Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15401 | 46426;46427;46428 | chr2:178620320;178620319;178620318 | chr2:179485047;179485046;179485045 |
| N2AB | 13760 | 41503;41504;41505 | chr2:178620320;178620319;178620318 | chr2:179485047;179485046;179485045 |
| N2A | 12833 | 38722;38723;38724 | chr2:178620320;178620319;178620318 | chr2:179485047;179485046;179485045 |
| N2B | 6336 | 19231;19232;19233 | chr2:178620320;178620319;178620318 | chr2:179485047;179485046;179485045 |
| Novex-1 | 6461 | 19606;19607;19608 | chr2:178620320;178620319;178620318 | chr2:179485047;179485046;179485045 |
| Novex-2 | 6528 | 19807;19808;19809 | chr2:178620320;178620319;178620318 | chr2:179485047;179485046;179485045 |
| 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 | None | None | 1.0 | D | 0.67 | 0.482 | 0.512707719942 | gnomAD-4.0.0 | 1.6578E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.92057E-05 | 0 | 0 | 0 | 0 |
| T/R | rs2058077890  |
None | 1.0 | N | 0.657 | 0.421 | 0.553063759574 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.06782E-04 | 0 |
| T/R | rs2058077890 |
None | 1.0 | N | 0.657 | 0.421 | 0.553063759574 | gnomAD-4.0.0 | 2.64855E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.4481E-05 | None | 0 | 0 | 0 | 1.43098E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.2632 | likely_benign | 0.2577 | benign | -0.291 | Destabilizing | 0.999 | D | 0.486 | neutral | D | 0.600166652 | None | None | N |
| T/C | 0.8152 | likely_pathogenic | 0.812 | pathogenic | -0.43 | Destabilizing | 1.0 | D | 0.58 | neutral | None | None | None | None | N |
| T/D | 0.7947 | likely_pathogenic | 0.8258 | pathogenic | 0.381 | Stabilizing | 1.0 | D | 0.687 | prob.neutral | None | None | None | None | N |
| T/E | 0.6222 | likely_pathogenic | 0.6167 | pathogenic | 0.33 | Stabilizing | 1.0 | D | 0.693 | prob.neutral | None | None | None | None | N |
| T/F | 0.6382 | likely_pathogenic | 0.6541 | pathogenic | -0.804 | Destabilizing | 1.0 | D | 0.629 | neutral | None | None | None | None | N |
| T/G | 0.7032 | likely_pathogenic | 0.7366 | pathogenic | -0.42 | Destabilizing | 1.0 | D | 0.636 | neutral | None | None | None | None | N |
| T/H | 0.5505 | ambiguous | 0.5449 | ambiguous | -0.548 | Destabilizing | 1.0 | D | 0.573 | neutral | None | None | None | None | N |
| T/I | 0.3997 | ambiguous | 0.43 | ambiguous | -0.069 | Destabilizing | 1.0 | D | 0.67 | neutral | D | 0.548782119 | None | None | N |
| T/K | 0.4275 | ambiguous | 0.4344 | ambiguous | -0.233 | Destabilizing | 1.0 | D | 0.694 | prob.neutral | N | 0.507816148 | None | None | N |
| T/L | 0.2807 | likely_benign | 0.298 | benign | -0.069 | Destabilizing | 0.999 | D | 0.639 | neutral | None | None | None | None | N |
| T/M | 0.1591 | likely_benign | 0.1511 | benign | -0.227 | Destabilizing | 1.0 | D | 0.597 | neutral | None | None | None | None | N |
| T/N | 0.3491 | ambiguous | 0.3624 | ambiguous | -0.187 | Destabilizing | 1.0 | D | 0.671 | neutral | None | None | None | None | N |
| T/P | 0.6672 | likely_pathogenic | 0.7165 | pathogenic | -0.115 | Destabilizing | 1.0 | D | 0.655 | neutral | D | 0.592189747 | None | None | N |
| T/Q | 0.4919 | ambiguous | 0.4864 | ambiguous | -0.306 | Destabilizing | 1.0 | D | 0.659 | neutral | None | None | None | None | N |
| T/R | 0.3897 | ambiguous | 0.3946 | ambiguous | 0.012 | Stabilizing | 1.0 | D | 0.657 | neutral | N | 0.506032827 | None | None | N |
| T/S | 0.3527 | ambiguous | 0.3601 | ambiguous | -0.397 | Destabilizing | 0.999 | D | 0.503 | neutral | D | 0.545161623 | None | None | N |
| T/V | 0.2679 | likely_benign | 0.2851 | benign | -0.115 | Destabilizing | 0.999 | D | 0.576 | neutral | None | None | None | None | N |
| T/W | 0.853 | likely_pathogenic | 0.875 | pathogenic | -0.869 | Destabilizing | 1.0 | D | 0.607 | neutral | None | None | None | None | N |
| T/Y | 0.6069 | likely_pathogenic | 0.6224 | pathogenic | -0.543 | Destabilizing | 1.0 | D | 0.608 | 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.