Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24989 | 75190;75191;75192 | chr2:178571167;178571166;178571165 | chr2:179435894;179435893;179435892 |
| N2AB | 23348 | 70267;70268;70269 | chr2:178571167;178571166;178571165 | chr2:179435894;179435893;179435892 |
| N2A | 22421 | 67486;67487;67488 | chr2:178571167;178571166;178571165 | chr2:179435894;179435893;179435892 |
| N2B | 15924 | 47995;47996;47997 | chr2:178571167;178571166;178571165 | chr2:179435894;179435893;179435892 |
| Novex-1 | 16049 | 48370;48371;48372 | chr2:178571167;178571166;178571165 | chr2:179435894;179435893;179435892 |
| Novex-2 | 16116 | 48571;48572;48573 | chr2:178571167;178571166;178571165 | chr2:179435894;179435893;179435892 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/M | rs567800207  |
-0.406 | 0.999 | N | 0.673 | 0.244 | 0.421427970867 | gnomAD-2.1.1 | 5.72221E-04 | None | None | None | None | I | None | 0 | 4.92782E-04 | None | 0 | 5.59E-05 | None | 3.98745E-03 | None | 0 | 0 | 3.31675E-04 |
| V/M | rs567800207 |
-0.406 | 0.999 | N | 0.673 | 0.244 | 0.421427970867 | gnomAD-3.1.2 | 1.57787E-04 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 4.76388E-03 | 4.77555E-04 |
| V/M | rs567800207 |
-0.406 | 0.999 | N | 0.673 | 0.244 | 0.421427970867 | 1000 genomes | 1.39776E-03 | None | None | None | None | I | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 7.2E-03 | None |
| V/M | rs567800207 |
-0.406 | 0.999 | N | 0.673 | 0.244 | 0.421427970867 | gnomAD-4.0.0 | 2.53491E-04 | None | None | None | None | I | None | 2.66645E-05 | 3.0002E-04 | None | 3.37952E-05 | 2.23254E-05 | None | 0 | 0 | 4.23859E-06 | 4.06263E-03 | 1.92105E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.1476 | likely_benign | 0.1574 | benign | -0.526 | Destabilizing | 0.025 | N | 0.319 | neutral | N | 0.403001212 | None | None | I |
| V/C | 0.7794 | likely_pathogenic | 0.7851 | pathogenic | -0.9 | Destabilizing | 0.997 | D | 0.694 | prob.neutral | None | None | None | None | I |
| V/D | 0.9571 | likely_pathogenic | 0.9571 | pathogenic | -0.362 | Destabilizing | 0.987 | D | 0.793 | deleterious | None | None | None | None | I |
| V/E | 0.8887 | likely_pathogenic | 0.8916 | pathogenic | -0.468 | Destabilizing | 0.967 | D | 0.749 | deleterious | N | 0.46772148 | None | None | I |
| V/F | 0.5157 | ambiguous | 0.5569 | ambiguous | -0.678 | Destabilizing | 0.987 | D | 0.691 | prob.neutral | None | None | None | None | I |
| V/G | 0.5584 | ambiguous | 0.548 | ambiguous | -0.637 | Destabilizing | 0.935 | D | 0.704 | prob.neutral | N | 0.473797867 | None | None | I |
| V/H | 0.9399 | likely_pathogenic | 0.9394 | pathogenic | -0.027 | Destabilizing | 0.999 | D | 0.81 | deleterious | None | None | None | None | I |
| V/I | 0.1573 | likely_benign | 0.167 | benign | -0.377 | Destabilizing | 0.818 | D | 0.449 | neutral | None | None | None | None | I |
| V/K | 0.9057 | likely_pathogenic | 0.905 | pathogenic | -0.542 | Destabilizing | 0.975 | D | 0.753 | deleterious | None | None | None | None | I |
| V/L | 0.6329 | likely_pathogenic | 0.661 | pathogenic | -0.377 | Destabilizing | 0.812 | D | 0.493 | neutral | N | 0.497202239 | None | None | I |
| V/M | 0.368 | ambiguous | 0.3871 | ambiguous | -0.558 | Destabilizing | 0.999 | D | 0.673 | neutral | N | 0.491576635 | None | None | I |
| V/N | 0.8504 | likely_pathogenic | 0.8561 | pathogenic | -0.429 | Destabilizing | 0.987 | D | 0.803 | deleterious | None | None | None | None | I |
| V/P | 0.9581 | likely_pathogenic | 0.9483 | pathogenic | -0.394 | Destabilizing | 0.987 | D | 0.772 | deleterious | None | None | None | None | I |
| V/Q | 0.8147 | likely_pathogenic | 0.8291 | pathogenic | -0.654 | Destabilizing | 0.987 | D | 0.782 | deleterious | None | None | None | None | I |
| V/R | 0.8083 | likely_pathogenic | 0.8074 | pathogenic | 0.02 | Stabilizing | 0.987 | D | 0.803 | deleterious | None | None | None | None | I |
| V/S | 0.3813 | ambiguous | 0.3807 | ambiguous | -0.789 | Destabilizing | 0.95 | D | 0.681 | prob.neutral | None | None | None | None | I |
| V/T | 0.3363 | likely_benign | 0.3551 | ambiguous | -0.795 | Destabilizing | 0.916 | D | 0.597 | neutral | None | None | None | None | I |
| V/W | 0.9772 | likely_pathogenic | 0.9771 | pathogenic | -0.721 | Destabilizing | 0.999 | D | 0.825 | deleterious | None | None | None | None | I |
| V/Y | 0.9184 | likely_pathogenic | 0.928 | pathogenic | -0.458 | Destabilizing | 0.996 | D | 0.697 | prob.neutral | None | None | None | None | I |
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.