Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 10115 | 30568;30569;30570 | chr2:178702544;178702543;178702542 | chr2:179567271;179567270;179567269 |
| N2AB | 9798 | 29617;29618;29619 | chr2:178702544;178702543;178702542 | chr2:179567271;179567270;179567269 |
| N2A | 8871 | 26836;26837;26838 | chr2:178702544;178702543;178702542 | chr2:179567271;179567270;179567269 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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/A | rs769099418  |
-0.55 | 0.201 | None | 0.314 | 0.127 | 0.201204373187 | gnomAD-2.1.1 | 1.78E-05 | None | None | None | None | N | None | 1.6533E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 7.78E-06 | 0 |
| T/A | rs769099418 |
-0.55 | 0.201 | None | 0.314 | 0.127 | 0.201204373187 | 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 |
| T/A | rs769099418 |
-0.55 | 0.201 | None | 0.314 | 0.127 | 0.201204373187 | gnomAD-4.0.0 | 1.42514E-05 | None | None | None | None | N | None | 5.3386E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 1.61033E-05 | 0 | 0 |
| T/K | rs747337002 |
-0.133 | 0.549 | None | 0.379 | 0.184 | 0.300110245524 | gnomAD-2.1.1 | 4.01E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.85E-06 | 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 | 0.1137 | likely_benign | 0.1132 | benign | -0.46 | Destabilizing | 0.201 | N | 0.314 | neutral | None | None | None | None | N |
| T/C | 0.7634 | likely_pathogenic | 0.7495 | pathogenic | -0.387 | Destabilizing | 0.992 | D | 0.379 | neutral | None | None | None | None | N |
| T/D | 0.5868 | likely_pathogenic | 0.5939 | pathogenic | 0.526 | Stabilizing | 0.447 | N | 0.427 | neutral | None | None | None | None | N |
| T/E | 0.3578 | ambiguous | 0.3565 | ambiguous | 0.501 | Stabilizing | 0.021 | N | 0.177 | neutral | None | None | None | None | N |
| T/F | 0.5235 | ambiguous | 0.4822 | ambiguous | -0.79 | Destabilizing | 0.85 | D | 0.478 | neutral | None | None | None | None | N |
| T/G | 0.4867 | ambiguous | 0.4928 | ambiguous | -0.643 | Destabilizing | 0.766 | D | 0.455 | neutral | None | None | None | None | N |
| T/H | 0.4797 | ambiguous | 0.4502 | ambiguous | -0.775 | Destabilizing | 0.972 | D | 0.431 | neutral | None | None | None | None | N |
| T/I | 0.2942 | likely_benign | 0.2372 | benign | -0.086 | Destabilizing | 0.379 | N | 0.434 | neutral | None | None | None | None | N |
| T/K | 0.3142 | likely_benign | 0.2768 | benign | -0.278 | Destabilizing | 0.549 | D | 0.379 | neutral | None | None | None | None | N |
| T/L | 0.1858 | likely_benign | 0.1671 | benign | -0.086 | Destabilizing | 0.103 | N | 0.342 | neutral | None | None | None | None | N |
| T/M | 0.1174 | likely_benign | 0.1147 | benign | -0.177 | Destabilizing | 0.021 | N | 0.247 | neutral | None | None | None | None | N |
| T/N | 0.2822 | likely_benign | 0.2698 | benign | -0.245 | Destabilizing | 0.92 | D | 0.367 | neutral | None | None | None | None | N |
| T/P | 0.7781 | likely_pathogenic | 0.7865 | pathogenic | -0.18 | Destabilizing | 0.963 | D | 0.419 | neutral | None | None | None | None | N |
| T/Q | 0.2736 | likely_benign | 0.2584 | benign | -0.336 | Destabilizing | 0.85 | D | 0.427 | neutral | None | None | None | None | N |
| T/R | 0.2672 | likely_benign | 0.2152 | benign | -0.071 | Destabilizing | 0.81 | D | 0.421 | neutral | None | None | None | None | N |
| T/S | 0.2002 | likely_benign | 0.2122 | benign | -0.522 | Destabilizing | 0.549 | D | 0.303 | neutral | None | None | None | None | N |
| T/V | 0.1729 | likely_benign | 0.1502 | benign | -0.18 | Destabilizing | 0.25 | N | 0.281 | neutral | None | None | None | None | N |
| T/W | 0.8359 | likely_pathogenic | 0.8113 | pathogenic | -0.813 | Destabilizing | 0.005 | N | 0.239 | neutral | None | None | None | None | N |
| T/Y | 0.5929 | likely_pathogenic | 0.5614 | ambiguous | -0.516 | Destabilizing | 0.85 | D | 0.477 | 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.