Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18618 | 56077;56078;56079 | chr2:178601052;178601051;178601050 | chr2:179465779;179465778;179465777 |
| N2AB | 16977 | 51154;51155;51156 | chr2:178601052;178601051;178601050 | chr2:179465779;179465778;179465777 |
| N2A | 16050 | 48373;48374;48375 | chr2:178601052;178601051;178601050 | chr2:179465779;179465778;179465777 |
| N2B | 9553 | 28882;28883;28884 | chr2:178601052;178601051;178601050 | chr2:179465779;179465778;179465777 |
| Novex-1 | 9678 | 29257;29258;29259 | chr2:178601052;178601051;178601050 | chr2:179465779;179465778;179465777 |
| Novex-2 | 9745 | 29458;29459;29460 | chr2:178601052;178601051;178601050 | chr2:179465779;179465778;179465777 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| C/F | None | None | 0.921 | N | 0.795 | 0.302 | 0.733974040729 | gnomAD-4.0.0 | 1.59314E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.02645E-05 |
| C/G | None | None | 0.351 | N | 0.737 | 0.266 | 0.644618625695 | gnomAD-4.0.0 | 2.73822E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.59923E-06 | 0 | 0 |
| C/R | rs369260968  |
-0.847 | None | N | 0.638 | 0.304 | None | gnomAD-2.1.1 | 6.45E-05 | None | None | None | None | N | None | 5.38391E-04 | 1.13411E-04 | None | 0 | 0 | None | 0 | None | 0 | 0 | 1.40885E-04 |
| C/R | rs369260968 |
-0.847 | None | N | 0.638 | 0.304 | None | gnomAD-3.1.2 | 1.90913E-04 | None | None | None | None | N | None | 6.52584E-04 | 6.56E-05 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| C/R | rs369260968 |
-0.847 | None | N | 0.638 | 0.304 | None | gnomAD-4.0.0 | 3.2244E-05 | None | None | None | None | N | None | 5.74959E-04 | 1.00123E-04 | None | 0 | 0 | None | 0 | 0 | 8.47953E-07 | 0 | 3.20359E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| C/A | 0.4494 | ambiguous | 0.3896 | ambiguous | -1.16 | Destabilizing | 0.114 | N | 0.436 | neutral | None | None | None | None | N |
| C/D | 0.9289 | likely_pathogenic | 0.8957 | pathogenic | -1.505 | Destabilizing | 0.418 | N | 0.767 | deleterious | None | None | None | None | N |
| C/E | 0.8792 | likely_pathogenic | 0.8131 | pathogenic | -1.242 | Destabilizing | 0.418 | N | 0.735 | prob.delet. | None | None | None | None | N |
| C/F | 0.3134 | likely_benign | 0.253 | benign | -0.639 | Destabilizing | 0.921 | D | 0.795 | deleterious | N | 0.403406644 | None | None | N |
| C/G | 0.3466 | ambiguous | 0.3136 | benign | -1.516 | Destabilizing | 0.351 | N | 0.737 | prob.delet. | N | 0.442061033 | None | None | N |
| C/H | 0.5554 | ambiguous | 0.3626 | ambiguous | -1.775 | Destabilizing | 0.836 | D | 0.799 | deleterious | None | None | None | None | N |
| C/I | 0.5684 | likely_pathogenic | 0.5074 | ambiguous | -0.184 | Destabilizing | 0.593 | D | 0.805 | deleterious | None | None | None | None | N |
| C/K | 0.6378 | likely_pathogenic | 0.4965 | ambiguous | -0.625 | Destabilizing | 0.004 | N | 0.629 | neutral | None | None | None | None | N |
| C/L | 0.4084 | ambiguous | 0.3697 | ambiguous | -0.184 | Destabilizing | 0.228 | N | 0.687 | prob.neutral | None | None | None | None | N |
| C/M | 0.5424 | ambiguous | 0.5048 | ambiguous | 0.242 | Stabilizing | 0.94 | D | 0.786 | deleterious | None | None | None | None | N |
| C/N | 0.7254 | likely_pathogenic | 0.633 | pathogenic | -1.434 | Destabilizing | 0.418 | N | 0.745 | deleterious | None | None | None | None | N |
| C/P | 0.9973 | likely_pathogenic | 0.9959 | pathogenic | -0.489 | Destabilizing | 0.836 | D | 0.803 | deleterious | None | None | None | None | N |
| C/Q | 0.5735 | likely_pathogenic | 0.431 | ambiguous | -0.862 | Destabilizing | 0.418 | N | 0.765 | deleterious | None | None | None | None | N |
| C/R | 0.3271 | likely_benign | 0.2136 | benign | -1.274 | Destabilizing | None | N | 0.638 | neutral | N | 0.340800747 | None | None | N |
| C/S | 0.43 | ambiguous | 0.3582 | ambiguous | -1.61 | Destabilizing | 0.183 | N | 0.695 | prob.neutral | N | 0.420261608 | None | None | N |
| C/T | 0.5842 | likely_pathogenic | 0.5188 | ambiguous | -1.168 | Destabilizing | 0.418 | N | 0.729 | prob.delet. | None | None | None | None | N |
| C/V | 0.4359 | ambiguous | 0.3862 | ambiguous | -0.489 | Destabilizing | 0.418 | N | 0.749 | deleterious | None | None | None | None | N |
| C/W | 0.6691 | likely_pathogenic | 0.5493 | ambiguous | -1.142 | Destabilizing | 0.978 | D | 0.776 | deleterious | N | 0.454064751 | None | None | N |
| C/Y | 0.2948 | likely_benign | 0.2297 | benign | -0.858 | Destabilizing | 0.921 | D | 0.796 | deleterious | N | 0.366554836 | 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.