Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 4845 | 14758;14759;14760 | chr2:178735913;178735912;178735911 | chr2:179600640;179600639;179600638 |
| N2AB | 4528 | 13807;13808;13809 | chr2:178735913;178735912;178735911 | chr2:179600640;179600639;179600638 |
| N2A | 3601 | 11026;11027;11028 | chr2:178735913;178735912;178735911 | chr2:179600640;179600639;179600638 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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/N | rs373378672  |
-0.411 | 0.038 | N | 0.392 | 0.105 | None | gnomAD-2.1.1 | 1.4269E-04 | None | None | None | None | N | None | 3.30579E-04 | 1.13141E-04 | None | 0 | 5.13E-05 | None | 3.59454E-04 | None | 0 | 1.17021E-04 | 1.40331E-04 |
| D/N | rs373378672 |
-0.411 | 0.038 | N | 0.392 | 0.105 | None | gnomAD-3.1.2 | 1.64296E-04 | None | None | None | None | N | None | 3.37838E-04 | 1.30959E-04 | 0 | 0 | 0 | None | 0 | 0 | 1.17595E-04 | 0 | 4.78469E-04 |
| D/N | rs373378672 |
-0.411 | 0.038 | N | 0.392 | 0.105 | None | gnomAD-4.0.0 | 1.10913E-04 | None | None | None | None | N | None | 2.93185E-04 | 8.33222E-05 | None | 0 | 6.68658E-05 | None | 0 | 4.9505E-04 | 7.79784E-05 | 3.84294E-04 | 3.04078E-04 |
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 | 0.1051 | likely_benign | 0.0869 | benign | -0.294 | Destabilizing | None | N | 0.409 | neutral | N | 0.475530382 | None | None | N |
| D/C | 0.379 | ambiguous | 0.2991 | benign | 0.104 | Stabilizing | None | N | 0.449 | neutral | None | None | None | None | N |
| D/E | 0.1198 | likely_benign | 0.1032 | benign | -0.338 | Destabilizing | None | N | 0.235 | neutral | N | 0.428095469 | None | None | N |
| D/F | 0.3528 | ambiguous | 0.2828 | benign | -0.335 | Destabilizing | 0.138 | N | 0.557 | neutral | None | None | None | None | N |
| D/G | 0.1266 | likely_benign | 0.1031 | benign | -0.509 | Destabilizing | 0.007 | N | 0.441 | neutral | N | 0.487241838 | None | None | N |
| D/H | 0.1199 | likely_benign | 0.1053 | benign | -0.39 | Destabilizing | None | N | 0.394 | neutral | N | 0.451111255 | None | None | N |
| D/I | 0.2398 | likely_benign | 0.1778 | benign | 0.227 | Stabilizing | 0.044 | N | 0.551 | neutral | None | None | None | None | N |
| D/K | 0.1864 | likely_benign | 0.1504 | benign | 0.098 | Stabilizing | None | N | 0.323 | neutral | None | None | None | None | N |
| D/L | 0.2323 | likely_benign | 0.1783 | benign | 0.227 | Stabilizing | 0.018 | N | 0.519 | neutral | None | None | None | None | N |
| D/M | 0.4639 | ambiguous | 0.3639 | ambiguous | 0.48 | Stabilizing | 0.497 | N | 0.527 | neutral | None | None | None | None | N |
| D/N | 0.08 | likely_benign | 0.0697 | benign | -0.053 | Destabilizing | 0.038 | N | 0.392 | neutral | N | 0.465162176 | None | None | N |
| D/P | 0.5222 | ambiguous | 0.3881 | ambiguous | 0.076 | Stabilizing | 0.085 | N | 0.483 | neutral | None | None | None | None | N |
| D/Q | 0.1907 | likely_benign | 0.1507 | benign | -0.017 | Destabilizing | 0.022 | N | 0.369 | neutral | None | None | None | None | N |
| D/R | 0.2033 | likely_benign | 0.1593 | benign | 0.206 | Stabilizing | None | N | 0.441 | neutral | None | None | None | None | N |
| D/S | 0.0901 | likely_benign | 0.0787 | benign | -0.201 | Destabilizing | None | N | 0.235 | neutral | None | None | None | None | N |
| D/T | 0.1542 | likely_benign | 0.1233 | benign | -0.045 | Destabilizing | 0.009 | N | 0.459 | neutral | None | None | None | None | N |
| D/V | 0.1449 | likely_benign | 0.1131 | benign | 0.076 | Stabilizing | 0.007 | N | 0.522 | neutral | N | 0.443653982 | None | None | N |
| D/W | 0.7423 | likely_pathogenic | 0.6455 | pathogenic | -0.258 | Destabilizing | 0.788 | D | 0.513 | neutral | None | None | None | None | N |
| D/Y | 0.1315 | likely_benign | 0.1129 | benign | -0.126 | Destabilizing | 0.133 | N | 0.56 | neutral | N | 0.384074971 | 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.