Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22596 | 68011;68012;68013 | chr2:178579244;178579243;178579242 | chr2:179443971;179443970;179443969 |
| N2AB | 20955 | 63088;63089;63090 | chr2:178579244;178579243;178579242 | chr2:179443971;179443970;179443969 |
| N2A | 20028 | 60307;60308;60309 | chr2:178579244;178579243;178579242 | chr2:179443971;179443970;179443969 |
| N2B | 13531 | 40816;40817;40818 | chr2:178579244;178579243;178579242 | chr2:179443971;179443970;179443969 |
| Novex-1 | 13656 | 41191;41192;41193 | chr2:178579244;178579243;178579242 | chr2:179443971;179443970;179443969 |
| Novex-2 | 13723 | 41392;41393;41394 | chr2:178579244;178579243;178579242 | chr2:179443971;179443970;179443969 |
| 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/G | rs761026013  |
-0.818 | 1.0 | N | 0.659 | 0.525 | 0.471620082127 | gnomAD-2.1.1 | 8.04E-06 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 8.89E-06 | 0 |
| R/G | rs761026013 |
-0.818 | 1.0 | N | 0.659 | 0.525 | 0.471620082127 | gnomAD-4.0.0 | 4.7905E-06 | None | None | None | None | N | None | 0 | 2.23634E-05 | None | 0 | 0 | None | 0 | 0 | 5.39788E-06 | 0 | 0 |
| R/T | rs1197078573 |
-0.227 | 1.0 | N | 0.703 | 0.479 | 0.482500522706 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| R/T | rs1197078573 |
-0.227 | 1.0 | N | 0.703 | 0.479 | 0.482500522706 | gnomAD-4.0.0 | 3.18399E-06 | None | None | None | None | N | None | 0 | 4.57352E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.9036 | likely_pathogenic | 0.8835 | pathogenic | -0.955 | Destabilizing | 0.999 | D | 0.593 | neutral | None | None | None | None | N |
| R/C | 0.6945 | likely_pathogenic | 0.6046 | pathogenic | -0.859 | Destabilizing | 1.0 | D | 0.722 | prob.delet. | None | None | None | None | N |
| R/D | 0.9363 | likely_pathogenic | 0.921 | pathogenic | -0.116 | Destabilizing | 1.0 | D | 0.688 | prob.neutral | None | None | None | None | N |
| R/E | 0.7937 | likely_pathogenic | 0.7619 | pathogenic | 0.012 | Stabilizing | 0.999 | D | 0.612 | neutral | None | None | None | None | N |
| R/F | 0.9536 | likely_pathogenic | 0.935 | pathogenic | -0.777 | Destabilizing | 1.0 | D | 0.704 | prob.neutral | None | None | None | None | N |
| R/G | 0.8057 | likely_pathogenic | 0.7643 | pathogenic | -1.275 | Destabilizing | 1.0 | D | 0.659 | neutral | N | 0.491907986 | None | None | N |
| R/H | 0.3264 | likely_benign | 0.279 | benign | -1.507 | Destabilizing | 1.0 | D | 0.691 | prob.neutral | None | None | None | None | N |
| R/I | 0.8834 | likely_pathogenic | 0.8605 | pathogenic | -0.088 | Destabilizing | 1.0 | D | 0.713 | prob.delet. | N | 0.496707379 | None | None | N |
| R/K | 0.3523 | ambiguous | 0.327 | benign | -0.957 | Destabilizing | 0.997 | D | 0.518 | neutral | N | 0.466406991 | None | None | N |
| R/L | 0.8215 | likely_pathogenic | 0.787 | pathogenic | -0.088 | Destabilizing | 1.0 | D | 0.659 | neutral | None | None | None | None | N |
| R/M | 0.8838 | likely_pathogenic | 0.8556 | pathogenic | -0.352 | Destabilizing | 1.0 | D | 0.673 | neutral | None | None | None | None | N |
| R/N | 0.9041 | likely_pathogenic | 0.8873 | pathogenic | -0.383 | Destabilizing | 1.0 | D | 0.704 | prob.neutral | None | None | None | None | N |
| R/P | 0.9517 | likely_pathogenic | 0.935 | pathogenic | -0.357 | Destabilizing | 1.0 | D | 0.661 | neutral | None | None | None | None | N |
| R/Q | 0.3647 | ambiguous | 0.329 | benign | -0.562 | Destabilizing | 1.0 | D | 0.7 | prob.neutral | None | None | None | None | N |
| R/S | 0.9111 | likely_pathogenic | 0.8938 | pathogenic | -1.211 | Destabilizing | 1.0 | D | 0.705 | prob.neutral | N | 0.47520931 | None | None | N |
| R/T | 0.8158 | likely_pathogenic | 0.7726 | pathogenic | -0.897 | Destabilizing | 1.0 | D | 0.703 | prob.neutral | N | 0.495946911 | None | None | N |
| R/V | 0.9049 | likely_pathogenic | 0.8836 | pathogenic | -0.357 | Destabilizing | 1.0 | D | 0.697 | prob.neutral | None | None | None | None | N |
| R/W | 0.6648 | likely_pathogenic | 0.5914 | pathogenic | -0.391 | Destabilizing | 1.0 | D | 0.728 | prob.delet. | None | None | None | None | N |
| R/Y | 0.873 | likely_pathogenic | 0.8294 | pathogenic | -0.109 | Destabilizing | 1.0 | D | 0.691 | 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.