Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1572 | 4939;4940;4941 | chr2:178777249;178777248;178777247 | chr2:179641976;179641975;179641974 |
| N2AB | 1572 | 4939;4940;4941 | chr2:178777249;178777248;178777247 | chr2:179641976;179641975;179641974 |
| N2A | 1572 | 4939;4940;4941 | chr2:178777249;178777248;178777247 | chr2:179641976;179641975;179641974 |
| N2B | 1526 | 4801;4802;4803 | chr2:178777249;178777248;178777247 | chr2:179641976;179641975;179641974 |
| Novex-1 | 1526 | 4801;4802;4803 | chr2:178777249;178777248;178777247 | chr2:179641976;179641975;179641974 |
| Novex-2 | 1526 | 4801;4802;4803 | chr2:178777249;178777248;178777247 | chr2:179641976;179641975;179641974 |
| Novex-3 | 1572 | 4939;4940;4941 | chr2:178777249;178777248;178777247 | chr2:179641976;179641975;179641974 |
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/L | rs12476289  |
0.032 | 0.001 | N | 0.146 | 0.215 | 0.280987212366 | gnomAD-2.1.1 | 3.99E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.83E-06 | 0 |
| R/L | rs12476289 |
0.032 | 0.001 | N | 0.146 | 0.215 | 0.280987212366 | gnomAD-4.0.0 | 6.84101E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99315E-07 | 0 | 0 |
| R/P | None | None | 0.001 | N | 0.145 | 0.259 | 0.166414681773 | gnomAD-4.0.0 | 2.0523E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.69794E-06 | 0 | 0 |
| R/Q | rs12476289 |
-0.084 | 0.753 | N | 0.332 | 0.064 | None | gnomAD-2.1.1 | 7.52661E-02 | None | None | None | None | N | None | 1.14583E-02 | 2.38153E-01 | None | 4.86674E-02 | 1.99176E-01 | None | 1.84568E-02 | None | 5.32415E-02 | 4.42459E-02 | 6.3939E-02 |
| R/Q | rs12476289 |
-0.084 | 0.753 | N | 0.332 | 0.064 | None | gnomAD-3.1.2 | 4.97469E-02 | None | None | None | None | N | None | 1.15886E-02 | 1.3777E-01 | 4.82456E-02 | 4.89914E-02 | 1.83218E-01 | None | 5.12917E-02 | 1.58228E-02 | 4.5127E-02 | 2.17842E-02 | 4.58891E-02 |
| R/Q | rs12476289 |
-0.084 | 0.753 | N | 0.332 | 0.064 | None | 1000 genomes | 7.52796E-02 | None | None | None | None | N | None | 2.3E-03 | 1.715E-01 | None | None | 1.895E-01 | 4.87E-02 | None | None | None | 1.53E-02 | None |
| R/Q | rs12476289 |
-0.084 | 0.753 | N | 0.332 | 0.064 | None | gnomAD-4.0.0 | 5.23823E-02 | None | None | None | None | N | None | 1.05977E-02 | 2.04774E-01 | None | 4.75644E-02 | 1.87341E-01 | None | 5.40245E-02 | 1.63312E-02 | 4.49706E-02 | 1.97329E-02 | 5.10687E-02 |
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 | 0.2208 | likely_benign | 0.1677 | benign | -0.355 | Destabilizing | 0.061 | N | 0.205 | neutral | None | None | None | None | N |
| R/C | 0.1316 | likely_benign | 0.111 | benign | -0.341 | Destabilizing | 0.94 | D | 0.253 | neutral | None | None | None | None | N |
| R/D | 0.5191 | ambiguous | 0.3972 | ambiguous | 0.05 | Stabilizing | 0.418 | N | 0.361 | neutral | None | None | None | None | N |
| R/E | 0.2736 | likely_benign | 0.2095 | benign | 0.144 | Stabilizing | 0.129 | N | 0.225 | neutral | None | None | None | None | N |
| R/F | 0.3511 | ambiguous | 0.2759 | benign | -0.384 | Destabilizing | 0.716 | D | 0.373 | neutral | None | None | None | None | N |
| R/G | 0.1589 | likely_benign | 0.1236 | benign | -0.618 | Destabilizing | 0.221 | N | 0.275 | neutral | N | 0.448028543 | None | None | N |
| R/H | 0.0854 | likely_benign | 0.0769 | benign | -1.017 | Destabilizing | 0.836 | D | 0.323 | neutral | None | None | None | None | N |
| R/I | 0.1614 | likely_benign | 0.1297 | benign | 0.324 | Stabilizing | 0.129 | N | 0.375 | neutral | None | None | None | None | N |
| R/K | 0.0763 | likely_benign | 0.0699 | benign | -0.354 | Destabilizing | 0.001 | N | 0.104 | neutral | None | None | None | None | N |
| R/L | 0.1449 | likely_benign | 0.1207 | benign | 0.324 | Stabilizing | 0.001 | N | 0.146 | neutral | N | 0.443671065 | None | None | N |
| R/M | 0.1831 | likely_benign | 0.1478 | benign | -0.032 | Destabilizing | 0.716 | D | 0.294 | neutral | None | None | None | None | N |
| R/N | 0.3695 | ambiguous | 0.2873 | benign | 0.097 | Stabilizing | 0.264 | N | 0.261 | neutral | None | None | None | None | N |
| R/P | 0.3101 | likely_benign | 0.2311 | benign | 0.119 | Stabilizing | 0.001 | N | 0.145 | neutral | N | 0.423109279 | None | None | N |
| R/Q | 0.0878 | likely_benign | 0.0712 | benign | -0.074 | Destabilizing | 0.753 | D | 0.332 | neutral | N | 0.443227221 | None | None | N |
| R/S | 0.2648 | likely_benign | 0.2018 | benign | -0.508 | Destabilizing | 0.004 | N | 0.147 | neutral | None | None | None | None | N |
| R/T | 0.1461 | likely_benign | 0.1176 | benign | -0.252 | Destabilizing | 0.129 | N | 0.286 | neutral | None | None | None | None | N |
| R/V | 0.2052 | likely_benign | 0.1633 | benign | 0.119 | Stabilizing | 0.129 | N | 0.291 | neutral | None | None | None | None | N |
| R/W | 0.1535 | likely_benign | 0.1219 | benign | -0.212 | Destabilizing | 0.983 | D | 0.264 | neutral | None | None | None | None | N |
| R/Y | 0.2784 | likely_benign | 0.2189 | benign | 0.142 | Stabilizing | 0.94 | D | 0.363 | 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.