Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2301 | 7126;7127;7128 | chr2:178774363;178774362;178774361 | chr2:179639090;179639089;179639088 |
| N2AB | 2301 | 7126;7127;7128 | chr2:178774363;178774362;178774361 | chr2:179639090;179639089;179639088 |
| N2A | 2301 | 7126;7127;7128 | chr2:178774363;178774362;178774361 | chr2:179639090;179639089;179639088 |
| N2B | 2255 | 6988;6989;6990 | chr2:178774363;178774362;178774361 | chr2:179639090;179639089;179639088 |
| Novex-1 | 2255 | 6988;6989;6990 | chr2:178774363;178774362;178774361 | chr2:179639090;179639089;179639088 |
| Novex-2 | 2255 | 6988;6989;6990 | chr2:178774363;178774362;178774361 | chr2:179639090;179639089;179639088 |
| Novex-3 | 2301 | 7126;7127;7128 | chr2:178774363;178774362;178774361 | chr2:179639090;179639089;179639088 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| H/L | rs746122611  |
-0.243 | 0.852 | N | 0.69 | 0.285 | 0.470237251169 | gnomAD-2.1.1 | 3.98E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.82E-06 | 0 |
| H/L | rs746122611 |
-0.243 | 0.852 | N | 0.69 | 0.285 | 0.470237251169 | gnomAD-4.0.0 | 6.84097E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99331E-07 | 0 | 0 |
| H/P | None | None | 0.996 | N | 0.742 | 0.342 | 0.342865806769 | gnomAD-4.0.0 | 6.84097E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99331E-07 | 0 | 0 |
| H/R | rs746122611 |
-1.211 | 0.996 | N | 0.695 | 0.286 | 0.158396225186 | gnomAD-2.1.1 | 3.18E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 2.88018E-04 | 0 | 0 |
| H/R | rs746122611 |
-1.211 | 0.996 | N | 0.695 | 0.286 | 0.158396225186 | gnomAD-4.0.0 | 5.47277E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.87224E-05 | 0 | 6.29532E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| H/A | 0.5289 | ambiguous | 0.5276 | ambiguous | -1.543 | Destabilizing | 0.969 | D | 0.666 | neutral | None | None | None | None | N |
| H/C | 0.1428 | likely_benign | 0.1392 | benign | -0.866 | Destabilizing | 0.999 | D | 0.715 | prob.delet. | None | None | None | None | N |
| H/D | 0.6948 | likely_pathogenic | 0.6828 | pathogenic | -1.346 | Destabilizing | 0.986 | D | 0.714 | prob.delet. | N | 0.451097803 | None | None | N |
| H/E | 0.5892 | likely_pathogenic | 0.5661 | pathogenic | -1.153 | Destabilizing | 0.99 | D | 0.664 | neutral | None | None | None | None | N |
| H/F | 0.333 | likely_benign | 0.3411 | ambiguous | 0.16 | Stabilizing | 0.02 | N | 0.385 | neutral | None | None | None | None | N |
| H/G | 0.6496 | likely_pathogenic | 0.6353 | pathogenic | -1.976 | Destabilizing | 0.99 | D | 0.677 | prob.neutral | None | None | None | None | N |
| H/I | 0.404 | ambiguous | 0.4024 | ambiguous | -0.277 | Destabilizing | 0.939 | D | 0.743 | deleterious | None | None | None | None | N |
| H/K | 0.1882 | likely_benign | 0.1789 | benign | -0.849 | Destabilizing | 0.99 | D | 0.704 | prob.neutral | None | None | None | None | N |
| H/L | 0.1889 | likely_benign | 0.1862 | benign | -0.277 | Destabilizing | 0.852 | D | 0.69 | prob.neutral | N | 0.445015288 | None | None | N |
| H/M | 0.5857 | likely_pathogenic | 0.5851 | pathogenic | -0.544 | Destabilizing | 0.997 | D | 0.703 | prob.neutral | None | None | None | None | N |
| H/N | 0.2952 | likely_benign | 0.2905 | benign | -1.535 | Destabilizing | 0.986 | D | 0.665 | neutral | N | 0.451097803 | None | None | N |
| H/P | 0.9142 | likely_pathogenic | 0.9156 | pathogenic | -0.687 | Destabilizing | 0.996 | D | 0.742 | deleterious | N | 0.451097803 | None | None | N |
| H/Q | 0.2019 | likely_benign | 0.1895 | benign | -1.154 | Destabilizing | 0.996 | D | 0.692 | prob.neutral | N | 0.438119291 | None | None | N |
| H/R | 0.0767 | likely_benign | 0.072 | benign | -1.009 | Destabilizing | 0.996 | D | 0.695 | prob.neutral | N | 0.411937544 | None | None | N |
| H/S | 0.4933 | ambiguous | 0.4896 | ambiguous | -1.732 | Destabilizing | 0.99 | D | 0.679 | prob.neutral | None | None | None | None | N |
| H/T | 0.5714 | likely_pathogenic | 0.5648 | pathogenic | -1.412 | Destabilizing | 0.99 | D | 0.719 | prob.delet. | None | None | None | None | N |
| H/V | 0.3687 | ambiguous | 0.3682 | ambiguous | -0.687 | Destabilizing | 0.939 | D | 0.707 | prob.neutral | None | None | None | None | N |
| H/W | 0.428 | ambiguous | 0.4278 | ambiguous | 0.736 | Stabilizing | 0.999 | D | 0.687 | prob.neutral | None | None | None | None | N |
| H/Y | 0.1206 | likely_benign | 0.1186 | benign | 0.636 | Stabilizing | 0.704 | D | 0.574 | neutral | N | 0.446682385 | 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.