Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 34276 | 103051;103052;103053 | chr2:178533789;178533788;178533787 | chr2:179398516;179398515;179398514 |
| N2AB | 32635 | 98128;98129;98130 | chr2:178533789;178533788;178533787 | chr2:179398516;179398515;179398514 |
| N2A | 31708 | 95347;95348;95349 | chr2:178533789;178533788;178533787 | chr2:179398516;179398515;179398514 |
| N2B | 25211 | 75856;75857;75858 | chr2:178533789;178533788;178533787 | chr2:179398516;179398515;179398514 |
| Novex-1 | 25336 | 76231;76232;76233 | chr2:178533789;178533788;178533787 | chr2:179398516;179398515;179398514 |
| Novex-2 | 25403 | 76432;76433;76434 | chr2:178533789;178533788;178533787 | chr2:179398516;179398515;179398514 |
| 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/L | None | None | 0.993 | N | 0.657 | 0.403 | 0.355034743287 | gnomAD-4.0.0 | 6.84158E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99412E-07 | 0 | 0 |
| R/Q | rs199932621  |
-0.427 | 0.997 | N | 0.683 | 0.348 | 0.0954503805726 | gnomAD-2.1.1 | 3.92E-05 | None | None | None | None | N | None | 0 | 1.41411E-04 | None | 0 | 1.02501E-04 | None | 3.27E-05 | None | 4E-05 | 1.56E-05 | 0 |
| R/Q | rs199932621 |
-0.427 | 0.997 | N | 0.683 | 0.348 | 0.0954503805726 | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 1.92901E-04 | None | 0 | 0 | 4.41E-05 | 0 | 0 |
| R/Q | rs199932621 |
-0.427 | 0.997 | N | 0.683 | 0.348 | 0.0954503805726 | gnomAD-4.0.0 | 2.41662E-05 | None | None | None | None | N | None | 2.66951E-05 | 1.16674E-04 | None | 0 | 2.22826E-05 | None | 1.56245E-05 | 1.64366E-04 | 2.03412E-05 | 2.19568E-05 | 1.60097E-05 |
| R/W | rs781432886 |
-0.341 | 1.0 | N | 0.716 | 0.298 | 0.19670166235 | gnomAD-2.1.1 | 3.61E-05 | None | None | None | None | N | None | 0 | 2.02852E-04 | None | 0 | 0 | None | 0 | None | 0 | 1.77E-05 | 0 |
| R/W | rs781432886 |
-0.341 | 1.0 | N | 0.716 | 0.298 | 0.19670166235 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 9.43E-05 | 0 | 1.47E-05 | 2.07469E-04 | 0 |
| R/W | rs781432886 |
-0.341 | 1.0 | N | 0.716 | 0.298 | 0.19670166235 | gnomAD-4.0.0 | 1.17735E-05 | None | None | None | None | N | None | 0 | 1.16671E-04 | None | 0 | 2.22806E-05 | None | 1.56245E-05 | 0 | 5.08532E-06 | 2.19592E-05 | 3.20195E-05 |
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 | 0.6835 | likely_pathogenic | 0.6564 | pathogenic | -0.231 | Destabilizing | 0.953 | D | 0.627 | neutral | None | None | None | None | N |
| R/C | 0.1865 | likely_benign | 0.2057 | benign | -0.201 | Destabilizing | 0.999 | D | 0.737 | prob.delet. | None | None | None | None | N |
| R/D | 0.8846 | likely_pathogenic | 0.8722 | pathogenic | 0.047 | Stabilizing | 0.986 | D | 0.688 | prob.neutral | None | None | None | None | N |
| R/E | 0.6334 | likely_pathogenic | 0.6139 | pathogenic | 0.13 | Stabilizing | 0.953 | D | 0.612 | neutral | None | None | None | None | N |
| R/F | 0.7753 | likely_pathogenic | 0.7873 | pathogenic | -0.319 | Destabilizing | 0.993 | D | 0.752 | deleterious | None | None | None | None | N |
| R/G | 0.6146 | likely_pathogenic | 0.6104 | pathogenic | -0.476 | Destabilizing | 0.975 | D | 0.644 | neutral | N | 0.458307055 | None | None | N |
| R/H | 0.1283 | likely_benign | 0.1321 | benign | -0.928 | Destabilizing | 0.128 | N | 0.414 | neutral | None | None | None | None | N |
| R/I | 0.4259 | ambiguous | 0.4088 | ambiguous | 0.396 | Stabilizing | 0.993 | D | 0.751 | deleterious | None | None | None | None | N |
| R/K | 0.1774 | likely_benign | 0.1834 | benign | -0.2 | Destabilizing | 0.893 | D | 0.61 | neutral | None | None | None | None | N |
| R/L | 0.4359 | ambiguous | 0.414 | ambiguous | 0.396 | Stabilizing | 0.993 | D | 0.657 | neutral | N | 0.463120511 | None | None | N |
| R/M | 0.5541 | ambiguous | 0.5406 | ambiguous | 0.047 | Stabilizing | 0.999 | D | 0.681 | prob.neutral | None | None | None | None | N |
| R/N | 0.7774 | likely_pathogenic | 0.7657 | pathogenic | 0.229 | Stabilizing | 0.953 | D | 0.622 | neutral | None | None | None | None | N |
| R/P | 0.9417 | likely_pathogenic | 0.9441 | pathogenic | 0.209 | Stabilizing | 0.999 | D | 0.719 | prob.delet. | N | 0.46966336 | None | None | N |
| R/Q | 0.1523 | likely_benign | 0.1506 | benign | 0.055 | Stabilizing | 0.997 | D | 0.683 | prob.neutral | N | 0.459042843 | None | None | N |
| R/S | 0.6774 | likely_pathogenic | 0.6549 | pathogenic | -0.317 | Destabilizing | 0.953 | D | 0.648 | neutral | None | None | None | None | N |
| R/T | 0.4202 | ambiguous | 0.3927 | ambiguous | -0.078 | Destabilizing | 0.993 | D | 0.685 | prob.neutral | None | None | None | None | N |
| R/V | 0.503 | ambiguous | 0.4908 | ambiguous | 0.209 | Stabilizing | 0.993 | D | 0.74 | deleterious | None | None | None | None | N |
| R/W | 0.3688 | ambiguous | 0.3919 | ambiguous | -0.206 | Destabilizing | 1.0 | D | 0.716 | prob.delet. | N | 0.458560545 | None | None | N |
| R/Y | 0.5773 | likely_pathogenic | 0.5911 | pathogenic | 0.169 | Stabilizing | 0.986 | D | 0.719 | prob.delet. | 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.