Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28460 | 85603;85604;85605 | chr2:178560754;178560753;178560752 | chr2:179425481;179425480;179425479 |
| N2AB | 26819 | 80680;80681;80682 | chr2:178560754;178560753;178560752 | chr2:179425481;179425480;179425479 |
| N2A | 25892 | 77899;77900;77901 | chr2:178560754;178560753;178560752 | chr2:179425481;179425480;179425479 |
| N2B | 19395 | 58408;58409;58410 | chr2:178560754;178560753;178560752 | chr2:179425481;179425480;179425479 |
| Novex-1 | 19520 | 58783;58784;58785 | chr2:178560754;178560753;178560752 | chr2:179425481;179425480;179425479 |
| Novex-2 | 19587 | 58984;58985;58986 | chr2:178560754;178560753;178560752 | chr2:179425481;179425480;179425479 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/M | rs768545532  |
-0.924 | 0.998 | N | 0.631 | 0.318 | 0.386071988338 | gnomAD-2.1.1 | 1.43E-05 | None | None | None | None | N | None | 1.24234E-04 | 2.83E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/M | rs768545532 |
-0.924 | 0.998 | N | 0.631 | 0.318 | 0.386071988338 | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | N | None | 1.20604E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/M | rs768545532 |
-0.924 | 0.998 | N | 0.631 | 0.318 | 0.386071988338 | gnomAD-4.0.0 | 5.57732E-06 | None | None | None | None | N | None | 1.06772E-04 | 1.66706E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 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 | 0.6486 | likely_pathogenic | 0.6566 | pathogenic | -2.086 | Highly Destabilizing | 0.992 | D | 0.619 | neutral | None | None | None | None | N |
| I/C | 0.7459 | likely_pathogenic | 0.7506 | pathogenic | -1.589 | Destabilizing | 1.0 | D | 0.715 | prob.delet. | None | None | None | None | N |
| I/D | 0.9272 | likely_pathogenic | 0.9191 | pathogenic | -1.115 | Destabilizing | 1.0 | D | 0.829 | deleterious | None | None | None | None | N |
| I/E | 0.8641 | likely_pathogenic | 0.8575 | pathogenic | -0.971 | Destabilizing | 1.0 | D | 0.821 | deleterious | None | None | None | None | N |
| I/F | 0.2022 | likely_benign | 0.2147 | benign | -1.267 | Destabilizing | 0.999 | D | 0.655 | neutral | None | None | None | None | N |
| I/G | 0.8597 | likely_pathogenic | 0.8592 | pathogenic | -2.549 | Highly Destabilizing | 1.0 | D | 0.811 | deleterious | None | None | None | None | N |
| I/H | 0.8541 | likely_pathogenic | 0.8493 | pathogenic | -1.665 | Destabilizing | 1.0 | D | 0.801 | deleterious | None | None | None | None | N |
| I/K | 0.7142 | likely_pathogenic | 0.7102 | pathogenic | -1.345 | Destabilizing | 0.999 | D | 0.821 | deleterious | N | 0.512176105 | None | None | N |
| I/L | 0.1914 | likely_benign | 0.1906 | benign | -0.808 | Destabilizing | 0.889 | D | 0.423 | neutral | N | 0.488273325 | None | None | N |
| I/M | 0.1385 | likely_benign | 0.1381 | benign | -0.843 | Destabilizing | 0.998 | D | 0.631 | neutral | N | 0.488791931 | None | None | N |
| I/N | 0.5928 | likely_pathogenic | 0.5769 | pathogenic | -1.419 | Destabilizing | 1.0 | D | 0.833 | deleterious | None | None | None | None | N |
| I/P | 0.8589 | likely_pathogenic | 0.857 | pathogenic | -1.207 | Destabilizing | 1.0 | D | 0.835 | deleterious | None | None | None | None | N |
| I/Q | 0.7981 | likely_pathogenic | 0.8006 | pathogenic | -1.362 | Destabilizing | 1.0 | D | 0.831 | deleterious | None | None | None | None | N |
| I/R | 0.6795 | likely_pathogenic | 0.6605 | pathogenic | -1.006 | Destabilizing | 0.999 | D | 0.835 | deleterious | N | 0.482715544 | None | None | N |
| I/S | 0.6635 | likely_pathogenic | 0.6655 | pathogenic | -2.262 | Highly Destabilizing | 0.999 | D | 0.775 | deleterious | None | None | None | None | N |
| I/T | 0.5773 | likely_pathogenic | 0.5961 | pathogenic | -1.958 | Destabilizing | 0.989 | D | 0.727 | prob.delet. | N | 0.47390368 | None | None | N |
| I/V | 0.0931 | likely_benign | 0.0983 | benign | -1.207 | Destabilizing | 0.333 | N | 0.221 | neutral | N | 0.381276359 | None | None | N |
| I/W | 0.842 | likely_pathogenic | 0.8223 | pathogenic | -1.353 | Destabilizing | 1.0 | D | 0.751 | deleterious | None | None | None | None | N |
| I/Y | 0.6118 | likely_pathogenic | 0.6128 | pathogenic | -1.126 | Destabilizing | 1.0 | D | 0.757 | 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.