Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 7 | 244;245;246 | chr2:178804624;178804623;178804622 | chr2:179669351;179669350;179669349 |
| N2AB | 7 | 244;245;246 | chr2:178804624;178804623;178804622 | chr2:179669351;179669350;179669349 |
| N2A | 7 | 244;245;246 | chr2:178804624;178804623;178804622 | chr2:179669351;179669350;179669349 |
| N2B | 7 | 244;245;246 | chr2:178804624;178804623;178804622 | chr2:179669351;179669350;179669349 |
| Novex-1 | 7 | 244;245;246 | chr2:178804624;178804623;178804622 | chr2:179669351;179669350;179669349 |
| Novex-2 | 7 | 244;245;246 | chr2:178804624;178804623;178804622 | chr2:179669351;179669350;179669349 |
| Novex-3 | 7 | 244;245;246 | chr2:178804624;178804623;178804622 | chr2:179669351;179669350;179669349 |
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 | rs752073551  |
-1.0 | 0.017 | N | 0.385 | 0.209 | 0.183819452728 | gnomAD-2.1.1 | 7.97E-06 | None | None | None | -0.829(TCAP) | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 4.62E-05 | 8.82E-06 | 0 |
| T/A | rs752073551 |
-1.0 | 0.017 | N | 0.385 | 0.209 | 0.183819452728 | gnomAD-4.0.0 | 1.59103E-06 | None | None | None | -0.829(TCAP) | N | None | 0 | 0 | None | 0 | 0 | None | 1.88182E-05 | 0 | 0 | 0 | 0 |
| T/K | rs761344572 |
-0.251 | 0.915 | N | 0.48 | 0.397 | 0.379366414296 | gnomAD-2.1.1 | 3.98E-06 | None | None | None | -1.585(TCAP) | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| T/K | rs761344572 |
-0.251 | 0.915 | N | 0.48 | 0.397 | 0.379366414296 | gnomAD-4.0.0 | 1.36833E-06 | None | None | None | -1.585(TCAP) | N | None | 2.98757E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.15988E-05 | 0 |
| T/M | rs761344572 |
-0.151 | 0.327 | N | 0.355 | 0.251 | 0.49118058892 | gnomAD-2.1.1 | 1.2E-05 | None | None | None | -0.053(TCAP) | N | None | 0 | 2.89E-05 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 8.82E-06 | 0 |
| T/M | rs761344572 |
-0.151 | 0.327 | N | 0.355 | 0.251 | 0.49118058892 | gnomAD-4.0.0 | 1.29992E-05 | None | None | None | -0.053(TCAP) | N | None | 0 | 2.23644E-05 | None | 0 | 2.51965E-05 | None | 0 | 0 | 9.89314E-06 | 3.47963E-05 | 4.96952E-05 |
| T/R | None | None | 0.967 | N | 0.513 | 0.427 | 0.531245695338 | gnomAD-4.0.0 | 6.84166E-07 | None | None | None | -1.392(TCAP) | N | None | 0 | 0 | None | 0 | 2.51965E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.0993 | likely_benign | 0.0847 | benign | -0.611 | Destabilizing | 0.017 | N | 0.385 | neutral | N | 0.483087197 | None | -0.829(TCAP) | N |
| T/C | 0.7803 | likely_pathogenic | 0.6591 | pathogenic | -0.403 | Destabilizing | 0.99 | D | 0.527 | neutral | None | None | None | -0.35(TCAP) | N |
| T/D | 0.5693 | likely_pathogenic | 0.4443 | ambiguous | 0.571 | Stabilizing | 0.548 | D | 0.484 | neutral | None | None | None | -1.641(TCAP) | N |
| T/E | 0.3775 | ambiguous | 0.2876 | benign | 0.539 | Stabilizing | 0.801 | D | 0.477 | neutral | None | None | None | -1.697(TCAP) | N |
| T/F | 0.3783 | ambiguous | 0.2627 | benign | -1.058 | Destabilizing | 0.938 | D | 0.578 | neutral | None | None | None | -0.694(TCAP) | N |
| T/G | 0.3702 | ambiguous | 0.2869 | benign | -0.773 | Destabilizing | 0.743 | D | 0.461 | neutral | None | None | None | -0.838(TCAP) | N |
| T/H | 0.3486 | ambiguous | 0.2582 | benign | -0.935 | Destabilizing | 0.992 | D | 0.604 | neutral | None | None | None | -0.369(TCAP) | N |
| T/I | 0.1904 | likely_benign | 0.1396 | benign | -0.293 | Destabilizing | 0.739 | D | 0.485 | neutral | None | None | None | -0.853(TCAP) | N |
| T/K | 0.2277 | likely_benign | 0.1794 | benign | -0.198 | Destabilizing | 0.915 | D | 0.48 | neutral | N | 0.383600826 | None | -1.585(TCAP) | N |
| T/L | 0.1492 | likely_benign | 0.1122 | benign | -0.293 | Destabilizing | 0.217 | N | 0.417 | neutral | None | None | None | -0.853(TCAP) | N |
| T/M | 0.1336 | likely_benign | 0.1054 | benign | -0.248 | Destabilizing | 0.327 | N | 0.355 | neutral | N | 0.481406815 | None | -0.053(TCAP) | N |
| T/N | 0.2015 | likely_benign | 0.16 | benign | -0.137 | Destabilizing | 0.548 | D | 0.469 | neutral | None | None | None | -0.711(TCAP) | N |
| T/P | 0.6295 | likely_pathogenic | 0.4948 | ambiguous | -0.37 | Destabilizing | 0.65 | D | 0.515 | neutral | N | 0.515130282 | None | -0.836(TCAP) | N |
| T/Q | 0.2367 | likely_benign | 0.1896 | benign | -0.247 | Destabilizing | 0.726 | D | 0.517 | neutral | None | None | None | -0.932(TCAP) | N |
| T/R | 0.1823 | likely_benign | 0.1351 | benign | -0.01 | Destabilizing | 0.967 | D | 0.513 | neutral | N | 0.396437873 | None | -1.392(TCAP) | N |
| T/S | 0.1299 | likely_benign | 0.1101 | benign | -0.447 | Destabilizing | 0.003 | N | 0.281 | neutral | N | 0.449425384 | None | -1.016(TCAP) | N |
| T/V | 0.1432 | likely_benign | 0.1139 | benign | -0.37 | Destabilizing | 0.366 | N | 0.365 | neutral | None | None | None | -0.836(TCAP) | N |
| T/W | 0.8214 | likely_pathogenic | 0.6821 | pathogenic | -1.037 | Destabilizing | 0.997 | D | 0.646 | neutral | None | None | None | -0.637(TCAP) | N |
| T/Y | 0.4766 | ambiguous | 0.3526 | ambiguous | -0.741 | Destabilizing | 0.968 | D | 0.597 | neutral | None | None | None | -0.333(TCAP) | 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.