Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28482 | 85669;85670;85671 | chr2:178560688;178560687;178560686 | chr2:179425415;179425414;179425413 |
| N2AB | 26841 | 80746;80747;80748 | chr2:178560688;178560687;178560686 | chr2:179425415;179425414;179425413 |
| N2A | 25914 | 77965;77966;77967 | chr2:178560688;178560687;178560686 | chr2:179425415;179425414;179425413 |
| N2B | 19417 | 58474;58475;58476 | chr2:178560688;178560687;178560686 | chr2:179425415;179425414;179425413 |
| Novex-1 | 19542 | 58849;58850;58851 | chr2:178560688;178560687;178560686 | chr2:179425415;179425414;179425413 |
| Novex-2 | 19609 | 59050;59051;59052 | chr2:178560688;178560687;178560686 | chr2:179425415;179425414;179425413 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | None | None | None | N | 0.127 | 0.113 | 0.144782658237 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| D/H | rs762526051  |
-0.374 | 0.171 | N | 0.467 | 0.096 | 0.141422826196 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.9E-06 | 0 |
| D/N | rs762526051 |
0.194 | None | N | 0.07 | 0.121 | 0.107399877778 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| D/N | rs762526051 |
0.194 | None | N | 0.07 | 0.121 | 0.107399877778 | gnomAD-4.0.0 | 1.59161E-06 | None | None | None | None | N | None | 0 | 2.28697E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.0688 | likely_benign | 0.0643 | benign | -0.065 | Destabilizing | None | N | 0.127 | neutral | N | 0.436903142 | None | None | N |
| D/C | 0.35 | ambiguous | 0.3432 | ambiguous | 0.17 | Stabilizing | 0.676 | D | 0.491 | neutral | None | None | None | None | N |
| D/E | 0.1035 | likely_benign | 0.0959 | benign | -0.148 | Destabilizing | None | N | 0.055 | neutral | N | 0.382028507 | None | None | N |
| D/F | 0.3815 | ambiguous | 0.3366 | benign | -0.162 | Destabilizing | 0.356 | N | 0.519 | neutral | None | None | None | None | N |
| D/G | 0.1042 | likely_benign | 0.0964 | benign | -0.227 | Destabilizing | 0.012 | N | 0.438 | neutral | N | 0.442887752 | None | None | N |
| D/H | 0.1437 | likely_benign | 0.1389 | benign | 0.054 | Stabilizing | 0.171 | N | 0.467 | neutral | N | 0.492988498 | None | None | N |
| D/I | 0.1655 | likely_benign | 0.1541 | benign | 0.302 | Stabilizing | 0.214 | N | 0.533 | neutral | None | None | None | None | N |
| D/K | 0.1264 | likely_benign | 0.1187 | benign | 0.426 | Stabilizing | 0.016 | N | 0.429 | neutral | None | None | None | None | N |
| D/L | 0.178 | likely_benign | 0.1607 | benign | 0.302 | Stabilizing | 0.038 | N | 0.532 | neutral | None | None | None | None | N |
| D/M | 0.3341 | likely_benign | 0.3042 | benign | 0.364 | Stabilizing | 0.356 | N | 0.503 | neutral | None | None | None | None | N |
| D/N | 0.0746 | likely_benign | 0.0727 | benign | 0.302 | Stabilizing | None | N | 0.07 | neutral | N | 0.442541035 | None | None | N |
| D/P | 0.2259 | likely_benign | 0.2 | benign | 0.201 | Stabilizing | None | N | 0.158 | neutral | None | None | None | None | N |
| D/Q | 0.1539 | likely_benign | 0.1449 | benign | 0.311 | Stabilizing | 0.038 | N | 0.233 | neutral | None | None | None | None | N |
| D/R | 0.1563 | likely_benign | 0.147 | benign | 0.546 | Stabilizing | 0.072 | N | 0.497 | neutral | None | None | None | None | N |
| D/S | 0.0785 | likely_benign | 0.0745 | benign | 0.165 | Stabilizing | None | N | 0.068 | neutral | None | None | None | None | N |
| D/T | 0.1252 | likely_benign | 0.1206 | benign | 0.286 | Stabilizing | 0.016 | N | 0.411 | neutral | None | None | None | None | N |
| D/V | 0.1014 | likely_benign | 0.0937 | benign | 0.201 | Stabilizing | 0.029 | N | 0.537 | neutral | N | 0.501626624 | None | None | N |
| D/W | 0.7402 | likely_pathogenic | 0.715 | pathogenic | -0.11 | Destabilizing | 0.864 | D | 0.521 | neutral | None | None | None | None | N |
| D/Y | 0.1464 | likely_benign | 0.1382 | benign | 0.062 | Stabilizing | 0.295 | N | 0.518 | neutral | N | 0.479473087 | 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.