Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2750 | 8473;8474;8475 | chr2:178770544;178770543;178770542 | chr2:179635271;179635270;179635269 |
| N2AB | 2750 | 8473;8474;8475 | chr2:178770544;178770543;178770542 | chr2:179635271;179635270;179635269 |
| N2A | 2750 | 8473;8474;8475 | chr2:178770544;178770543;178770542 | chr2:179635271;179635270;179635269 |
| N2B | 2704 | 8335;8336;8337 | chr2:178770544;178770543;178770542 | chr2:179635271;179635270;179635269 |
| Novex-1 | 2704 | 8335;8336;8337 | chr2:178770544;178770543;178770542 | chr2:179635271;179635270;179635269 |
| Novex-2 | 2704 | 8335;8336;8337 | chr2:178770544;178770543;178770542 | chr2:179635271;179635270;179635269 |
| Novex-3 | 2750 | 8473;8474;8475 | chr2:178770544;178770543;178770542 | chr2:179635271;179635270;179635269 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/I | rs1471538206  |
-0.024 | 0.317 | D | 0.471 | 0.248 | 0.437314048365 | gnomAD-2.1.1 | 3.98E-06 | None | None | None | None | N | None | 0 | 2.89E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| N/I | rs1471538206 |
-0.024 | 0.317 | D | 0.471 | 0.248 | 0.437314048365 | gnomAD-4.0.0 | 3.42032E-06 | None | None | None | None | N | None | 0 | 4.47207E-05 | None | 0 | 0 | None | 0 | 0 | 2.69788E-06 | 0 | 0 |
| N/S | rs1471538206 |
-0.148 | None | N | 0.154 | 0.06 | 0.126345400529 | gnomAD-2.1.1 | 3.98E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.82E-06 | 0 |
| N/S | rs1471538206 |
-0.148 | None | N | 0.154 | 0.06 | 0.126345400529 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| N/S | rs1471538206 |
-0.148 | None | N | 0.154 | 0.06 | 0.126345400529 | gnomAD-4.0.0 | 5.57615E-06 | None | None | None | None | N | None | 0 | 1.66689E-05 | None | 0 | 1.11408E-04 | None | 0 | 0 | 2.54237E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/A | 0.1711 | likely_benign | 0.2142 | benign | -0.506 | Destabilizing | 0.035 | N | 0.345 | neutral | None | None | None | None | N |
| N/C | 0.2275 | likely_benign | 0.2773 | benign | 0.228 | Stabilizing | 0.824 | D | 0.432 | neutral | None | None | None | None | N |
| N/D | 0.0761 | likely_benign | 0.0755 | benign | 0.323 | Stabilizing | 0.062 | N | 0.381 | neutral | N | 0.491722785 | None | None | N |
| N/E | 0.2769 | likely_benign | 0.3375 | benign | 0.328 | Stabilizing | 0.081 | N | 0.333 | neutral | None | None | None | None | N |
| N/F | 0.5688 | likely_pathogenic | 0.6751 | pathogenic | -0.742 | Destabilizing | 0.555 | D | 0.443 | neutral | None | None | None | None | N |
| N/G | 0.154 | likely_benign | 0.1737 | benign | -0.725 | Destabilizing | None | N | 0.177 | neutral | None | None | None | None | N |
| N/H | 0.1185 | likely_benign | 0.1303 | benign | -0.64 | Destabilizing | 0.484 | N | 0.375 | neutral | D | 0.571767091 | None | None | N |
| N/I | 0.3233 | likely_benign | 0.4439 | ambiguous | -0.006 | Destabilizing | 0.317 | N | 0.471 | neutral | D | 0.571919121 | None | None | N |
| N/K | 0.2478 | likely_benign | 0.3072 | benign | 0.099 | Stabilizing | 0.062 | N | 0.338 | neutral | D | 0.567140517 | None | None | N |
| N/L | 0.2549 | likely_benign | 0.3334 | benign | -0.006 | Destabilizing | 0.149 | N | 0.453 | neutral | None | None | None | None | N |
| N/M | 0.3663 | ambiguous | 0.4377 | ambiguous | 0.283 | Stabilizing | 0.935 | D | 0.389 | neutral | None | None | None | None | N |
| N/P | 0.5787 | likely_pathogenic | 0.7037 | pathogenic | -0.145 | Destabilizing | 0.38 | N | 0.433 | neutral | None | None | None | None | N |
| N/Q | 0.2928 | likely_benign | 0.3464 | ambiguous | -0.388 | Destabilizing | 0.38 | N | 0.383 | neutral | None | None | None | None | N |
| N/R | 0.2829 | likely_benign | 0.3493 | ambiguous | 0.1 | Stabilizing | 0.38 | N | 0.383 | neutral | None | None | None | None | N |
| N/S | 0.0568 | likely_benign | 0.0599 | benign | -0.309 | Destabilizing | None | N | 0.154 | neutral | N | 0.400693053 | None | None | N |
| N/T | 0.0901 | likely_benign | 0.1044 | benign | -0.132 | Destabilizing | 0.062 | N | 0.331 | neutral | D | 0.525059299 | None | None | N |
| N/V | 0.281 | likely_benign | 0.3816 | ambiguous | -0.145 | Destabilizing | 0.38 | N | 0.479 | neutral | None | None | None | None | N |
| N/W | 0.7764 | likely_pathogenic | 0.8436 | pathogenic | -0.655 | Destabilizing | 0.935 | D | 0.528 | neutral | None | None | None | None | N |
| N/Y | 0.2489 | likely_benign | 0.3158 | benign | -0.405 | Destabilizing | 0.484 | N | 0.409 | neutral | D | 0.571919121 | 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.