Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20722 | 62389;62390;62391 | chr2:178589561;178589560;178589559 | chr2:179454288;179454287;179454286 |
| N2AB | 19081 | 57466;57467;57468 | chr2:178589561;178589560;178589559 | chr2:179454288;179454287;179454286 |
| N2A | 18154 | 54685;54686;54687 | chr2:178589561;178589560;178589559 | chr2:179454288;179454287;179454286 |
| N2B | 11657 | 35194;35195;35196 | chr2:178589561;178589560;178589559 | chr2:179454288;179454287;179454286 |
| Novex-1 | 11782 | 35569;35570;35571 | chr2:178589561;178589560;178589559 | chr2:179454288;179454287;179454286 |
| Novex-2 | 11849 | 35770;35771;35772 | chr2:178589561;178589560;178589559 | chr2:179454288;179454287;179454286 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/N | rs568728579  |
None | 0.007 | N | 0.154 | 0.172 | 0.158396225186 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| S/N | rs568728579 |
None | 0.007 | N | 0.154 | 0.172 | 0.158396225186 | gnomAD-4.0.0 | 2.56401E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.78822E-06 | 0 | 0 |
| S/R | rs750725073 |
-0.65 | 0.794 | N | 0.447 | 0.248 | 0.228597637076 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| S/R | rs750725073 |
-0.65 | 0.794 | N | 0.447 | 0.248 | 0.228597637076 | gnomAD-4.0.0 | 2.05309E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.31922E-05 | 1.65673E-05 |
| S/T | rs568728579 |
-0.791 | 0.183 | N | 0.331 | 0.172 | 0.16115917748 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| S/T | rs568728579 |
-0.791 | 0.183 | N | 0.331 | 0.172 | 0.16115917748 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.07383E-04 | 0 |
| S/T | rs568728579 |
-0.791 | 0.183 | N | 0.331 | 0.172 | 0.16115917748 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 1E-03 | None |
| S/T | rs568728579 |
-0.791 | 0.183 | N | 0.331 | 0.172 | 0.16115917748 | gnomAD-4.0.0 | 6.57722E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.07555E-04 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.0796 | likely_benign | 0.0954 | benign | -0.394 | Destabilizing | 0.061 | N | 0.251 | neutral | None | None | None | None | N |
| S/C | 0.1595 | likely_benign | 0.1746 | benign | -0.155 | Destabilizing | 0.978 | D | 0.381 | neutral | D | 0.52281276 | None | None | N |
| S/D | 0.6809 | likely_pathogenic | 0.6141 | pathogenic | 0.019 | Stabilizing | 0.264 | N | 0.299 | neutral | None | None | None | None | N |
| S/E | 0.7493 | likely_pathogenic | 0.6954 | pathogenic | -0.061 | Destabilizing | 0.418 | N | 0.295 | neutral | None | None | None | None | N |
| S/F | 0.3503 | ambiguous | 0.3838 | ambiguous | -0.859 | Destabilizing | 0.716 | D | 0.457 | neutral | None | None | None | None | N |
| S/G | 0.1468 | likely_benign | 0.1737 | benign | -0.541 | Destabilizing | 0.001 | N | 0.097 | neutral | N | 0.462609663 | None | None | N |
| S/H | 0.5899 | likely_pathogenic | 0.5484 | ambiguous | -1.01 | Destabilizing | 0.836 | D | 0.399 | neutral | None | None | None | None | N |
| S/I | 0.2233 | likely_benign | 0.2247 | benign | -0.13 | Destabilizing | 0.213 | N | 0.427 | neutral | N | 0.460860224 | None | None | N |
| S/K | 0.8946 | likely_pathogenic | 0.8776 | pathogenic | -0.568 | Destabilizing | 0.418 | N | 0.294 | neutral | None | None | None | None | N |
| S/L | 0.1627 | likely_benign | 0.1771 | benign | -0.13 | Destabilizing | 0.002 | N | 0.297 | neutral | None | None | None | None | N |
| S/M | 0.2427 | likely_benign | 0.2624 | benign | 0.108 | Stabilizing | 0.716 | D | 0.409 | neutral | None | None | None | None | N |
| S/N | 0.2023 | likely_benign | 0.2049 | benign | -0.197 | Destabilizing | 0.007 | N | 0.154 | neutral | N | 0.440234236 | None | None | N |
| S/P | 0.2349 | likely_benign | 0.2614 | benign | -0.187 | Destabilizing | 0.002 | N | 0.213 | neutral | None | None | None | None | N |
| S/Q | 0.6698 | likely_pathogenic | 0.6367 | pathogenic | -0.433 | Destabilizing | 0.836 | D | 0.402 | neutral | None | None | None | None | N |
| S/R | 0.8764 | likely_pathogenic | 0.8613 | pathogenic | -0.341 | Destabilizing | 0.794 | D | 0.447 | neutral | N | 0.459993433 | None | None | N |
| S/T | 0.1032 | likely_benign | 0.1147 | benign | -0.283 | Destabilizing | 0.183 | N | 0.331 | neutral | N | 0.441887674 | None | None | N |
| S/V | 0.2085 | likely_benign | 0.2248 | benign | -0.187 | Destabilizing | 0.004 | N | 0.245 | neutral | None | None | None | None | N |
| S/W | 0.56 | ambiguous | 0.5438 | ambiguous | -0.878 | Destabilizing | 0.983 | D | 0.503 | neutral | None | None | None | None | N |
| S/Y | 0.3379 | likely_benign | 0.3421 | ambiguous | -0.614 | Destabilizing | 0.94 | D | 0.443 | 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.