Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2314 | 7165;7166;7167 | chr2:178774324;178774323;178774322 | chr2:179639051;179639050;179639049 |
| N2AB | 2314 | 7165;7166;7167 | chr2:178774324;178774323;178774322 | chr2:179639051;179639050;179639049 |
| N2A | 2314 | 7165;7166;7167 | chr2:178774324;178774323;178774322 | chr2:179639051;179639050;179639049 |
| N2B | 2268 | 7027;7028;7029 | chr2:178774324;178774323;178774322 | chr2:179639051;179639050;179639049 |
| Novex-1 | 2268 | 7027;7028;7029 | chr2:178774324;178774323;178774322 | chr2:179639051;179639050;179639049 |
| Novex-2 | 2268 | 7027;7028;7029 | chr2:178774324;178774323;178774322 | chr2:179639051;179639050;179639049 |
| Novex-3 | 2314 | 7165;7166;7167 | chr2:178774324;178774323;178774322 | chr2:179639051;179639050;179639049 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/T | rs397517708  |
-1.194 | 0.642 | D | 0.491 | 0.549 | 0.726439522792 | gnomAD-2.1.1 | 3.98E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.82E-06 | 0 |
| I/T | rs397517708 |
-1.194 | 0.642 | D | 0.491 | 0.549 | 0.726439522792 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| I/T | rs397517708 |
-1.194 | 0.642 | D | 0.491 | 0.549 | 0.726439522792 | gnomAD-4.0.0 | 1.11528E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.52544E-05 | 0 | 0 |
| I/V | rs2091945518 |
None | 0.002 | N | 0.117 | 0.102 | 0.573031010871 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.6065 | likely_pathogenic | 0.5779 | pathogenic | -2.024 | Highly Destabilizing | 0.329 | N | 0.365 | neutral | None | None | None | None | N |
| I/C | 0.8757 | likely_pathogenic | 0.8714 | pathogenic | -1.5 | Destabilizing | 0.995 | D | 0.519 | neutral | None | None | None | None | N |
| I/D | 0.9536 | likely_pathogenic | 0.9506 | pathogenic | -1.129 | Destabilizing | 0.981 | D | 0.639 | neutral | None | None | None | None | N |
| I/E | 0.8411 | likely_pathogenic | 0.8303 | pathogenic | -1.041 | Destabilizing | 0.944 | D | 0.645 | neutral | None | None | None | None | N |
| I/F | 0.2279 | likely_benign | 0.2292 | benign | -1.45 | Destabilizing | 0.006 | N | 0.234 | neutral | D | 0.540082072 | None | None | N |
| I/G | 0.9135 | likely_pathogenic | 0.9044 | pathogenic | -2.437 | Highly Destabilizing | 0.828 | D | 0.623 | neutral | None | None | None | None | N |
| I/H | 0.8208 | likely_pathogenic | 0.8028 | pathogenic | -1.671 | Destabilizing | 0.995 | D | 0.593 | neutral | None | None | None | None | N |
| I/K | 0.6746 | likely_pathogenic | 0.6459 | pathogenic | -1.195 | Destabilizing | 0.828 | D | 0.645 | neutral | None | None | None | None | N |
| I/L | 0.174 | likely_benign | 0.1703 | benign | -0.91 | Destabilizing | 0.002 | N | 0.133 | neutral | D | 0.542308769 | None | None | N |
| I/M | 0.1152 | likely_benign | 0.113 | benign | -0.84 | Destabilizing | 0.065 | N | 0.159 | neutral | N | 0.48865105 | None | None | N |
| I/N | 0.6733 | likely_pathogenic | 0.6501 | pathogenic | -1.161 | Destabilizing | 0.975 | D | 0.623 | neutral | D | 0.625461462 | None | None | N |
| I/P | 0.9451 | likely_pathogenic | 0.9502 | pathogenic | -1.253 | Destabilizing | 0.981 | D | 0.625 | neutral | None | None | None | None | N |
| I/Q | 0.7257 | likely_pathogenic | 0.705 | pathogenic | -1.212 | Destabilizing | 0.944 | D | 0.625 | neutral | None | None | None | None | N |
| I/R | 0.6018 | likely_pathogenic | 0.5742 | pathogenic | -0.783 | Destabilizing | 0.944 | D | 0.626 | neutral | None | None | None | None | N |
| I/S | 0.6646 | likely_pathogenic | 0.6348 | pathogenic | -1.961 | Destabilizing | 0.784 | D | 0.581 | neutral | D | 0.60064423 | None | None | N |
| I/T | 0.5336 | ambiguous | 0.4807 | ambiguous | -1.727 | Destabilizing | 0.642 | D | 0.491 | neutral | D | 0.581772319 | None | None | N |
| I/V | 0.0818 | likely_benign | 0.0772 | benign | -1.253 | Destabilizing | 0.002 | N | 0.117 | neutral | N | 0.501917695 | None | None | N |
| I/W | 0.8941 | likely_pathogenic | 0.8933 | pathogenic | -1.537 | Destabilizing | 0.995 | D | 0.606 | neutral | None | None | None | None | N |
| I/Y | 0.7153 | likely_pathogenic | 0.7141 | pathogenic | -1.283 | Destabilizing | 0.807 | D | 0.579 | 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.