Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24994 | 75205;75206;75207 | chr2:178571152;178571151;178571150 | chr2:179435879;179435878;179435877 |
| N2AB | 23353 | 70282;70283;70284 | chr2:178571152;178571151;178571150 | chr2:179435879;179435878;179435877 |
| N2A | 22426 | 67501;67502;67503 | chr2:178571152;178571151;178571150 | chr2:179435879;179435878;179435877 |
| N2B | 15929 | 48010;48011;48012 | chr2:178571152;178571151;178571150 | chr2:179435879;179435878;179435877 |
| Novex-1 | 16054 | 48385;48386;48387 | chr2:178571152;178571151;178571150 | chr2:179435879;179435878;179435877 |
| Novex-2 | 16121 | 48586;48587;48588 | chr2:178571152;178571151;178571150 | chr2:179435879;179435878;179435877 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/L | rs531281558  |
-0.552 | 0.476 | N | 0.432 | 0.273 | None | gnomAD-2.1.1 | 2.42E-05 | None | None | None | None | I | None | 0 | 1.44978E-04 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| P/L | rs531281558 |
-0.552 | 0.476 | N | 0.432 | 0.273 | None | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 2.07469E-04 | 0 |
| P/L | rs531281558 |
-0.552 | 0.476 | N | 0.432 | 0.273 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | I | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 1E-03 | None |
| P/L | rs531281558 |
-0.552 | 0.476 | N | 0.432 | 0.273 | None | gnomAD-4.0.0 | 1.4876E-05 | None | None | None | None | I | None | 1.33362E-05 | 1.16698E-04 | None | 0 | 0 | None | 0 | 0 | 1.01732E-05 | 1.0981E-05 | 4.80369E-05 |
| P/T | rs1416288780 |
-0.873 | 0.01 | N | 0.263 | 0.124 | 0.24896430686 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 6.49E-05 | 0 |
| P/T | rs1416288780 |
-0.873 | 0.01 | N | 0.263 | 0.124 | 0.24896430686 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| P/T | rs1416288780 |
-0.873 | 0.01 | N | 0.263 | 0.124 | 0.24896430686 | gnomAD-4.0.0 | 6.57851E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.47089E-05 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.0618 | likely_benign | 0.0596 | benign | -1.203 | Destabilizing | 0.001 | N | 0.254 | neutral | N | 0.456622266 | None | None | I |
| P/C | 0.2931 | likely_benign | 0.3202 | benign | -0.832 | Destabilizing | 0.944 | D | 0.577 | neutral | None | None | None | None | I |
| P/D | 0.6456 | likely_pathogenic | 0.6583 | pathogenic | -0.867 | Destabilizing | 0.704 | D | 0.439 | neutral | None | None | None | None | I |
| P/E | 0.4369 | ambiguous | 0.4612 | ambiguous | -0.949 | Destabilizing | 0.495 | N | 0.398 | neutral | None | None | None | None | I |
| P/F | 0.3747 | ambiguous | 0.3946 | ambiguous | -1.188 | Destabilizing | 0.944 | D | 0.621 | neutral | None | None | None | None | I |
| P/G | 0.315 | likely_benign | 0.3068 | benign | -1.415 | Destabilizing | 0.329 | N | 0.439 | neutral | None | None | None | None | I |
| P/H | 0.2783 | likely_benign | 0.2838 | benign | -0.872 | Destabilizing | 0.981 | D | 0.585 | neutral | None | None | None | None | I |
| P/I | 0.1728 | likely_benign | 0.2167 | benign | -0.761 | Destabilizing | 0.329 | N | 0.429 | neutral | None | None | None | None | I |
| P/K | 0.5077 | ambiguous | 0.5487 | ambiguous | -0.879 | Destabilizing | 0.495 | N | 0.405 | neutral | None | None | None | None | I |
| P/L | 0.1114 | likely_benign | 0.1301 | benign | -0.761 | Destabilizing | 0.476 | N | 0.432 | neutral | N | 0.487583254 | None | None | I |
| P/M | 0.2016 | likely_benign | 0.2316 | benign | -0.526 | Destabilizing | 0.944 | D | 0.587 | neutral | None | None | None | None | I |
| P/N | 0.3491 | ambiguous | 0.368 | ambiguous | -0.574 | Destabilizing | 0.704 | D | 0.545 | neutral | None | None | None | None | I |
| P/Q | 0.2404 | likely_benign | 0.252 | benign | -0.868 | Destabilizing | 0.902 | D | 0.564 | neutral | N | 0.504752911 | None | None | I |
| P/R | 0.3775 | ambiguous | 0.4126 | ambiguous | -0.273 | Destabilizing | 0.902 | D | 0.589 | neutral | N | 0.492725042 | None | None | I |
| P/S | 0.1364 | likely_benign | 0.1339 | benign | -1.04 | Destabilizing | 0.029 | N | 0.264 | neutral | N | 0.503298706 | None | None | I |
| P/T | 0.0912 | likely_benign | 0.1044 | benign | -1.023 | Destabilizing | 0.01 | N | 0.263 | neutral | N | 0.470265921 | None | None | I |
| P/V | 0.1127 | likely_benign | 0.1388 | benign | -0.873 | Destabilizing | 0.001 | N | 0.381 | neutral | None | None | None | None | I |
| P/W | 0.6266 | likely_pathogenic | 0.6465 | pathogenic | -1.228 | Destabilizing | 0.995 | D | 0.616 | neutral | None | None | None | None | I |
| P/Y | 0.3969 | ambiguous | 0.401 | ambiguous | -0.966 | Destabilizing | 0.981 | D | 0.617 | 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.