Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2487 | 7684;7685;7686 | chr2:178773597;178773596;178773595 | chr2:179638324;179638323;179638322 |
| N2AB | 2487 | 7684;7685;7686 | chr2:178773597;178773596;178773595 | chr2:179638324;179638323;179638322 |
| N2A | 2487 | 7684;7685;7686 | chr2:178773597;178773596;178773595 | chr2:179638324;179638323;179638322 |
| N2B | 2441 | 7546;7547;7548 | chr2:178773597;178773596;178773595 | chr2:179638324;179638323;179638322 |
| Novex-1 | 2441 | 7546;7547;7548 | chr2:178773597;178773596;178773595 | chr2:179638324;179638323;179638322 |
| Novex-2 | 2441 | 7546;7547;7548 | chr2:178773597;178773596;178773595 | chr2:179638324;179638323;179638322 |
| Novex-3 | 2487 | 7684;7685;7686 | chr2:178773597;178773596;178773595 | chr2:179638324;179638323;179638322 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/S | rs759448340  |
None | 0.016 | N | 0.203 | 0.104 | 0.225902525712 | gnomAD-4.0.0 | 1.59072E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85677E-06 | 0 | 0 |
| P/T | rs759448340 |
-0.492 | 0.016 | D | 0.201 | 0.205 | None | gnomAD-2.1.1 | 1.42E-05 | None | None | None | None | N | None | 1.60269E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| P/T | rs759448340 |
-0.492 | 0.016 | D | 0.201 | 0.205 | None | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | N | None | 1.20726E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| P/T | rs759448340 |
-0.492 | 0.016 | D | 0.201 | 0.205 | None | gnomAD-4.0.0 | 1.15275E-05 | None | None | None | None | N | None | 1.52279E-04 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.0881 | likely_benign | 0.0839 | benign | -0.501 | Destabilizing | 0.016 | N | 0.198 | neutral | N | 0.495149577 | None | None | N |
| P/C | 0.6367 | likely_pathogenic | 0.6288 | pathogenic | -0.707 | Destabilizing | 0.992 | D | 0.469 | neutral | None | None | None | None | N |
| P/D | 0.6173 | likely_pathogenic | 0.5996 | pathogenic | -0.416 | Destabilizing | 0.85 | D | 0.379 | neutral | None | None | None | None | N |
| P/E | 0.4139 | ambiguous | 0.4002 | ambiguous | -0.516 | Destabilizing | 0.617 | D | 0.368 | neutral | None | None | None | None | N |
| P/F | 0.6344 | likely_pathogenic | 0.6346 | pathogenic | -0.67 | Destabilizing | 0.85 | D | 0.459 | neutral | None | None | None | None | N |
| P/G | 0.3772 | ambiguous | 0.363 | ambiguous | -0.642 | Destabilizing | 0.447 | N | 0.371 | neutral | None | None | None | None | N |
| P/H | 0.3014 | likely_benign | 0.2977 | benign | -0.203 | Destabilizing | 0.97 | D | 0.444 | neutral | D | 0.575071621 | None | None | N |
| P/I | 0.4096 | ambiguous | 0.4053 | ambiguous | -0.272 | Destabilizing | 0.739 | D | 0.421 | neutral | None | None | None | None | N |
| P/K | 0.4729 | ambiguous | 0.4689 | ambiguous | -0.569 | Destabilizing | 0.447 | N | 0.363 | neutral | None | None | None | None | N |
| P/L | 0.1669 | likely_benign | 0.1633 | benign | -0.272 | Destabilizing | 0.004 | N | 0.315 | neutral | N | 0.512322306 | None | None | N |
| P/M | 0.358 | ambiguous | 0.3504 | ambiguous | -0.435 | Destabilizing | 0.85 | D | 0.429 | neutral | None | None | None | None | N |
| P/N | 0.4398 | ambiguous | 0.4162 | ambiguous | -0.344 | Destabilizing | 0.739 | D | 0.422 | neutral | None | None | None | None | N |
| P/Q | 0.2324 | likely_benign | 0.2259 | benign | -0.556 | Destabilizing | 0.85 | D | 0.389 | neutral | None | None | None | None | N |
| P/R | 0.3183 | likely_benign | 0.3221 | benign | -0.062 | Destabilizing | 0.81 | D | 0.441 | neutral | D | 0.531301329 | None | None | N |
| P/S | 0.1764 | likely_benign | 0.1699 | benign | -0.682 | Destabilizing | 0.016 | N | 0.203 | neutral | N | 0.50289787 | None | None | N |
| P/T | 0.1312 | likely_benign | 0.1258 | benign | -0.68 | Destabilizing | 0.016 | N | 0.201 | neutral | D | 0.52950918 | None | None | N |
| P/V | 0.2771 | likely_benign | 0.2665 | benign | -0.315 | Destabilizing | 0.447 | N | 0.368 | neutral | None | None | None | None | N |
| P/W | 0.7685 | likely_pathogenic | 0.7746 | pathogenic | -0.769 | Destabilizing | 0.992 | D | 0.564 | neutral | None | None | None | None | N |
| P/Y | 0.5804 | likely_pathogenic | 0.5805 | pathogenic | -0.478 | Destabilizing | 0.972 | D | 0.46 | neutral | None | None | 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.