Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17425 | 52498;52499;52500 | chr2:178608738;178608737;178608736 | chr2:179473465;179473464;179473463 |
| N2AB | 15784 | 47575;47576;47577 | chr2:178608738;178608737;178608736 | chr2:179473465;179473464;179473463 |
| N2A | 14857 | 44794;44795;44796 | chr2:178608738;178608737;178608736 | chr2:179473465;179473464;179473463 |
| N2B | 8360 | 25303;25304;25305 | chr2:178608738;178608737;178608736 | chr2:179473465;179473464;179473463 |
| Novex-1 | 8485 | 25678;25679;25680 | chr2:178608738;178608737;178608736 | chr2:179473465;179473464;179473463 |
| Novex-2 | 8552 | 25879;25880;25881 | chr2:178608738;178608737;178608736 | chr2:179473465;179473464;179473463 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/F | None | None | 0.032 | N | 0.348 | 0.089 | 0.534907319155 | gnomAD-4.0.0 | 3.42336E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99839E-07 | 3.47931E-05 | 1.65854E-05 |
| L/I | rs764049705  |
-0.746 | 0.444 | N | 0.491 | 0.118 | 0.449572021084 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.9E-06 | 0 |
| L/I | rs764049705 |
-0.746 | 0.444 | N | 0.491 | 0.118 | 0.449572021084 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| L/I | rs764049705 |
-0.746 | 0.444 | N | 0.491 | 0.118 | 0.449572021084 | gnomAD-4.0.0 | 3.72086E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.24003E-06 | 1.09823E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.6207 | likely_pathogenic | 0.6142 | pathogenic | -2.484 | Highly Destabilizing | 0.754 | D | 0.499 | neutral | None | None | None | None | N |
| L/C | 0.6936 | likely_pathogenic | 0.735 | pathogenic | -1.959 | Destabilizing | 0.998 | D | 0.729 | prob.delet. | None | None | None | None | N |
| L/D | 0.9752 | likely_pathogenic | 0.9816 | pathogenic | -2.487 | Highly Destabilizing | 0.993 | D | 0.808 | deleterious | None | None | None | None | N |
| L/E | 0.8549 | likely_pathogenic | 0.8861 | pathogenic | -2.247 | Highly Destabilizing | 0.978 | D | 0.799 | deleterious | None | None | None | None | N |
| L/F | 0.5307 | ambiguous | 0.5896 | pathogenic | -1.495 | Destabilizing | 0.032 | N | 0.348 | neutral | N | 0.503320135 | None | None | N |
| L/G | 0.9041 | likely_pathogenic | 0.9125 | pathogenic | -3.055 | Highly Destabilizing | 0.978 | D | 0.775 | deleterious | None | None | None | None | N |
| L/H | 0.6744 | likely_pathogenic | 0.7552 | pathogenic | -2.522 | Highly Destabilizing | 0.997 | D | 0.783 | deleterious | N | 0.49533537 | None | None | N |
| L/I | 0.1641 | likely_benign | 0.1689 | benign | -0.826 | Destabilizing | 0.444 | N | 0.491 | neutral | N | 0.413719638 | None | None | N |
| L/K | 0.815 | likely_pathogenic | 0.8603 | pathogenic | -1.686 | Destabilizing | 0.978 | D | 0.746 | deleterious | None | None | None | None | N |
| L/M | 0.2241 | likely_benign | 0.2318 | benign | -0.923 | Destabilizing | 0.956 | D | 0.653 | neutral | None | None | None | None | N |
| L/N | 0.7831 | likely_pathogenic | 0.8114 | pathogenic | -2.026 | Highly Destabilizing | 0.993 | D | 0.8 | deleterious | None | None | None | None | N |
| L/P | 0.819 | likely_pathogenic | 0.8547 | pathogenic | -1.36 | Destabilizing | 0.99 | D | 0.804 | deleterious | N | 0.431379892 | None | None | N |
| L/Q | 0.5409 | ambiguous | 0.5961 | pathogenic | -1.855 | Destabilizing | 0.993 | D | 0.768 | deleterious | None | None | None | None | N |
| L/R | 0.7509 | likely_pathogenic | 0.8039 | pathogenic | -1.529 | Destabilizing | 0.971 | D | 0.775 | deleterious | N | 0.466071958 | None | None | N |
| L/S | 0.7548 | likely_pathogenic | 0.7719 | pathogenic | -2.817 | Highly Destabilizing | 0.956 | D | 0.734 | prob.delet. | None | None | None | None | N |
| L/T | 0.6284 | likely_pathogenic | 0.6384 | pathogenic | -2.416 | Highly Destabilizing | 0.956 | D | 0.675 | neutral | None | None | None | None | N |
| L/V | 0.1602 | likely_benign | 0.1592 | benign | -1.36 | Destabilizing | 0.014 | N | 0.401 | neutral | N | 0.374393246 | None | None | N |
| L/W | 0.8036 | likely_pathogenic | 0.8456 | pathogenic | -1.824 | Destabilizing | 0.998 | D | 0.749 | deleterious | None | None | None | None | N |
| L/Y | 0.8242 | likely_pathogenic | 0.8667 | pathogenic | -1.554 | Destabilizing | 0.915 | D | 0.735 | prob.delet. | 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.