Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 7230 | 21913;21914;21915 | chr2:178723319;178723318;178723317 | chr2:179588046;179588045;179588044 |
| N2AB | 6913 | 20962;20963;20964 | chr2:178723319;178723318;178723317 | chr2:179588046;179588045;179588044 |
| N2A | 5986 | 18181;18182;18183 | chr2:178723319;178723318;178723317 | chr2:179588046;179588045;179588044 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/S | rs1458297684  |
None | 0.994 | N | 0.527 | 0.355 | 0.335164054921 | gnomAD-4.0.0 | 6.00161E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 6.56251E-06 | 0 | 0 |
| A/V | rs761223583 |
-0.2 | 0.733 | N | 0.251 | 0.386 | 0.473931330248 | gnomAD-2.1.1 | 5.29E-05 | None | None | None | None | I | None | 0 | 2.63204E-04 | None | 0 | 0 | None | 0 | None | 0 | 3.61E-05 | 0 |
| A/V | rs761223583 |
-0.2 | 0.733 | N | 0.251 | 0.386 | 0.473931330248 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | I | None | 2.41E-05 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| A/V | rs761223583 |
-0.2 | 0.733 | N | 0.251 | 0.386 | 0.473931330248 | gnomAD-4.0.0 | 2.73078E-05 | None | None | None | None | I | None | 1.3379E-05 | 1.84088E-04 | None | 0 | 0 | None | 0 | 0 | 2.71518E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.8555 | likely_pathogenic | 0.8747 | pathogenic | -1.276 | Destabilizing | 1.0 | D | 0.602 | neutral | None | None | None | None | I |
| A/D | 0.9853 | likely_pathogenic | 0.9889 | pathogenic | -1.723 | Destabilizing | 0.998 | D | 0.709 | prob.delet. | N | 0.501716215 | None | None | I |
| A/E | 0.9647 | likely_pathogenic | 0.9746 | pathogenic | -1.721 | Destabilizing | 0.999 | D | 0.633 | neutral | None | None | None | None | I |
| A/F | 0.9567 | likely_pathogenic | 0.9718 | pathogenic | -1.168 | Destabilizing | 0.999 | D | 0.69 | prob.neutral | None | None | None | None | I |
| A/G | 0.4521 | ambiguous | 0.4427 | ambiguous | -1.39 | Destabilizing | 0.994 | D | 0.515 | neutral | N | 0.512223147 | None | None | I |
| A/H | 0.9877 | likely_pathogenic | 0.9904 | pathogenic | -1.536 | Destabilizing | 1.0 | D | 0.689 | prob.neutral | None | None | None | None | I |
| A/I | 0.7477 | likely_pathogenic | 0.891 | pathogenic | -0.436 | Destabilizing | 0.995 | D | 0.604 | neutral | None | None | None | None | I |
| A/K | 0.9873 | likely_pathogenic | 0.9914 | pathogenic | -1.321 | Destabilizing | 0.999 | D | 0.632 | neutral | None | None | None | None | I |
| A/L | 0.6968 | likely_pathogenic | 0.7978 | pathogenic | -0.436 | Destabilizing | 0.983 | D | 0.522 | neutral | None | None | None | None | I |
| A/M | 0.849 | likely_pathogenic | 0.9203 | pathogenic | -0.45 | Destabilizing | 1.0 | D | 0.641 | neutral | None | None | None | None | I |
| A/N | 0.971 | likely_pathogenic | 0.9796 | pathogenic | -1.183 | Destabilizing | 1.0 | D | 0.699 | prob.neutral | None | None | None | None | I |
| A/P | 0.4245 | ambiguous | 0.3876 | ambiguous | -0.615 | Destabilizing | 0.391 | N | 0.289 | neutral | N | 0.487825015 | None | None | I |
| A/Q | 0.9633 | likely_pathogenic | 0.971 | pathogenic | -1.33 | Destabilizing | 1.0 | D | 0.649 | neutral | None | None | None | None | I |
| A/R | 0.9682 | likely_pathogenic | 0.9741 | pathogenic | -1.002 | Destabilizing | 1.0 | D | 0.645 | neutral | None | None | None | None | I |
| A/S | 0.3461 | ambiguous | 0.3802 | ambiguous | -1.554 | Destabilizing | 0.994 | D | 0.527 | neutral | N | 0.511716168 | None | None | I |
| A/T | 0.4742 | ambiguous | 0.6337 | pathogenic | -1.454 | Destabilizing | 0.989 | D | 0.551 | neutral | N | 0.512223147 | None | None | I |
| A/V | 0.3868 | ambiguous | 0.5999 | pathogenic | -0.615 | Destabilizing | 0.733 | D | 0.251 | neutral | N | 0.512223147 | None | None | I |
| A/W | 0.9957 | likely_pathogenic | 0.9968 | pathogenic | -1.543 | Destabilizing | 1.0 | D | 0.717 | prob.delet. | None | None | None | None | I |
| A/Y | 0.9835 | likely_pathogenic | 0.9878 | pathogenic | -1.124 | Destabilizing | 1.0 | D | 0.689 | prob.neutral | 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.