Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16337 | 49234;49235;49236 | chr2:178614505;178614504;178614503 | chr2:179479232;179479231;179479230 |
| N2AB | 14696 | 44311;44312;44313 | chr2:178614505;178614504;178614503 | chr2:179479232;179479231;179479230 |
| N2A | 13769 | 41530;41531;41532 | chr2:178614505;178614504;178614503 | chr2:179479232;179479231;179479230 |
| N2B | 7272 | 22039;22040;22041 | chr2:178614505;178614504;178614503 | chr2:179479232;179479231;179479230 |
| Novex-1 | 7397 | 22414;22415;22416 | chr2:178614505;178614504;178614503 | chr2:179479232;179479231;179479230 |
| Novex-2 | 7464 | 22615;22616;22617 | chr2:178614505;178614504;178614503 | chr2:179479232;179479231;179479230 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| C/S | None | None | 0.001 | N | 0.347 | 0.206 | 0.627239104411 | gnomAD-4.0.0 | 8.9083E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.9052E-06 | 0 | 3.31917E-05 |
| C/W | rs575621631  |
-0.529 | 0.978 | N | 0.566 | 0.376 | 0.420939154896 | gnomAD-2.1.1 | 4.05E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 2.96971E-04 | None | 0 | 8.93E-06 | 0 |
| C/W | rs575621631 |
-0.529 | 0.978 | N | 0.566 | 0.376 | 0.420939154896 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 4.14766E-04 | 0 |
| C/W | rs575621631 |
-0.529 | 0.978 | N | 0.566 | 0.376 | 0.420939154896 | 1000 genomes | 1.99681E-04 | None | None | None | None | I | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 1E-03 | None |
| C/W | rs575621631 |
-0.529 | 0.978 | N | 0.566 | 0.376 | 0.420939154896 | gnomAD-4.0.0 | 2.6688E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.69728E-06 | 4.18677E-04 | 4.81062E-05 |
| C/Y | rs1335648118 |
-0.526 | 0.921 | N | 0.563 | 0.255 | 0.754999209091 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 6.48E-05 | 0 |
| C/Y | rs1335648118 |
-0.526 | 0.921 | N | 0.563 | 0.255 | 0.754999209091 | gnomAD-4.0.0 | 1.59713E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86873E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| C/A | 0.5984 | likely_pathogenic | 0.5231 | ambiguous | -0.372 | Destabilizing | 0.061 | N | 0.342 | neutral | None | None | None | None | I |
| C/D | 0.9731 | likely_pathogenic | 0.9432 | pathogenic | 0.271 | Stabilizing | 0.418 | N | 0.565 | neutral | None | None | None | None | I |
| C/E | 0.9778 | likely_pathogenic | 0.9565 | pathogenic | 0.215 | Stabilizing | 0.418 | N | 0.556 | neutral | None | None | None | None | I |
| C/F | 0.4591 | ambiguous | 0.3713 | ambiguous | -0.59 | Destabilizing | 0.794 | D | 0.569 | neutral | N | 0.40955951 | None | None | I |
| C/G | 0.5436 | ambiguous | 0.4149 | ambiguous | -0.43 | Destabilizing | 0.101 | N | 0.603 | neutral | N | 0.44123471 | None | None | I |
| C/H | 0.7795 | likely_pathogenic | 0.6639 | pathogenic | -0.307 | Destabilizing | 0.836 | D | 0.558 | neutral | None | None | None | None | I |
| C/I | 0.8922 | likely_pathogenic | 0.8442 | pathogenic | -0.307 | Destabilizing | 0.418 | N | 0.471 | neutral | None | None | None | None | I |
| C/K | 0.9671 | likely_pathogenic | 0.9263 | pathogenic | 0.117 | Stabilizing | 0.129 | N | 0.575 | neutral | None | None | None | None | I |
| C/L | 0.7299 | likely_pathogenic | 0.6547 | pathogenic | -0.307 | Destabilizing | 0.228 | N | 0.519 | neutral | None | None | None | None | I |
| C/M | 0.8295 | likely_pathogenic | 0.7756 | pathogenic | -0.087 | Destabilizing | 0.94 | D | 0.505 | neutral | None | None | None | None | I |
| C/N | 0.8189 | likely_pathogenic | 0.7255 | pathogenic | 0.395 | Stabilizing | 0.264 | N | 0.56 | neutral | None | None | None | None | I |
| C/P | 0.995 | likely_pathogenic | 0.9897 | pathogenic | -0.31 | Destabilizing | 0.593 | D | 0.54 | neutral | None | None | None | None | I |
| C/Q | 0.9023 | likely_pathogenic | 0.8409 | pathogenic | 0.228 | Stabilizing | 0.418 | N | 0.544 | neutral | None | None | None | None | I |
| C/R | 0.8495 | likely_pathogenic | 0.7393 | pathogenic | 0.439 | Stabilizing | 0.002 | N | 0.458 | neutral | N | 0.474681462 | None | None | I |
| C/S | 0.516 | ambiguous | 0.4158 | ambiguous | 0.011 | Stabilizing | 0.001 | N | 0.347 | neutral | N | 0.328294646 | None | None | I |
| C/T | 0.7761 | likely_pathogenic | 0.6887 | pathogenic | 0.047 | Stabilizing | 0.004 | N | 0.34 | neutral | None | None | None | None | I |
| C/V | 0.7682 | likely_pathogenic | 0.7175 | pathogenic | -0.31 | Destabilizing | 0.228 | N | 0.479 | neutral | None | None | None | None | I |
| C/W | 0.8195 | likely_pathogenic | 0.7346 | pathogenic | -0.6 | Destabilizing | 0.978 | D | 0.566 | neutral | N | 0.491978594 | None | None | I |
| C/Y | 0.6847 | likely_pathogenic | 0.5496 | ambiguous | -0.403 | Destabilizing | 0.921 | D | 0.563 | neutral | N | 0.420994742 | 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.