Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19534 | 58825;58826;58827 | chr2:178593700;178593699;178593698 | chr2:179458427;179458426;179458425 |
| N2AB | 17893 | 53902;53903;53904 | chr2:178593700;178593699;178593698 | chr2:179458427;179458426;179458425 |
| N2A | 16966 | 51121;51122;51123 | chr2:178593700;178593699;178593698 | chr2:179458427;179458426;179458425 |
| N2B | 10469 | 31630;31631;31632 | chr2:178593700;178593699;178593698 | chr2:179458427;179458426;179458425 |
| Novex-1 | 10594 | 32005;32006;32007 | chr2:178593700;178593699;178593698 | chr2:179458427;179458426;179458425 |
| Novex-2 | 10661 | 32206;32207;32208 | chr2:178593700;178593699;178593698 | chr2:179458427;179458426;179458425 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/G | None | None | 0.012 | N | 0.347 | 0.057 | 0.101711395817 | gnomAD-4.0.0 | 1.59211E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43308E-05 | 0 |
| S/N | rs563833549  |
-0.681 | None | N | 0.14 | 0.119 | 0.104622674875 | gnomAD-2.1.1 | 3.22E-05 | None | None | None | None | N | None | 8.27E-05 | 1.13385E-04 | None | 1.93573E-04 | 0 | None | 0 | None | 0 | 7.83E-06 | 0 |
| S/N | rs563833549 |
-0.681 | None | N | 0.14 | 0.119 | 0.104622674875 | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | N | None | 9.65E-05 | 6.56E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| S/N | rs563833549 |
-0.681 | None | N | 0.14 | 0.119 | 0.104622674875 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 8E-04 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| S/N | rs563833549 |
-0.681 | None | N | 0.14 | 0.119 | 0.104622674875 | gnomAD-4.0.0 | 1.67353E-05 | None | None | None | None | N | None | 9.33134E-05 | 1.00087E-04 | None | 0 | 0 | None | 0 | 0 | 8.47736E-06 | 0 | 6.40389E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.085 | likely_benign | 0.0835 | benign | -0.822 | Destabilizing | 0.007 | N | 0.307 | neutral | None | None | None | None | N |
| S/C | 0.0834 | likely_benign | 0.0853 | benign | -0.615 | Destabilizing | None | N | 0.283 | neutral | N | 0.409911329 | None | None | N |
| S/D | 0.6847 | likely_pathogenic | 0.6119 | pathogenic | -0.669 | Destabilizing | 0.038 | N | 0.372 | neutral | None | None | None | None | N |
| S/E | 0.7424 | likely_pathogenic | 0.6775 | pathogenic | -0.627 | Destabilizing | 0.072 | N | 0.395 | neutral | None | None | None | None | N |
| S/F | 0.3463 | ambiguous | 0.247 | benign | -0.911 | Destabilizing | 0.356 | N | 0.601 | neutral | None | None | None | None | N |
| S/G | 0.1329 | likely_benign | 0.1325 | benign | -1.109 | Destabilizing | 0.012 | N | 0.347 | neutral | N | 0.475842745 | None | None | N |
| S/H | 0.5452 | ambiguous | 0.4924 | ambiguous | -1.593 | Destabilizing | 0.214 | N | 0.573 | neutral | None | None | None | None | N |
| S/I | 0.1704 | likely_benign | 0.1458 | benign | -0.15 | Destabilizing | 0.055 | N | 0.568 | neutral | N | 0.428150373 | None | None | N |
| S/K | 0.8811 | likely_pathogenic | 0.8283 | pathogenic | -0.682 | Destabilizing | 0.072 | N | 0.395 | neutral | None | None | None | None | N |
| S/L | 0.1282 | likely_benign | 0.0942 | benign | -0.15 | Destabilizing | 0.016 | N | 0.503 | neutral | None | None | None | None | N |
| S/M | 0.2113 | likely_benign | 0.163 | benign | 0.102 | Stabilizing | 0.628 | D | 0.573 | neutral | None | None | None | None | N |
| S/N | 0.2036 | likely_benign | 0.1732 | benign | -0.806 | Destabilizing | None | N | 0.14 | neutral | N | 0.475440101 | None | None | N |
| S/P | 0.6265 | likely_pathogenic | 0.6124 | pathogenic | -0.34 | Destabilizing | 0.136 | N | 0.601 | neutral | None | None | None | None | N |
| S/Q | 0.6951 | likely_pathogenic | 0.6347 | pathogenic | -0.912 | Destabilizing | 0.214 | N | 0.526 | neutral | None | None | None | None | N |
| S/R | 0.8384 | likely_pathogenic | 0.7842 | pathogenic | -0.673 | Destabilizing | 0.055 | N | 0.605 | neutral | N | 0.489772048 | None | None | N |
| S/T | 0.0824 | likely_benign | 0.0772 | benign | -0.742 | Destabilizing | None | N | 0.086 | neutral | N | 0.463263024 | None | None | N |
| S/V | 0.1603 | likely_benign | 0.1399 | benign | -0.34 | Destabilizing | 0.016 | N | 0.507 | neutral | None | None | None | None | N |
| S/W | 0.5628 | ambiguous | 0.4653 | ambiguous | -0.92 | Destabilizing | 0.864 | D | 0.594 | neutral | None | None | None | None | N |
| S/Y | 0.2905 | likely_benign | 0.2236 | benign | -0.622 | Destabilizing | 0.628 | D | 0.599 | 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.