Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14155 | 42688;42689;42690 | chr2:178634036;178634035;178634034 | chr2:179498763;179498762;179498761 |
| N2AB | 12514 | 37765;37766;37767 | chr2:178634036;178634035;178634034 | chr2:179498763;179498762;179498761 |
| N2A | 11587 | 34984;34985;34986 | chr2:178634036;178634035;178634034 | chr2:179498763;179498762;179498761 |
| N2B | 5090 | 15493;15494;15495 | chr2:178634036;178634035;178634034 | chr2:179498763;179498762;179498761 |
| Novex-1 | 5215 | 15868;15869;15870 | chr2:178634036;178634035;178634034 | chr2:179498763;179498762;179498761 |
| Novex-2 | 5282 | 16069;16070;16071 | chr2:178634036;178634035;178634034 | chr2:179498763;179498762;179498761 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| E/G | rs767378433  |
-1.202 | 1.0 | D | 0.641 | 0.546 | 0.444404870569 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.92E-06 | 0 |
| E/G | rs767378433 |
-1.202 | 1.0 | D | 0.641 | 0.546 | 0.444404870569 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| E/G | rs767378433 |
-1.202 | 1.0 | D | 0.641 | 0.546 | 0.444404870569 | gnomAD-4.0.0 | 3.04515E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.61495E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| E/A | 0.6637 | likely_pathogenic | 0.5092 | ambiguous | -0.691 | Destabilizing | 0.999 | D | 0.601 | neutral | N | 0.491040088 | None | None | N |
| E/C | 0.9957 | likely_pathogenic | 0.9917 | pathogenic | -0.276 | Destabilizing | 1.0 | D | 0.701 | prob.neutral | None | None | None | None | N |
| E/D | 0.906 | likely_pathogenic | 0.8374 | pathogenic | -0.675 | Destabilizing | 0.999 | D | 0.43 | neutral | D | 0.595942091 | None | None | N |
| E/F | 0.9963 | likely_pathogenic | 0.9916 | pathogenic | -0.248 | Destabilizing | 1.0 | D | 0.681 | prob.neutral | None | None | None | None | N |
| E/G | 0.8415 | likely_pathogenic | 0.7453 | pathogenic | -0.983 | Destabilizing | 1.0 | D | 0.641 | neutral | D | 0.635264162 | None | None | N |
| E/H | 0.9915 | likely_pathogenic | 0.9804 | pathogenic | -0.25 | Destabilizing | 1.0 | D | 0.627 | neutral | None | None | None | None | N |
| E/I | 0.9306 | likely_pathogenic | 0.8617 | pathogenic | 0.081 | Stabilizing | 1.0 | D | 0.715 | prob.delet. | None | None | None | None | N |
| E/K | 0.8626 | likely_pathogenic | 0.765 | pathogenic | -0.055 | Destabilizing | 0.999 | D | 0.577 | neutral | N | 0.48661841 | None | None | N |
| E/L | 0.9726 | likely_pathogenic | 0.9318 | pathogenic | 0.081 | Stabilizing | 1.0 | D | 0.699 | prob.neutral | None | None | None | None | N |
| E/M | 0.9618 | likely_pathogenic | 0.9252 | pathogenic | 0.319 | Stabilizing | 1.0 | D | 0.638 | neutral | None | None | None | None | N |
| E/N | 0.9624 | likely_pathogenic | 0.9181 | pathogenic | -0.565 | Destabilizing | 1.0 | D | 0.692 | prob.neutral | None | None | None | None | N |
| E/P | 0.9754 | likely_pathogenic | 0.9667 | pathogenic | -0.155 | Destabilizing | 1.0 | D | 0.645 | neutral | None | None | None | None | N |
| E/Q | 0.7592 | likely_pathogenic | 0.6251 | pathogenic | -0.477 | Destabilizing | 1.0 | D | 0.607 | neutral | D | 0.57137898 | None | None | N |
| E/R | 0.9316 | likely_pathogenic | 0.8837 | pathogenic | 0.221 | Stabilizing | 1.0 | D | 0.68 | prob.neutral | None | None | None | None | N |
| E/S | 0.9099 | likely_pathogenic | 0.8254 | pathogenic | -0.771 | Destabilizing | 0.999 | D | 0.627 | neutral | None | None | None | None | N |
| E/T | 0.9078 | likely_pathogenic | 0.8197 | pathogenic | -0.527 | Destabilizing | 1.0 | D | 0.686 | prob.neutral | None | None | None | None | N |
| E/V | 0.8422 | likely_pathogenic | 0.7022 | pathogenic | -0.155 | Destabilizing | 1.0 | D | 0.684 | prob.neutral | N | 0.475171803 | None | None | N |
| E/W | 0.9991 | likely_pathogenic | 0.9982 | pathogenic | 0.02 | Stabilizing | 1.0 | D | 0.703 | prob.neutral | None | None | None | None | N |
| E/Y | 0.9925 | likely_pathogenic | 0.9841 | pathogenic | 0.018 | Stabilizing | 1.0 | D | 0.668 | 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.