Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14652 | 44179;44180;44181 | chr2:178631094;178631093;178631092 | chr2:179495821;179495820;179495819 |
| N2AB | 13011 | 39256;39257;39258 | chr2:178631094;178631093;178631092 | chr2:179495821;179495820;179495819 |
| N2A | 12084 | 36475;36476;36477 | chr2:178631094;178631093;178631092 | chr2:179495821;179495820;179495819 |
| N2B | 5587 | 16984;16985;16986 | chr2:178631094;178631093;178631092 | chr2:179495821;179495820;179495819 |
| Novex-1 | 5712 | 17359;17360;17361 | chr2:178631094;178631093;178631092 | chr2:179495821;179495820;179495819 |
| Novex-2 | 5779 | 17560;17561;17562 | chr2:178631094;178631093;178631092 | chr2:179495821;179495820;179495819 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/S | rs767038885  |
-0.484 | 0.681 | N | 0.411 | 0.218 | 0.694585858326 | 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 |
| I/S | rs767038885 |
-0.484 | 0.681 | N | 0.411 | 0.218 | 0.694585858326 | gnomAD-4.0.0 | 2.73755E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.59835E-06 | 0 | 0 |
| I/T | rs767038885 |
-0.463 | 0.912 | N | 0.483 | 0.23 | 0.674560721455 | gnomAD-2.1.1 | 8.05E-06 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 8.9E-06 | 0 |
| I/T | rs767038885 |
-0.463 | 0.912 | N | 0.483 | 0.23 | 0.674560721455 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| I/T | rs767038885 |
-0.463 | 0.912 | N | 0.483 | 0.23 | 0.674560721455 | gnomAD-4.0.0 | 4.33924E-06 | None | None | None | None | N | None | 0 | 1.66822E-05 | None | 0 | 0 | None | 0 | 0 | 5.08641E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.1219 | likely_benign | 0.1219 | benign | -0.966 | Destabilizing | 0.025 | N | 0.203 | neutral | None | None | None | None | N |
| I/C | 0.7274 | likely_pathogenic | 0.6954 | pathogenic | -0.697 | Destabilizing | 0.997 | D | 0.501 | neutral | None | None | None | None | N |
| I/D | 0.6708 | likely_pathogenic | 0.6403 | pathogenic | 0.009 | Stabilizing | 0.873 | D | 0.481 | neutral | None | None | None | None | N |
| I/E | 0.4379 | ambiguous | 0.3798 | ambiguous | -0.05 | Destabilizing | 0.155 | N | 0.355 | neutral | None | None | None | None | N |
| I/F | 0.2235 | likely_benign | 0.205 | benign | -0.817 | Destabilizing | 0.973 | D | 0.532 | neutral | N | 0.508332558 | None | None | N |
| I/G | 0.5344 | ambiguous | 0.5069 | ambiguous | -1.19 | Destabilizing | 0.932 | D | 0.463 | neutral | None | None | None | None | N |
| I/H | 0.5193 | ambiguous | 0.4829 | ambiguous | -0.436 | Destabilizing | 0.997 | D | 0.473 | neutral | None | None | None | None | N |
| I/K | 0.2275 | likely_benign | 0.2084 | benign | -0.422 | Destabilizing | 0.932 | D | 0.477 | neutral | None | None | None | None | N |
| I/L | 0.1718 | likely_benign | 0.1538 | benign | -0.478 | Destabilizing | 0.483 | N | 0.235 | neutral | N | 0.497510516 | None | None | N |
| I/M | 0.1146 | likely_benign | 0.1002 | benign | -0.394 | Destabilizing | 0.483 | N | 0.243 | neutral | N | 0.502504019 | None | None | N |
| I/N | 0.2963 | likely_benign | 0.2735 | benign | -0.195 | Destabilizing | 0.987 | D | 0.535 | neutral | N | 0.481527145 | None | None | N |
| I/P | 0.7889 | likely_pathogenic | 0.7957 | pathogenic | -0.607 | Destabilizing | 0.99 | D | 0.533 | neutral | None | None | None | None | N |
| I/Q | 0.3699 | ambiguous | 0.3269 | benign | -0.395 | Destabilizing | 0.98 | D | 0.535 | neutral | None | None | None | None | N |
| I/R | 0.1556 | likely_benign | 0.1441 | benign | 0.101 | Stabilizing | 0.98 | D | 0.535 | neutral | None | None | None | None | N |
| I/S | 0.1805 | likely_benign | 0.1715 | benign | -0.801 | Destabilizing | 0.681 | D | 0.411 | neutral | N | 0.425575939 | None | None | N |
| I/T | 0.0721 | likely_benign | 0.0758 | benign | -0.742 | Destabilizing | 0.912 | D | 0.483 | neutral | N | 0.434318218 | None | None | N |
| I/V | 0.0807 | likely_benign | 0.0802 | benign | -0.607 | Destabilizing | 0.483 | N | 0.253 | neutral | N | 0.485126855 | None | None | N |
| I/W | 0.8431 | likely_pathogenic | 0.821 | pathogenic | -0.817 | Destabilizing | 0.999 | D | 0.487 | neutral | None | None | None | None | N |
| I/Y | 0.619 | likely_pathogenic | 0.5878 | pathogenic | -0.566 | Destabilizing | 0.997 | D | 0.539 | 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.