Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15355 | 46288;46289;46290 | chr2:178620458;178620457;178620456 | chr2:179485185;179485184;179485183 |
| N2AB | 13714 | 41365;41366;41367 | chr2:178620458;178620457;178620456 | chr2:179485185;179485184;179485183 |
| N2A | 12787 | 38584;38585;38586 | chr2:178620458;178620457;178620456 | chr2:179485185;179485184;179485183 |
| N2B | 6290 | 19093;19094;19095 | chr2:178620458;178620457;178620456 | chr2:179485185;179485184;179485183 |
| Novex-1 | 6415 | 19468;19469;19470 | chr2:178620458;178620457;178620456 | chr2:179485185;179485184;179485183 |
| Novex-2 | 6482 | 19669;19670;19671 | chr2:178620458;178620457;178620456 | chr2:179485185;179485184;179485183 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/N | rs397517583  |
-1.757 | 0.999 | D | 0.683 | 0.306 | 0.243972157842 | gnomAD-2.1.1 | 2.98811E-04 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 2.42004E-03 | None | 0 | 0 | 0 |
| K/N | rs397517583 |
-1.757 | 0.999 | D | 0.683 | 0.306 | 0.243972157842 | gnomAD-3.1.2 | 8.56E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.6904E-03 | 0 |
| K/N | rs397517583 |
-1.757 | 0.999 | D | 0.683 | 0.306 | 0.243972157842 | 1000 genomes | 5.99042E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 3.1E-03 | None |
| K/N | rs397517583 |
-1.757 | 0.999 | D | 0.683 | 0.306 | 0.243972157842 | gnomAD-4.0.0 | 1.35205E-04 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.3403E-03 | 8.01231E-05 |
| K/Q | None | None | 0.999 | D | 0.669 | 0.418 | 0.365892764245 | gnomAD-4.0.0 | 1.3695E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.80004E-06 | 0 | 0 |
| K/R | rs776832569 |
-1.377 | 0.64 | N | 0.275 | 0.21 | None | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.94E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/A | 0.7468 | likely_pathogenic | 0.8087 | pathogenic | -0.991 | Destabilizing | 0.998 | D | 0.55 | neutral | None | None | None | None | N |
| K/C | 0.8222 | likely_pathogenic | 0.8859 | pathogenic | -0.862 | Destabilizing | 1.0 | D | 0.818 | deleterious | None | None | None | None | N |
| K/D | 0.907 | likely_pathogenic | 0.9351 | pathogenic | -1.386 | Destabilizing | 1.0 | D | 0.825 | deleterious | None | None | None | None | N |
| K/E | 0.4669 | ambiguous | 0.5348 | ambiguous | -1.168 | Destabilizing | 0.996 | D | 0.437 | neutral | D | 0.599953977 | None | None | N |
| K/F | 0.9209 | likely_pathogenic | 0.9521 | pathogenic | -0.135 | Destabilizing | 1.0 | D | 0.816 | deleterious | None | None | None | None | N |
| K/G | 0.8345 | likely_pathogenic | 0.8792 | pathogenic | -1.454 | Destabilizing | 1.0 | D | 0.723 | prob.delet. | None | None | None | None | N |
| K/H | 0.497 | ambiguous | 0.5717 | pathogenic | -1.813 | Destabilizing | 1.0 | D | 0.804 | deleterious | None | None | None | None | N |
| K/I | 0.5791 | likely_pathogenic | 0.6593 | pathogenic | 0.292 | Stabilizing | 1.0 | D | 0.848 | deleterious | None | None | None | None | N |
| K/L | 0.6078 | likely_pathogenic | 0.6819 | pathogenic | 0.292 | Stabilizing | 1.0 | D | 0.723 | prob.delet. | None | None | None | None | N |
| K/M | 0.4641 | ambiguous | 0.5555 | ambiguous | 0.167 | Stabilizing | 1.0 | D | 0.799 | deleterious | D | 0.647428514 | None | None | N |
| K/N | 0.7614 | likely_pathogenic | 0.8081 | pathogenic | -1.535 | Destabilizing | 0.999 | D | 0.683 | prob.neutral | D | 0.560652647 | None | None | N |
| K/P | 0.9867 | likely_pathogenic | 0.9903 | pathogenic | -0.111 | Destabilizing | 1.0 | D | 0.826 | deleterious | None | None | None | None | N |
| K/Q | 0.2421 | likely_benign | 0.2976 | benign | -1.264 | Destabilizing | 0.999 | D | 0.669 | neutral | D | 0.580163295 | None | None | N |
| K/R | 0.0951 | likely_benign | 0.1114 | benign | -1.445 | Destabilizing | 0.64 | D | 0.275 | neutral | N | 0.498490791 | None | None | N |
| K/S | 0.7444 | likely_pathogenic | 0.8038 | pathogenic | -1.945 | Destabilizing | 0.998 | D | 0.521 | neutral | None | None | None | None | N |
| K/T | 0.3811 | ambiguous | 0.4499 | ambiguous | -1.508 | Destabilizing | 0.999 | D | 0.741 | deleterious | N | 0.50672401 | None | None | N |
| K/V | 0.5535 | ambiguous | 0.6443 | pathogenic | -0.111 | Destabilizing | 1.0 | D | 0.81 | deleterious | None | None | None | None | N |
| K/W | 0.8781 | likely_pathogenic | 0.9245 | pathogenic | -0.265 | Destabilizing | 1.0 | D | 0.807 | deleterious | None | None | None | None | N |
| K/Y | 0.7998 | likely_pathogenic | 0.8531 | pathogenic | 0.016 | Stabilizing | 1.0 | D | 0.83 | deleterious | 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.