Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28065 | 84418;84419;84420 | chr2:178561939;178561938;178561937 | chr2:179426666;179426665;179426664 |
| N2AB | 26424 | 79495;79496;79497 | chr2:178561939;178561938;178561937 | chr2:179426666;179426665;179426664 |
| N2A | 25497 | 76714;76715;76716 | chr2:178561939;178561938;178561937 | chr2:179426666;179426665;179426664 |
| N2B | 19000 | 57223;57224;57225 | chr2:178561939;178561938;178561937 | chr2:179426666;179426665;179426664 |
| Novex-1 | 19125 | 57598;57599;57600 | chr2:178561939;178561938;178561937 | chr2:179426666;179426665;179426664 |
| Novex-2 | 19192 | 57799;57800;57801 | chr2:178561939;178561938;178561937 | chr2:179426666;179426665;179426664 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/E | rs2154160302  |
None | 0.099 | N | 0.173 | 0.041 | 0.185906805712 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 1.92901E-04 | None | 0 | 0 | 0 | 0 | 0 |
| D/E | rs2154160302 |
None | 0.099 | N | 0.173 | 0.041 | 0.185906805712 | gnomAD-4.0.0 | 6.56676E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 1.93349E-04 | None | 0 | 0 | 0 | 0 | 0 |
| D/H | rs764469970 |
-0.464 | 0.999 | N | 0.617 | 0.404 | 0.344251166708 | gnomAD-2.1.1 | 2.82E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 2.28893E-04 | None | 0 | 0 | 0 |
| D/H | rs764469970 |
-0.464 | 0.999 | N | 0.617 | 0.404 | 0.344251166708 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 3.16456E-03 | 0 | 0 | 0 |
| D/H | rs764469970 |
-0.464 | 0.999 | N | 0.617 | 0.404 | 0.344251166708 | gnomAD-4.0.0 | 1.91621E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 1.73551E-04 | 5.39739E-06 | 2.43506E-04 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.2533 | likely_benign | 0.2272 | benign | -0.62 | Destabilizing | 0.025 | N | 0.343 | neutral | N | 0.514670492 | None | None | I |
| D/C | 0.7066 | likely_pathogenic | 0.669 | pathogenic | -0.07 | Destabilizing | 0.997 | D | 0.708 | prob.delet. | None | None | None | None | I |
| D/E | 0.1781 | likely_benign | 0.1843 | benign | -0.502 | Destabilizing | 0.099 | N | 0.173 | neutral | N | 0.427704869 | None | None | I |
| D/F | 0.7753 | likely_pathogenic | 0.7311 | pathogenic | -0.54 | Destabilizing | 0.987 | D | 0.714 | prob.delet. | None | None | None | None | I |
| D/G | 0.2726 | likely_benign | 0.2145 | benign | -0.852 | Destabilizing | 0.805 | D | 0.521 | neutral | N | 0.473268115 | None | None | I |
| D/H | 0.3952 | ambiguous | 0.3557 | ambiguous | -0.575 | Destabilizing | 0.999 | D | 0.617 | neutral | N | 0.477382719 | None | None | I |
| D/I | 0.5126 | ambiguous | 0.4706 | ambiguous | -0.043 | Destabilizing | 0.975 | D | 0.716 | prob.delet. | None | None | None | None | I |
| D/K | 0.504 | ambiguous | 0.4337 | ambiguous | 0.063 | Stabilizing | 0.916 | D | 0.559 | neutral | None | None | None | None | I |
| D/L | 0.4884 | ambiguous | 0.4675 | ambiguous | -0.043 | Destabilizing | 0.95 | D | 0.691 | prob.neutral | None | None | None | None | I |
| D/M | 0.6763 | likely_pathogenic | 0.6564 | pathogenic | 0.306 | Stabilizing | 0.999 | D | 0.697 | prob.neutral | None | None | None | None | I |
| D/N | 0.1268 | likely_benign | 0.117 | benign | -0.287 | Destabilizing | 0.983 | D | 0.526 | neutral | N | 0.50074119 | None | None | I |
| D/P | 0.9284 | likely_pathogenic | 0.9094 | pathogenic | -0.213 | Destabilizing | 0.987 | D | 0.641 | neutral | None | None | None | None | I |
| D/Q | 0.4287 | ambiguous | 0.3909 | ambiguous | -0.256 | Destabilizing | 0.975 | D | 0.539 | neutral | None | None | None | None | I |
| D/R | 0.559 | ambiguous | 0.4733 | ambiguous | 0.189 | Stabilizing | 0.975 | D | 0.702 | prob.neutral | None | None | None | None | I |
| D/S | 0.151 | likely_benign | 0.139 | benign | -0.422 | Destabilizing | 0.845 | D | 0.461 | neutral | None | None | None | None | I |
| D/T | 0.2625 | likely_benign | 0.2488 | benign | -0.24 | Destabilizing | 0.975 | D | 0.589 | neutral | None | None | None | None | I |
| D/V | 0.3294 | likely_benign | 0.2942 | benign | -0.213 | Destabilizing | 0.935 | D | 0.645 | neutral | N | 0.485675737 | None | None | I |
| D/W | 0.9387 | likely_pathogenic | 0.9188 | pathogenic | -0.36 | Destabilizing | 0.999 | D | 0.679 | prob.neutral | None | None | None | None | I |
| D/Y | 0.429 | ambiguous | 0.3553 | ambiguous | -0.299 | Destabilizing | 0.999 | D | 0.713 | prob.delet. | N | 0.47533203 | 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.