Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24877 | 74854;74855;74856 | chr2:178571503;178571502;178571501 | chr2:179436230;179436229;179436228 |
| N2AB | 23236 | 69931;69932;69933 | chr2:178571503;178571502;178571501 | chr2:179436230;179436229;179436228 |
| N2A | 22309 | 67150;67151;67152 | chr2:178571503;178571502;178571501 | chr2:179436230;179436229;179436228 |
| N2B | 15812 | 47659;47660;47661 | chr2:178571503;178571502;178571501 | chr2:179436230;179436229;179436228 |
| Novex-1 | 15937 | 48034;48035;48036 | chr2:178571503;178571502;178571501 | chr2:179436230;179436229;179436228 |
| Novex-2 | 16004 | 48235;48236;48237 | chr2:178571503;178571502;178571501 | chr2:179436230;179436229;179436228 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| C/R | None | None | 0.863 | N | 0.497 | 0.262 | 0.389904358541 | gnomAD-4.0.0 | 3.60097E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.93751E-06 | 0 | 0 |
| C/Y | rs373130280  |
-1.485 | 0.975 | N | 0.451 | 0.276 | None | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.95E-06 | 0 |
| C/Y | rs373130280 |
-1.485 | 0.975 | N | 0.451 | 0.276 | None | gnomAD-4.0.0 | 3.28519E-05 | None | None | None | None | N | None | 2.98954E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 4.13818E-05 | 0 | 1.65733E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| C/A | 0.1887 | likely_benign | 0.1859 | benign | -1.794 | Destabilizing | 0.176 | N | 0.211 | neutral | None | None | None | None | N |
| C/D | 0.4332 | ambiguous | 0.447 | ambiguous | -0.229 | Destabilizing | 0.704 | D | 0.471 | neutral | None | None | None | None | N |
| C/E | 0.5147 | ambiguous | 0.5244 | ambiguous | -0.147 | Destabilizing | 0.704 | D | 0.425 | neutral | None | None | None | None | N |
| C/F | 0.1277 | likely_benign | 0.1277 | benign | -1.207 | Destabilizing | 0.642 | D | 0.431 | neutral | N | 0.502106627 | None | None | N |
| C/G | 0.142 | likely_benign | 0.1419 | benign | -2.084 | Highly Destabilizing | 0.27 | N | 0.319 | neutral | N | 0.436209709 | None | None | N |
| C/H | 0.2814 | likely_benign | 0.2765 | benign | -2.004 | Highly Destabilizing | 0.981 | D | 0.435 | neutral | None | None | None | None | N |
| C/I | 0.245 | likely_benign | 0.2542 | benign | -1.056 | Destabilizing | 0.329 | N | 0.307 | neutral | None | None | None | None | N |
| C/K | 0.5342 | ambiguous | 0.5297 | ambiguous | -0.93 | Destabilizing | 0.704 | D | 0.386 | neutral | None | None | None | None | N |
| C/L | 0.2251 | likely_benign | 0.2313 | benign | -1.056 | Destabilizing | 0.003 | N | 0.128 | neutral | None | None | None | None | N |
| C/M | 0.2639 | likely_benign | 0.2705 | benign | -0.136 | Destabilizing | 0.085 | N | 0.207 | neutral | None | None | None | None | N |
| C/N | 0.2076 | likely_benign | 0.2077 | benign | -0.839 | Destabilizing | 0.704 | D | 0.477 | neutral | None | None | None | None | N |
| C/P | 0.9659 | likely_pathogenic | 0.9653 | pathogenic | -1.276 | Destabilizing | 0.828 | D | 0.5 | neutral | None | None | None | None | N |
| C/Q | 0.3374 | likely_benign | 0.3358 | benign | -0.792 | Destabilizing | 0.944 | D | 0.501 | neutral | None | None | None | None | N |
| C/R | 0.3052 | likely_benign | 0.306 | benign | -0.717 | Destabilizing | 0.863 | D | 0.497 | neutral | N | 0.416986443 | None | None | N |
| C/S | 0.1177 | likely_benign | 0.1137 | benign | -1.42 | Destabilizing | 0.01 | N | 0.131 | neutral | N | 0.364000107 | None | None | N |
| C/T | 0.1716 | likely_benign | 0.1708 | benign | -1.158 | Destabilizing | 0.329 | N | 0.316 | neutral | None | None | None | None | N |
| C/V | 0.1924 | likely_benign | 0.2018 | benign | -1.276 | Destabilizing | 0.013 | N | 0.147 | neutral | None | None | None | None | N |
| C/W | 0.3611 | ambiguous | 0.35 | ambiguous | -1.138 | Destabilizing | 0.993 | D | 0.397 | neutral | N | 0.468610129 | None | None | N |
| C/Y | 0.1759 | likely_benign | 0.1789 | benign | -1.152 | Destabilizing | 0.975 | D | 0.451 | neutral | N | 0.520692388 | 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.