Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22315 | 67168;67169;67170 | chr2:178580436;178580435;178580434 | chr2:179445163;179445162;179445161 |
| N2AB | 20674 | 62245;62246;62247 | chr2:178580436;178580435;178580434 | chr2:179445163;179445162;179445161 |
| N2A | 19747 | 59464;59465;59466 | chr2:178580436;178580435;178580434 | chr2:179445163;179445162;179445161 |
| N2B | 13250 | 39973;39974;39975 | chr2:178580436;178580435;178580434 | chr2:179445163;179445162;179445161 |
| Novex-1 | 13375 | 40348;40349;40350 | chr2:178580436;178580435;178580434 | chr2:179445163;179445162;179445161 |
| Novex-2 | 13442 | 40549;40550;40551 | chr2:178580436;178580435;178580434 | chr2:179445163;179445162;179445161 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/L | rs746811214  |
None | 0.166 | N | 0.308 | 0.222 | 0.323886383625 | gnomAD-4.0.0 | 2.05329E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.69902E-06 | 0 | 0 |
| F/V | rs746811214 |
-0.263 | 0.491 | N | 0.415 | 0.232 | 0.49118058892 | gnomAD-2.1.1 | 2.01E-05 | None | None | None | None | N | None | 0 | 0 | None | 4.97711E-04 | 0 | None | 0 | None | 0 | 0 | 0 |
| F/V | rs746811214 |
-0.263 | 0.491 | N | 0.415 | 0.232 | 0.49118058892 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 8.65052E-04 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| F/V | rs746811214 |
-0.263 | 0.491 | N | 0.415 | 0.232 | 0.49118058892 | gnomAD-4.0.0 | 1.11583E-05 | None | None | None | None | N | None | 0 | 0 | None | 5.07065E-04 | 0 | None | 0 | 0 | 8.47814E-07 | 0 | 3.2039E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/A | 0.4398 | ambiguous | 0.4756 | ambiguous | -1.002 | Destabilizing | 0.345 | N | 0.451 | neutral | None | None | None | None | N |
| F/C | 0.3291 | likely_benign | 0.372 | ambiguous | -0.129 | Destabilizing | 0.987 | D | 0.42 | neutral | N | 0.493962438 | None | None | N |
| F/D | 0.7109 | likely_pathogenic | 0.7323 | pathogenic | 0.553 | Stabilizing | 0.722 | D | 0.448 | neutral | None | None | None | None | N |
| F/E | 0.7774 | likely_pathogenic | 0.789 | pathogenic | 0.533 | Stabilizing | 0.561 | D | 0.464 | neutral | None | None | None | None | N |
| F/G | 0.6956 | likely_pathogenic | 0.7175 | pathogenic | -1.219 | Destabilizing | 0.722 | D | 0.455 | neutral | None | None | None | None | N |
| F/H | 0.4252 | ambiguous | 0.4526 | ambiguous | 0.151 | Stabilizing | 0.004 | N | 0.281 | neutral | None | None | None | None | N |
| F/I | 0.2546 | likely_benign | 0.2864 | benign | -0.438 | Destabilizing | 0.491 | N | 0.297 | neutral | N | 0.441360104 | None | None | N |
| F/K | 0.7565 | likely_pathogenic | 0.7666 | pathogenic | -0.055 | Destabilizing | 0.561 | D | 0.489 | neutral | None | None | None | None | N |
| F/L | 0.8357 | likely_pathogenic | 0.8576 | pathogenic | -0.438 | Destabilizing | 0.166 | N | 0.308 | neutral | N | 0.482668009 | None | None | N |
| F/M | 0.4601 | ambiguous | 0.4752 | ambiguous | -0.273 | Destabilizing | 0.965 | D | 0.328 | neutral | None | None | None | None | N |
| F/N | 0.4482 | ambiguous | 0.4929 | ambiguous | 0.068 | Stabilizing | 0.561 | D | 0.451 | neutral | None | None | None | None | N |
| F/P | 0.9888 | likely_pathogenic | 0.99 | pathogenic | -0.607 | Destabilizing | 0.965 | D | 0.431 | neutral | None | None | None | None | N |
| F/Q | 0.6689 | likely_pathogenic | 0.6858 | pathogenic | -0.018 | Destabilizing | 0.818 | D | 0.437 | neutral | None | None | None | None | N |
| F/R | 0.6554 | likely_pathogenic | 0.666 | pathogenic | 0.428 | Stabilizing | 0.818 | D | 0.441 | neutral | None | None | None | None | N |
| F/S | 0.2829 | likely_benign | 0.3159 | benign | -0.596 | Destabilizing | 0.491 | N | 0.463 | neutral | N | 0.374711038 | None | None | N |
| F/T | 0.2782 | likely_benign | 0.2997 | benign | -0.521 | Destabilizing | 0.722 | D | 0.454 | neutral | None | None | None | None | N |
| F/V | 0.2441 | likely_benign | 0.2736 | benign | -0.607 | Destabilizing | 0.491 | N | 0.415 | neutral | N | 0.46390889 | None | None | N |
| F/W | 0.3783 | ambiguous | 0.3807 | ambiguous | -0.294 | Destabilizing | 0.002 | N | 0.212 | neutral | None | None | None | None | N |
| F/Y | 0.118 | likely_benign | 0.1234 | benign | -0.274 | Destabilizing | None | N | 0.194 | neutral | N | 0.459772507 | 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.