Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28509 | 85750;85751;85752 | chr2:178560607;178560606;178560605 | chr2:179425334;179425333;179425332 |
| N2AB | 26868 | 80827;80828;80829 | chr2:178560607;178560606;178560605 | chr2:179425334;179425333;179425332 |
| N2A | 25941 | 78046;78047;78048 | chr2:178560607;178560606;178560605 | chr2:179425334;179425333;179425332 |
| N2B | 19444 | 58555;58556;58557 | chr2:178560607;178560606;178560605 | chr2:179425334;179425333;179425332 |
| Novex-1 | 19569 | 58930;58931;58932 | chr2:178560607;178560606;178560605 | chr2:179425334;179425333;179425332 |
| Novex-2 | 19636 | 59131;59132;59133 | chr2:178560607;178560606;178560605 | chr2:179425334;179425333;179425332 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/F | rs1575614269  |
None | None | N | 0.464 | 0.202 | 0.482574385019 | gnomAD-4.0.0 | 1.59209E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.78133E-05 | None | 0 | 0 | 0 | 0 | 0 |
| S/T | rs1329788185 |
-0.159 | 0.001 | N | 0.254 | 0.119 | 0.168933306366 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.94E-06 | 0 |
| S/T | rs1329788185 |
-0.159 | 0.001 | N | 0.254 | 0.119 | 0.168933306366 | gnomAD-4.0.0 | 1.36869E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79899E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.0947 | likely_benign | 0.0902 | benign | -0.712 | Destabilizing | 0.052 | N | 0.457 | neutral | N | 0.479614899 | None | None | N |
| S/C | 0.105 | likely_benign | 0.1127 | benign | -0.401 | Destabilizing | 0.915 | D | 0.51 | neutral | N | 0.478769206 | None | None | N |
| S/D | 0.4254 | ambiguous | 0.4039 | ambiguous | 0.152 | Stabilizing | 0.262 | N | 0.415 | neutral | None | None | None | None | N |
| S/E | 0.5015 | ambiguous | 0.4756 | ambiguous | 0.15 | Stabilizing | 0.262 | N | 0.397 | neutral | None | None | None | None | N |
| S/F | 0.1333 | likely_benign | 0.1538 | benign | -0.972 | Destabilizing | None | N | 0.464 | neutral | N | 0.492403236 | None | None | N |
| S/G | 0.1084 | likely_benign | 0.1047 | benign | -0.95 | Destabilizing | 0.262 | N | 0.442 | neutral | None | None | None | None | N |
| S/H | 0.2315 | likely_benign | 0.2382 | benign | -1.315 | Destabilizing | 0.824 | D | 0.523 | neutral | None | None | None | None | N |
| S/I | 0.1735 | likely_benign | 0.169 | benign | -0.188 | Destabilizing | 0.081 | N | 0.574 | neutral | None | None | None | None | N |
| S/K | 0.552 | ambiguous | 0.5369 | ambiguous | -0.512 | Destabilizing | 0.149 | N | 0.409 | neutral | None | None | None | None | N |
| S/L | 0.1228 | likely_benign | 0.1288 | benign | -0.188 | Destabilizing | 0.081 | N | 0.52 | neutral | None | None | None | None | N |
| S/M | 0.1968 | likely_benign | 0.2058 | benign | -0.062 | Destabilizing | 0.555 | D | 0.526 | neutral | None | None | None | None | N |
| S/N | 0.1416 | likely_benign | 0.1411 | benign | -0.46 | Destabilizing | 0.262 | N | 0.438 | neutral | None | None | None | None | N |
| S/P | 0.8337 | likely_pathogenic | 0.8312 | pathogenic | -0.329 | Destabilizing | 0.741 | D | 0.527 | neutral | N | 0.480882347 | None | None | N |
| S/Q | 0.4033 | ambiguous | 0.3856 | ambiguous | -0.544 | Destabilizing | 0.791 | D | 0.474 | neutral | None | None | None | None | N |
| S/R | 0.437 | ambiguous | 0.4103 | ambiguous | -0.421 | Destabilizing | 0.555 | D | 0.53 | neutral | None | None | None | None | N |
| S/T | 0.0792 | likely_benign | 0.0806 | benign | -0.505 | Destabilizing | 0.001 | N | 0.254 | neutral | N | 0.446389417 | None | None | N |
| S/V | 0.1728 | likely_benign | 0.1685 | benign | -0.329 | Destabilizing | 0.081 | N | 0.523 | neutral | None | None | None | None | N |
| S/W | 0.2598 | likely_benign | 0.2826 | benign | -0.97 | Destabilizing | 0.824 | D | 0.619 | neutral | None | None | None | None | N |
| S/Y | 0.1323 | likely_benign | 0.1511 | benign | -0.685 | Destabilizing | 0.188 | N | 0.573 | neutral | N | 0.501050517 | 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.