Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14474 | 43645;43646;43647 | chr2:178632586;178632585;178632584 | chr2:179497313;179497312;179497311 |
| N2AB | 12833 | 38722;38723;38724 | chr2:178632586;178632585;178632584 | chr2:179497313;179497312;179497311 |
| N2A | 11906 | 35941;35942;35943 | chr2:178632586;178632585;178632584 | chr2:179497313;179497312;179497311 |
| N2B | 5409 | 16450;16451;16452 | chr2:178632586;178632585;178632584 | chr2:179497313;179497312;179497311 |
| Novex-1 | 5534 | 16825;16826;16827 | chr2:178632586;178632585;178632584 | chr2:179497313;179497312;179497311 |
| Novex-2 | 5601 | 17026;17027;17028 | chr2:178632586;178632585;178632584 | chr2:179497313;179497312;179497311 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| E/D | rs998106657  |
-0.504 | 0.999 | D | 0.499 | 0.311 | 0.308904156042 | gnomAD-2.1.1 | 8.06E-06 | None | None | None | None | N | None | 1.29282E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| E/D | rs998106657 |
-0.504 | 0.999 | D | 0.499 | 0.311 | 0.308904156042 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 7.24E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| E/D | rs998106657 |
-0.504 | 0.999 | D | 0.499 | 0.311 | 0.308904156042 | gnomAD-4.0.0 | 6.84393E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99638E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| E/A | 0.4298 | ambiguous | 0.3549 | ambiguous | -0.806 | Destabilizing | 0.999 | D | 0.699 | prob.neutral | N | 0.504313917 | None | None | N |
| E/C | 0.9911 | likely_pathogenic | 0.9849 | pathogenic | -0.405 | Destabilizing | 1.0 | D | 0.753 | deleterious | None | None | None | None | N |
| E/D | 0.778 | likely_pathogenic | 0.7061 | pathogenic | -0.934 | Destabilizing | 0.999 | D | 0.499 | neutral | D | 0.547745572 | None | None | N |
| E/F | 0.9922 | likely_pathogenic | 0.9868 | pathogenic | -0.147 | Destabilizing | 1.0 | D | 0.735 | prob.delet. | None | None | None | None | N |
| E/G | 0.5633 | ambiguous | 0.4609 | ambiguous | -1.158 | Destabilizing | 1.0 | D | 0.711 | prob.delet. | D | 0.556364691 | None | None | N |
| E/H | 0.9646 | likely_pathogenic | 0.9418 | pathogenic | -0.213 | Destabilizing | 1.0 | D | 0.637 | neutral | None | None | None | None | N |
| E/I | 0.9277 | likely_pathogenic | 0.9023 | pathogenic | 0.153 | Stabilizing | 1.0 | D | 0.755 | deleterious | None | None | None | None | N |
| E/K | 0.5773 | likely_pathogenic | 0.4911 | ambiguous | -0.334 | Destabilizing | 0.999 | D | 0.607 | neutral | D | 0.587242697 | None | None | N |
| E/L | 0.9553 | likely_pathogenic | 0.9306 | pathogenic | 0.153 | Stabilizing | 1.0 | D | 0.762 | deleterious | None | None | None | None | N |
| E/M | 0.9142 | likely_pathogenic | 0.8705 | pathogenic | 0.475 | Stabilizing | 1.0 | D | 0.728 | prob.delet. | None | None | None | None | N |
| E/N | 0.8681 | likely_pathogenic | 0.8164 | pathogenic | -0.947 | Destabilizing | 1.0 | D | 0.709 | prob.delet. | None | None | None | None | N |
| E/P | 0.9935 | likely_pathogenic | 0.9904 | pathogenic | -0.145 | Destabilizing | 1.0 | D | 0.777 | deleterious | None | None | None | None | N |
| E/Q | 0.5029 | ambiguous | 0.4099 | ambiguous | -0.811 | Destabilizing | 1.0 | D | 0.637 | neutral | N | 0.515496372 | None | None | N |
| E/R | 0.7833 | likely_pathogenic | 0.7137 | pathogenic | 0.018 | Stabilizing | 1.0 | D | 0.701 | prob.neutral | None | None | None | None | N |
| E/S | 0.6289 | likely_pathogenic | 0.5447 | ambiguous | -1.201 | Destabilizing | 0.999 | D | 0.647 | neutral | None | None | None | None | N |
| E/T | 0.7287 | likely_pathogenic | 0.6523 | pathogenic | -0.901 | Destabilizing | 1.0 | D | 0.772 | deleterious | None | None | None | None | N |
| E/V | 0.8038 | likely_pathogenic | 0.7476 | pathogenic | -0.145 | Destabilizing | 1.0 | D | 0.761 | deleterious | D | 0.540731517 | None | None | N |
| E/W | 0.9985 | likely_pathogenic | 0.9973 | pathogenic | 0.167 | Stabilizing | 1.0 | D | 0.753 | deleterious | None | None | None | None | N |
| E/Y | 0.9861 | likely_pathogenic | 0.9775 | pathogenic | 0.133 | Stabilizing | 1.0 | D | 0.729 | 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.