Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30247 | 90964;90965;90966 | chr2:178552161;178552160;178552159 | chr2:179416888;179416887;179416886 |
| N2AB | 28606 | 86041;86042;86043 | chr2:178552161;178552160;178552159 | chr2:179416888;179416887;179416886 |
| N2A | 27679 | 83260;83261;83262 | chr2:178552161;178552160;178552159 | chr2:179416888;179416887;179416886 |
| N2B | 21182 | 63769;63770;63771 | chr2:178552161;178552160;178552159 | chr2:179416888;179416887;179416886 |
| Novex-1 | 21307 | 64144;64145;64146 | chr2:178552161;178552160;178552159 | chr2:179416888;179416887;179416886 |
| Novex-2 | 21374 | 64345;64346;64347 | chr2:178552161;178552160;178552159 | chr2:179416888;179416887;179416886 |
| 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 | rs1351789713  |
None | 0.026 | N | 0.163 | 0.054 | 0.0884992946249 | gnomAD-4.0.0 | 1.59126E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43316E-05 | 0 |
| D/G | rs540756997 |
-1.025 | 0.026 | N | 0.348 | 0.185 | 0.184867976434 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| D/G | rs540756997 |
-1.025 | 0.026 | N | 0.348 | 0.185 | 0.184867976434 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| D/G | rs540756997 |
-1.025 | 0.026 | N | 0.348 | 0.185 | 0.184867976434 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 1.4E-03 | None | None | 0 | 0 | None | None | None | 0 | None |
| D/G | rs540756997 |
-1.025 | 0.026 | N | 0.348 | 0.185 | 0.184867976434 | gnomAD-4.0.0 | 2.56167E-06 | None | None | None | None | N | None | 0 | 3.38914E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.1666 | likely_benign | 0.1725 | benign | -0.336 | Destabilizing | 0.811 | D | 0.577 | neutral | N | 0.454662184 | None | None | N |
| D/C | 0.6322 | likely_pathogenic | 0.6642 | pathogenic | -0.17 | Destabilizing | 0.999 | D | 0.757 | deleterious | None | None | None | None | N |
| D/E | 0.1206 | likely_benign | 0.1494 | benign | -0.646 | Destabilizing | 0.026 | N | 0.163 | neutral | N | 0.398363397 | None | None | N |
| D/F | 0.6933 | likely_pathogenic | 0.7117 | pathogenic | -0.005 | Destabilizing | 0.996 | D | 0.719 | prob.delet. | None | None | None | None | N |
| D/G | 0.1844 | likely_benign | 0.1823 | benign | -0.664 | Destabilizing | 0.026 | N | 0.348 | neutral | N | 0.498010316 | None | None | N |
| D/H | 0.3837 | ambiguous | 0.3991 | ambiguous | -0.315 | Destabilizing | 0.996 | D | 0.689 | prob.neutral | N | 0.477573756 | None | None | N |
| D/I | 0.4782 | ambiguous | 0.5146 | ambiguous | 0.514 | Stabilizing | 0.988 | D | 0.716 | prob.delet. | None | None | None | None | N |
| D/K | 0.4495 | ambiguous | 0.4823 | ambiguous | -0.268 | Destabilizing | 0.851 | D | 0.596 | neutral | None | None | None | None | N |
| D/L | 0.4035 | ambiguous | 0.4495 | ambiguous | 0.514 | Stabilizing | 0.976 | D | 0.703 | prob.neutral | None | None | None | None | N |
| D/M | 0.5584 | ambiguous | 0.6114 | pathogenic | 0.797 | Stabilizing | 0.999 | D | 0.733 | prob.delet. | None | None | None | None | N |
| D/N | 0.1126 | likely_benign | 0.1179 | benign | -0.643 | Destabilizing | 0.211 | N | 0.268 | neutral | N | 0.438249936 | None | None | N |
| D/P | 0.8784 | likely_pathogenic | 0.8818 | pathogenic | 0.257 | Stabilizing | 0.988 | D | 0.685 | prob.neutral | None | None | None | None | N |
| D/Q | 0.3324 | likely_benign | 0.3886 | ambiguous | -0.52 | Destabilizing | 0.952 | D | 0.587 | neutral | None | None | None | None | N |
| D/R | 0.5227 | ambiguous | 0.5624 | ambiguous | -0.101 | Destabilizing | 0.976 | D | 0.698 | prob.neutral | None | None | None | None | N |
| D/S | 0.1606 | likely_benign | 0.1681 | benign | -0.848 | Destabilizing | 0.919 | D | 0.492 | neutral | None | None | None | None | N |
| D/T | 0.288 | likely_benign | 0.3131 | benign | -0.587 | Destabilizing | 0.919 | D | 0.604 | neutral | None | None | None | None | N |
| D/V | 0.2937 | likely_benign | 0.3188 | benign | 0.257 | Stabilizing | 0.984 | D | 0.704 | prob.neutral | N | 0.49972247 | None | None | N |
| D/W | 0.9143 | likely_pathogenic | 0.923 | pathogenic | 0.131 | Stabilizing | 0.999 | D | 0.736 | prob.delet. | None | None | None | None | N |
| D/Y | 0.3424 | ambiguous | 0.3466 | ambiguous | 0.22 | Stabilizing | 0.995 | D | 0.719 | prob.delet. | N | 0.516769435 | 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.