Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 5299 | 16120;16121;16122 | chr2:178733398;178733397;178733396 | chr2:179598125;179598124;179598123 |
| N2AB | 4982 | 15169;15170;15171 | chr2:178733398;178733397;178733396 | chr2:179598125;179598124;179598123 |
| N2A | 4055 | 12388;12389;12390 | chr2:178733398;178733397;178733396 | chr2:179598125;179598124;179598123 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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/T | rs563456537  |
-0.016 | 0.006 | N | 0.293 | 0.277 | 0.461058313273 | gnomAD-2.1.1 | 1.04578E-04 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 8.49729E-04 | None | 0 | 0 | 0 |
| R/T | rs563456537 |
-0.016 | 0.006 | N | 0.293 | 0.277 | 0.461058313273 | gnomAD-3.1.2 | 5.92E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 1.86722E-03 | 0 |
| R/T | rs563456537 |
-0.016 | 0.006 | N | 0.293 | 0.277 | 0.461058313273 | 1000 genomes | 7.98722E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 4.1E-03 | None |
| R/T | rs563456537 |
-0.016 | 0.006 | N | 0.293 | 0.277 | 0.461058313273 | gnomAD-4.0.0 | 5.94866E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.47608E-07 | 1.01021E-03 | 4.80184E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.2934 | likely_benign | 0.3589 | ambiguous | 0.087 | Stabilizing | 0.116 | N | 0.357 | neutral | None | None | None | None | N |
| R/C | 0.1466 | likely_benign | 0.1803 | benign | -0.078 | Destabilizing | 0.981 | D | 0.351 | neutral | None | None | None | None | N |
| R/D | 0.5247 | ambiguous | 0.5733 | pathogenic | -0.143 | Destabilizing | 0.388 | N | 0.391 | neutral | None | None | None | None | N |
| R/E | 0.252 | likely_benign | 0.2837 | benign | -0.083 | Destabilizing | 0.116 | N | 0.31 | neutral | None | None | None | None | N |
| R/F | 0.331 | likely_benign | 0.3746 | ambiguous | -0.148 | Destabilizing | 0.932 | D | 0.358 | neutral | None | None | None | None | N |
| R/G | 0.2253 | likely_benign | 0.2783 | benign | -0.098 | Destabilizing | 0.324 | N | 0.385 | neutral | N | 0.511664359 | None | None | N |
| R/H | 0.0818 | likely_benign | 0.091 | benign | -0.64 | Destabilizing | 0.818 | D | 0.346 | neutral | None | None | None | None | N |
| R/I | 0.1384 | likely_benign | 0.1377 | benign | 0.537 | Stabilizing | 0.627 | D | 0.379 | neutral | N | 0.512245263 | None | None | N |
| R/K | 0.0657 | likely_benign | 0.071 | benign | -0.018 | Destabilizing | None | N | 0.178 | neutral | N | 0.425315141 | None | None | N |
| R/L | 0.1497 | likely_benign | 0.1714 | benign | 0.537 | Stabilizing | 0.388 | N | 0.347 | neutral | None | None | None | None | N |
| R/M | 0.156 | likely_benign | 0.1621 | benign | 0.073 | Stabilizing | 0.932 | D | 0.363 | neutral | None | None | None | None | N |
| R/N | 0.3439 | ambiguous | 0.3654 | ambiguous | 0.165 | Stabilizing | 0.388 | N | 0.299 | neutral | None | None | None | None | N |
| R/P | 0.818 | likely_pathogenic | 0.876 | pathogenic | 0.407 | Stabilizing | 0.818 | D | 0.357 | neutral | None | None | None | None | N |
| R/Q | 0.0781 | likely_benign | 0.0863 | benign | 0.097 | Stabilizing | 0.241 | N | 0.343 | neutral | None | None | None | None | N |
| R/S | 0.3206 | likely_benign | 0.3728 | ambiguous | -0.098 | Destabilizing | 0.09 | N | 0.351 | neutral | N | 0.50210207 | None | None | N |
| R/T | 0.1737 | likely_benign | 0.2535 | benign | 0.089 | Stabilizing | 0.006 | N | 0.293 | neutral | N | 0.510691388 | None | None | N |
| R/V | 0.1938 | likely_benign | 0.2164 | benign | 0.407 | Stabilizing | 0.388 | N | 0.405 | neutral | None | None | None | None | N |
| R/W | 0.1584 | likely_benign | 0.1883 | benign | -0.258 | Destabilizing | 0.981 | D | 0.37 | neutral | None | None | None | None | N |
| R/Y | 0.2619 | likely_benign | 0.2941 | benign | 0.158 | Stabilizing | 0.932 | D | 0.367 | 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.