Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 9376 | 28351;28352;28353 | chr2:178711110;178711109;178711108 | chr2:179575837;179575836;179575835 |
| N2AB | 9059 | 27400;27401;27402 | chr2:178711110;178711109;178711108 | chr2:179575837;179575836;179575835 |
| N2A | 8132 | 24619;24620;24621 | chr2:178711110;178711109;178711108 | chr2:179575837;179575836;179575835 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | None | None | 0.002 | None | 0.101 | 0.23 | 0.177238962908 | gnomAD-4.0.0 | 3.18384E-06 | None | None | None | None | N | None | 0 | 2.28718E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.02499E-05 |
| T/K | None | None | 0.549 | None | 0.374 | 0.34 | 0.457106177737 | gnomAD-4.0.0 | 6.84347E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99596E-07 | 0 | 0 |
| T/R | rs749875409  |
-0.048 | 0.81 | None | 0.447 | 0.433 | 0.66854072215 | gnomAD-2.1.1 | 3.22E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.63773E-04 | None | 0 | 2.67E-05 | 0 |
| T/R | rs749875409 |
-0.048 | 0.81 | None | 0.447 | 0.433 | 0.66854072215 | gnomAD-4.0.0 | 1.64243E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 1.73491E-04 | 7.19677E-06 | 1.39243E-04 | 4.97067E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.0818 | likely_benign | 0.0825 | benign | -0.815 | Destabilizing | 0.002 | N | 0.101 | neutral | None | None | None | None | N |
| T/C | 0.4396 | ambiguous | 0.4149 | ambiguous | -0.632 | Destabilizing | 0.977 | D | 0.45 | neutral | None | None | None | None | N |
| T/D | 0.3347 | likely_benign | 0.3616 | ambiguous | -0.842 | Destabilizing | 0.617 | D | 0.437 | neutral | None | None | None | None | N |
| T/E | 0.2478 | likely_benign | 0.2605 | benign | -0.871 | Destabilizing | 0.617 | D | 0.373 | neutral | None | None | None | None | N |
| T/F | 0.2127 | likely_benign | 0.2155 | benign | -1.204 | Destabilizing | 0.92 | D | 0.548 | neutral | None | None | None | None | N |
| T/G | 0.2268 | likely_benign | 0.2308 | benign | -1.005 | Destabilizing | 0.25 | N | 0.486 | neutral | None | None | None | None | N |
| T/H | 0.2107 | likely_benign | 0.2104 | benign | -1.42 | Destabilizing | 0.992 | D | 0.504 | neutral | None | None | None | None | N |
| T/I | 0.1698 | likely_benign | 0.167 | benign | -0.409 | Destabilizing | 0.379 | N | 0.385 | neutral | None | None | None | None | N |
| T/K | 0.1733 | likely_benign | 0.1907 | benign | -0.712 | Destabilizing | 0.549 | D | 0.374 | neutral | None | None | None | None | N |
| T/L | 0.1274 | likely_benign | 0.1252 | benign | -0.409 | Destabilizing | 0.25 | N | 0.393 | neutral | None | None | None | None | N |
| T/M | 0.1138 | likely_benign | 0.1073 | benign | 0.067 | Stabilizing | 0.92 | D | 0.451 | neutral | None | None | None | None | N |
| T/N | 0.1169 | likely_benign | 0.1206 | benign | -0.705 | Destabilizing | 0.617 | D | 0.387 | neutral | None | None | None | None | N |
| T/P | 0.7266 | likely_pathogenic | 0.7701 | pathogenic | -0.516 | Destabilizing | 0.896 | D | 0.429 | neutral | None | None | None | None | N |
| T/Q | 0.1746 | likely_benign | 0.1774 | benign | -1.045 | Destabilizing | 0.92 | D | 0.47 | neutral | None | None | None | None | N |
| T/R | 0.1303 | likely_benign | 0.1385 | benign | -0.377 | Destabilizing | 0.81 | D | 0.447 | neutral | None | None | None | None | N |
| T/S | 0.0829 | likely_benign | 0.0837 | benign | -0.886 | Destabilizing | 0.007 | N | 0.087 | neutral | None | None | None | None | N |
| T/V | 0.1342 | likely_benign | 0.1269 | benign | -0.516 | Destabilizing | 0.005 | N | 0.129 | neutral | None | None | None | None | N |
| T/W | 0.5044 | ambiguous | 0.5398 | ambiguous | -1.133 | Destabilizing | 0.992 | D | 0.565 | neutral | None | None | None | None | N |
| T/Y | 0.2389 | likely_benign | 0.254 | benign | -0.856 | Destabilizing | 0.972 | D | 0.535 | 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.