Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24435 | 73528;73529;73530 | chr2:178572829;178572828;178572827 | chr2:179437556;179437555;179437554 |
| N2AB | 22794 | 68605;68606;68607 | chr2:178572829;178572828;178572827 | chr2:179437556;179437555;179437554 |
| N2A | 21867 | 65824;65825;65826 | chr2:178572829;178572828;178572827 | chr2:179437556;179437555;179437554 |
| N2B | 15370 | 46333;46334;46335 | chr2:178572829;178572828;178572827 | chr2:179437556;179437555;179437554 |
| Novex-1 | 15495 | 46708;46709;46710 | chr2:178572829;178572828;178572827 | chr2:179437556;179437555;179437554 |
| Novex-2 | 15562 | 46909;46910;46911 | chr2:178572829;178572828;178572827 | chr2:179437556;179437555;179437554 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/C | rs200028088  |
-0.076 | 1.0 | N | 0.776 | 0.5 | None | gnomAD-2.1.1 | 1.10956E-04 | None | None | None | None | I | None | 8.27E-05 | 5.66E-05 | None | 0 | 0 | None | 3.27E-05 | None | 1.20106E-04 | 1.64706E-04 | 2.81532E-04 |
| R/C | rs200028088 |
-0.076 | 1.0 | N | 0.776 | 0.5 | None | gnomAD-3.1.2 | 1.38154E-04 | None | None | None | None | I | None | 2.42E-05 | 5.24109E-04 | 0 | 0 | 0 | None | 0 | 0 | 1.47111E-04 | 0 | 9.57854E-04 |
| R/C | rs200028088 |
-0.076 | 1.0 | N | 0.776 | 0.5 | None | gnomAD-4.0.0 | 1.15289E-04 | None | None | None | None | I | None | 2.6678E-05 | 3.33389E-04 | None | 0 | 0 | None | 6.25078E-05 | 0 | 1.26318E-04 | 1.09827E-05 | 1.60102E-04 |
| R/H | rs794727456 |
-0.627 | 1.0 | N | 0.743 | 0.437 | 0.37762505005 | gnomAD-2.1.1 | 2.15E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 2.57918E-04 | None | 0 | None | 0 | 7.84E-06 | 0 |
| R/H | rs794727456 |
-0.627 | 1.0 | N | 0.743 | 0.437 | 0.37762505005 | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 5.81621E-04 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/H | rs794727456 |
-0.627 | 1.0 | N | 0.743 | 0.437 | 0.37762505005 | gnomAD-4.0.0 | 1.23981E-05 | None | None | None | None | I | None | 0 | 1.66795E-05 | None | 3.38112E-05 | 1.11692E-04 | None | 0 | 1.64636E-04 | 9.32573E-06 | 0 | 1.60164E-05 |
| R/L | rs794727456 |
None | 1.0 | N | 0.654 | 0.417 | 0.681325144492 | gnomAD-4.0.0 | 6.8439E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 1.657E-05 |
| R/S | rs200028088 |
0.032 | 1.0 | N | 0.677 | 0.493 | 0.588051273532 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.92E-06 | 0 |
| R/S | rs200028088 |
0.032 | 1.0 | N | 0.677 | 0.493 | 0.588051273532 | gnomAD-4.0.0 | 2.05309E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.69882E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.9615 | likely_pathogenic | 0.9622 | pathogenic | 0.091 | Stabilizing | 0.999 | D | 0.685 | prob.neutral | None | None | None | None | I |
| R/C | 0.7429 | likely_pathogenic | 0.7417 | pathogenic | -0.067 | Destabilizing | 1.0 | D | 0.776 | deleterious | N | 0.512137923 | None | None | I |
| R/D | 0.9929 | likely_pathogenic | 0.9937 | pathogenic | -0.125 | Destabilizing | 1.0 | D | 0.732 | prob.delet. | None | None | None | None | I |
| R/E | 0.9434 | likely_pathogenic | 0.9464 | pathogenic | -0.067 | Destabilizing | 0.999 | D | 0.713 | prob.delet. | None | None | None | None | I |
| R/F | 0.9812 | likely_pathogenic | 0.9831 | pathogenic | -0.15 | Destabilizing | 1.0 | D | 0.758 | deleterious | None | None | None | None | I |
| R/G | 0.9017 | likely_pathogenic | 0.9108 | pathogenic | -0.09 | Destabilizing | 1.0 | D | 0.654 | neutral | N | 0.508947747 | None | None | I |
| R/H | 0.5966 | likely_pathogenic | 0.6087 | pathogenic | -0.601 | Destabilizing | 1.0 | D | 0.743 | deleterious | N | 0.500021149 | None | None | I |
| R/I | 0.9475 | likely_pathogenic | 0.9501 | pathogenic | 0.53 | Stabilizing | 1.0 | D | 0.757 | deleterious | None | None | None | None | I |
| R/K | 0.3957 | ambiguous | 0.4037 | ambiguous | 0.013 | Stabilizing | 0.998 | D | 0.682 | prob.neutral | None | None | None | None | I |
| R/L | 0.853 | likely_pathogenic | 0.8577 | pathogenic | 0.53 | Stabilizing | 1.0 | D | 0.654 | neutral | N | 0.48824677 | None | None | I |
| R/M | 0.9159 | likely_pathogenic | 0.9196 | pathogenic | 0.077 | Stabilizing | 1.0 | D | 0.732 | prob.delet. | None | None | None | None | I |
| R/N | 0.9826 | likely_pathogenic | 0.9846 | pathogenic | 0.2 | Stabilizing | 1.0 | D | 0.713 | prob.delet. | None | None | None | None | I |
| R/P | 0.9873 | likely_pathogenic | 0.988 | pathogenic | 0.404 | Stabilizing | 1.0 | D | 0.712 | prob.delet. | N | 0.497442674 | None | None | I |
| R/Q | 0.4274 | ambiguous | 0.4396 | ambiguous | 0.123 | Stabilizing | 1.0 | D | 0.711 | prob.delet. | None | None | None | None | I |
| R/S | 0.9773 | likely_pathogenic | 0.9805 | pathogenic | -0.076 | Destabilizing | 1.0 | D | 0.677 | prob.neutral | N | 0.508842559 | None | None | I |
| R/T | 0.9555 | likely_pathogenic | 0.9558 | pathogenic | 0.108 | Stabilizing | 1.0 | D | 0.674 | neutral | None | None | None | None | I |
| R/V | 0.9562 | likely_pathogenic | 0.958 | pathogenic | 0.404 | Stabilizing | 1.0 | D | 0.747 | deleterious | None | None | None | None | I |
| R/W | 0.7647 | likely_pathogenic | 0.7613 | pathogenic | -0.262 | Destabilizing | 1.0 | D | 0.786 | deleterious | None | None | None | None | I |
| R/Y | 0.9383 | likely_pathogenic | 0.9437 | pathogenic | 0.154 | Stabilizing | 1.0 | D | 0.736 | prob.delet. | None | None | 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.