Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15822 | 47689;47690;47691 | chr2:178617887;178617886;178617885 | chr2:179482614;179482613;179482612 |
| N2AB | 14181 | 42766;42767;42768 | chr2:178617887;178617886;178617885 | chr2:179482614;179482613;179482612 |
| N2A | 13254 | 39985;39986;39987 | chr2:178617887;178617886;178617885 | chr2:179482614;179482613;179482612 |
| N2B | 6757 | 20494;20495;20496 | chr2:178617887;178617886;178617885 | chr2:179482614;179482613;179482612 |
| Novex-1 | 6882 | 20869;20870;20871 | chr2:178617887;178617886;178617885 | chr2:179482614;179482613;179482612 |
| Novex-2 | 6949 | 21070;21071;21072 | chr2:178617887;178617886;178617885 | chr2:179482614;179482613;179482612 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/N | None | None | 1.0 | N | 0.655 | 0.365 | 0.327419511103 | gnomAD-4.0.0 | 2.05384E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.69977E-06 | 0 | 0 |
| D/Y | rs1180743833  |
0.145 | 1.0 | D | 0.653 | 0.495 | 0.739327834083 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 6.47E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| D/Y | rs1180743833 |
0.145 | 1.0 | D | 0.653 | 0.495 | 0.739327834083 | gnomAD-4.0.0 | 2.73845E-06 | None | None | None | None | N | None | 2.99419E-05 | 0 | None | 0 | 7.57079E-05 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.4291 | ambiguous | 0.3752 | ambiguous | 0.111 | Stabilizing | 1.0 | D | 0.629 | neutral | D | 0.627150127 | None | None | N |
| D/C | 0.9204 | likely_pathogenic | 0.8856 | pathogenic | -0.153 | Destabilizing | 1.0 | D | 0.677 | prob.neutral | None | None | None | None | N |
| D/E | 0.3685 | ambiguous | 0.3275 | benign | -0.281 | Destabilizing | 1.0 | D | 0.44 | neutral | N | 0.518723976 | None | None | N |
| D/F | 0.9037 | likely_pathogenic | 0.8802 | pathogenic | 0.133 | Stabilizing | 1.0 | D | 0.659 | neutral | None | None | None | None | N |
| D/G | 0.3287 | likely_benign | 0.2809 | benign | -0.037 | Destabilizing | 1.0 | D | 0.657 | neutral | N | 0.470105916 | None | None | N |
| D/H | 0.6395 | likely_pathogenic | 0.5727 | pathogenic | 0.709 | Stabilizing | 1.0 | D | 0.621 | neutral | D | 0.572284578 | None | None | N |
| D/I | 0.8777 | likely_pathogenic | 0.841 | pathogenic | 0.438 | Stabilizing | 1.0 | D | 0.643 | neutral | None | None | None | None | N |
| D/K | 0.7709 | likely_pathogenic | 0.6897 | pathogenic | 0.485 | Stabilizing | 1.0 | D | 0.633 | neutral | None | None | None | None | N |
| D/L | 0.8095 | likely_pathogenic | 0.7508 | pathogenic | 0.438 | Stabilizing | 1.0 | D | 0.645 | neutral | None | None | None | None | N |
| D/M | 0.9031 | likely_pathogenic | 0.8749 | pathogenic | 0.157 | Stabilizing | 1.0 | D | 0.665 | neutral | None | None | None | None | N |
| D/N | 0.2005 | likely_benign | 0.1793 | benign | 0.13 | Stabilizing | 1.0 | D | 0.655 | neutral | N | 0.479787632 | None | None | N |
| D/P | 0.9373 | likely_pathogenic | 0.9012 | pathogenic | 0.35 | Stabilizing | 1.0 | D | 0.609 | neutral | None | None | None | None | N |
| D/Q | 0.7037 | likely_pathogenic | 0.6423 | pathogenic | 0.167 | Stabilizing | 1.0 | D | 0.637 | neutral | None | None | None | None | N |
| D/R | 0.7586 | likely_pathogenic | 0.6855 | pathogenic | 0.759 | Stabilizing | 1.0 | D | 0.633 | neutral | None | None | None | None | N |
| D/S | 0.291 | likely_benign | 0.2481 | benign | 0.055 | Stabilizing | 1.0 | D | 0.681 | prob.neutral | None | None | None | None | N |
| D/T | 0.5931 | likely_pathogenic | 0.5417 | ambiguous | 0.183 | Stabilizing | 1.0 | D | 0.641 | neutral | None | None | None | None | N |
| D/V | 0.6918 | likely_pathogenic | 0.6339 | pathogenic | 0.35 | Stabilizing | 1.0 | D | 0.638 | neutral | D | 0.717350258 | None | None | N |
| D/W | 0.9692 | likely_pathogenic | 0.9605 | pathogenic | 0.191 | Stabilizing | 1.0 | D | 0.681 | prob.neutral | None | None | None | None | N |
| D/Y | 0.5942 | likely_pathogenic | 0.5225 | ambiguous | 0.371 | Stabilizing | 1.0 | D | 0.653 | neutral | D | 0.618446307 | 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.