Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26134 | 78625;78626;78627 | chr2:178567732;178567731;178567730 | chr2:179432459;179432458;179432457 |
| N2AB | 24493 | 73702;73703;73704 | chr2:178567732;178567731;178567730 | chr2:179432459;179432458;179432457 |
| N2A | 23566 | 70921;70922;70923 | chr2:178567732;178567731;178567730 | chr2:179432459;179432458;179432457 |
| N2B | 17069 | 51430;51431;51432 | chr2:178567732;178567731;178567730 | chr2:179432459;179432458;179432457 |
| Novex-1 | 17194 | 51805;51806;51807 | chr2:178567732;178567731;178567730 | chr2:179432459;179432458;179432457 |
| Novex-2 | 17261 | 52006;52007;52008 | chr2:178567732;178567731;178567730 | chr2:179432459;179432458;179432457 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/C | rs753708513  |
-0.102 | 1.0 | N | 0.547 | 0.361 | 0.597594485103 | gnomAD-2.1.1 | 8.07E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.79E-05 | 0 |
| R/C | rs753708513 |
-0.102 | 1.0 | N | 0.547 | 0.361 | 0.597594485103 | gnomAD-4.0.0 | 9.56813E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.43325E-05 | 0 | 3.02975E-05 |
| R/H | rs377668457 |
-1.076 | 1.0 | N | 0.383 | 0.297 | None | gnomAD-2.1.1 | 2.87E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.15E-05 | None | 6.54E-05 | None | 0 | 3.93E-05 | 0 |
| R/H | rs377668457 |
-1.076 | 1.0 | N | 0.383 | 0.297 | 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 |
| R/H | rs377668457 |
-1.076 | 1.0 | N | 0.383 | 0.297 | None | gnomAD-4.0.0 | 7.93874E-05 | None | None | None | None | N | None | 0 | 1.66856E-05 | None | 0 | 4.46648E-05 | None | 0 | 0 | 1.00103E-04 | 4.39319E-05 | 4.80661E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.9656 | likely_pathogenic | 0.9564 | pathogenic | 0.117 | Stabilizing | 0.964 | D | 0.405 | neutral | None | None | None | None | N |
| R/C | 0.7325 | likely_pathogenic | 0.6936 | pathogenic | -0.165 | Destabilizing | 1.0 | D | 0.547 | neutral | N | 0.482751543 | None | None | N |
| R/D | 0.9839 | likely_pathogenic | 0.9797 | pathogenic | -0.271 | Destabilizing | 0.998 | D | 0.417 | neutral | None | None | None | None | N |
| R/E | 0.9286 | likely_pathogenic | 0.9117 | pathogenic | -0.222 | Destabilizing | 0.985 | D | 0.412 | neutral | None | None | None | None | N |
| R/F | 0.9558 | likely_pathogenic | 0.9449 | pathogenic | -0.183 | Destabilizing | 0.999 | D | 0.509 | neutral | None | None | None | None | N |
| R/G | 0.9251 | likely_pathogenic | 0.9129 | pathogenic | -0.035 | Destabilizing | 0.996 | D | 0.411 | neutral | N | 0.511032754 | None | None | N |
| R/H | 0.4362 | ambiguous | 0.3977 | ambiguous | -0.586 | Destabilizing | 1.0 | D | 0.383 | neutral | N | 0.468988928 | None | None | N |
| R/I | 0.8753 | likely_pathogenic | 0.8504 | pathogenic | 0.473 | Stabilizing | 0.999 | D | 0.499 | neutral | None | None | None | None | N |
| R/K | 0.3649 | ambiguous | 0.3354 | benign | -0.061 | Destabilizing | 0.271 | N | 0.166 | neutral | None | None | None | None | N |
| R/L | 0.8432 | likely_pathogenic | 0.8277 | pathogenic | 0.473 | Stabilizing | 0.996 | D | 0.411 | neutral | N | 0.51520921 | None | None | N |
| R/M | 0.9083 | likely_pathogenic | 0.8833 | pathogenic | -0.03 | Destabilizing | 1.0 | D | 0.421 | neutral | None | None | None | None | N |
| R/N | 0.9651 | likely_pathogenic | 0.9594 | pathogenic | 0.024 | Stabilizing | 0.993 | D | 0.37 | neutral | None | None | None | None | N |
| R/P | 0.9666 | likely_pathogenic | 0.9588 | pathogenic | 0.373 | Stabilizing | 1.0 | D | 0.478 | neutral | N | 0.468481949 | None | None | N |
| R/Q | 0.4798 | ambiguous | 0.4468 | ambiguous | -0.001 | Destabilizing | 0.985 | D | 0.404 | neutral | None | None | None | None | N |
| R/S | 0.9748 | likely_pathogenic | 0.9688 | pathogenic | -0.141 | Destabilizing | 0.992 | D | 0.377 | neutral | N | 0.506837656 | None | None | N |
| R/T | 0.9394 | likely_pathogenic | 0.929 | pathogenic | 0.021 | Stabilizing | 0.993 | D | 0.394 | neutral | None | None | None | None | N |
| R/V | 0.9215 | likely_pathogenic | 0.9051 | pathogenic | 0.373 | Stabilizing | 0.998 | D | 0.457 | neutral | None | None | None | None | N |
| R/W | 0.7113 | likely_pathogenic | 0.6592 | pathogenic | -0.372 | Destabilizing | 1.0 | D | 0.587 | neutral | None | None | None | None | N |
| R/Y | 0.8828 | likely_pathogenic | 0.856 | pathogenic | 0.045 | Stabilizing | 0.999 | D | 0.483 | 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.