Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16706 | 50341;50342;50343 | chr2:178612409;178612408;178612407 | chr2:179477136;179477135;179477134 |
| N2AB | 15065 | 45418;45419;45420 | chr2:178612409;178612408;178612407 | chr2:179477136;179477135;179477134 |
| N2A | 14138 | 42637;42638;42639 | chr2:178612409;178612408;178612407 | chr2:179477136;179477135;179477134 |
| N2B | 7641 | 23146;23147;23148 | chr2:178612409;178612408;178612407 | chr2:179477136;179477135;179477134 |
| Novex-1 | 7766 | 23521;23522;23523 | chr2:178612409;178612408;178612407 | chr2:179477136;179477135;179477134 |
| Novex-2 | 7833 | 23722;23723;23724 | chr2:178612409;178612408;178612407 | chr2:179477136;179477135;179477134 |
| 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 | None | None | 0.999 | N | 0.638 | 0.407 | 0.358540694251 | gnomAD-4.0.0 | 2.40064E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.21507E-04 | 0 |
| K/R | rs879111780  |
0.142 | 0.999 | N | 0.583 | 0.324 | 0.300784259202 | gnomAD-2.1.1 | 7.18E-06 | None | None | None | None | N | None | 0 | 2.84E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 1.41243E-04 |
| K/R | rs879111780 |
0.142 | 0.999 | N | 0.583 | 0.324 | 0.300784259202 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 0 | 6.56E-05 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| K/R | rs879111780 |
0.142 | 0.999 | N | 0.583 | 0.324 | 0.300784259202 | gnomAD-4.0.0 | 6.41578E-06 | None | None | None | None | N | None | 0 | 3.39547E-05 | None | 0 | 0 | None | 0 | 0 | 7.18845E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/A | 0.7814 | likely_pathogenic | 0.8103 | pathogenic | -0.091 | Destabilizing | 0.999 | D | 0.663 | neutral | None | None | None | None | N |
| K/C | 0.954 | likely_pathogenic | 0.9628 | pathogenic | -0.29 | Destabilizing | 1.0 | D | 0.693 | prob.neutral | None | None | None | None | N |
| K/D | 0.9102 | likely_pathogenic | 0.9195 | pathogenic | 0.179 | Stabilizing | 1.0 | D | 0.713 | prob.delet. | None | None | None | None | N |
| K/E | 0.6158 | likely_pathogenic | 0.6829 | pathogenic | 0.203 | Stabilizing | 0.999 | D | 0.638 | neutral | N | 0.466984545 | None | None | N |
| K/F | 0.9772 | likely_pathogenic | 0.9851 | pathogenic | -0.231 | Destabilizing | 1.0 | D | 0.675 | prob.neutral | None | None | None | None | N |
| K/G | 0.8085 | likely_pathogenic | 0.8499 | pathogenic | -0.319 | Destabilizing | 1.0 | D | 0.622 | neutral | None | None | None | None | N |
| K/H | 0.7216 | likely_pathogenic | 0.7356 | pathogenic | -0.615 | Destabilizing | 1.0 | D | 0.685 | prob.neutral | None | None | None | None | N |
| K/I | 0.8724 | likely_pathogenic | 0.9101 | pathogenic | 0.435 | Stabilizing | 1.0 | D | 0.687 | prob.neutral | None | None | None | None | N |
| K/L | 0.8 | likely_pathogenic | 0.8466 | pathogenic | 0.435 | Stabilizing | 1.0 | D | 0.622 | neutral | None | None | None | None | N |
| K/M | 0.7317 | likely_pathogenic | 0.7901 | pathogenic | 0.23 | Stabilizing | 1.0 | D | 0.678 | prob.neutral | D | 0.539768394 | None | None | N |
| K/N | 0.8114 | likely_pathogenic | 0.852 | pathogenic | 0.116 | Stabilizing | 1.0 | D | 0.744 | deleterious | N | 0.474969979 | None | None | N |
| K/P | 0.856 | likely_pathogenic | 0.8692 | pathogenic | 0.289 | Stabilizing | 1.0 | D | 0.697 | prob.neutral | None | None | None | None | N |
| K/Q | 0.3877 | ambiguous | 0.4229 | ambiguous | -0.035 | Destabilizing | 1.0 | D | 0.727 | prob.delet. | N | 0.468488537 | None | None | N |
| K/R | 0.1275 | likely_benign | 0.1321 | benign | -0.125 | Destabilizing | 0.999 | D | 0.583 | neutral | N | 0.476789619 | None | None | N |
| K/S | 0.8047 | likely_pathogenic | 0.844 | pathogenic | -0.427 | Destabilizing | 0.999 | D | 0.677 | prob.neutral | None | None | None | None | N |
| K/T | 0.5472 | ambiguous | 0.6032 | pathogenic | -0.239 | Destabilizing | 1.0 | D | 0.694 | prob.neutral | N | 0.460895764 | None | None | N |
| K/V | 0.8234 | likely_pathogenic | 0.8614 | pathogenic | 0.289 | Stabilizing | 1.0 | D | 0.659 | neutral | None | None | None | None | N |
| K/W | 0.9635 | likely_pathogenic | 0.9731 | pathogenic | -0.212 | Destabilizing | 1.0 | D | 0.704 | prob.neutral | None | None | None | None | N |
| K/Y | 0.952 | likely_pathogenic | 0.9645 | pathogenic | 0.136 | Stabilizing | 1.0 | D | 0.66 | 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.