Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23773 | 71542;71543;71544 | chr2:178574815;178574814;178574813 | chr2:179439542;179439541;179439540 |
| N2AB | 22132 | 66619;66620;66621 | chr2:178574815;178574814;178574813 | chr2:179439542;179439541;179439540 |
| N2A | 21205 | 63838;63839;63840 | chr2:178574815;178574814;178574813 | chr2:179439542;179439541;179439540 |
| N2B | 14708 | 44347;44348;44349 | chr2:178574815;178574814;178574813 | chr2:179439542;179439541;179439540 |
| Novex-1 | 14833 | 44722;44723;44724 | chr2:178574815;178574814;178574813 | chr2:179439542;179439541;179439540 |
| Novex-2 | 14900 | 44923;44924;44925 | chr2:178574815;178574814;178574813 | chr2:179439542;179439541;179439540 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/I | rs775492043  |
-0.104 | 0.949 | N | 0.423 | 0.328 | 0.350964488264 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| T/I | rs775492043 |
-0.104 | 0.949 | N | 0.423 | 0.328 | 0.350964488264 | gnomAD-4.0.0 | 1.24027E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.69596E-06 | 0 | 0 |
| T/N | None | None | 0.565 | N | 0.399 | 0.24 | 0.270889551736 | gnomAD-4.0.0 | 6.84655E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.9985E-07 | 0 | 0 |
| T/S | rs775492043 |
-0.29 | 0.014 | N | 0.231 | 0.058 | 0.171388866994 | gnomAD-2.1.1 | 8.1E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 6.56E-05 | None | 0 | 0 | 0 |
| T/S | rs775492043 |
-0.29 | 0.014 | N | 0.231 | 0.058 | 0.171388866994 | gnomAD-4.0.0 | 4.79258E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 8.1248E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.0652 | likely_benign | 0.0639 | benign | -0.381 | Destabilizing | 0.349 | N | 0.377 | neutral | N | 0.456680982 | None | None | I |
| T/C | 0.3232 | likely_benign | 0.2977 | benign | -0.355 | Destabilizing | 0.996 | D | 0.46 | neutral | None | None | None | None | I |
| T/D | 0.3415 | ambiguous | 0.3255 | benign | 0.288 | Stabilizing | 0.775 | D | 0.411 | neutral | None | None | None | None | I |
| T/E | 0.285 | likely_benign | 0.273 | benign | 0.217 | Stabilizing | 0.775 | D | 0.411 | neutral | None | None | None | None | I |
| T/F | 0.2458 | likely_benign | 0.2244 | benign | -0.902 | Destabilizing | 0.961 | D | 0.567 | neutral | None | None | None | None | I |
| T/G | 0.1783 | likely_benign | 0.1707 | benign | -0.499 | Destabilizing | 0.633 | D | 0.47 | neutral | None | None | None | None | I |
| T/H | 0.2475 | likely_benign | 0.2183 | benign | -0.674 | Destabilizing | 0.989 | D | 0.576 | neutral | None | None | None | None | I |
| T/I | 0.1401 | likely_benign | 0.1338 | benign | -0.191 | Destabilizing | 0.949 | D | 0.423 | neutral | N | 0.479981916 | None | None | I |
| T/K | 0.2384 | likely_benign | 0.2255 | benign | -0.324 | Destabilizing | 0.633 | D | 0.411 | neutral | None | None | None | None | I |
| T/L | 0.0878 | likely_benign | 0.0895 | benign | -0.191 | Destabilizing | 0.775 | D | 0.385 | neutral | None | None | None | None | I |
| T/M | 0.0909 | likely_benign | 0.0881 | benign | -0.157 | Destabilizing | 0.996 | D | 0.433 | neutral | None | None | None | None | I |
| T/N | 0.1003 | likely_benign | 0.0894 | benign | -0.141 | Destabilizing | 0.565 | D | 0.399 | neutral | N | 0.460990723 | None | None | I |
| T/P | 0.4298 | ambiguous | 0.4382 | ambiguous | -0.226 | Destabilizing | 0.949 | D | 0.418 | neutral | N | 0.471477076 | None | None | I |
| T/Q | 0.2147 | likely_benign | 0.198 | benign | -0.331 | Destabilizing | 0.923 | D | 0.423 | neutral | None | None | None | None | I |
| T/R | 0.2279 | likely_benign | 0.2127 | benign | -0.037 | Destabilizing | 0.923 | D | 0.437 | neutral | None | None | None | None | I |
| T/S | 0.0855 | likely_benign | 0.0792 | benign | -0.37 | Destabilizing | 0.014 | N | 0.231 | neutral | N | 0.417775877 | None | None | I |
| T/V | 0.0973 | likely_benign | 0.0948 | benign | -0.226 | Destabilizing | 0.775 | D | 0.373 | neutral | None | None | None | None | I |
| T/W | 0.6705 | likely_pathogenic | 0.6308 | pathogenic | -0.923 | Destabilizing | 0.996 | D | 0.658 | neutral | None | None | None | None | I |
| T/Y | 0.2843 | likely_benign | 0.2569 | benign | -0.629 | Destabilizing | 0.987 | D | 0.572 | 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.