Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25052 | 75379;75380;75381 | chr2:178570978;178570977;178570976 | chr2:179435705;179435704;179435703 |
| N2AB | 23411 | 70456;70457;70458 | chr2:178570978;178570977;178570976 | chr2:179435705;179435704;179435703 |
| N2A | 22484 | 67675;67676;67677 | chr2:178570978;178570977;178570976 | chr2:179435705;179435704;179435703 |
| N2B | 15987 | 48184;48185;48186 | chr2:178570978;178570977;178570976 | chr2:179435705;179435704;179435703 |
| Novex-1 | 16112 | 48559;48560;48561 | chr2:178570978;178570977;178570976 | chr2:179435705;179435704;179435703 |
| Novex-2 | 16179 | 48760;48761;48762 | chr2:178570978;178570977;178570976 | chr2:179435705;179435704;179435703 |
| 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/C | rs1303893206  |
-0.114 | 1.0 | N | 0.591 | 0.414 | 0.612105117874 | gnomAD-2.1.1 | 1.07E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 8E-05 | 7.83E-06 | 0 |
| R/C | rs1303893206 |
-0.114 | 1.0 | N | 0.591 | 0.414 | 0.612105117874 | gnomAD-4.0.0 | 8.21181E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 7.49232E-05 | 0 | 6.29726E-06 | 1.15945E-05 | 0 |
| R/H | rs542720402 |
-0.692 | 0.999 | D | 0.458 | 0.366 | 0.321108458156 | gnomAD-2.1.1 | 1.61E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 1.11359E-04 | None | 3.27E-05 | None | 0 | 8.9E-06 | 0 |
| R/H | rs542720402 |
-0.692 | 0.999 | D | 0.458 | 0.366 | 0.321108458156 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 3.87898E-04 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/H | rs542720402 |
-0.692 | 0.999 | D | 0.458 | 0.366 | 0.321108458156 | 1000 genomes | 1.99681E-04 | None | None | None | None | I | None | 0 | 0 | None | None | 1E-03 | 0 | None | None | None | 0 | None |
| R/H | rs542720402 |
-0.692 | 0.999 | D | 0.458 | 0.366 | 0.321108458156 | gnomAD-4.0.0 | 6.19769E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 6.69135E-05 | None | 0 | 0 | 3.39099E-06 | 3.29388E-05 | 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 | 0.9038 | likely_pathogenic | 0.8998 | pathogenic | 0.114 | Stabilizing | 0.693 | D | 0.487 | neutral | None | None | None | None | I |
| R/C | 0.5244 | ambiguous | 0.547 | ambiguous | -0.165 | Destabilizing | 1.0 | D | 0.591 | neutral | N | 0.487524483 | None | None | I |
| R/D | 0.951 | likely_pathogenic | 0.9498 | pathogenic | -0.262 | Destabilizing | 0.975 | D | 0.441 | neutral | None | None | None | None | I |
| R/E | 0.8177 | likely_pathogenic | 0.8241 | pathogenic | -0.21 | Destabilizing | 0.916 | D | 0.467 | neutral | None | None | None | None | I |
| R/F | 0.8863 | likely_pathogenic | 0.8952 | pathogenic | -0.176 | Destabilizing | 0.987 | D | 0.569 | neutral | None | None | None | None | I |
| R/G | 0.8099 | likely_pathogenic | 0.8088 | pathogenic | -0.044 | Destabilizing | 0.913 | D | 0.453 | neutral | N | 0.499180965 | None | None | I |
| R/H | 0.2665 | likely_benign | 0.2792 | benign | -0.595 | Destabilizing | 0.999 | D | 0.458 | neutral | D | 0.524522127 | None | None | I |
| R/I | 0.7354 | likely_pathogenic | 0.7296 | pathogenic | 0.487 | Stabilizing | 0.987 | D | 0.566 | neutral | None | None | None | None | I |
| R/K | 0.2593 | likely_benign | 0.2581 | benign | -0.062 | Destabilizing | 0.818 | D | 0.507 | neutral | None | None | None | None | I |
| R/L | 0.6977 | likely_pathogenic | 0.695 | pathogenic | 0.487 | Stabilizing | 0.954 | D | 0.409 | neutral | N | 0.50362678 | None | None | I |
| R/M | 0.7827 | likely_pathogenic | 0.7806 | pathogenic | -0.02 | Destabilizing | 0.999 | D | 0.451 | neutral | None | None | None | None | I |
| R/N | 0.9039 | likely_pathogenic | 0.9092 | pathogenic | 0.024 | Stabilizing | 0.916 | D | 0.415 | neutral | None | None | None | None | I |
| R/P | 0.9258 | likely_pathogenic | 0.9217 | pathogenic | 0.381 | Stabilizing | 0.993 | D | 0.51 | neutral | N | 0.471938216 | None | None | I |
| R/Q | 0.2868 | likely_benign | 0.3001 | benign | -0.003 | Destabilizing | 0.975 | D | 0.435 | neutral | None | None | None | None | I |
| R/S | 0.9255 | likely_pathogenic | 0.9259 | pathogenic | -0.152 | Destabilizing | 0.219 | N | 0.41 | neutral | N | 0.476669465 | None | None | I |
| R/T | 0.8209 | likely_pathogenic | 0.8266 | pathogenic | 0.016 | Stabilizing | 0.845 | D | 0.45 | neutral | None | None | None | None | I |
| R/V | 0.8153 | likely_pathogenic | 0.8186 | pathogenic | 0.381 | Stabilizing | 0.975 | D | 0.579 | neutral | None | None | None | None | I |
| R/W | 0.4872 | ambiguous | 0.4992 | ambiguous | -0.357 | Destabilizing | 0.999 | D | 0.647 | neutral | None | None | None | None | I |
| R/Y | 0.736 | likely_pathogenic | 0.7599 | pathogenic | 0.062 | Stabilizing | 0.996 | D | 0.507 | neutral | None | None | 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.