7841 | likely_pathogenic | 0.704 | pathogenic | -0.887 | Destabilizing | 0.998 | D | 0.612 | neutral | None | None | None | None | N |
| T/Y | 0.4519 | ambiguous | 0.3848 | ambiguous | -0.58 | Destabilizing | 0.949 | D | 0.617 | neutral | None | None | 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.