Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2453 | 7582;7583;7584 | chr2:178773699;178773698;178773697 | chr2:179638426;179638425;179638424 |
| N2AB | 2453 | 7582;7583;7584 | chr2:178773699;178773698;178773697 | chr2:179638426;179638425;179638424 |
| N2A | 2453 | 7582;7583;7584 | chr2:178773699;178773698;178773697 | chr2:179638426;179638425;179638424 |
| N2B | 2407 | 7444;7445;7446 | chr2:178773699;178773698;178773697 | chr2:179638426;179638425;179638424 |
| Novex-1 | 2407 | 7444;7445;7446 | chr2:178773699;178773698;178773697 | chr2:179638426;179638425;179638424 |
| Novex-2 | 2407 | 7444;7445;7446 | chr2:178773699;178773698;178773697 | chr2:179638426;179638425;179638424 |
| Novex-3 | 2453 | 7582;7583;7584 | chr2:178773699;178773698;178773697 | chr2:179638426;179638425;179638424 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | None | None | 1.0 | D | 0.717 | 0.575 | 0.352048277211 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| D/E | rs1002418895  |
-0.078 | 1.0 | D | 0.415 | 0.326 | 0.295974979623 | gnomAD-2.1.1 | 3.99E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.83E-06 | 0 |
| D/E | rs1002418895 |
-0.078 | 1.0 | D | 0.415 | 0.326 | 0.295974979623 | gnomAD-4.0.0 | 1.59072E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85673E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.3903 | ambiguous | 0.3876 | ambiguous | -0.197 | Destabilizing | 1.0 | D | 0.717 | prob.delet. | D | 0.53828729 | None | None | N |
| D/C | 0.8792 | likely_pathogenic | 0.8745 | pathogenic | 0.18 | Stabilizing | 1.0 | D | 0.681 | prob.neutral | None | None | None | None | N |
| D/E | 0.402 | ambiguous | 0.3903 | ambiguous | -0.356 | Destabilizing | 1.0 | D | 0.415 | neutral | D | 0.550699244 | None | None | N |
| D/F | 0.9179 | likely_pathogenic | 0.9168 | pathogenic | -0.348 | Destabilizing | 1.0 | D | 0.697 | prob.neutral | None | None | None | None | N |
| D/G | 0.3237 | likely_benign | 0.3175 | benign | -0.382 | Destabilizing | 1.0 | D | 0.723 | prob.delet. | D | 0.622302165 | None | None | N |
| D/H | 0.5983 | likely_pathogenic | 0.5908 | pathogenic | -0.305 | Destabilizing | 1.0 | D | 0.663 | neutral | D | 0.664653922 | None | None | N |
| D/I | 0.834 | likely_pathogenic | 0.8279 | pathogenic | 0.234 | Stabilizing | 1.0 | D | 0.712 | prob.delet. | None | None | None | None | N |
| D/K | 0.7607 | likely_pathogenic | 0.7523 | pathogenic | 0.265 | Stabilizing | 1.0 | D | 0.753 | deleterious | None | None | None | None | N |
| D/L | 0.8316 | likely_pathogenic | 0.8301 | pathogenic | 0.234 | Stabilizing | 1.0 | D | 0.729 | prob.delet. | None | None | None | None | N |
| D/M | 0.9154 | likely_pathogenic | 0.9139 | pathogenic | 0.433 | Stabilizing | 1.0 | D | 0.685 | prob.neutral | None | None | None | None | N |
| D/N | 0.1491 | likely_benign | 0.148 | benign | 0.14 | Stabilizing | 1.0 | D | 0.603 | neutral | N | 0.476323233 | None | None | N |
| D/P | 0.7123 | likely_pathogenic | 0.7154 | pathogenic | 0.113 | Stabilizing | 1.0 | D | 0.728 | prob.delet. | None | None | None | None | N |
| D/Q | 0.7524 | likely_pathogenic | 0.7507 | pathogenic | 0.149 | Stabilizing | 1.0 | D | 0.653 | neutral | None | None | None | None | N |
| D/R | 0.8 | likely_pathogenic | 0.7982 | pathogenic | 0.35 | Stabilizing | 1.0 | D | 0.706 | prob.neutral | None | None | None | None | N |
| D/S | 0.2627 | likely_benign | 0.2597 | benign | 0.016 | Stabilizing | 1.0 | D | 0.637 | neutral | None | None | None | None | N |
| D/T | 0.5674 | likely_pathogenic | 0.5625 | ambiguous | 0.148 | Stabilizing | 1.0 | D | 0.757 | deleterious | None | None | None | None | N |
| D/V | 0.6315 | likely_pathogenic | 0.6225 | pathogenic | 0.113 | Stabilizing | 1.0 | D | 0.731 | prob.delet. | D | 0.601273331 | None | None | N |
| D/W | 0.9784 | likely_pathogenic | 0.9781 | pathogenic | -0.301 | Destabilizing | 1.0 | D | 0.681 | prob.neutral | None | None | None | None | N |
| D/Y | 0.5451 | ambiguous | 0.5417 | ambiguous | -0.134 | Destabilizing | 1.0 | D | 0.69 | prob.neutral | D | 0.626311465 | 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.