Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21205 | 63838;63839;63840 | chr2:178587696;178587695;178587694 | chr2:179452423;179452422;179452421 |
| N2AB | 19564 | 58915;58916;58917 | chr2:178587696;178587695;178587694 | chr2:179452423;179452422;179452421 |
| N2A | 18637 | 56134;56135;56136 | chr2:178587696;178587695;178587694 | chr2:179452423;179452422;179452421 |
| N2B | 12140 | 36643;36644;36645 | chr2:178587696;178587695;178587694 | chr2:179452423;179452422;179452421 |
| Novex-1 | 12265 | 37018;37019;37020 | chr2:178587696;178587695;178587694 | chr2:179452423;179452422;179452421 |
| Novex-2 | 12332 | 37219;37220;37221 | chr2:178587696;178587695;178587694 | chr2:179452423;179452422;179452421 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/E | rs794727409  |
0.384 | 0.41 | N | 0.576 | 0.283 | 0.303781844768 | gnomAD-2.1.1 | 7.16E-06 | None | None | None | None | I | None | 0 | 2.84E-05 | None | 0 | 0 | None | 0 | None | 0 | 7.84E-06 | 0 |
| K/E | rs794727409 |
0.384 | 0.41 | N | 0.576 | 0.283 | 0.303781844768 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| K/E | rs794727409 |
0.384 | 0.41 | N | 0.576 | 0.283 | 0.303781844768 | gnomAD-4.0.0 | 6.20028E-06 | None | None | None | None | I | None | 1.33622E-05 | 1.66856E-05 | None | 0 | 0 | None | 0 | 0 | 6.78306E-06 | 0 | 0 |
| K/I | rs886042512 |
0.863 | 0.908 | N | 0.737 | 0.392 | 0.523082183605 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | I | None | 0 | 8.72E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| K/I | rs886042512 |
0.863 | 0.908 | N | 0.737 | 0.392 | 0.523082183605 | gnomAD-4.0.0 | 4.7792E-06 | None | None | None | None | I | None | 0 | 6.8653E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| K/N | rs771189924 |
0.093 | 0.83 | N | 0.693 | 0.215 | 0.310458034454 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| K/N | rs771189924 |
0.093 | 0.83 | N | 0.693 | 0.215 | 0.310458034454 | gnomAD-4.0.0 | 1.59312E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43361E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/A | 0.3076 | likely_benign | 0.2778 | benign | 0.014 | Stabilizing | 0.648 | D | 0.607 | neutral | None | None | None | None | I |
| K/C | 0.7218 | likely_pathogenic | 0.7098 | pathogenic | -0.338 | Destabilizing | 0.993 | D | 0.757 | deleterious | None | None | None | None | I |
| K/D | 0.5613 | ambiguous | 0.4974 | ambiguous | 0.016 | Stabilizing | 0.866 | D | 0.721 | prob.delet. | None | None | None | None | I |
| K/E | 0.1824 | likely_benign | 0.1473 | benign | 0.057 | Stabilizing | 0.41 | N | 0.576 | neutral | N | 0.414634863 | None | None | I |
| K/F | 0.8354 | likely_pathogenic | 0.8129 | pathogenic | -0.026 | Destabilizing | 0.98 | D | 0.724 | prob.delet. | None | None | None | None | I |
| K/G | 0.5252 | ambiguous | 0.487 | ambiguous | -0.228 | Destabilizing | 0.866 | D | 0.595 | neutral | None | None | None | None | I |
| K/H | 0.3104 | likely_benign | 0.2843 | benign | -0.426 | Destabilizing | 0.98 | D | 0.717 | prob.delet. | None | None | None | None | I |
| K/I | 0.3573 | ambiguous | 0.3161 | benign | 0.588 | Stabilizing | 0.908 | D | 0.737 | prob.delet. | N | 0.489139504 | None | None | I |
| K/L | 0.3893 | ambiguous | 0.3491 | ambiguous | 0.588 | Stabilizing | 0.866 | D | 0.595 | neutral | None | None | None | None | I |
| K/M | 0.2536 | likely_benign | 0.2142 | benign | 0.159 | Stabilizing | 0.993 | D | 0.723 | prob.delet. | None | None | None | None | I |
| K/N | 0.4137 | ambiguous | 0.3452 | ambiguous | -0.015 | Destabilizing | 0.83 | D | 0.693 | prob.neutral | N | 0.514935143 | None | None | I |
| K/P | 0.8481 | likely_pathogenic | 0.8329 | pathogenic | 0.426 | Stabilizing | 0.929 | D | 0.733 | prob.delet. | None | None | None | None | I |
| K/Q | 0.1328 | likely_benign | 0.1238 | benign | -0.098 | Destabilizing | 0.83 | D | 0.681 | prob.neutral | N | 0.501773845 | None | None | I |
| K/R | 0.09 | likely_benign | 0.0882 | benign | -0.174 | Destabilizing | 0.01 | N | 0.345 | neutral | N | 0.491327565 | None | None | I |
| K/S | 0.3778 | ambiguous | 0.3281 | benign | -0.467 | Destabilizing | 0.648 | D | 0.641 | neutral | None | None | None | None | I |
| K/T | 0.1376 | likely_benign | 0.1208 | benign | -0.264 | Destabilizing | 0.83 | D | 0.677 | prob.neutral | N | 0.453193251 | None | None | I |
| K/V | 0.2785 | likely_benign | 0.2535 | benign | 0.426 | Stabilizing | 0.866 | D | 0.699 | prob.neutral | None | None | None | None | I |
| K/W | 0.8421 | likely_pathogenic | 0.8279 | pathogenic | -0.063 | Destabilizing | 0.993 | D | 0.763 | deleterious | None | None | None | None | I |
| K/Y | 0.7093 | likely_pathogenic | 0.6762 | pathogenic | 0.276 | Stabilizing | 0.929 | D | 0.732 | prob.delet. | None | None | None | None | I |
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.