Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 3831 | 11716;11717;11718 | chr2:178741742;178741741;178741740 | chr2:179606469;179606468;179606467 |
| N2AB | 3514 | 10765;10766;10767 | chr2:178741742;178741741;178741740 | chr2:179606469;179606468;179606467 |
| N2A | None | None | chr2:None | chr2:None |
| N2B | 3468 | 10627;10628;10629 | chr2:178741742;178741741;178741740 | chr2:179606469;179606468;179606467 |
| Novex-1 | 3593 | 11002;11003;11004 | chr2:178741742;178741741;178741740 | chr2:179606469;179606468;179606467 |
| Novex-2 | 3660 | 11203;11204;11205 | chr2:178741742;178741741;178741740 | chr2:179606469;179606468;179606467 |
| 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 | rs1183777377  |
-0.85 | 0.427 | N | 0.497 | 0.112 | None | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 6.48E-05 | 0 |
| I/M | rs1183777377 |
-0.85 | 0.427 | N | 0.497 | 0.112 | None | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 0 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| I/M | rs1183777377 |
-0.85 | 0.427 | N | 0.497 | 0.112 | None | gnomAD-4.0.0 | 6.40653E-06 | None | None | None | None | N | None | 0 | 1.6956E-05 | None | 0 | 0 | None | 0 | 0 | 9.57304E-06 | 0 | 0 |
| I/T | None | None | None | N | 0.265 | 0.213 | None | 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 | 0.2031 | likely_benign | 0.2089 | benign | -1.742 | Destabilizing | 0.025 | N | 0.321 | neutral | None | None | None | None | N |
| I/C | 0.4885 | ambiguous | 0.4976 | ambiguous | -1.359 | Destabilizing | 0.667 | D | 0.524 | neutral | None | None | None | None | N |
| I/D | 0.5711 | likely_pathogenic | 0.5799 | pathogenic | -1.68 | Destabilizing | 0.22 | N | 0.575 | neutral | None | None | None | None | N |
| I/E | 0.5381 | ambiguous | 0.5502 | ambiguous | -1.694 | Destabilizing | 0.22 | N | 0.537 | neutral | None | None | None | None | N |
| I/F | 0.1458 | likely_benign | 0.1522 | benign | -1.527 | Destabilizing | 0.124 | N | 0.499 | neutral | None | None | None | None | N |
| I/G | 0.4931 | ambiguous | 0.4945 | ambiguous | -2.039 | Highly Destabilizing | 0.124 | N | 0.479 | neutral | None | None | None | None | N |
| I/H | 0.4511 | ambiguous | 0.4556 | ambiguous | -1.288 | Destabilizing | 0.859 | D | 0.555 | neutral | None | None | None | None | N |
| I/K | 0.3366 | likely_benign | 0.3236 | benign | -1.111 | Destabilizing | 0.175 | N | 0.527 | neutral | N | 0.510827137 | None | None | N |
| I/L | 0.1339 | likely_benign | 0.1289 | benign | -0.995 | Destabilizing | None | N | 0.113 | neutral | N | 0.474247147 | None | None | N |
| I/M | 0.1119 | likely_benign | 0.1092 | benign | -0.794 | Destabilizing | 0.427 | N | 0.497 | neutral | N | 0.515766947 | None | None | N |
| I/N | 0.2018 | likely_benign | 0.2038 | benign | -1.004 | Destabilizing | 0.22 | N | 0.59 | neutral | None | None | None | None | N |
| I/P | 0.7662 | likely_pathogenic | 0.7795 | pathogenic | -1.215 | Destabilizing | 0.364 | N | 0.605 | neutral | None | None | None | None | N |
| I/Q | 0.436 | ambiguous | 0.4266 | ambiguous | -1.273 | Destabilizing | 0.667 | D | 0.607 | neutral | None | None | None | None | N |
| I/R | 0.233 | likely_benign | 0.2273 | benign | -0.499 | Destabilizing | 0.427 | N | 0.611 | neutral | N | 0.504267245 | None | None | N |
| I/S | 0.1833 | likely_benign | 0.1905 | benign | -1.59 | Destabilizing | 0.002 | N | 0.307 | neutral | None | None | None | None | N |
| I/T | 0.0939 | likely_benign | 0.1037 | benign | -1.49 | Destabilizing | None | N | 0.265 | neutral | N | 0.494703273 | None | None | N |
| I/V | 0.0801 | likely_benign | 0.0754 | benign | -1.215 | Destabilizing | None | N | 0.116 | neutral | N | 0.350655065 | None | None | N |
| I/W | 0.7659 | likely_pathogenic | 0.7779 | pathogenic | -1.578 | Destabilizing | 0.958 | D | 0.537 | neutral | None | None | None | None | N |
| I/Y | 0.4467 | ambiguous | 0.4626 | ambiguous | -1.308 | Destabilizing | 0.667 | D | 0.562 | 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.