Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17382 | 52369;52370;52371 | chr2:178608867;178608866;178608865 | chr2:179473594;179473593;179473592 |
| N2AB | 15741 | 47446;47447;47448 | chr2:178608867;178608866;178608865 | chr2:179473594;179473593;179473592 |
| N2A | 14814 | 44665;44666;44667 | chr2:178608867;178608866;178608865 | chr2:179473594;179473593;179473592 |
| N2B | 8317 | 25174;25175;25176 | chr2:178608867;178608866;178608865 | chr2:179473594;179473593;179473592 |
| Novex-1 | 8442 | 25549;25550;25551 | chr2:178608867;178608866;178608865 | chr2:179473594;179473593;179473592 |
| Novex-2 | 8509 | 25750;25751;25752 | chr2:178608867;178608866;178608865 | chr2:179473594;179473593;179473592 |
| 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/G | rs397517607  |
-0.834 | 1.0 | N | 0.674 | 0.334 | 0.401042353794 | gnomAD-2.1.1 | 2.7264E-04 | None | None | None | None | N | None | 0 | 2.83E-05 | None | 0 | 0 | None | 2.35356E-03 | None | 0 | 0 | 4.22773E-04 |
| R/G | rs397517607 |
-0.834 | 1.0 | N | 0.674 | 0.334 | 0.401042353794 | gnomAD-3.1.2 | 3.95E-05 | None | None | None | None | N | None | 0 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 8.285E-04 | 0 |
| R/G | rs397517607 |
-0.834 | 1.0 | N | 0.674 | 0.334 | 0.401042353794 | gnomAD-4.0.0 | 1.39624E-04 | None | None | None | None | N | None | 1.33661E-05 | 5.00551E-05 | None | 0 | 0 | None | 0 | 3.29815E-04 | 4.24025E-06 | 2.27328E-03 | 1.12201E-04 |
| R/S | None | None | 1.0 | N | 0.707 | 0.341 | 0.238705975628 | gnomAD-4.0.0 | 1.59655E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86254E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.7178 | likely_pathogenic | 0.6851 | pathogenic | -0.983 | Destabilizing | 0.999 | D | 0.586 | neutral | None | None | None | None | N |
| R/C | 0.3011 | likely_benign | 0.2531 | benign | -0.93 | Destabilizing | 1.0 | D | 0.762 | deleterious | None | None | None | None | N |
| R/D | 0.8832 | likely_pathogenic | 0.8653 | pathogenic | -0.237 | Destabilizing | 1.0 | D | 0.747 | deleterious | None | None | None | None | N |
| R/E | 0.635 | likely_pathogenic | 0.6168 | pathogenic | -0.135 | Destabilizing | 0.999 | D | 0.627 | neutral | None | None | None | None | N |
| R/F | 0.8377 | likely_pathogenic | 0.8043 | pathogenic | -0.994 | Destabilizing | 1.0 | D | 0.737 | prob.delet. | None | None | None | None | N |
| R/G | 0.4016 | ambiguous | 0.3756 | ambiguous | -1.266 | Destabilizing | 1.0 | D | 0.674 | neutral | N | 0.483403436 | None | None | N |
| R/H | 0.1832 | likely_benign | 0.1597 | benign | -1.512 | Destabilizing | 1.0 | D | 0.754 | deleterious | None | None | None | None | N |
| R/I | 0.7234 | likely_pathogenic | 0.6887 | pathogenic | -0.227 | Destabilizing | 1.0 | D | 0.757 | deleterious | N | 0.467609803 | None | None | N |
| R/K | 0.1401 | likely_benign | 0.1465 | benign | -1.022 | Destabilizing | 0.997 | D | 0.512 | neutral | N | 0.494911296 | None | None | N |
| R/L | 0.5221 | ambiguous | 0.4959 | ambiguous | -0.227 | Destabilizing | 1.0 | D | 0.674 | neutral | None | None | None | None | N |
| R/M | 0.5742 | likely_pathogenic | 0.5449 | ambiguous | -0.399 | Destabilizing | 1.0 | D | 0.707 | prob.neutral | None | None | None | None | N |
| R/N | 0.8015 | likely_pathogenic | 0.7785 | pathogenic | -0.403 | Destabilizing | 1.0 | D | 0.741 | deleterious | None | None | None | None | N |
| R/P | 0.9586 | likely_pathogenic | 0.9314 | pathogenic | -0.459 | Destabilizing | 1.0 | D | 0.731 | prob.delet. | None | None | None | None | N |
| R/Q | 0.1508 | likely_benign | 0.1364 | benign | -0.666 | Destabilizing | 1.0 | D | 0.728 | prob.delet. | None | None | None | None | N |
| R/S | 0.6944 | likely_pathogenic | 0.6734 | pathogenic | -1.214 | Destabilizing | 1.0 | D | 0.707 | prob.neutral | N | 0.447231992 | None | None | N |
| R/T | 0.3933 | ambiguous | 0.3734 | ambiguous | -0.943 | Destabilizing | 1.0 | D | 0.711 | prob.delet. | N | 0.383719231 | None | None | N |
| R/V | 0.7401 | likely_pathogenic | 0.7157 | pathogenic | -0.459 | Destabilizing | 1.0 | D | 0.744 | deleterious | None | None | None | None | N |
| R/W | 0.4101 | ambiguous | 0.3186 | benign | -0.636 | Destabilizing | 1.0 | D | 0.763 | deleterious | None | None | None | None | N |
| R/Y | 0.707 | likely_pathogenic | 0.6405 | pathogenic | -0.326 | Destabilizing | 1.0 | D | 0.748 | deleterious | 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.