Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1744 | 5455;5456;5457 | chr2:178776634;178776633;178776632 | chr2:179641361;179641360;179641359 |
| N2AB | 1744 | 5455;5456;5457 | chr2:178776634;178776633;178776632 | chr2:179641361;179641360;179641359 |
| N2A | 1744 | 5455;5456;5457 | chr2:178776634;178776633;178776632 | chr2:179641361;179641360;179641359 |
| N2B | 1698 | 5317;5318;5319 | chr2:178776634;178776633;178776632 | chr2:179641361;179641360;179641359 |
| Novex-1 | 1698 | 5317;5318;5319 | chr2:178776634;178776633;178776632 | chr2:179641361;179641360;179641359 |
| Novex-2 | 1698 | 5317;5318;5319 | chr2:178776634;178776633;178776632 | chr2:179641361;179641360;179641359 |
| Novex-3 | 1744 | 5455;5456;5457 | chr2:178776634;178776633;178776632 | chr2:179641361;179641360;179641359 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/L | rs75686037  |
0.045 | 1.0 | D | 0.732 | 0.554 | None | gnomAD-2.1.1 | 6.73712E-03 | None | None | None | None | N | None | 2.00321E-04 | 3.58132E-02 | None | 5.79598E-04 | 2.68055E-02 | None | 7.18719E-04 | None | 1.5935E-04 | 2.79759E-04 | 3.88889E-03 |
| P/L | rs75686037 |
0.045 | 1.0 | D | 0.732 | 0.554 | None | gnomAD-3.1.2 | 2.37911E-03 | None | None | None | None | N | None | 2.41429E-04 | 1.21728E-02 | 0 | 1.15274E-03 | 2.6772E-02 | None | 2.82486E-04 | 0 | 1.46998E-04 | 8.28157E-04 | 2.87081E-03 |
| P/L | rs75686037 |
0.045 | 1.0 | D | 0.732 | 0.554 | None | 1000 genomes | 6.98882E-03 | None | None | None | None | N | None | 8E-04 | 2.45E-02 | None | None | 1.69E-02 | 0 | None | None | None | 0 | None |
| P/L | rs75686037 |
0.045 | 1.0 | D | 0.732 | 0.554 | None | gnomAD-4.0.0 | 1.99004E-03 | None | None | None | None | N | None | 3.06601E-04 | 2.80167E-02 | None | 8.10701E-04 | 2.33709E-02 | None | 1.87465E-04 | 4.94886E-04 | 1.91525E-04 | 8.34395E-04 | 1.90388E-03 |
| P/S | rs761807419 |
-0.337 | 1.0 | D | 0.735 | 0.605 | 0.42805410278 | gnomAD-2.1.1 | 3.99E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.83E-06 | 0 |
| P/S | rs761807419 |
-0.337 | 1.0 | D | 0.735 | 0.605 | 0.42805410278 | gnomAD-4.0.0 | 1.2314E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.5288E-05 | 0 | 1.65585E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.1396 | likely_benign | 0.128 | benign | -0.679 | Destabilizing | 1.0 | D | 0.679 | prob.neutral | D | 0.628126256 | None | None | N |
| P/C | 0.9135 | likely_pathogenic | 0.8885 | pathogenic | -0.542 | Destabilizing | 1.0 | D | 0.695 | prob.neutral | None | None | None | None | N |
| P/D | 0.8603 | likely_pathogenic | 0.8298 | pathogenic | -0.532 | Destabilizing | 1.0 | D | 0.713 | prob.delet. | None | None | None | None | N |
| P/E | 0.6374 | likely_pathogenic | 0.5898 | pathogenic | -0.623 | Destabilizing | 1.0 | D | 0.723 | prob.delet. | None | None | None | None | N |
| P/F | 0.8632 | likely_pathogenic | 0.8244 | pathogenic | -0.748 | Destabilizing | 1.0 | D | 0.665 | neutral | None | None | None | None | N |
| P/G | 0.7017 | likely_pathogenic | 0.6484 | pathogenic | -0.858 | Destabilizing | 1.0 | D | 0.751 | deleterious | None | None | None | None | N |
| P/H | 0.5151 | ambiguous | 0.4546 | ambiguous | -0.425 | Destabilizing | 1.0 | D | 0.659 | neutral | None | None | None | None | N |
| P/I | 0.5487 | ambiguous | 0.5065 | ambiguous | -0.339 | Destabilizing | 1.0 | D | 0.717 | prob.delet. | None | None | None | None | N |
| P/K | 0.5956 | likely_pathogenic | 0.5256 | ambiguous | -0.667 | Destabilizing | 1.0 | D | 0.713 | prob.delet. | None | None | None | None | N |
| P/L | 0.2692 | likely_benign | 0.2147 | benign | -0.339 | Destabilizing | 1.0 | D | 0.732 | prob.delet. | D | 0.575071621 | None | None | N |
| P/M | 0.5894 | likely_pathogenic | 0.5463 | ambiguous | -0.353 | Destabilizing | 1.0 | D | 0.663 | neutral | None | None | None | None | N |
| P/N | 0.7095 | likely_pathogenic | 0.6687 | pathogenic | -0.326 | Destabilizing | 1.0 | D | 0.719 | prob.delet. | None | None | None | None | N |
| P/Q | 0.3527 | ambiguous | 0.3086 | benign | -0.563 | Destabilizing | 1.0 | D | 0.709 | prob.delet. | D | 0.58556516 | None | None | N |
| P/R | 0.4652 | ambiguous | 0.3962 | ambiguous | -0.124 | Destabilizing | 1.0 | D | 0.711 | prob.delet. | D | 0.58587405 | None | None | N |
| P/S | 0.3312 | likely_benign | 0.2889 | benign | -0.691 | Destabilizing | 1.0 | D | 0.735 | prob.delet. | D | 0.618650714 | None | None | N |
| P/T | 0.2739 | likely_benign | 0.2392 | benign | -0.684 | Destabilizing | 1.0 | D | 0.726 | prob.delet. | D | 0.65820175 | None | None | N |
| P/V | 0.3891 | ambiguous | 0.351 | ambiguous | -0.417 | Destabilizing | 1.0 | D | 0.721 | prob.delet. | None | None | None | None | N |
| P/W | 0.9548 | likely_pathogenic | 0.9379 | pathogenic | -0.857 | Destabilizing | 1.0 | D | 0.69 | prob.neutral | None | None | None | None | N |
| P/Y | 0.8274 | likely_pathogenic | 0.7807 | pathogenic | -0.572 | Destabilizing | 1.0 | D | 0.682 | prob.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.