Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22670 | 68233;68234;68235 | chr2:178579022;178579021;178579020 | chr2:179443749;179443748;179443747 |
| N2AB | 21029 | 63310;63311;63312 | chr2:178579022;178579021;178579020 | chr2:179443749;179443748;179443747 |
| N2A | 20102 | 60529;60530;60531 | chr2:178579022;178579021;178579020 | chr2:179443749;179443748;179443747 |
| N2B | 13605 | 41038;41039;41040 | chr2:178579022;178579021;178579020 | chr2:179443749;179443748;179443747 |
| Novex-1 | 13730 | 41413;41414;41415 | chr2:178579022;178579021;178579020 | chr2:179443749;179443748;179443747 |
| Novex-2 | 13797 | 41614;41615;41616 | chr2:178579022;178579021;178579020 | chr2:179443749;179443748;179443747 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/G | rs377188703  |
-0.085 | 0.698 | N | 0.535 | 0.39 | None | 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 |
| D/G | rs377188703 |
-0.085 | 0.698 | N | 0.535 | 0.39 | None | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| D/G | rs377188703 |
-0.085 | 0.698 | N | 0.535 | 0.39 | None | gnomAD-4.0.0 | 6.57687E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.47128E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.6352 | likely_pathogenic | 0.5958 | pathogenic | -0.315 | Destabilizing | 0.822 | D | 0.517 | neutral | N | 0.487129182 | None | None | N |
| D/C | 0.8971 | likely_pathogenic | 0.8934 | pathogenic | 0.141 | Stabilizing | 0.998 | D | 0.687 | prob.neutral | None | None | None | None | N |
| D/E | 0.4418 | ambiguous | 0.4164 | ambiguous | -0.279 | Destabilizing | 0.698 | D | 0.417 | neutral | N | 0.468517948 | None | None | N |
| D/F | 0.8292 | likely_pathogenic | 0.8218 | pathogenic | -0.336 | Destabilizing | 0.956 | D | 0.666 | neutral | None | None | None | None | N |
| D/G | 0.5685 | likely_pathogenic | 0.5254 | ambiguous | -0.503 | Destabilizing | 0.698 | D | 0.535 | neutral | N | 0.500967476 | None | None | N |
| D/H | 0.7368 | likely_pathogenic | 0.7341 | pathogenic | -0.271 | Destabilizing | 0.071 | N | 0.429 | neutral | N | 0.47726736 | None | None | N |
| D/I | 0.7725 | likely_pathogenic | 0.7451 | pathogenic | 0.129 | Stabilizing | 0.978 | D | 0.688 | prob.neutral | None | None | None | None | N |
| D/K | 0.8864 | likely_pathogenic | 0.8758 | pathogenic | 0.366 | Stabilizing | 0.956 | D | 0.523 | neutral | None | None | None | None | N |
| D/L | 0.7871 | likely_pathogenic | 0.7538 | pathogenic | 0.129 | Stabilizing | 0.956 | D | 0.687 | prob.neutral | None | None | None | None | N |
| D/M | 0.8842 | likely_pathogenic | 0.8699 | pathogenic | 0.363 | Stabilizing | 0.998 | D | 0.663 | neutral | None | None | None | None | N |
| D/N | 0.2191 | likely_benign | 0.2006 | benign | 0.09 | Stabilizing | 0.032 | N | 0.241 | neutral | N | 0.463402613 | None | None | N |
| D/P | 0.9918 | likely_pathogenic | 0.9902 | pathogenic | 0.002 | Stabilizing | 0.978 | D | 0.586 | neutral | None | None | None | None | N |
| D/Q | 0.8089 | likely_pathogenic | 0.7897 | pathogenic | 0.121 | Stabilizing | 0.956 | D | 0.539 | neutral | None | None | None | None | N |
| D/R | 0.8905 | likely_pathogenic | 0.8852 | pathogenic | 0.437 | Stabilizing | 0.956 | D | 0.643 | neutral | None | None | None | None | N |
| D/S | 0.4129 | ambiguous | 0.3798 | ambiguous | -0.008 | Destabilizing | 0.754 | D | 0.491 | neutral | None | None | None | None | N |
| D/T | 0.6201 | likely_pathogenic | 0.5847 | pathogenic | 0.142 | Stabilizing | 0.956 | D | 0.524 | neutral | None | None | None | None | N |
| D/V | 0.5738 | likely_pathogenic | 0.5381 | ambiguous | 0.002 | Stabilizing | 0.971 | D | 0.685 | prob.neutral | N | 0.493877131 | None | None | N |
| D/W | 0.9619 | likely_pathogenic | 0.9605 | pathogenic | -0.222 | Destabilizing | 0.998 | D | 0.7 | prob.neutral | None | None | None | None | N |
| D/Y | 0.4182 | ambiguous | 0.4137 | ambiguous | -0.105 | Destabilizing | 0.89 | D | 0.688 | prob.neutral | N | 0.516113287 | 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.