Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 35174 | 105745;105746;105747 | chr2:178531095;178531094;178531093 | chr2:179395822;179395821;179395820 |
| N2AB | 33533 | 100822;100823;100824 | chr2:178531095;178531094;178531093 | chr2:179395822;179395821;179395820 |
| N2A | 32606 | 98041;98042;98043 | chr2:178531095;178531094;178531093 | chr2:179395822;179395821;179395820 |
| N2B | 26109 | 78550;78551;78552 | chr2:178531095;178531094;178531093 | chr2:179395822;179395821;179395820 |
| Novex-1 | 26234 | 78925;78926;78927 | chr2:178531095;178531094;178531093 | chr2:179395822;179395821;179395820 |
| Novex-2 | 26301 | 79126;79127;79128 | chr2:178531095;178531094;178531093 | chr2:179395822;179395821;179395820 |
| 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 | rs778207634  |
-0.859 | 0.997 | D | 0.583 | 0.52 | 0.720114801303 | gnomAD-2.1.1 | 4.82E-05 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 5.00779E-04 | None | 3.27E-05 | None | 0 | 8.86E-06 | 0 |
| R/C | rs778207634 |
-0.859 | 0.997 | D | 0.583 | 0.52 | 0.720114801303 | gnomAD-3.1.2 | 4.6E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 1.15473E-03 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/C | rs778207634 |
-0.859 | 0.997 | D | 0.583 | 0.52 | 0.720114801303 | gnomAD-4.0.0 | 4.70925E-05 | None | None | None | None | N | None | 0 | 1.6665E-05 | None | 0 | 1.31415E-03 | None | 0 | 1.64366E-04 | 8.4754E-06 | 5.48932E-05 | 0 |
| R/H | rs756575734 |
-1.479 | 0.028 | N | 0.229 | 0.154 | None | gnomAD-2.1.1 | 2.85E-05 | None | None | None | None | N | None | 4.13E-05 | 2.83E-05 | None | 0 | 0 | None | 0 | None | 0 | 4.67E-05 | 0 |
| R/H | rs756575734 |
-1.479 | 0.028 | N | 0.229 | 0.154 | None | gnomAD-3.1.2 | 5.26E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 7.35E-05 | 2.07641E-04 | 0 |
| R/H | rs756575734 |
-1.479 | 0.028 | N | 0.229 | 0.154 | None | gnomAD-4.0.0 | 7.3738E-05 | None | None | None | None | N | None | 6.67575E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 8.64489E-05 | 1.09801E-05 | 1.76113E-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 | 0.3694 | ambiguous | 0.5382 | ambiguous | -0.876 | Destabilizing | 0.484 | N | 0.425 | neutral | None | None | None | None | N |
| R/C | 0.1466 | likely_benign | 0.2197 | benign | -0.734 | Destabilizing | 0.997 | D | 0.583 | neutral | D | 0.538613882 | None | None | N |
| R/D | 0.5651 | likely_pathogenic | 0.7323 | pathogenic | -0.189 | Destabilizing | 0.767 | D | 0.452 | neutral | None | None | None | None | N |
| R/E | 0.3682 | ambiguous | 0.5089 | ambiguous | -0.082 | Destabilizing | 0.32 | N | 0.42 | neutral | None | None | None | None | N |
| R/F | 0.477 | ambiguous | 0.678 | pathogenic | -0.873 | Destabilizing | 0.767 | D | 0.555 | neutral | None | None | None | None | N |
| R/G | 0.2388 | likely_benign | 0.3473 | ambiguous | -1.171 | Destabilizing | 0.643 | D | 0.428 | neutral | N | 0.486641294 | None | None | N |
| R/H | 0.0913 | likely_benign | 0.1299 | benign | -1.52 | Destabilizing | 0.028 | N | 0.229 | neutral | N | 0.472335701 | None | None | N |
| R/I | 0.3184 | likely_benign | 0.4474 | ambiguous | -0.09 | Destabilizing | 0.87 | D | 0.548 | neutral | None | None | None | None | N |
| R/K | 0.1643 | likely_benign | 0.2017 | benign | -0.867 | Destabilizing | 0.279 | N | 0.463 | neutral | None | None | None | None | N |
| R/L | 0.2206 | likely_benign | 0.3376 | benign | -0.09 | Destabilizing | 0.863 | D | 0.414 | neutral | N | 0.507885874 | None | None | N |
| R/M | 0.4347 | ambiguous | 0.5672 | pathogenic | -0.251 | Destabilizing | 0.987 | D | 0.421 | neutral | None | None | None | None | N |
| R/N | 0.4405 | ambiguous | 0.6296 | pathogenic | -0.27 | Destabilizing | 0.32 | N | 0.451 | neutral | None | None | None | None | N |
| R/P | 0.5261 | ambiguous | 0.7019 | pathogenic | -0.331 | Destabilizing | 0.928 | D | 0.475 | neutral | N | 0.511608857 | None | None | N |
| R/Q | 0.105 | likely_benign | 0.1331 | benign | -0.505 | Destabilizing | 0.767 | D | 0.474 | neutral | None | None | None | None | N |
| R/S | 0.3709 | ambiguous | 0.5612 | ambiguous | -1.049 | Destabilizing | 0.643 | D | 0.453 | neutral | N | 0.486894783 | None | None | N |
| R/T | 0.2759 | likely_benign | 0.3903 | ambiguous | -0.765 | Destabilizing | 0.87 | D | 0.426 | neutral | None | None | None | None | N |
| R/V | 0.4057 | ambiguous | 0.5538 | ambiguous | -0.331 | Destabilizing | 0.87 | D | 0.552 | neutral | None | None | None | None | N |
| R/W | 0.1718 | likely_benign | 0.2571 | benign | -0.549 | Destabilizing | 0.987 | D | 0.595 | neutral | None | None | None | None | N |
| R/Y | 0.2957 | likely_benign | 0.4712 | ambiguous | -0.229 | Destabilizing | 0.622 | D | 0.489 | 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.