Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22111 | 66556;66557;66558 | chr2:178582038;178582037;178582036 | chr2:179446765;179446764;179446763 |
| N2AB | 20470 | 61633;61634;61635 | chr2:178582038;178582037;178582036 | chr2:179446765;179446764;179446763 |
| N2A | 19543 | 58852;58853;58854 | chr2:178582038;178582037;178582036 | chr2:179446765;179446764;179446763 |
| N2B | 13046 | 39361;39362;39363 | chr2:178582038;178582037;178582036 | chr2:179446765;179446764;179446763 |
| Novex-1 | 13171 | 39736;39737;39738 | chr2:178582038;178582037;178582036 | chr2:179446765;179446764;179446763 |
| Novex-2 | 13238 | 39937;39938;39939 | chr2:178582038;178582037;178582036 | chr2:179446765;179446764;179446763 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/K | rs374614550  |
-0.136 | 0.884 | N | 0.409 | 0.372 | 0.759901358487 | gnomAD-2.1.1 | 8.05E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.78E-05 | 0 |
| I/K | rs374614550 |
-0.136 | 0.884 | N | 0.409 | 0.372 | 0.759901358487 | gnomAD-4.0.0 | 1.095E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.43948E-05 | 0 | 0 |
| I/T | rs374614550 |
-0.517 | 0.684 | N | 0.42 | 0.232 | None | gnomAD-4.0.0 | 4.10624E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 2.52054E-05 | None | 0 | 0 | 4.49839E-06 | 0 | 0 |
| I/V | rs1453348748 |
-0.212 | 0.164 | N | 0.323 | 0.079 | 0.469660041277 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.9E-06 | 0 |
| I/V | rs1453348748 |
-0.212 | 0.164 | N | 0.323 | 0.079 | 0.469660041277 | gnomAD-4.0.0 | 1.59211E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86031E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.1799 | likely_benign | 0.1451 | benign | -1.132 | Destabilizing | 0.543 | D | 0.407 | neutral | None | None | None | None | I |
| I/C | 0.6812 | likely_pathogenic | 0.6299 | pathogenic | -0.823 | Destabilizing | 0.996 | D | 0.429 | neutral | None | None | None | None | I |
| I/D | 0.8181 | likely_pathogenic | 0.6906 | pathogenic | -0.427 | Destabilizing | 0.953 | D | 0.435 | neutral | None | None | None | None | I |
| I/E | 0.6844 | likely_pathogenic | 0.5242 | ambiguous | -0.425 | Destabilizing | 0.91 | D | 0.421 | neutral | None | None | None | None | I |
| I/F | 0.1992 | likely_benign | 0.1738 | benign | -0.672 | Destabilizing | 0.91 | D | 0.402 | neutral | None | None | None | None | I |
| I/G | 0.5192 | ambiguous | 0.4271 | ambiguous | -1.412 | Destabilizing | 0.91 | D | 0.405 | neutral | None | None | None | None | I |
| I/H | 0.5879 | likely_pathogenic | 0.464 | ambiguous | -0.421 | Destabilizing | 0.996 | D | 0.443 | neutral | None | None | None | None | I |
| I/K | 0.5284 | ambiguous | 0.3488 | ambiguous | -0.713 | Destabilizing | 0.884 | D | 0.409 | neutral | N | 0.435265559 | None | None | I |
| I/L | 0.0891 | likely_benign | 0.0818 | benign | -0.456 | Destabilizing | 0.063 | N | 0.239 | neutral | N | 0.428686304 | None | None | I |
| I/M | 0.0851 | likely_benign | 0.0799 | benign | -0.563 | Destabilizing | 0.078 | N | 0.24 | neutral | N | 0.492391066 | None | None | I |
| I/N | 0.35 | ambiguous | 0.2589 | benign | -0.659 | Destabilizing | 0.953 | D | 0.442 | neutral | None | None | None | None | I |
| I/P | 0.3853 | ambiguous | 0.3491 | ambiguous | -0.649 | Destabilizing | 0.009 | N | 0.355 | neutral | None | None | None | None | I |
| I/Q | 0.471 | ambiguous | 0.3419 | ambiguous | -0.78 | Destabilizing | 0.953 | D | 0.443 | neutral | None | None | None | None | I |
| I/R | 0.4282 | ambiguous | 0.2732 | benign | -0.163 | Destabilizing | 0.939 | D | 0.443 | neutral | N | 0.439730017 | None | None | I |
| I/S | 0.23 | likely_benign | 0.1799 | benign | -1.238 | Destabilizing | 0.742 | D | 0.415 | neutral | None | None | None | None | I |
| I/T | 0.1034 | likely_benign | 0.0865 | benign | -1.113 | Destabilizing | 0.684 | D | 0.42 | neutral | N | 0.425853855 | None | None | I |
| I/V | 0.0835 | likely_benign | 0.0749 | benign | -0.649 | Destabilizing | 0.164 | N | 0.323 | neutral | N | 0.459566571 | None | None | I |
| I/W | 0.7659 | likely_pathogenic | 0.7034 | pathogenic | -0.716 | Destabilizing | 0.996 | D | 0.531 | neutral | None | None | None | None | I |
| I/Y | 0.5796 | likely_pathogenic | 0.4911 | ambiguous | -0.487 | Destabilizing | 0.953 | D | 0.426 | 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.