Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19123 | 57592;57593;57594 | chr2:178597715;178597714;178597713 | chr2:179462442;179462441;179462440 |
| N2AB | 17482 | 52669;52670;52671 | chr2:178597715;178597714;178597713 | chr2:179462442;179462441;179462440 |
| N2A | 16555 | 49888;49889;49890 | chr2:178597715;178597714;178597713 | chr2:179462442;179462441;179462440 |
| N2B | 10058 | 30397;30398;30399 | chr2:178597715;178597714;178597713 | chr2:179462442;179462441;179462440 |
| Novex-1 | 10183 | 30772;30773;30774 | chr2:178597715;178597714;178597713 | chr2:179462442;179462441;179462440 |
| Novex-2 | 10250 | 30973;30974;30975 | chr2:178597715;178597714;178597713 | chr2:179462442;179462441;179462440 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | rs587782985  |
-0.264 | 0.002 | N | 0.143 | 0.123 | 0.206339911435 | gnomAD-2.1.1 | 3.63E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 1.96078E-04 | None | 0 | 2.68E-05 | 0 |
| T/A | rs587782985 |
-0.264 | 0.002 | N | 0.143 | 0.123 | 0.206339911435 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 2.07039E-04 | 0 |
| T/A | rs587782985 |
-0.264 | 0.002 | N | 0.143 | 0.123 | 0.206339911435 | gnomAD-4.0.0 | 1.92162E-05 | None | None | None | None | I | None | 0 | 1.66845E-05 | None | 0 | 0 | None | 0 | 1.64474E-04 | 1.18687E-05 | 1.53725E-04 | 1.60164E-05 |
| T/I | None | None | 0.473 | N | 0.325 | 0.13 | 0.307016933798 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | I | None | 6.33473E-05 | 0 | None | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.064 | likely_benign | 0.0669 | benign | -0.25 | Destabilizing | 0.002 | N | 0.143 | neutral | N | 0.513337633 | None | None | I |
| T/C | 0.318 | likely_benign | 0.3045 | benign | -0.27 | Destabilizing | 0.985 | D | 0.323 | neutral | None | None | None | None | I |
| T/D | 0.2512 | likely_benign | 0.2414 | benign | 0.145 | Stabilizing | 0.007 | N | 0.213 | neutral | None | None | None | None | I |
| T/E | 0.1539 | likely_benign | 0.1501 | benign | 0.07 | Stabilizing | 0.003 | N | 0.177 | neutral | None | None | None | None | I |
| T/F | 0.1932 | likely_benign | 0.1971 | benign | -0.747 | Destabilizing | 0.893 | D | 0.377 | neutral | None | None | None | None | I |
| T/G | 0.2193 | likely_benign | 0.2108 | benign | -0.377 | Destabilizing | 0.329 | N | 0.299 | neutral | None | None | None | None | I |
| T/H | 0.1758 | likely_benign | 0.1725 | benign | -0.641 | Destabilizing | 0.944 | D | 0.349 | neutral | None | None | None | None | I |
| T/I | 0.0857 | likely_benign | 0.0827 | benign | -0.039 | Destabilizing | 0.473 | N | 0.325 | neutral | N | 0.484401593 | None | None | I |
| T/K | 0.1131 | likely_benign | 0.1187 | benign | -0.354 | Destabilizing | 0.329 | N | 0.275 | neutral | None | None | None | None | I |
| T/L | 0.0747 | likely_benign | 0.0761 | benign | -0.039 | Destabilizing | 0.007 | N | 0.235 | neutral | None | None | None | None | I |
| T/M | 0.0791 | likely_benign | 0.0825 | benign | 0.008 | Stabilizing | 0.893 | D | 0.339 | neutral | None | None | None | None | I |
| T/N | 0.1042 | likely_benign | 0.0995 | benign | -0.149 | Destabilizing | 0.642 | D | 0.165 | neutral | N | 0.50435279 | None | None | I |
| T/P | 0.3399 | likely_benign | 0.3856 | ambiguous | -0.081 | Destabilizing | 0.784 | D | 0.367 | neutral | N | 0.496621469 | None | None | I |
| T/Q | 0.1415 | likely_benign | 0.1387 | benign | -0.356 | Destabilizing | 0.085 | N | 0.207 | neutral | None | None | None | None | I |
| T/R | 0.1139 | likely_benign | 0.1298 | benign | -0.083 | Destabilizing | 0.704 | D | 0.303 | neutral | None | None | None | None | I |
| T/S | 0.0906 | likely_benign | 0.0871 | benign | -0.332 | Destabilizing | 0.065 | N | 0.161 | neutral | N | 0.49825075 | None | None | I |
| T/V | 0.0707 | likely_benign | 0.0684 | benign | -0.081 | Destabilizing | 0.329 | N | 0.165 | neutral | None | None | None | None | I |
| T/W | 0.5342 | ambiguous | 0.5603 | ambiguous | -0.79 | Destabilizing | 0.995 | D | 0.379 | neutral | None | None | None | None | I |
| T/Y | 0.2329 | likely_benign | 0.2319 | benign | -0.491 | Destabilizing | 0.981 | D | 0.366 | neutral | None | None | None | None | I |
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.