Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26696 | 80311;80312;80313 | chr2:178566046;178566045;178566044 | chr2:179430773;179430772;179430771 |
| N2AB | 25055 | 75388;75389;75390 | chr2:178566046;178566045;178566044 | chr2:179430773;179430772;179430771 |
| N2A | 24128 | 72607;72608;72609 | chr2:178566046;178566045;178566044 | chr2:179430773;179430772;179430771 |
| N2B | 17631 | 53116;53117;53118 | chr2:178566046;178566045;178566044 | chr2:179430773;179430772;179430771 |
| Novex-1 | 17756 | 53491;53492;53493 | chr2:178566046;178566045;178566044 | chr2:179430773;179430772;179430771 |
| Novex-2 | 17823 | 53692;53693;53694 | chr2:178566046;178566045;178566044 | chr2:179430773;179430772;179430771 |
| 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/K | rs769866606  |
-1.328 | None | N | 0.039 | 0.107 | 0.0716867268079 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| R/K | rs769866606 |
-1.328 | None | N | 0.039 | 0.107 | 0.0716867268079 | gnomAD-4.0.0 | 1.36865E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99598E-07 | 1.15947E-05 | 0 |
| R/S | None | None | 0.005 | N | 0.273 | 0.051 | 0.101711395817 | gnomAD-4.0.0 | 1.59188E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85954E-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 | 0.2963 | likely_benign | 0.3286 | benign | -0.749 | Destabilizing | 0.007 | N | 0.26 | neutral | None | None | None | None | N |
| R/C | 0.1712 | likely_benign | 0.1687 | benign | -0.632 | Destabilizing | 0.864 | D | 0.301 | neutral | None | None | None | None | N |
| R/D | 0.6123 | likely_pathogenic | 0.6536 | pathogenic | -0.206 | Destabilizing | 0.016 | N | 0.209 | neutral | None | None | None | None | N |
| R/E | 0.3408 | ambiguous | 0.3649 | ambiguous | -0.105 | Destabilizing | 0.016 | N | 0.226 | neutral | None | None | None | None | N |
| R/F | 0.5841 | likely_pathogenic | 0.5906 | pathogenic | -0.712 | Destabilizing | 0.628 | D | 0.329 | neutral | None | None | None | None | N |
| R/G | 0.1537 | likely_benign | 0.1524 | benign | -1.041 | Destabilizing | 0.012 | N | 0.216 | neutral | N | 0.406366804 | None | None | N |
| R/H | 0.119 | likely_benign | 0.1213 | benign | -1.336 | Destabilizing | 0.214 | N | 0.29 | neutral | None | None | None | None | N |
| R/I | 0.3988 | ambiguous | 0.4168 | ambiguous | 0.03 | Stabilizing | 0.055 | N | 0.377 | neutral | N | 0.497028881 | None | None | N |
| R/K | 0.0575 | likely_benign | 0.0647 | benign | -0.853 | Destabilizing | None | N | 0.039 | neutral | N | 0.406022875 | None | None | N |
| R/L | 0.2617 | likely_benign | 0.2707 | benign | 0.03 | Stabilizing | 0.031 | N | 0.248 | neutral | None | None | None | None | N |
| R/M | 0.2227 | likely_benign | 0.2344 | benign | -0.154 | Destabilizing | 0.628 | D | 0.309 | neutral | None | None | None | None | N |
| R/N | 0.3938 | ambiguous | 0.4595 | ambiguous | -0.226 | Destabilizing | None | N | 0.111 | neutral | None | None | None | None | N |
| R/P | 0.8673 | likely_pathogenic | 0.8738 | pathogenic | -0.209 | Destabilizing | 0.136 | N | 0.331 | neutral | None | None | None | None | N |
| R/Q | 0.0958 | likely_benign | 0.0965 | benign | -0.463 | Destabilizing | 0.038 | N | 0.151 | neutral | None | None | None | None | N |
| R/S | 0.2975 | likely_benign | 0.3428 | ambiguous | -0.947 | Destabilizing | 0.005 | N | 0.273 | neutral | N | 0.364000107 | None | None | N |
| R/T | 0.1223 | likely_benign | 0.1441 | benign | -0.679 | Destabilizing | None | N | 0.117 | neutral | N | 0.327961949 | None | None | N |
| R/V | 0.3753 | ambiguous | 0.4098 | ambiguous | -0.209 | Destabilizing | 0.031 | N | 0.266 | neutral | None | None | None | None | N |
| R/W | 0.2881 | likely_benign | 0.2544 | benign | -0.393 | Destabilizing | 0.864 | D | 0.309 | neutral | None | None | None | None | N |
| R/Y | 0.4672 | ambiguous | 0.4751 | ambiguous | -0.078 | Destabilizing | 0.356 | N | 0.349 | 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.