Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 13890 | 41893;41894;41895 | chr2:178635656;178635655;178635654 | chr2:179500383;179500382;179500381 |
| N2AB | 12249 | 36970;36971;36972 | chr2:178635656;178635655;178635654 | chr2:179500383;179500382;179500381 |
| N2A | 11322 | 34189;34190;34191 | chr2:178635656;178635655;178635654 | chr2:179500383;179500382;179500381 |
| N2B | 4825 | 14698;14699;14700 | chr2:178635656;178635655;178635654 | chr2:179500383;179500382;179500381 |
| Novex-1 | 4950 | 15073;15074;15075 | chr2:178635656;178635655;178635654 | chr2:179500383;179500382;179500381 |
| Novex-2 | 5017 | 15274;15275;15276 | chr2:178635656;178635655;178635654 | chr2:179500383;179500382;179500381 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/I | rs780566983  |
-0.135 | 0.987 | N | 0.382 | 0.263 | 0.331365685468 | gnomAD-2.1.1 | 4.41E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.59E-05 | None | 0 | 0 | 0 |
| T/I | rs780566983 |
-0.135 | 0.987 | N | 0.382 | 0.263 | 0.331365685468 | gnomAD-4.0.0 | 2.07224E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 3.47705E-04 | 0 | 1.19022E-05 | 0 |
| T/R | rs780566983 |
-0.138 | 0.844 | N | 0.372 | 0.226 | 0.443999229985 | gnomAD-4.0.0 | 1.38149E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.05315E-07 | 0 | 1.6695E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.2394 | likely_benign | 0.229 | benign | -0.474 | Destabilizing | 0.057 | N | 0.101 | neutral | N | 0.51018345 | None | None | N |
| T/C | 0.862 | likely_pathogenic | 0.8578 | pathogenic | -0.302 | Destabilizing | 0.999 | D | 0.319 | neutral | None | None | None | None | N |
| T/D | 0.5913 | likely_pathogenic | 0.6785 | pathogenic | 0.426 | Stabilizing | 0.935 | D | 0.306 | neutral | None | None | None | None | N |
| T/E | 0.5864 | likely_pathogenic | 0.6039 | pathogenic | 0.386 | Stabilizing | 0.935 | D | 0.291 | neutral | None | None | None | None | N |
| T/F | 0.6659 | likely_pathogenic | 0.6369 | pathogenic | -0.825 | Destabilizing | 0.997 | D | 0.418 | neutral | None | None | None | None | N |
| T/G | 0.674 | likely_pathogenic | 0.7061 | pathogenic | -0.657 | Destabilizing | 0.855 | D | 0.273 | neutral | None | None | None | None | N |
| T/H | 0.6795 | likely_pathogenic | 0.6824 | pathogenic | -0.898 | Destabilizing | 0.999 | D | 0.373 | neutral | None | None | None | None | N |
| T/I | 0.4811 | ambiguous | 0.4147 | ambiguous | -0.103 | Destabilizing | 0.987 | D | 0.382 | neutral | N | 0.514817334 | None | None | N |
| T/K | 0.7069 | likely_pathogenic | 0.6811 | pathogenic | -0.313 | Destabilizing | 0.126 | N | 0.214 | neutral | N | 0.457202832 | None | None | N |
| T/L | 0.3078 | likely_benign | 0.2826 | benign | -0.103 | Destabilizing | 0.935 | D | 0.274 | neutral | None | None | None | None | N |
| T/M | 0.1924 | likely_benign | 0.1743 | benign | 0.018 | Stabilizing | 0.997 | D | 0.341 | neutral | None | None | None | None | N |
| T/N | 0.2326 | likely_benign | 0.2635 | benign | -0.172 | Destabilizing | 0.935 | D | 0.301 | neutral | None | None | None | None | N |
| T/P | 0.429 | ambiguous | 0.4252 | ambiguous | -0.195 | Destabilizing | 0.033 | N | 0.216 | neutral | N | 0.507782433 | None | None | N |
| T/Q | 0.592 | likely_pathogenic | 0.5833 | pathogenic | -0.328 | Destabilizing | 0.98 | D | 0.395 | neutral | None | None | None | None | N |
| T/R | 0.6752 | likely_pathogenic | 0.6411 | pathogenic | -0.103 | Destabilizing | 0.844 | D | 0.372 | neutral | N | 0.454982682 | None | None | N |
| T/S | 0.2384 | likely_benign | 0.267 | benign | -0.464 | Destabilizing | 0.296 | N | 0.173 | neutral | N | 0.500478255 | None | None | N |
| T/V | 0.3427 | ambiguous | 0.2961 | benign | -0.195 | Destabilizing | 0.935 | D | 0.202 | neutral | None | None | None | None | N |
| T/W | 0.8971 | likely_pathogenic | 0.9001 | pathogenic | -0.804 | Destabilizing | 0.999 | D | 0.477 | neutral | None | None | None | None | N |
| T/Y | 0.7026 | likely_pathogenic | 0.6899 | pathogenic | -0.522 | Destabilizing | 0.997 | D | 0.402 | 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.