Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30654 | 92185;92186;92187 | chr2:178549762;178549761;178549760 | chr2:179414489;179414488;179414487 |
| N2AB | 29013 | 87262;87263;87264 | chr2:178549762;178549761;178549760 | chr2:179414489;179414488;179414487 |
| N2A | 28086 | 84481;84482;84483 | chr2:178549762;178549761;178549760 | chr2:179414489;179414488;179414487 |
| N2B | 21589 | 64990;64991;64992 | chr2:178549762;178549761;178549760 | chr2:179414489;179414488;179414487 |
| Novex-1 | 21714 | 65365;65366;65367 | chr2:178549762;178549761;178549760 | chr2:179414489;179414488;179414487 |
| Novex-2 | 21781 | 65566;65567;65568 | chr2:178549762;178549761;178549760 | chr2:179414489;179414488;179414487 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| H/D | rs761280624  |
-1.097 | 0.925 | N | 0.589 | 0.295 | 0.32471235697 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 6.48E-05 | 0 |
| H/D | rs761280624 |
-1.097 | 0.925 | N | 0.589 | 0.295 | 0.32471235697 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| H/D | rs761280624 |
-1.097 | 0.925 | N | 0.589 | 0.295 | 0.32471235697 | gnomAD-4.0.0 | 1.23952E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.69534E-06 | 0 | 0 |
| H/N | rs761280624 |
-1.419 | 0.248 | N | 0.353 | 0.233 | 0.201204373187 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 8.88E-06 | 1.65728E-04 |
| H/N | rs761280624 |
-1.419 | 0.248 | N | 0.353 | 0.233 | 0.201204373187 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 4.15282E-04 | 0 |
| H/N | rs761280624 |
-1.419 | 0.248 | N | 0.353 | 0.233 | 0.201204373187 | gnomAD-4.0.0 | 4.9577E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.47676E-07 | 6.58993E-05 | 1.60072E-05 |
| H/Y | None | None | 0.993 | N | 0.498 | 0.35 | 0.367425347029 | gnomAD-4.0.0 | 6.84273E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99538E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| H/A | 0.5489 | ambiguous | 0.5469 | ambiguous | -1.175 | Destabilizing | 0.985 | D | 0.592 | neutral | None | None | None | None | N |
| H/C | 0.2404 | likely_benign | 0.2357 | benign | -0.369 | Destabilizing | 1.0 | D | 0.758 | deleterious | None | None | None | None | N |
| H/D | 0.482 | ambiguous | 0.505 | ambiguous | -0.925 | Destabilizing | 0.925 | D | 0.589 | neutral | N | 0.471911762 | None | None | N |
| H/E | 0.6437 | likely_pathogenic | 0.6879 | pathogenic | -0.786 | Destabilizing | 0.97 | D | 0.438 | neutral | None | None | None | None | N |
| H/F | 0.5491 | ambiguous | 0.5204 | ambiguous | 0.318 | Stabilizing | 0.999 | D | 0.663 | neutral | None | None | None | None | N |
| H/G | 0.3812 | ambiguous | 0.3866 | ambiguous | -1.562 | Destabilizing | 0.97 | D | 0.562 | neutral | None | None | None | None | N |
| H/I | 0.9123 | likely_pathogenic | 0.9159 | pathogenic | -0.075 | Destabilizing | 0.999 | D | 0.777 | deleterious | None | None | None | None | N |
| H/K | 0.6668 | likely_pathogenic | 0.6818 | pathogenic | -0.85 | Destabilizing | 0.97 | D | 0.604 | neutral | None | None | None | None | N |
| H/L | 0.587 | likely_pathogenic | 0.5864 | pathogenic | -0.075 | Destabilizing | 0.994 | D | 0.693 | prob.neutral | N | 0.509134231 | None | None | N |
| H/M | 0.851 | likely_pathogenic | 0.847 | pathogenic | -0.24 | Destabilizing | 1.0 | D | 0.67 | neutral | None | None | None | None | N |
| H/N | 0.1501 | likely_benign | 0.1476 | benign | -1.095 | Destabilizing | 0.248 | N | 0.353 | neutral | N | 0.447098706 | None | None | N |
| H/P | 0.9637 | likely_pathogenic | 0.9691 | pathogenic | -0.425 | Destabilizing | 0.998 | D | 0.689 | prob.neutral | N | 0.50964121 | None | None | N |
| H/Q | 0.4611 | ambiguous | 0.4802 | ambiguous | -0.767 | Destabilizing | 0.994 | D | 0.479 | neutral | N | 0.478913202 | None | None | N |
| H/R | 0.3265 | likely_benign | 0.3481 | ambiguous | -1.223 | Destabilizing | 0.994 | D | 0.493 | neutral | N | 0.495313941 | None | None | N |
| H/S | 0.271 | likely_benign | 0.2699 | benign | -1.183 | Destabilizing | 0.97 | D | 0.543 | neutral | None | None | None | None | N |
| H/T | 0.5918 | likely_pathogenic | 0.5795 | pathogenic | -0.941 | Destabilizing | 0.991 | D | 0.629 | neutral | None | None | None | None | N |
| H/V | 0.8453 | likely_pathogenic | 0.8441 | pathogenic | -0.425 | Destabilizing | 0.999 | D | 0.741 | deleterious | None | None | None | None | N |
| H/W | 0.6184 | likely_pathogenic | 0.5864 | pathogenic | 0.687 | Stabilizing | 1.0 | D | 0.682 | prob.neutral | None | None | None | None | N |
| H/Y | 0.1497 | likely_benign | 0.1361 | benign | 0.701 | Stabilizing | 0.993 | D | 0.498 | neutral | N | 0.463761669 | 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.