Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21703 | 65332;65333;65334 | chr2:178584444;178584443;178584442 | chr2:179449171;179449170;179449169 |
| N2AB | 20062 | 60409;60410;60411 | chr2:178584444;178584443;178584442 | chr2:179449171;179449170;179449169 |
| N2A | 19135 | 57628;57629;57630 | chr2:178584444;178584443;178584442 | chr2:179449171;179449170;179449169 |
| N2B | 12638 | 38137;38138;38139 | chr2:178584444;178584443;178584442 | chr2:179449171;179449170;179449169 |
| Novex-1 | 12763 | 38512;38513;38514 | chr2:178584444;178584443;178584442 | chr2:179449171;179449170;179449169 |
| Novex-2 | 12830 | 38713;38714;38715 | chr2:178584444;178584443;178584442 | chr2:179449171;179449170;179449169 |
| 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/G | rs938258873  |
-0.661 | 0.999 | N | 0.422 | 0.193 | 0.202949470691 | gnomAD-2.1.1 | 6.38E-05 | None | None | None | None | N | None | 2.29568E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| S/G | rs938258873 |
-0.661 | 0.999 | N | 0.422 | 0.193 | 0.202949470691 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| S/G | rs938258873 |
-0.661 | 0.999 | N | 0.422 | 0.193 | 0.202949470691 | gnomAD-4.0.0 | 1.31517E-05 | None | None | None | None | N | None | 4.82789E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| S/N | None | None | 0.999 | N | 0.521 | 0.328 | 0.213573922156 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.2995 | likely_benign | 0.2944 | benign | -0.41 | Destabilizing | 0.998 | D | 0.435 | neutral | None | None | None | None | N |
| S/C | 0.3675 | ambiguous | 0.3426 | ambiguous | -0.313 | Destabilizing | 1.0 | D | 0.712 | prob.delet. | N | 0.515579465 | None | None | N |
| S/D | 0.9627 | likely_pathogenic | 0.9571 | pathogenic | 0.234 | Stabilizing | 0.999 | D | 0.538 | neutral | None | None | None | None | N |
| S/E | 0.9778 | likely_pathogenic | 0.9772 | pathogenic | 0.162 | Stabilizing | 0.999 | D | 0.525 | neutral | None | None | None | None | N |
| S/F | 0.9161 | likely_pathogenic | 0.9171 | pathogenic | -0.839 | Destabilizing | 1.0 | D | 0.721 | prob.delet. | None | None | None | None | N |
| S/G | 0.3236 | likely_benign | 0.3185 | benign | -0.566 | Destabilizing | 0.999 | D | 0.422 | neutral | N | 0.464212307 | None | None | N |
| S/H | 0.8773 | likely_pathogenic | 0.8808 | pathogenic | -1.021 | Destabilizing | 1.0 | D | 0.718 | prob.delet. | None | None | None | None | N |
| S/I | 0.8976 | likely_pathogenic | 0.8946 | pathogenic | -0.125 | Destabilizing | 1.0 | D | 0.662 | neutral | N | 0.500184235 | None | None | N |
| S/K | 0.9913 | likely_pathogenic | 0.9915 | pathogenic | -0.54 | Destabilizing | 0.999 | D | 0.531 | neutral | None | None | None | None | N |
| S/L | 0.6092 | likely_pathogenic | 0.5998 | pathogenic | -0.125 | Destabilizing | 1.0 | D | 0.593 | neutral | None | None | None | None | N |
| S/M | 0.7844 | likely_pathogenic | 0.7801 | pathogenic | 0.069 | Stabilizing | 1.0 | D | 0.721 | prob.delet. | None | None | None | None | N |
| S/N | 0.7164 | likely_pathogenic | 0.7135 | pathogenic | -0.278 | Destabilizing | 0.999 | D | 0.521 | neutral | N | 0.480190195 | None | None | N |
| S/P | 0.9879 | likely_pathogenic | 0.9864 | pathogenic | -0.188 | Destabilizing | 1.0 | D | 0.647 | neutral | None | None | None | None | N |
| S/Q | 0.9369 | likely_pathogenic | 0.9404 | pathogenic | -0.496 | Destabilizing | 1.0 | D | 0.669 | neutral | None | None | None | None | N |
| S/R | 0.9802 | likely_pathogenic | 0.9807 | pathogenic | -0.341 | Destabilizing | 1.0 | D | 0.642 | neutral | N | 0.484179894 | None | None | N |
| S/T | 0.3372 | likely_benign | 0.3305 | benign | -0.393 | Destabilizing | 0.999 | D | 0.417 | neutral | N | 0.511822188 | None | None | N |
| S/V | 0.8506 | likely_pathogenic | 0.842 | pathogenic | -0.188 | Destabilizing | 1.0 | D | 0.649 | neutral | None | None | None | None | N |
| S/W | 0.9469 | likely_pathogenic | 0.9438 | pathogenic | -0.831 | Destabilizing | 1.0 | D | 0.769 | deleterious | None | None | None | None | N |
| S/Y | 0.8395 | likely_pathogenic | 0.8419 | pathogenic | -0.566 | Destabilizing | 1.0 | D | 0.736 | prob.delet. | 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.