Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1466 | 4621;4622;4623 | chr2:178777788;178777787;178777786 | chr2:179642515;179642514;179642513 |
| N2AB | 1466 | 4621;4622;4623 | chr2:178777788;178777787;178777786 | chr2:179642515;179642514;179642513 |
| N2A | 1466 | 4621;4622;4623 | chr2:178777788;178777787;178777786 | chr2:179642515;179642514;179642513 |
| N2B | 1420 | 4483;4484;4485 | chr2:178777788;178777787;178777786 | chr2:179642515;179642514;179642513 |
| Novex-1 | 1420 | 4483;4484;4485 | chr2:178777788;178777787;178777786 | chr2:179642515;179642514;179642513 |
| Novex-2 | 1420 | 4483;4484;4485 | chr2:178777788;178777787;178777786 | chr2:179642515;179642514;179642513 |
| Novex-3 | 1466 | 4621;4622;4623 | chr2:178777788;178777787;178777786 | chr2:179642515;179642514;179642513 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/L | rs151310601  |
-1.027 | 0.005 | N | 0.137 | 0.221 | 0.301122078929 | gnomAD-2.1.1 | 6.8711E-04 | None | None | None | None | I | None | 4.80731E-04 | 2.8247E-04 | None | 4.82812E-04 | 0 | None | 6.53E-05 | None | 3.98E-05 | 1.24245E-03 | 5.55401E-04 |
| F/L | rs151310601 |
-1.027 | 0.005 | N | 0.137 | 0.221 | 0.301122078929 | gnomAD-3.1.2 | 8.67325E-04 | None | None | None | None | I | None | 5.06634E-04 | 3.27097E-04 | 0 | 5.77034E-04 | 0 | None | 0 | 0 | 1.49921E-03 | 2.07211E-04 | 4.78011E-04 |
| F/L | rs151310601 |
-1.027 | 0.005 | N | 0.137 | 0.221 | 0.301122078929 | 1000 genomes | 3.99361E-04 | None | None | None | None | I | None | 0 | 0 | None | None | 0 | 1E-03 | None | None | None | 1E-03 | None |
| F/L | rs151310601 |
-1.027 | 0.005 | N | 0.137 | 0.221 | 0.301122078929 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/A | 0.614 | likely_pathogenic | 0.5974 | pathogenic | -1.868 | Destabilizing | 0.525 | D | 0.385 | neutral | None | None | None | None | I |
| F/C | 0.3117 | likely_benign | 0.2979 | benign | -0.968 | Destabilizing | 0.997 | D | 0.509 | neutral | N | 0.476401897 | None | None | I |
| F/D | 0.94 | likely_pathogenic | 0.9306 | pathogenic | 0.021 | Stabilizing | 0.991 | D | 0.578 | neutral | None | None | None | None | I |
| F/E | 0.8961 | likely_pathogenic | 0.8883 | pathogenic | 0.124 | Stabilizing | 0.974 | D | 0.585 | neutral | None | None | None | None | I |
| F/G | 0.8404 | likely_pathogenic | 0.8249 | pathogenic | -2.203 | Highly Destabilizing | 0.915 | D | 0.563 | neutral | None | None | None | None | I |
| F/H | 0.6935 | likely_pathogenic | 0.6845 | pathogenic | -0.44 | Destabilizing | 0.998 | D | 0.494 | neutral | None | None | None | None | I |
| F/I | 0.2358 | likely_benign | 0.239 | benign | -0.874 | Destabilizing | 0.022 | N | 0.123 | neutral | N | 0.437537006 | None | None | I |
| F/K | 0.8533 | likely_pathogenic | 0.8516 | pathogenic | -0.873 | Destabilizing | 0.974 | D | 0.585 | neutral | None | None | None | None | I |
| F/L | 0.7825 | likely_pathogenic | 0.7743 | pathogenic | -0.874 | Destabilizing | 0.005 | N | 0.137 | neutral | N | 0.363299689 | None | None | I |
| F/M | 0.4376 | ambiguous | 0.4364 | ambiguous | -0.715 | Destabilizing | 0.949 | D | 0.46 | neutral | None | None | None | None | I |
| F/N | 0.7957 | likely_pathogenic | 0.7785 | pathogenic | -0.923 | Destabilizing | 0.991 | D | 0.566 | neutral | None | None | None | None | I |
| F/P | 0.9966 | likely_pathogenic | 0.9957 | pathogenic | -1.197 | Destabilizing | 0.991 | D | 0.564 | neutral | None | None | None | None | I |
| F/Q | 0.733 | likely_pathogenic | 0.7275 | pathogenic | -0.91 | Destabilizing | 0.991 | D | 0.563 | neutral | None | None | None | None | I |
| F/R | 0.7599 | likely_pathogenic | 0.7491 | pathogenic | -0.372 | Destabilizing | 0.974 | D | 0.565 | neutral | None | None | None | None | I |
| F/S | 0.5721 | likely_pathogenic | 0.5471 | ambiguous | -1.815 | Destabilizing | 0.891 | D | 0.544 | neutral | N | 0.489593165 | None | None | I |
| F/T | 0.5532 | ambiguous | 0.5454 | ambiguous | -1.618 | Destabilizing | 0.842 | D | 0.507 | neutral | None | None | None | None | I |
| F/V | 0.2165 | likely_benign | 0.2185 | benign | -1.197 | Destabilizing | 0.005 | N | 0.207 | neutral | N | 0.392921931 | None | None | I |
| F/W | 0.741 | likely_pathogenic | 0.7252 | pathogenic | 0.036 | Stabilizing | 0.998 | D | 0.463 | neutral | None | None | None | None | I |
| F/Y | 0.2792 | likely_benign | 0.2644 | benign | -0.21 | Destabilizing | 0.961 | D | 0.398 | neutral | N | 0.478621272 | 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.