Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19966 | 60121;60122;60123 | chr2:178592008;178592007;178592006 | chr2:179456735;179456734;179456733 |
| N2AB | 18325 | 55198;55199;55200 | chr2:178592008;178592007;178592006 | chr2:179456735;179456734;179456733 |
| N2A | 17398 | 52417;52418;52419 | chr2:178592008;178592007;178592006 | chr2:179456735;179456734;179456733 |
| N2B | 10901 | 32926;32927;32928 | chr2:178592008;178592007;178592006 | chr2:179456735;179456734;179456733 |
| Novex-1 | 11026 | 33301;33302;33303 | chr2:178592008;178592007;178592006 | chr2:179456735;179456734;179456733 |
| Novex-2 | 11093 | 33502;33503;33504 | chr2:178592008;178592007;178592006 | chr2:179456735;179456734;179456733 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/L | None | None | None | N | 0.286 | 0.134 | 0.30921473904 | gnomAD-4.0.0 | 1.59321E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86058E-06 | 0 | 0 |
| P/S | None | None | 0.001 | N | 0.18 | 0.106 | 0.18274738541 | gnomAD-4.0.0 | 1.59315E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.02718E-05 |
| P/T | rs2154185337  |
None | None | N | 0.126 | 0.135 | 0.215109475489 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 1.93723E-04 | None | 0 | 0 | 0 | 0 | 0 |
| P/T | rs2154185337 |
None | None | N | 0.126 | 0.135 | 0.215109475489 | gnomAD-4.0.0 | 6.57022E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.94175E-04 | 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 | 0.0644 | likely_benign | 0.0603 | benign | -0.445 | Destabilizing | 0.012 | N | 0.318 | neutral | N | 0.475614157 | None | None | N |
| P/C | 0.3527 | ambiguous | 0.3533 | ambiguous | -0.853 | Destabilizing | 0.869 | D | 0.52 | neutral | None | None | None | None | N |
| P/D | 0.2414 | likely_benign | 0.2296 | benign | -0.522 | Destabilizing | 0.075 | N | 0.505 | neutral | None | None | None | None | N |
| P/E | 0.1593 | likely_benign | 0.153 | benign | -0.624 | Destabilizing | 0.075 | N | 0.43 | neutral | None | None | None | None | N |
| P/F | 0.3536 | ambiguous | 0.3351 | benign | -0.701 | Destabilizing | 0.125 | N | 0.665 | prob.neutral | None | None | None | None | N |
| P/G | 0.1679 | likely_benign | 0.1526 | benign | -0.534 | Destabilizing | 0.039 | N | 0.499 | neutral | None | None | None | None | N |
| P/H | 0.1421 | likely_benign | 0.1369 | benign | -0.029 | Destabilizing | 0.685 | D | 0.484 | neutral | None | None | None | None | N |
| P/I | 0.1905 | likely_benign | 0.1756 | benign | -0.344 | Destabilizing | 0.039 | N | 0.577 | neutral | None | None | None | None | N |
| P/K | 0.1426 | likely_benign | 0.1388 | benign | -0.556 | Destabilizing | 0.039 | N | 0.395 | neutral | None | None | None | None | N |
| P/L | 0.09 | likely_benign | 0.0792 | benign | -0.344 | Destabilizing | None | N | 0.286 | neutral | N | 0.473332751 | None | None | N |
| P/M | 0.1782 | likely_benign | 0.1661 | benign | -0.647 | Destabilizing | 0.125 | N | 0.517 | neutral | None | None | None | None | N |
| P/N | 0.1719 | likely_benign | 0.1692 | benign | -0.411 | Destabilizing | 0.039 | N | 0.557 | neutral | None | None | None | None | N |
| P/Q | 0.0966 | likely_benign | 0.0927 | benign | -0.614 | Destabilizing | 0.177 | N | 0.468 | neutral | N | 0.500012289 | None | None | N |
| P/R | 0.1258 | likely_benign | 0.1189 | benign | -0.062 | Destabilizing | 0.177 | N | 0.571 | neutral | N | 0.488491399 | None | None | N |
| P/S | 0.0876 | likely_benign | 0.0832 | benign | -0.703 | Destabilizing | 0.001 | N | 0.18 | neutral | N | 0.517915867 | None | None | N |
| P/T | 0.0744 | likely_benign | 0.0723 | benign | -0.712 | Destabilizing | None | N | 0.126 | neutral | N | 0.468359228 | None | None | N |
| P/V | 0.1275 | likely_benign | 0.1165 | benign | -0.348 | Destabilizing | 0.016 | N | 0.421 | neutral | None | None | None | None | N |
| P/W | 0.442 | ambiguous | 0.4101 | ambiguous | -0.77 | Destabilizing | 0.869 | D | 0.551 | neutral | None | None | None | None | N |
| P/Y | 0.3138 | likely_benign | 0.3115 | benign | -0.504 | Destabilizing | 0.366 | N | 0.6 | 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.