Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14058 | 42397;42398;42399 | chr2:178634609;178634608;178634607 | chr2:179499336;179499335;179499334 |
| N2AB | 12417 | 37474;37475;37476 | chr2:178634609;178634608;178634607 | chr2:179499336;179499335;179499334 |
| N2A | 11490 | 34693;34694;34695 | chr2:178634609;178634608;178634607 | chr2:179499336;179499335;179499334 |
| N2B | 4993 | 15202;15203;15204 | chr2:178634609;178634608;178634607 | chr2:179499336;179499335;179499334 |
| Novex-1 | 5118 | 15577;15578;15579 | chr2:178634609;178634608;178634607 | chr2:179499336;179499335;179499334 |
| Novex-2 | 5185 | 15778;15779;15780 | chr2:178634609;178634608;178634607 | chr2:179499336;179499335;179499334 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/M | rs774014126  |
-0.276 | 0.999 | N | 0.545 | 0.267 | 0.479818277033 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.91E-06 | 0 |
| V/M | rs774014126 |
-0.276 | 0.999 | N | 0.545 | 0.267 | 0.479818277033 | gnomAD-4.0.0 | 1.5925E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.8604E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.2803 | likely_benign | 0.332 | benign | -1.191 | Destabilizing | 0.953 | D | 0.482 | neutral | N | 0.507265823 | None | None | N |
| V/C | 0.878 | likely_pathogenic | 0.8838 | pathogenic | -0.705 | Destabilizing | 1.0 | D | 0.613 | neutral | None | None | None | None | N |
| V/D | 0.4915 | ambiguous | 0.5709 | pathogenic | -0.978 | Destabilizing | 0.171 | N | 0.393 | neutral | None | None | None | None | N |
| V/E | 0.3222 | likely_benign | 0.3623 | ambiguous | -1.01 | Destabilizing | 0.961 | D | 0.515 | neutral | N | 0.476810875 | None | None | N |
| V/F | 0.2522 | likely_benign | 0.298 | benign | -0.939 | Destabilizing | 0.999 | D | 0.61 | neutral | None | None | None | None | N |
| V/G | 0.4278 | ambiguous | 0.4795 | ambiguous | -1.467 | Destabilizing | 0.99 | D | 0.553 | neutral | N | 0.50734225 | None | None | N |
| V/H | 0.6895 | likely_pathogenic | 0.7299 | pathogenic | -0.963 | Destabilizing | 1.0 | D | 0.658 | neutral | None | None | None | None | N |
| V/I | 0.0918 | likely_benign | 0.0957 | benign | -0.552 | Destabilizing | 0.985 | D | 0.467 | neutral | None | None | None | None | N |
| V/K | 0.4391 | ambiguous | 0.471 | ambiguous | -1.032 | Destabilizing | 0.998 | D | 0.561 | neutral | None | None | None | None | N |
| V/L | 0.2712 | likely_benign | 0.3011 | benign | -0.552 | Destabilizing | 0.953 | D | 0.487 | neutral | N | 0.508913938 | None | None | N |
| V/M | 0.1967 | likely_benign | 0.2214 | benign | -0.387 | Destabilizing | 0.999 | D | 0.545 | neutral | N | 0.507258065 | None | None | N |
| V/N | 0.3714 | ambiguous | 0.4176 | ambiguous | -0.766 | Destabilizing | 0.996 | D | 0.655 | neutral | None | None | None | None | N |
| V/P | 0.9262 | likely_pathogenic | 0.9468 | pathogenic | -0.729 | Destabilizing | 0.999 | D | 0.646 | neutral | None | None | None | None | N |
| V/Q | 0.3744 | ambiguous | 0.4003 | ambiguous | -0.966 | Destabilizing | 0.998 | D | 0.643 | neutral | None | None | None | None | N |
| V/R | 0.4321 | ambiguous | 0.489 | ambiguous | -0.463 | Destabilizing | 0.998 | D | 0.669 | neutral | None | None | None | None | N |
| V/S | 0.3007 | likely_benign | 0.3414 | ambiguous | -1.234 | Destabilizing | 0.971 | D | 0.529 | neutral | None | None | None | None | N |
| V/T | 0.239 | likely_benign | 0.2482 | benign | -1.163 | Destabilizing | 0.469 | N | 0.259 | neutral | None | None | None | None | N |
| V/W | 0.9261 | likely_pathogenic | 0.9443 | pathogenic | -1.103 | Destabilizing | 1.0 | D | 0.668 | neutral | None | None | None | None | N |
| V/Y | 0.6907 | likely_pathogenic | 0.7281 | pathogenic | -0.822 | Destabilizing | 0.999 | D | 0.62 | 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.