Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31450 | 94573;94574;94575 | chr2:178547177;178547176;178547175 | chr2:179411904;179411903;179411902 |
| N2AB | 29809 | 89650;89651;89652 | chr2:178547177;178547176;178547175 | chr2:179411904;179411903;179411902 |
| N2A | 28882 | 86869;86870;86871 | chr2:178547177;178547176;178547175 | chr2:179411904;179411903;179411902 |
| N2B | 22385 | 67378;67379;67380 | chr2:178547177;178547176;178547175 | chr2:179411904;179411903;179411902 |
| Novex-1 | 22510 | 67753;67754;67755 | chr2:178547177;178547176;178547175 | chr2:179411904;179411903;179411902 |
| Novex-2 | 22577 | 67954;67955;67956 | chr2:178547177;178547176;178547175 | chr2:179411904;179411903;179411902 |
| 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 | rs541040798  |
-0.081 | 1.0 | N | 0.701 | 0.41 | 0.553833332621 | gnomAD-2.1.1 | 3.24608E-04 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 2.67956E-03 | None | 0 | 6.24E-05 | 1.40331E-04 |
| R/C | rs541040798 |
-0.081 | 1.0 | N | 0.701 | 0.41 | 0.553833332621 | gnomAD-3.1.2 | 9.21E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 4.41E-05 | 2.07641E-03 | 4.80307E-04 |
| R/C | rs541040798 |
-0.081 | 1.0 | N | 0.701 | 0.41 | 0.553833332621 | 1000 genomes | 3.99361E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 2E-03 | None |
| R/C | rs541040798 |
-0.081 | 1.0 | N | 0.701 | 0.41 | 0.553833332621 | gnomAD-4.0.0 | 1.59878E-04 | None | None | None | None | N | None | 0 | 0 | None | 0 | 4.45851E-05 | None | 0 | 1.64962E-04 | 2.37334E-05 | 2.3718E-03 | 1.76101E-04 |
| R/H | rs751985617 |
-1.003 | 0.998 | N | 0.511 | 0.414 | 0.374613414588 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.87E-06 | 0 |
| R/H | rs751985617 |
-1.003 | 0.998 | N | 0.511 | 0.414 | 0.374613414588 | gnomAD-4.0.0 | 3.421E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.49738E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.9467 | likely_pathogenic | 0.9462 | pathogenic | -0.197 | Destabilizing | 0.754 | D | 0.583 | neutral | None | None | None | None | N |
| R/C | 0.7184 | likely_pathogenic | 0.7254 | pathogenic | -0.166 | Destabilizing | 1.0 | D | 0.701 | prob.neutral | N | 0.492471553 | None | None | N |
| R/D | 0.9875 | likely_pathogenic | 0.9879 | pathogenic | -0.024 | Destabilizing | 0.956 | D | 0.592 | neutral | None | None | None | None | N |
| R/E | 0.9199 | likely_pathogenic | 0.9295 | pathogenic | 0.05 | Stabilizing | 0.926 | D | 0.547 | neutral | None | None | None | None | N |
| R/F | 0.9727 | likely_pathogenic | 0.9746 | pathogenic | -0.337 | Destabilizing | 0.993 | D | 0.666 | neutral | None | None | None | None | N |
| R/G | 0.8967 | likely_pathogenic | 0.8929 | pathogenic | -0.428 | Destabilizing | 0.036 | N | 0.478 | neutral | N | 0.486387813 | None | None | N |
| R/H | 0.5084 | ambiguous | 0.5266 | ambiguous | -0.916 | Destabilizing | 0.998 | D | 0.511 | neutral | N | 0.471115295 | None | None | N |
| R/I | 0.8439 | likely_pathogenic | 0.8616 | pathogenic | 0.387 | Stabilizing | 0.978 | D | 0.669 | neutral | None | None | None | None | N |
| R/K | 0.2535 | likely_benign | 0.2613 | benign | -0.204 | Destabilizing | 0.717 | D | 0.487 | neutral | None | None | None | None | N |
| R/L | 0.8246 | likely_pathogenic | 0.8387 | pathogenic | 0.387 | Stabilizing | 0.988 | D | 0.554 | neutral | N | 0.482115357 | None | None | N |
| R/M | 0.8625 | likely_pathogenic | 0.8747 | pathogenic | 0.064 | Stabilizing | 0.998 | D | 0.553 | neutral | None | None | None | None | N |
| R/N | 0.9694 | likely_pathogenic | 0.971 | pathogenic | 0.225 | Stabilizing | 0.956 | D | 0.519 | neutral | None | None | None | None | N |
| R/P | 0.987 | likely_pathogenic | 0.9844 | pathogenic | 0.213 | Stabilizing | 0.996 | D | 0.639 | neutral | N | 0.465473823 | None | None | N |
| R/Q | 0.3981 | ambiguous | 0.4125 | ambiguous | 0.046 | Stabilizing | 0.993 | D | 0.539 | neutral | None | None | None | None | N |
| R/S | 0.9732 | likely_pathogenic | 0.9739 | pathogenic | -0.271 | Destabilizing | 0.922 | D | 0.593 | neutral | N | 0.484096869 | None | None | N |
| R/T | 0.9162 | likely_pathogenic | 0.9221 | pathogenic | -0.051 | Destabilizing | 0.978 | D | 0.523 | neutral | None | None | None | None | N |
| R/V | 0.8873 | likely_pathogenic | 0.9005 | pathogenic | 0.213 | Stabilizing | 0.978 | D | 0.668 | neutral | None | None | None | None | N |
| R/W | 0.7166 | likely_pathogenic | 0.7321 | pathogenic | -0.257 | Destabilizing | 0.998 | D | 0.707 | prob.neutral | None | None | None | None | N |
| R/Y | 0.9108 | likely_pathogenic | 0.912 | pathogenic | 0.124 | Stabilizing | 0.993 | D | 0.639 | 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.