Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24101 | 72526;72527;72528 | chr2:178573831;178573830;178573829 | chr2:179438558;179438557;179438556 |
| N2AB | 22460 | 67603;67604;67605 | chr2:178573831;178573830;178573829 | chr2:179438558;179438557;179438556 |
| N2A | 21533 | 64822;64823;64824 | chr2:178573831;178573830;178573829 | chr2:179438558;179438557;179438556 |
| N2B | 15036 | 45331;45332;45333 | chr2:178573831;178573830;178573829 | chr2:179438558;179438557;179438556 |
| Novex-1 | 15161 | 45706;45707;45708 | chr2:178573831;178573830;178573829 | chr2:179438558;179438557;179438556 |
| Novex-2 | 15228 | 45907;45908;45909 | chr2:178573831;178573830;178573829 | chr2:179438558;179438557;179438556 |
| 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/I | rs192962624  |
0.032 | 0.002 | N | 0.485 | 0.045 | 0.151104730317 | gnomAD-2.1.1 | 2.82E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 2.29373E-04 | None | 0 | 0 | 0 |
| T/I | rs192962624 |
0.032 | 0.002 | N | 0.485 | 0.045 | 0.151104730317 | gnomAD-4.0.0 | 1.23266E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 1.73671E-04 | 9.00148E-07 | 1.85766E-04 | 0 |
| T/N | None | -0.688 | 0.002 | N | 0.477 | 0.156 | None | gnomAD-2.1.1 | 3.64752E-04 | None | None | None | None | N | None | 0 | 2.84E-05 | None | 0 | 4.37783E-03 | None | 4.91513E-04 | None | 0 | 0 | 1.41163E-04 |
| T/N | None | -0.688 | 0.002 | N | 0.477 | 0.156 | None | gnomAD-3.1.2 | 1.84135E-04 | None | None | None | None | N | None | 2.41E-05 | 6.56E-05 | 0 | 0 | 3.67932E-03 | None | 0 | 0 | 0 | 1.45048E-03 | 0 |
| T/N | None | -0.688 | 0.002 | N | 0.477 | 0.156 | None | 1000 genomes | 3.99361E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 2E-03 | 0 | None | None | None | 0 | None |
| T/N | None | -0.688 | 0.002 | N | 0.477 | 0.156 | None | gnomAD-4.0.0 | 1.383E-04 | None | None | None | None | N | None | 2.66731E-05 | 3.33734E-05 | None | 0 | 3.0173E-03 | None | 0 | 0 | 0 | 6.15709E-04 | 4.48545E-04 |
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 | 0.0929 | likely_benign | 0.1038 | benign | -1.344 | Destabilizing | 0.055 | N | 0.607 | neutral | N | 0.514624846 | None | None | N |
| T/C | 0.2447 | likely_benign | 0.3105 | benign | -0.937 | Destabilizing | 0.909 | D | 0.663 | neutral | None | None | None | None | N |
| T/D | 0.5278 | ambiguous | 0.6192 | pathogenic | -1.115 | Destabilizing | 0.396 | N | 0.649 | neutral | None | None | None | None | N |
| T/E | 0.2837 | likely_benign | 0.3315 | benign | -0.907 | Destabilizing | 0.567 | D | 0.649 | neutral | None | None | None | None | N |
| T/F | 0.1342 | likely_benign | 0.18 | benign | -1.085 | Destabilizing | 0.567 | D | 0.712 | prob.delet. | None | None | None | None | N |
| T/G | 0.3123 | likely_benign | 0.3901 | ambiguous | -1.76 | Destabilizing | 0.157 | N | 0.652 | neutral | None | None | None | None | N |
| T/H | 0.2149 | likely_benign | 0.2529 | benign | -1.746 | Destabilizing | 0.909 | D | 0.711 | prob.delet. | None | None | None | None | N |
| T/I | 0.0604 | likely_benign | 0.0752 | benign | -0.247 | Destabilizing | 0.002 | N | 0.485 | neutral | N | 0.482224426 | None | None | N |
| T/K | 0.2441 | likely_benign | 0.2824 | benign | -0.36 | Destabilizing | 0.567 | D | 0.647 | neutral | None | None | None | None | N |
| T/L | 0.0602 | likely_benign | 0.0749 | benign | -0.247 | Destabilizing | 0.026 | N | 0.614 | neutral | None | None | None | None | N |
| T/M | 0.0656 | likely_benign | 0.0773 | benign | -0.25 | Destabilizing | 0.567 | D | 0.682 | prob.neutral | None | None | None | None | N |
| T/N | 0.1443 | likely_benign | 0.1868 | benign | -1.043 | Destabilizing | 0.002 | N | 0.477 | neutral | N | 0.4827405 | None | None | N |
| T/P | 0.7235 | likely_pathogenic | 0.7146 | pathogenic | -0.583 | Destabilizing | 0.859 | D | 0.683 | prob.neutral | N | 0.51245455 | None | None | N |
| T/Q | 0.215 | likely_benign | 0.2502 | benign | -0.841 | Destabilizing | 0.726 | D | 0.687 | prob.neutral | None | None | None | None | N |
| T/R | 0.1858 | likely_benign | 0.2099 | benign | -0.57 | Destabilizing | 0.567 | D | 0.681 | prob.neutral | None | None | None | None | N |
| T/S | 0.1127 | likely_benign | 0.1356 | benign | -1.397 | Destabilizing | 0.124 | N | 0.619 | neutral | N | 0.497423165 | None | None | N |
| T/V | 0.0605 | likely_benign | 0.0741 | benign | -0.583 | Destabilizing | 0.001 | N | 0.499 | neutral | None | None | None | None | N |
| T/W | 0.4868 | ambiguous | 0.5645 | pathogenic | -1.105 | Destabilizing | 0.968 | D | 0.723 | prob.delet. | None | None | None | None | N |
| T/Y | 0.1823 | likely_benign | 0.2276 | benign | -0.751 | Destabilizing | 0.726 | D | 0.718 | prob.delet. | 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.