Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32839 | 98740;98741;98742 | chr2:178539550;178539549;178539548 | chr2:179404277;179404276;179404275 |
| N2AB | 31198 | 93817;93818;93819 | chr2:178539550;178539549;178539548 | chr2:179404277;179404276;179404275 |
| N2A | 30271 | 91036;91037;91038 | chr2:178539550;178539549;178539548 | chr2:179404277;179404276;179404275 |
| N2B | 23774 | 71545;71546;71547 | chr2:178539550;178539549;178539548 | chr2:179404277;179404276;179404275 |
| Novex-1 | 23899 | 71920;71921;71922 | chr2:178539550;178539549;178539548 | chr2:179404277;179404276;179404275 |
| Novex-2 | 23966 | 72121;72122;72123 | chr2:178539550;178539549;178539548 | chr2:179404277;179404276;179404275 |
| 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/R | None | None | 0.83 | N | 0.665 | 0.368 | 0.286081765059 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| P/T | rs949917519  |
None | 0.709 | N | 0.547 | 0.219 | 0.221734844693 | gnomAD-4.0.0 | 2.25781E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.69838E-05 | 0 | 4.96952E-05 |
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 | 0.1373 | likely_benign | 0.1261 | benign | -0.502 | Destabilizing | 0.41 | N | 0.443 | neutral | N | 0.431675389 | None | None | N |
| P/C | 0.674 | likely_pathogenic | 0.6058 | pathogenic | -0.844 | Destabilizing | 0.98 | D | 0.697 | prob.neutral | None | None | None | None | N |
| P/D | 0.5327 | ambiguous | 0.4609 | ambiguous | -0.651 | Destabilizing | 0.764 | D | 0.576 | neutral | None | None | None | None | N |
| P/E | 0.3909 | ambiguous | 0.3375 | benign | -0.76 | Destabilizing | 0.764 | D | 0.575 | neutral | None | None | None | None | N |
| P/F | 0.7727 | likely_pathogenic | 0.6764 | pathogenic | -0.752 | Destabilizing | 0.98 | D | 0.701 | prob.neutral | None | None | None | None | N |
| P/G | 0.287 | likely_benign | 0.2438 | benign | -0.599 | Destabilizing | 0.48 | N | 0.529 | neutral | None | None | None | None | N |
| P/H | 0.3543 | ambiguous | 0.2902 | benign | -0.065 | Destabilizing | 0.974 | D | 0.659 | neutral | N | 0.449165071 | None | None | N |
| P/I | 0.6716 | likely_pathogenic | 0.5751 | pathogenic | -0.387 | Destabilizing | 0.866 | D | 0.705 | prob.neutral | None | None | None | None | N |
| P/K | 0.4572 | ambiguous | 0.4251 | ambiguous | -0.612 | Destabilizing | 0.764 | D | 0.571 | neutral | None | None | None | None | N |
| P/L | 0.282 | likely_benign | 0.2347 | benign | -0.387 | Destabilizing | 0.83 | D | 0.68 | prob.neutral | N | 0.447895635 | None | None | N |
| P/M | 0.5762 | likely_pathogenic | 0.489 | ambiguous | -0.616 | Destabilizing | 0.993 | D | 0.659 | neutral | None | None | None | None | N |
| P/N | 0.4038 | ambiguous | 0.3216 | benign | -0.441 | Destabilizing | 0.764 | D | 0.641 | neutral | None | None | None | None | N |
| P/Q | 0.2549 | likely_benign | 0.2263 | benign | -0.681 | Destabilizing | 0.866 | D | 0.611 | neutral | None | None | None | None | N |
| P/R | 0.323 | likely_benign | 0.2968 | benign | -0.05 | Destabilizing | 0.83 | D | 0.665 | neutral | N | 0.435619771 | None | None | N |
| P/S | 0.1691 | likely_benign | 0.1478 | benign | -0.728 | Destabilizing | 0.01 | N | 0.351 | neutral | N | 0.361524657 | None | None | N |
| P/T | 0.1808 | likely_benign | 0.1517 | benign | -0.746 | Destabilizing | 0.709 | D | 0.547 | neutral | N | 0.411473475 | None | None | N |
| P/V | 0.4827 | ambiguous | 0.3921 | ambiguous | -0.394 | Destabilizing | 0.866 | D | 0.647 | neutral | None | None | None | None | N |
| P/W | 0.8237 | likely_pathogenic | 0.7502 | pathogenic | -0.809 | Destabilizing | 0.993 | D | 0.719 | prob.delet. | None | None | None | None | N |
| P/Y | 0.6806 | likely_pathogenic | 0.5767 | pathogenic | -0.544 | Destabilizing | 0.98 | D | 0.701 | prob.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.