Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27743 | 83452;83453;83454 | chr2:178562905;178562904;178562903 | chr2:179427632;179427631;179427630 |
| N2AB | 26102 | 78529;78530;78531 | chr2:178562905;178562904;178562903 | chr2:179427632;179427631;179427630 |
| N2A | 25175 | 75748;75749;75750 | chr2:178562905;178562904;178562903 | chr2:179427632;179427631;179427630 |
| N2B | 18678 | 56257;56258;56259 | chr2:178562905;178562904;178562903 | chr2:179427632;179427631;179427630 |
| Novex-1 | 18803 | 56632;56633;56634 | chr2:178562905;178562904;178562903 | chr2:179427632;179427631;179427630 |
| Novex-2 | 18870 | 56833;56834;56835 | chr2:178562905;178562904;178562903 | chr2:179427632;179427631;179427630 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/L | None | None | 0.846 | N | 0.505 | 0.307 | 0.682070973213 | gnomAD-4.0.0 | 6.84351E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99541E-07 | 0 | 0 |
| R/Q | rs768262273  |
-0.26 | 0.924 | N | 0.501 | 0.216 | 0.255270683199 | gnomAD-2.1.1 | 2.42E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 1.12296E-04 | None | 0 | None | 0 | 3.56E-05 | 0 |
| R/Q | rs768262273 |
-0.26 | 0.924 | N | 0.501 | 0.216 | 0.255270683199 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 2.42E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/Q | rs768262273 |
-0.26 | 0.924 | N | 0.501 | 0.216 | 0.255270683199 | gnomAD-4.0.0 | 1.30171E-05 | None | None | None | None | I | None | 1.33601E-05 | 0 | None | 0 | 6.70451E-05 | None | 0 | 0 | 1.35629E-05 | 0 | 1.60195E-05 |
| R/W | rs1185542536 |
-0.389 | 0.999 | N | 0.513 | 0.46 | 0.614776886339 | gnomAD-2.1.1 | 8.06E-06 | None | None | None | None | I | None | 6.46E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.91E-06 | 0 |
| R/W | rs1185542536 |
-0.389 | 0.999 | N | 0.513 | 0.46 | 0.614776886339 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/W | rs1185542536 |
-0.389 | 0.999 | N | 0.513 | 0.46 | 0.614776886339 | gnomAD-4.0.0 | 7.43828E-06 | None | None | None | None | I | None | 2.67123E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 7.62916E-06 | 1.09844E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.8586 | likely_pathogenic | 0.8808 | pathogenic | -1.137 | Destabilizing | 0.373 | N | 0.45 | neutral | None | None | None | None | I |
| R/C | 0.4652 | ambiguous | 0.4827 | ambiguous | -1.029 | Destabilizing | 0.996 | D | 0.501 | neutral | None | None | None | None | I |
| R/D | 0.9696 | likely_pathogenic | 0.9711 | pathogenic | -0.158 | Destabilizing | 0.742 | D | 0.507 | neutral | None | None | None | None | I |
| R/E | 0.849 | likely_pathogenic | 0.8599 | pathogenic | -0.008 | Destabilizing | 0.373 | N | 0.467 | neutral | None | None | None | None | I |
| R/F | 0.9057 | likely_pathogenic | 0.9157 | pathogenic | -0.832 | Destabilizing | 0.984 | D | 0.521 | neutral | None | None | None | None | I |
| R/G | 0.8207 | likely_pathogenic | 0.8383 | pathogenic | -1.474 | Destabilizing | 0.846 | D | 0.505 | neutral | D | 0.522130474 | None | None | I |
| R/H | 0.2581 | likely_benign | 0.2616 | benign | -1.724 | Destabilizing | 0.953 | D | 0.531 | neutral | None | None | None | None | I |
| R/I | 0.6135 | likely_pathogenic | 0.6474 | pathogenic | -0.215 | Destabilizing | 0.953 | D | 0.531 | neutral | None | None | None | None | I |
| R/K | 0.1395 | likely_benign | 0.1344 | benign | -1.043 | Destabilizing | 0.001 | N | 0.17 | neutral | None | None | None | None | I |
| R/L | 0.6278 | likely_pathogenic | 0.6653 | pathogenic | -0.215 | Destabilizing | 0.846 | D | 0.505 | neutral | N | 0.469258782 | None | None | I |
| R/M | 0.6635 | likely_pathogenic | 0.6956 | pathogenic | -0.55 | Destabilizing | 0.984 | D | 0.533 | neutral | None | None | None | None | I |
| R/N | 0.9041 | likely_pathogenic | 0.9143 | pathogenic | -0.529 | Destabilizing | 0.742 | D | 0.5 | neutral | None | None | None | None | I |
| R/P | 0.9559 | likely_pathogenic | 0.9611 | pathogenic | -0.503 | Destabilizing | 0.918 | D | 0.53 | neutral | N | 0.513278918 | None | None | I |
| R/Q | 0.2553 | likely_benign | 0.2672 | benign | -0.655 | Destabilizing | 0.924 | D | 0.501 | neutral | N | 0.472528373 | None | None | I |
| R/S | 0.8926 | likely_pathogenic | 0.9077 | pathogenic | -1.388 | Destabilizing | 0.543 | D | 0.512 | neutral | None | None | None | None | I |
| R/T | 0.695 | likely_pathogenic | 0.7218 | pathogenic | -1.042 | Destabilizing | 0.742 | D | 0.533 | neutral | None | None | None | None | I |
| R/V | 0.723 | likely_pathogenic | 0.7511 | pathogenic | -0.503 | Destabilizing | 0.742 | D | 0.527 | neutral | None | None | None | None | I |
| R/W | 0.5872 | likely_pathogenic | 0.6033 | pathogenic | -0.401 | Destabilizing | 0.999 | D | 0.513 | neutral | N | 0.492987392 | None | None | I |
| R/Y | 0.762 | likely_pathogenic | 0.7807 | pathogenic | -0.155 | Destabilizing | 0.984 | D | 0.526 | neutral | 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.