Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25774 | 77545;77546;77547 | chr2:178568812;178568811;178568810 | chr2:179433539;179433538;179433537 |
| N2AB | 24133 | 72622;72623;72624 | chr2:178568812;178568811;178568810 | chr2:179433539;179433538;179433537 |
| N2A | 23206 | 69841;69842;69843 | chr2:178568812;178568811;178568810 | chr2:179433539;179433538;179433537 |
| N2B | 16709 | 50350;50351;50352 | chr2:178568812;178568811;178568810 | chr2:179433539;179433538;179433537 |
| Novex-1 | 16834 | 50725;50726;50727 | chr2:178568812;178568811;178568810 | chr2:179433539;179433538;179433537 |
| Novex-2 | 16901 | 50926;50927;50928 | chr2:178568812;178568811;178568810 | chr2:179433539;179433538;179433537 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/I | rs56340968  |
-0.772 | 0.099 | N | 0.385 | 0.055 | 0.342865806769 | gnomAD-2.1.1 | 1.79E-05 | None | None | None | None | N | None | 1.2408E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.57E-05 | 0 |
| V/I | rs56340968 |
-0.772 | 0.099 | N | 0.385 | 0.055 | 0.342865806769 | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | N | None | 9.65E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/I | rs56340968 |
-0.772 | 0.099 | N | 0.385 | 0.055 | 0.342865806769 | gnomAD-4.0.0 | 4.95942E-06 | None | None | None | None | N | None | 8.01239E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 1.69555E-06 | 0 | 0 |
| V/L | rs56340968 |
None | 0.63 | N | 0.407 | 0.186 | 0.359151904892 | gnomAD-4.0.0 | 2.05333E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79925E-06 | 0 | 1.65717E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.2948 | likely_benign | 0.285 | benign | -2.232 | Highly Destabilizing | 0.892 | D | 0.455 | neutral | N | 0.484177711 | None | None | N |
| V/C | 0.7515 | likely_pathogenic | 0.7574 | pathogenic | -1.873 | Destabilizing | 0.999 | D | 0.696 | prob.neutral | None | None | None | None | N |
| V/D | 0.7946 | likely_pathogenic | 0.7853 | pathogenic | -2.859 | Highly Destabilizing | 0.987 | D | 0.795 | deleterious | None | None | None | None | N |
| V/E | 0.4111 | ambiguous | 0.4006 | ambiguous | -2.674 | Highly Destabilizing | 0.967 | D | 0.656 | neutral | N | 0.497189171 | None | None | N |
| V/F | 0.2334 | likely_benign | 0.2374 | benign | -1.339 | Destabilizing | 0.987 | D | 0.728 | prob.delet. | None | None | None | None | N |
| V/G | 0.5333 | ambiguous | 0.5145 | ambiguous | -2.707 | Highly Destabilizing | 0.967 | D | 0.708 | prob.delet. | N | 0.509816837 | None | None | N |
| V/H | 0.7982 | likely_pathogenic | 0.7999 | pathogenic | -2.31 | Highly Destabilizing | 0.997 | D | 0.778 | deleterious | None | None | None | None | N |
| V/I | 0.0714 | likely_benign | 0.0752 | benign | -0.913 | Destabilizing | 0.099 | N | 0.385 | neutral | N | 0.480160848 | None | None | N |
| V/K | 0.6598 | likely_pathogenic | 0.6333 | pathogenic | -1.756 | Destabilizing | 0.95 | D | 0.645 | neutral | None | None | None | None | N |
| V/L | 0.2195 | likely_benign | 0.23 | benign | -0.913 | Destabilizing | 0.63 | D | 0.407 | neutral | N | 0.473920588 | None | None | N |
| V/M | 0.1428 | likely_benign | 0.1468 | benign | -1.106 | Destabilizing | 0.987 | D | 0.571 | neutral | None | None | None | None | N |
| V/N | 0.6488 | likely_pathogenic | 0.6448 | pathogenic | -2.026 | Highly Destabilizing | 0.975 | D | 0.798 | deleterious | None | None | None | None | N |
| V/P | 0.9916 | likely_pathogenic | 0.9895 | pathogenic | -1.328 | Destabilizing | 0.996 | D | 0.742 | deleterious | None | None | None | None | N |
| V/Q | 0.4529 | ambiguous | 0.444 | ambiguous | -1.941 | Destabilizing | 0.975 | D | 0.749 | deleterious | None | None | None | None | N |
| V/R | 0.6261 | likely_pathogenic | 0.6064 | pathogenic | -1.505 | Destabilizing | 0.073 | N | 0.478 | neutral | None | None | None | None | N |
| V/S | 0.4259 | ambiguous | 0.4139 | ambiguous | -2.605 | Highly Destabilizing | 0.975 | D | 0.639 | neutral | None | None | None | None | N |
| V/T | 0.3066 | likely_benign | 0.2885 | benign | -2.296 | Highly Destabilizing | 0.916 | D | 0.541 | neutral | None | None | None | None | N |
| V/W | 0.8812 | likely_pathogenic | 0.8899 | pathogenic | -1.778 | Destabilizing | 0.999 | D | 0.727 | prob.delet. | None | None | None | None | N |
| V/Y | 0.6802 | likely_pathogenic | 0.6743 | pathogenic | -1.463 | Destabilizing | 0.996 | D | 0.733 | 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.