Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24908 | 74947;74948;74949 | chr2:178571410;178571409;178571408 | chr2:179436137;179436136;179436135 |
| N2AB | 23267 | 70024;70025;70026 | chr2:178571410;178571409;178571408 | chr2:179436137;179436136;179436135 |
| N2A | 22340 | 67243;67244;67245 | chr2:178571410;178571409;178571408 | chr2:179436137;179436136;179436135 |
| N2B | 15843 | 47752;47753;47754 | chr2:178571410;178571409;178571408 | chr2:179436137;179436136;179436135 |
| Novex-1 | 15968 | 48127;48128;48129 | chr2:178571410;178571409;178571408 | chr2:179436137;179436136;179436135 |
| Novex-2 | 16035 | 48328;48329;48330 | chr2:178571410;178571409;178571408 | chr2:179436137;179436136;179436135 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | rs1185511652  |
None | 0.469 | N | 0.345 | 0.132 | 0.327952845175 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| V/A | rs1185511652 |
None | 0.469 | N | 0.345 | 0.132 | 0.327952845175 | gnomAD-4.0.0 | 3.84537E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 7.18284E-06 | 0 | 0 |
| V/I | rs1463655441 |
None | 0.028 | N | 0.171 | 0.066 | 0.212008924253 | 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 |
| V/I | rs1463655441 |
None | 0.028 | N | 0.171 | 0.066 | 0.212008924253 | gnomAD-4.0.0 | 6.57609E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.47102E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.1492 | likely_benign | 0.1358 | benign | -0.51 | Destabilizing | 0.469 | N | 0.345 | neutral | N | 0.490001334 | None | None | I |
| V/C | 0.6676 | likely_pathogenic | 0.6257 | pathogenic | -0.656 | Destabilizing | 0.996 | D | 0.512 | neutral | None | None | None | None | I |
| V/D | 0.4708 | ambiguous | 0.4311 | ambiguous | -0.019 | Destabilizing | 0.938 | D | 0.726 | deleterious | N | 0.490016017 | None | None | I |
| V/E | 0.2332 | likely_benign | 0.2115 | benign | -0.131 | Destabilizing | 0.909 | D | 0.643 | neutral | None | None | None | None | I |
| V/F | 0.255 | likely_benign | 0.2283 | benign | -0.784 | Destabilizing | 0.883 | D | 0.545 | neutral | N | 0.467138823 | None | None | I |
| V/G | 0.2764 | likely_benign | 0.256 | benign | -0.632 | Destabilizing | 0.883 | D | 0.637 | neutral | N | 0.490016017 | None | None | I |
| V/H | 0.624 | likely_pathogenic | 0.5536 | ambiguous | -0.229 | Destabilizing | 0.996 | D | 0.754 | deleterious | None | None | None | None | I |
| V/I | 0.0761 | likely_benign | 0.0748 | benign | -0.342 | Destabilizing | 0.028 | N | 0.171 | neutral | N | 0.475381386 | None | None | I |
| V/K | 0.3456 | ambiguous | 0.309 | benign | -0.218 | Destabilizing | 0.909 | D | 0.637 | neutral | None | None | None | None | I |
| V/L | 0.1573 | likely_benign | 0.1284 | benign | -0.342 | Destabilizing | 0.007 | N | 0.166 | neutral | N | 0.487059817 | None | None | I |
| V/M | 0.1428 | likely_benign | 0.1266 | benign | -0.296 | Destabilizing | 0.909 | D | 0.405 | neutral | None | None | None | None | I |
| V/N | 0.3213 | likely_benign | 0.2878 | benign | -0.007 | Destabilizing | 0.953 | D | 0.698 | prob.delet. | None | None | None | None | I |
| V/P | 0.2072 | likely_benign | 0.1814 | benign | -0.363 | Destabilizing | 0.02 | N | 0.405 | neutral | None | None | None | None | I |
| V/Q | 0.2825 | likely_benign | 0.2531 | benign | -0.273 | Destabilizing | 0.953 | D | 0.689 | prob.delet. | None | None | None | None | I |
| V/R | 0.3619 | ambiguous | 0.3283 | benign | 0.232 | Stabilizing | 0.953 | D | 0.697 | prob.delet. | None | None | None | None | I |
| V/S | 0.2271 | likely_benign | 0.2024 | benign | -0.432 | Destabilizing | 0.909 | D | 0.532 | neutral | None | None | None | None | I |
| V/T | 0.1708 | likely_benign | 0.1538 | benign | -0.444 | Destabilizing | 0.74 | D | 0.481 | neutral | None | None | None | None | I |
| V/W | 0.8513 | likely_pathogenic | 0.8223 | pathogenic | -0.823 | Destabilizing | 0.996 | D | 0.743 | deleterious | None | None | None | None | I |
| V/Y | 0.5594 | ambiguous | 0.4992 | ambiguous | -0.495 | Destabilizing | 0.953 | D | 0.451 | 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.