Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 35979 | 108160;108161;108162 | chr2:178527053;178527052;178527051 | chr2:179391780;179391779;179391778 |
| N2AB | 34338 | 103237;103238;103239 | chr2:178527053;178527052;178527051 | chr2:179391780;179391779;179391778 |
| N2A | 33411 | 100456;100457;100458 | chr2:178527053;178527052;178527051 | chr2:179391780;179391779;179391778 |
| N2B | 26914 | 80965;80966;80967 | chr2:178527053;178527052;178527051 | chr2:179391780;179391779;179391778 |
| Novex-1 | 27039 | 81340;81341;81342 | chr2:178527053;178527052;178527051 | chr2:179391780;179391779;179391778 |
| Novex-2 | 27106 | 81541;81542;81543 | chr2:178527053;178527052;178527051 | chr2:179391780;179391779;179391778 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/P | None | None | 0.966 | N | 0.476 | 0.456 | 0.37262878642 | gnomAD-4.0.0 | 1.59126E-06 | None | None | None | 0.09(OBSL1) 0.116(OBSCN) | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85789E-06 | 0 | 0 |
| S/Y | None | None | 0.876 | D | 0.581 | 0.487 | 0.653374280352 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | 0.423(OBSL1) 0.494(OBSCN) | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.1026 | likely_benign | 0.1014 | benign | -0.418 | Destabilizing | 0.454 | N | 0.371 | neutral | D | 0.526170857 | None | 0.066(OBSL1) 0.062(OBSCN) | N |
| S/C | 0.1361 | likely_benign | 0.1388 | benign | -0.28 | Destabilizing | 0.028 | N | 0.351 | neutral | N | 0.510966742 | None | 0.281(OBSL1) 0.431(OBSCN) | N |
| S/D | 0.4564 | ambiguous | 0.4317 | ambiguous | 0.079 | Stabilizing | 0.842 | D | 0.375 | neutral | None | None | None | 0.019(OBSL1) 0.105(OBSCN) | N |
| S/E | 0.475 | ambiguous | 0.4435 | ambiguous | -0.031 | Destabilizing | 0.842 | D | 0.374 | neutral | None | None | None | -0.027(OBSL1) 0.078(OBSCN) | N |
| S/F | 0.2256 | likely_benign | 0.2343 | benign | -1.104 | Destabilizing | 0.028 | N | 0.403 | neutral | N | 0.492862487 | None | 0.194(OBSL1) 0.26(OBSCN) | N |
| S/G | 0.1469 | likely_benign | 0.1405 | benign | -0.488 | Destabilizing | 0.842 | D | 0.336 | neutral | None | None | None | 0.047(OBSL1) 0.029(OBSCN) | N |
| S/H | 0.3482 | ambiguous | 0.3287 | benign | -0.991 | Destabilizing | 0.998 | D | 0.479 | neutral | None | None | None | 0.787(OBSL1) 0.772(OBSCN) | N |
| S/I | 0.238 | likely_benign | 0.222 | benign | -0.362 | Destabilizing | 0.904 | D | 0.534 | neutral | None | None | None | 0.093(OBSL1) 0.135(OBSCN) | N |
| S/K | 0.6 | likely_pathogenic | 0.5378 | ambiguous | -0.404 | Destabilizing | 0.842 | D | 0.369 | neutral | None | None | None | 0.256(OBSL1) 0.413(OBSCN) | N |
| S/L | 0.1452 | likely_benign | 0.1449 | benign | -0.362 | Destabilizing | 0.728 | D | 0.523 | neutral | None | None | None | 0.093(OBSL1) 0.135(OBSCN) | N |
| S/M | 0.2521 | likely_benign | 0.2484 | benign | -0.042 | Destabilizing | 0.993 | D | 0.478 | neutral | None | None | None | 0.469(OBSL1) 0.549(OBSCN) | N |
| S/N | 0.1678 | likely_benign | 0.1535 | benign | -0.107 | Destabilizing | 0.842 | D | 0.408 | neutral | None | None | None | -0.164(OBSL1) -0.015(OBSCN) | N |
| S/P | 0.7331 | likely_pathogenic | 0.721 | pathogenic | -0.355 | Destabilizing | 0.966 | D | 0.476 | neutral | N | 0.510713253 | None | 0.09(OBSL1) 0.116(OBSCN) | N |
| S/Q | 0.4687 | ambiguous | 0.4415 | ambiguous | -0.41 | Destabilizing | 0.974 | D | 0.407 | neutral | None | None | None | -0.031(OBSL1) 0.113(OBSCN) | N |
| S/R | 0.4649 | ambiguous | 0.4114 | ambiguous | -0.176 | Destabilizing | 0.949 | D | 0.478 | neutral | None | None | None | 0.282(OBSL1) 0.425(OBSCN) | N |
| S/T | 0.0947 | likely_benign | 0.0907 | benign | -0.246 | Destabilizing | 0.051 | N | 0.188 | neutral | N | 0.480014493 | None | -0.023(OBSL1) 0.071(OBSCN) | N |
| S/V | 0.2374 | likely_benign | 0.2299 | benign | -0.355 | Destabilizing | 0.728 | D | 0.56 | neutral | None | None | None | 0.09(OBSL1) 0.116(OBSCN) | N |
| S/W | 0.388 | ambiguous | 0.3883 | ambiguous | -1.095 | Destabilizing | 0.998 | D | 0.608 | neutral | None | None | None | 0.282(OBSL1) 0.377(OBSCN) | N |
| S/Y | 0.2148 | likely_benign | 0.2129 | benign | -0.815 | Destabilizing | 0.876 | D | 0.581 | neutral | D | 0.522069558 | None | 0.423(OBSL1) 0.494(OBSCN) | 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.