Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30391 | 91396;91397;91398 | chr2:178551729;178551728;178551727 | chr2:179416456;179416455;179416454 |
| N2AB | 28750 | 86473;86474;86475 | chr2:178551729;178551728;178551727 | chr2:179416456;179416455;179416454 |
| N2A | 27823 | 83692;83693;83694 | chr2:178551729;178551728;178551727 | chr2:179416456;179416455;179416454 |
| N2B | 21326 | 64201;64202;64203 | chr2:178551729;178551728;178551727 | chr2:179416456;179416455;179416454 |
| Novex-1 | 21451 | 64576;64577;64578 | chr2:178551729;178551728;178551727 | chr2:179416456;179416455;179416454 |
| Novex-2 | 21518 | 64777;64778;64779 | chr2:178551729;178551728;178551727 | chr2:179416456;179416455;179416454 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| E/D | rs199505541  |
-0.454 | 0.999 | N | 0.583 | 0.37 | 0.396494342077 | gnomAD-2.1.1 | 3.4656E-04 | None | None | None | None | N | None | 4.13E-05 | 8.49E-05 | None | 7.64615E-03 | 0 | None | 0 | None | 0 | 9.39E-05 | 2.81373E-04 |
| E/D | rs199505541 |
-0.454 | 0.999 | N | 0.583 | 0.37 | 0.396494342077 | gnomAD-3.1.2 | 2.29933E-04 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 8.07848E-03 | 0 | None | 0 | 0 | 5.88E-05 | 0 | 9.5511E-04 |
| E/D | rs199505541 |
-0.454 | 0.999 | N | 0.583 | 0.37 | 0.396494342077 | gnomAD-4.0.0 | 2.13793E-04 | None | None | None | None | N | None | 2.66966E-05 | 5.00017E-05 | None | 8.51581E-03 | 0 | None | 0 | 0 | 4.32283E-05 | 0 | 5.92417E-04 |
| E/Q | rs758395481 |
-0.043 | 1.0 | N | 0.682 | 0.33 | 0.42989457901 | gnomAD-2.1.1 | 8.05E-06 | None | None | None | None | N | None | 6.46E-05 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| E/Q | rs758395481 |
-0.043 | 1.0 | N | 0.682 | 0.33 | 0.42989457901 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| E/Q | rs758395481 |
-0.043 | 1.0 | N | 0.682 | 0.33 | 0.42989457901 | gnomAD-4.0.0 | 1.85907E-06 | None | None | None | None | N | None | 1.33451E-05 | 1.66678E-05 | None | 0 | 0 | None | 0 | 0 | 8.47617E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| E/A | 0.4516 | ambiguous | 0.3678 | ambiguous | -0.634 | Destabilizing | 0.999 | D | 0.655 | neutral | N | 0.510206035 | None | None | N |
| E/C | 0.9764 | likely_pathogenic | 0.9772 | pathogenic | -0.035 | Destabilizing | 1.0 | D | 0.653 | neutral | None | None | None | None | N |
| E/D | 0.5187 | ambiguous | 0.5629 | ambiguous | -0.477 | Destabilizing | 0.999 | D | 0.583 | neutral | N | 0.486803695 | None | None | N |
| E/F | 0.9888 | likely_pathogenic | 0.9904 | pathogenic | -0.528 | Destabilizing | 1.0 | D | 0.617 | neutral | None | None | None | None | N |
| E/G | 0.6899 | likely_pathogenic | 0.7001 | pathogenic | -0.851 | Destabilizing | 1.0 | D | 0.612 | neutral | N | 0.497096816 | None | None | N |
| E/H | 0.9448 | likely_pathogenic | 0.9452 | pathogenic | -0.482 | Destabilizing | 1.0 | D | 0.633 | neutral | None | None | None | None | N |
| E/I | 0.8973 | likely_pathogenic | 0.9146 | pathogenic | -0.088 | Destabilizing | 1.0 | D | 0.63 | neutral | None | None | None | None | N |
| E/K | 0.7296 | likely_pathogenic | 0.7038 | pathogenic | 0.247 | Stabilizing | 0.999 | D | 0.705 | prob.neutral | N | 0.480687628 | None | None | N |
| E/L | 0.9233 | likely_pathogenic | 0.9315 | pathogenic | -0.088 | Destabilizing | 1.0 | D | 0.626 | neutral | None | None | None | None | N |
| E/M | 0.9146 | likely_pathogenic | 0.9236 | pathogenic | 0.201 | Stabilizing | 1.0 | D | 0.593 | neutral | None | None | None | None | N |
| E/N | 0.8278 | likely_pathogenic | 0.8433 | pathogenic | -0.12 | Destabilizing | 1.0 | D | 0.692 | prob.neutral | None | None | None | None | N |
| E/P | 0.7542 | likely_pathogenic | 0.7557 | pathogenic | -0.25 | Destabilizing | 1.0 | D | 0.614 | neutral | None | None | None | None | N |
| E/Q | 0.4724 | ambiguous | 0.4508 | ambiguous | -0.09 | Destabilizing | 1.0 | D | 0.682 | prob.neutral | N | 0.468926476 | None | None | N |
| E/R | 0.8181 | likely_pathogenic | 0.8033 | pathogenic | 0.368 | Stabilizing | 1.0 | D | 0.683 | prob.neutral | None | None | None | None | N |
| E/S | 0.6522 | likely_pathogenic | 0.6707 | pathogenic | -0.285 | Destabilizing | 0.999 | D | 0.701 | prob.neutral | None | None | None | None | N |
| E/T | 0.7697 | likely_pathogenic | 0.7881 | pathogenic | -0.104 | Destabilizing | 1.0 | D | 0.645 | neutral | None | None | None | None | N |
| E/V | 0.748 | likely_pathogenic | 0.7821 | pathogenic | -0.25 | Destabilizing | 1.0 | D | 0.617 | neutral | N | 0.494209981 | None | None | N |
| E/W | 0.9968 | likely_pathogenic | 0.9971 | pathogenic | -0.34 | Destabilizing | 1.0 | D | 0.655 | neutral | None | None | None | None | N |
| E/Y | 0.9789 | likely_pathogenic | 0.981 | pathogenic | -0.275 | Destabilizing | 1.0 | D | 0.603 | 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.