Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14084 | 42475;42476;42477 | chr2:178634531;178634530;178634529 | chr2:179499258;179499257;179499256 |
| N2AB | 12443 | 37552;37553;37554 | chr2:178634531;178634530;178634529 | chr2:179499258;179499257;179499256 |
| N2A | 11516 | 34771;34772;34773 | chr2:178634531;178634530;178634529 | chr2:179499258;179499257;179499256 |
| N2B | 5019 | 15280;15281;15282 | chr2:178634531;178634530;178634529 | chr2:179499258;179499257;179499256 |
| Novex-1 | 5144 | 15655;15656;15657 | chr2:178634531;178634530;178634529 | chr2:179499258;179499257;179499256 |
| Novex-2 | 5211 | 15856;15857;15858 | chr2:178634531;178634530;178634529 | chr2:179499258;179499257;179499256 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/M | rs1163597313  |
-0.488 | 0.136 | N | 0.231 | 0.047 | 0.3349148499 | gnomAD-2.1.1 | 8.06E-06 | None | None | None | None | N | None | 0 | 5.8E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/M | rs1163597313 |
-0.488 | 0.136 | N | 0.231 | 0.047 | 0.3349148499 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.07039E-04 | 0 |
| I/M | rs1163597313 |
-0.488 | 0.136 | N | 0.231 | 0.047 | 0.3349148499 | gnomAD-4.0.0 | 4.33899E-06 | None | None | None | None | N | None | 0 | 3.335E-05 | None | 0 | 0 | None | 0 | 0 | 1.69558E-06 | 2.19626E-05 | 1.60179E-05 |
| I/T | rs757636133 |
-1.196 | 0.801 | N | 0.547 | 0.313 | 0.619433965396 | gnomAD-4.0.0 | 1.59216E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43308E-05 | 0 |
| I/V | None | None | 0.005 | N | 0.179 | 0.061 | 0.543254643676 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.66327E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.5322 | ambiguous | 0.5705 | pathogenic | -1.179 | Destabilizing | 0.525 | D | 0.505 | neutral | None | None | None | None | N |
| I/C | 0.8038 | likely_pathogenic | 0.817 | pathogenic | -0.731 | Destabilizing | 0.998 | D | 0.549 | neutral | None | None | None | None | N |
| I/D | 0.8341 | likely_pathogenic | 0.8547 | pathogenic | -0.553 | Destabilizing | 0.991 | D | 0.635 | neutral | None | None | None | None | N |
| I/E | 0.7063 | likely_pathogenic | 0.7271 | pathogenic | -0.576 | Destabilizing | 0.974 | D | 0.615 | neutral | None | None | None | None | N |
| I/F | 0.1807 | likely_benign | 0.194 | benign | -0.786 | Destabilizing | 0.842 | D | 0.549 | neutral | None | None | None | None | N |
| I/G | 0.8185 | likely_pathogenic | 0.8422 | pathogenic | -1.452 | Destabilizing | 0.974 | D | 0.609 | neutral | None | None | None | None | N |
| I/H | 0.5559 | ambiguous | 0.5875 | pathogenic | -0.59 | Destabilizing | 0.998 | D | 0.619 | neutral | None | None | None | None | N |
| I/K | 0.4479 | ambiguous | 0.4846 | ambiguous | -0.77 | Destabilizing | 0.934 | D | 0.611 | neutral | N | 0.378586555 | None | None | N |
| I/L | 0.1155 | likely_benign | 0.1131 | benign | -0.533 | Destabilizing | 0.005 | N | 0.207 | neutral | N | 0.462323146 | None | None | N |
| I/M | 0.1085 | likely_benign | 0.1088 | benign | -0.514 | Destabilizing | 0.136 | N | 0.231 | neutral | N | 0.451733917 | None | None | N |
| I/N | 0.3887 | ambiguous | 0.4249 | ambiguous | -0.583 | Destabilizing | 0.974 | D | 0.623 | neutral | None | None | None | None | N |
| I/P | 0.948 | likely_pathogenic | 0.9507 | pathogenic | -0.716 | Destabilizing | 0.991 | D | 0.63 | neutral | None | None | None | None | N |
| I/Q | 0.4995 | ambiguous | 0.51 | ambiguous | -0.758 | Destabilizing | 0.974 | D | 0.627 | neutral | None | None | None | None | N |
| I/R | 0.3381 | likely_benign | 0.383 | ambiguous | -0.187 | Destabilizing | 0.966 | D | 0.633 | neutral | N | 0.437615535 | None | None | N |
| I/S | 0.4238 | ambiguous | 0.4666 | ambiguous | -1.135 | Destabilizing | 0.915 | D | 0.565 | neutral | None | None | None | None | N |
| I/T | 0.3384 | likely_benign | 0.3728 | ambiguous | -1.043 | Destabilizing | 0.801 | D | 0.547 | neutral | N | 0.375310542 | None | None | N |
| I/V | 0.1224 | likely_benign | 0.1251 | benign | -0.716 | Destabilizing | 0.005 | N | 0.179 | neutral | N | 0.460010046 | None | None | N |
| I/W | 0.7943 | likely_pathogenic | 0.8043 | pathogenic | -0.829 | Destabilizing | 0.998 | D | 0.642 | neutral | None | None | None | None | N |
| I/Y | 0.5219 | ambiguous | 0.5258 | ambiguous | -0.606 | Destabilizing | 0.974 | D | 0.577 | 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.