Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24268 | 73027;73028;73029 | chr2:178573330;178573329;178573328 | chr2:179438057;179438056;179438055 |
| N2AB | 22627 | 68104;68105;68106 | chr2:178573330;178573329;178573328 | chr2:179438057;179438056;179438055 |
| N2A | 21700 | 65323;65324;65325 | chr2:178573330;178573329;178573328 | chr2:179438057;179438056;179438055 |
| N2B | 15203 | 45832;45833;45834 | chr2:178573330;178573329;178573328 | chr2:179438057;179438056;179438055 |
| Novex-1 | 15328 | 46207;46208;46209 | chr2:178573330;178573329;178573328 | chr2:179438057;179438056;179438055 |
| Novex-2 | 15395 | 46408;46409;46410 | chr2:178573330;178573329;178573328 | chr2:179438057;179438056;179438055 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/C | rs370474301  |
-0.418 | 1.0 | D | 0.738 | 0.51 | None | gnomAD-2.1.1 | 1.39115E-04 | None | None | None | None | N | None | 4.24E-05 | 3.71E-05 | None | 2.68908E-03 | 2.76213E-04 | None | 0 | None | 0 | 7.31E-05 | 1.75131E-04 |
| R/C | rs370474301 |
-0.418 | 1.0 | D | 0.738 | 0.51 | None | gnomAD-3.1.2 | 9.87E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 2.30415E-03 | 1.93798E-04 | None | 0 | 0 | 5.89E-05 | 0 | 0 |
| R/C | rs370474301 |
-0.418 | 1.0 | D | 0.738 | 0.51 | None | gnomAD-4.0.0 | 7.66042E-05 | None | None | None | None | N | None | 2.74055E-05 | 1.95442E-05 | None | 2.13261E-03 | 2.2607E-04 | None | 0 | 0 | 3.64775E-05 | 3.7772E-05 | 1.00204E-04 |
| R/H | rs140018785 |
-1.061 | 1.0 | N | 0.715 | 0.415 | None | gnomAD-2.1.1 | 3.52233E-04 | None | None | None | None | N | None | 1.34156E-04 | 0 | None | 0 | 4.02838E-03 | None | 0 | None | 0 | 1.06E-05 | 0 |
| R/H | rs140018785 |
-1.061 | 1.0 | N | 0.715 | 0.415 | None | gnomAD-3.1.2 | 7.23E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 1.74149E-03 | None | 0 | 0 | 0 | 0 | 0 |
| R/H | rs140018785 |
-1.061 | 1.0 | N | 0.715 | 0.415 | None | 1000 genomes | 9.98403E-04 | None | None | None | None | N | None | 2.3E-03 | 0 | None | None | 2E-03 | 0 | None | None | None | 0 | None |
| R/H | rs140018785 |
-1.061 | 1.0 | N | 0.715 | 0.415 | None | gnomAD-4.0.0 | 2.19458E-04 | None | None | None | None | N | None | 4.1061E-05 | 0 | None | 0 | 7.20643E-03 | None | 0 | 0 | 9.55246E-06 | 1.25856E-05 | 1.16815E-04 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.8602 | likely_pathogenic | 0.8111 | pathogenic | 0.095 | Stabilizing | 0.999 | D | 0.571 | neutral | None | None | None | None | N |
| R/C | 0.4658 | ambiguous | 0.3679 | ambiguous | -0.275 | Destabilizing | 1.0 | D | 0.738 | prob.delet. | D | 0.528012181 | None | None | N |
| R/D | 0.9482 | likely_pathogenic | 0.9306 | pathogenic | -0.251 | Destabilizing | 1.0 | D | 0.625 | neutral | None | None | None | None | N |
| R/E | 0.8585 | likely_pathogenic | 0.8074 | pathogenic | -0.188 | Destabilizing | 0.999 | D | 0.627 | neutral | None | None | None | None | N |
| R/F | 0.8617 | likely_pathogenic | 0.8064 | pathogenic | -0.186 | Destabilizing | 1.0 | D | 0.701 | prob.neutral | None | None | None | None | N |
| R/G | 0.6921 | likely_pathogenic | 0.6172 | pathogenic | -0.072 | Destabilizing | 1.0 | D | 0.541 | neutral | D | 0.522615185 | None | None | N |
| R/H | 0.2176 | likely_benign | 0.1878 | benign | -0.607 | Destabilizing | 1.0 | D | 0.715 | prob.delet. | N | 0.482649411 | None | None | N |
| R/I | 0.7046 | likely_pathogenic | 0.621 | pathogenic | 0.494 | Stabilizing | 1.0 | D | 0.701 | prob.neutral | None | None | None | None | N |
| R/K | 0.1875 | likely_benign | 0.1844 | benign | -0.106 | Destabilizing | 0.998 | D | 0.581 | neutral | None | None | None | None | N |
| R/L | 0.6438 | likely_pathogenic | 0.574 | pathogenic | 0.494 | Stabilizing | 1.0 | D | 0.541 | neutral | N | 0.492313708 | None | None | N |
| R/M | 0.7306 | likely_pathogenic | 0.6633 | pathogenic | -0.072 | Destabilizing | 1.0 | D | 0.662 | neutral | None | None | None | None | N |
| R/N | 0.8784 | likely_pathogenic | 0.8504 | pathogenic | -0.099 | Destabilizing | 1.0 | D | 0.663 | neutral | None | None | None | None | N |
| R/P | 0.9317 | likely_pathogenic | 0.9094 | pathogenic | 0.38 | Stabilizing | 1.0 | D | 0.633 | neutral | N | 0.48724454 | None | None | N |
| R/Q | 0.2783 | likely_benign | 0.2297 | benign | -0.097 | Destabilizing | 1.0 | D | 0.654 | neutral | None | None | None | None | N |
| R/S | 0.8978 | likely_pathogenic | 0.8593 | pathogenic | -0.284 | Destabilizing | 1.0 | D | 0.571 | neutral | N | 0.464034496 | None | None | N |
| R/T | 0.7822 | likely_pathogenic | 0.7292 | pathogenic | -0.098 | Destabilizing | 1.0 | D | 0.581 | neutral | None | None | None | None | N |
| R/V | 0.7765 | likely_pathogenic | 0.7071 | pathogenic | 0.38 | Stabilizing | 1.0 | D | 0.676 | prob.neutral | None | None | None | None | N |
| R/W | 0.4717 | ambiguous | 0.3773 | ambiguous | -0.363 | Destabilizing | 1.0 | D | 0.756 | deleterious | None | None | None | None | N |
| R/Y | 0.6488 | likely_pathogenic | 0.5903 | pathogenic | 0.061 | Stabilizing | 1.0 | D | 0.659 | 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.