Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23912 | 71959;71960;71961 | chr2:178574398;178574397;178574396 | chr2:179439125;179439124;179439123 |
| N2AB | 22271 | 67036;67037;67038 | chr2:178574398;178574397;178574396 | chr2:179439125;179439124;179439123 |
| N2A | 21344 | 64255;64256;64257 | chr2:178574398;178574397;178574396 | chr2:179439125;179439124;179439123 |
| N2B | 14847 | 44764;44765;44766 | chr2:178574398;178574397;178574396 | chr2:179439125;179439124;179439123 |
| Novex-1 | 14972 | 45139;45140;45141 | chr2:178574398;178574397;178574396 | chr2:179439125;179439124;179439123 |
| Novex-2 | 15039 | 45340;45341;45342 | chr2:178574398;178574397;178574396 | chr2:179439125;179439124;179439123 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | rs773568399  |
None | 0.006 | N | 0.349 | 0.152 | 0.130388298395 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| P/A | rs773568399 |
None | 0.006 | N | 0.349 | 0.152 | 0.130388298395 | gnomAD-4.0.0 | 1.23964E-06 | None | None | None | None | I | None | 0 | 1.66761E-05 | None | 0 | 0 | None | 0 | 0 | 8.47732E-07 | 0 | 0 |
| P/T | None | -1.195 | 0.125 | N | 0.418 | 0.193 | None | gnomAD-2.1.1 | 1.43E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.35E-05 | 1.40687E-04 |
| P/T | None | -1.195 | 0.125 | N | 0.418 | 0.193 | None | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 9.42E-05 | 0 | 1.47E-05 | 0 | 0 |
| P/T | None | -1.195 | 0.125 | N | 0.418 | 0.193 | None | gnomAD-4.0.0 | 1.0537E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 1.5626E-05 | 0 | 1.2716E-05 | 0 | 1.60143E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.0678 | likely_benign | 0.077 | benign | -1.493 | Destabilizing | 0.006 | N | 0.349 | neutral | N | 0.456891625 | None | None | I |
| P/C | 0.4188 | ambiguous | 0.4718 | ambiguous | -0.917 | Destabilizing | 0.994 | D | 0.749 | deleterious | None | None | None | None | I |
| P/D | 0.8287 | likely_pathogenic | 0.8633 | pathogenic | -1.259 | Destabilizing | 0.956 | D | 0.529 | neutral | None | None | None | None | I |
| P/E | 0.5984 | likely_pathogenic | 0.6563 | pathogenic | -1.302 | Destabilizing | 0.956 | D | 0.53 | neutral | None | None | None | None | I |
| P/F | 0.4618 | ambiguous | 0.5194 | ambiguous | -1.285 | Destabilizing | 0.978 | D | 0.751 | deleterious | None | None | None | None | I |
| P/G | 0.4227 | ambiguous | 0.4586 | ambiguous | -1.762 | Destabilizing | 0.754 | D | 0.56 | neutral | None | None | None | None | I |
| P/H | 0.4019 | ambiguous | 0.4388 | ambiguous | -1.259 | Destabilizing | 0.998 | D | 0.685 | prob.neutral | None | None | None | None | I |
| P/I | 0.3042 | likely_benign | 0.383 | ambiguous | -0.866 | Destabilizing | 0.956 | D | 0.713 | prob.delet. | None | None | None | None | I |
| P/K | 0.7104 | likely_pathogenic | 0.7503 | pathogenic | -1.177 | Destabilizing | 0.956 | D | 0.526 | neutral | None | None | None | None | I |
| P/L | 0.1874 | likely_benign | 0.2368 | benign | -0.866 | Destabilizing | 0.698 | D | 0.647 | neutral | N | 0.494331204 | None | None | I |
| P/M | 0.3512 | ambiguous | 0.4079 | ambiguous | -0.607 | Destabilizing | 0.998 | D | 0.675 | neutral | None | None | None | None | I |
| P/N | 0.6006 | likely_pathogenic | 0.657 | pathogenic | -0.872 | Destabilizing | 0.956 | D | 0.649 | neutral | None | None | None | None | I |
| P/Q | 0.3485 | ambiguous | 0.3995 | ambiguous | -1.122 | Destabilizing | 0.97 | D | 0.589 | neutral | N | 0.507715425 | None | None | I |
| P/R | 0.5482 | ambiguous | 0.6017 | pathogenic | -0.585 | Destabilizing | 0.97 | D | 0.655 | neutral | N | 0.489104191 | None | None | I |
| P/S | 0.1928 | likely_benign | 0.2196 | benign | -1.356 | Destabilizing | 0.698 | D | 0.493 | neutral | N | 0.475924234 | None | None | I |
| P/T | 0.1734 | likely_benign | 0.2108 | benign | -1.3 | Destabilizing | 0.125 | N | 0.418 | neutral | N | 0.478001376 | None | None | I |
| P/V | 0.1908 | likely_benign | 0.2402 | benign | -1.04 | Destabilizing | 0.754 | D | 0.555 | neutral | None | None | None | None | I |
| P/W | 0.7466 | likely_pathogenic | 0.7787 | pathogenic | -1.391 | Destabilizing | 0.998 | D | 0.718 | prob.delet. | None | None | None | None | I |
| P/Y | 0.4966 | ambiguous | 0.5471 | ambiguous | -1.138 | Destabilizing | 0.993 | D | 0.752 | deleterious | None | None | 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.