Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2114 | 6565;6566;6567 | chr2:178775524;178775523;178775522 | chr2:179640251;179640250;179640249 |
| N2AB | 2114 | 6565;6566;6567 | chr2:178775524;178775523;178775522 | chr2:179640251;179640250;179640249 |
| N2A | 2114 | 6565;6566;6567 | chr2:178775524;178775523;178775522 | chr2:179640251;179640250;179640249 |
| N2B | 2068 | 6427;6428;6429 | chr2:178775524;178775523;178775522 | chr2:179640251;179640250;179640249 |
| Novex-1 | 2068 | 6427;6428;6429 | chr2:178775524;178775523;178775522 | chr2:179640251;179640250;179640249 |
| Novex-2 | 2068 | 6427;6428;6429 | chr2:178775524;178775523;178775522 | chr2:179640251;179640250;179640249 |
| Novex-3 | 2114 | 6565;6566;6567 | chr2:178775524;178775523;178775522 | chr2:179640251;179640250;179640249 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/S | rs372289753  |
0.015 | 0.999 | D | 0.575 | 0.632 | None | gnomAD-2.1.1 | 3.98E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.81E-06 | 0 |
| N/S | rs372289753 |
0.015 | 0.999 | D | 0.575 | 0.632 | None | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| N/S | rs372289753 |
0.015 | 0.999 | D | 0.575 | 0.632 | None | gnomAD-4.0.0 | 5.1231E-06 | None | None | None | None | N | None | 0 | 0 | None | 4.08998E-05 | 0 | None | 0 | 0 | 7.17542E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/A | 0.8782 | likely_pathogenic | 0.881 | pathogenic | -0.3 | Destabilizing | 1.0 | D | 0.607 | neutral | None | None | None | None | N |
| N/C | 0.904 | likely_pathogenic | 0.9013 | pathogenic | 0.319 | Stabilizing | 1.0 | D | 0.629 | neutral | None | None | None | None | N |
| N/D | 0.5725 | likely_pathogenic | 0.5688 | pathogenic | 0.135 | Stabilizing | 0.999 | D | 0.603 | neutral | D | 0.530960646 | None | None | N |
| N/E | 0.9429 | likely_pathogenic | 0.9387 | pathogenic | 0.083 | Stabilizing | 0.999 | D | 0.631 | neutral | None | None | None | None | N |
| N/F | 0.9781 | likely_pathogenic | 0.9763 | pathogenic | -0.785 | Destabilizing | 1.0 | D | 0.619 | neutral | None | None | None | None | N |
| N/G | 0.7308 | likely_pathogenic | 0.7392 | pathogenic | -0.434 | Destabilizing | 0.999 | D | 0.567 | neutral | None | None | None | None | N |
| N/H | 0.6883 | likely_pathogenic | 0.6747 | pathogenic | -0.5 | Destabilizing | 1.0 | D | 0.59 | neutral | D | 0.723836238 | None | None | N |
| N/I | 0.9601 | likely_pathogenic | 0.9577 | pathogenic | -0.04 | Destabilizing | 1.0 | D | 0.658 | neutral | D | 0.738986854 | None | None | N |
| N/K | 0.9662 | likely_pathogenic | 0.9595 | pathogenic | 0.195 | Stabilizing | 1.0 | D | 0.635 | neutral | D | 0.598981844 | None | None | N |
| N/L | 0.8925 | likely_pathogenic | 0.8939 | pathogenic | -0.04 | Destabilizing | 1.0 | D | 0.663 | neutral | None | None | None | None | N |
| N/M | 0.9267 | likely_pathogenic | 0.9244 | pathogenic | 0.319 | Stabilizing | 1.0 | D | 0.573 | neutral | None | None | None | None | N |
| N/P | 0.9944 | likely_pathogenic | 0.9943 | pathogenic | -0.101 | Destabilizing | 1.0 | D | 0.637 | neutral | None | None | None | None | N |
| N/Q | 0.9169 | likely_pathogenic | 0.9147 | pathogenic | -0.307 | Destabilizing | 1.0 | D | 0.606 | neutral | None | None | None | None | N |
| N/R | 0.9586 | likely_pathogenic | 0.9507 | pathogenic | 0.257 | Stabilizing | 1.0 | D | 0.647 | neutral | None | None | None | None | N |
| N/S | 0.3809 | ambiguous | 0.3931 | ambiguous | -0.05 | Destabilizing | 0.999 | D | 0.575 | neutral | D | 0.68183331 | None | None | N |
| N/T | 0.8363 | likely_pathogenic | 0.8385 | pathogenic | 0.032 | Stabilizing | 0.999 | D | 0.631 | neutral | D | 0.796833204 | None | None | N |
| N/V | 0.9502 | likely_pathogenic | 0.9478 | pathogenic | -0.101 | Destabilizing | 1.0 | D | 0.646 | neutral | None | None | None | None | N |
| N/W | 0.9899 | likely_pathogenic | 0.9882 | pathogenic | -0.8 | Destabilizing | 1.0 | D | 0.633 | neutral | None | None | None | None | N |
| N/Y | 0.7648 | likely_pathogenic | 0.7488 | pathogenic | -0.513 | Destabilizing | 1.0 | D | 0.607 | neutral | D | 0.795953322 | 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.