Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19018 | 57277;57278;57279 | chr2:178598565;178598564;178598563 | chr2:179463292;179463291;179463290 |
| N2AB | 17377 | 52354;52355;52356 | chr2:178598565;178598564;178598563 | chr2:179463292;179463291;179463290 |
| N2A | 16450 | 49573;49574;49575 | chr2:178598565;178598564;178598563 | chr2:179463292;179463291;179463290 |
| N2B | 9953 | 30082;30083;30084 | chr2:178598565;178598564;178598563 | chr2:179463292;179463291;179463290 |
| Novex-1 | 10078 | 30457;30458;30459 | chr2:178598565;178598564;178598563 | chr2:179463292;179463291;179463290 |
| Novex-2 | 10145 | 30658;30659;30660 | chr2:178598565;178598564;178598563 | chr2:179463292;179463291;179463290 |
| 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/A | rs367822879  |
-0.662 | 0.997 | N | 0.609 | 0.281 | None | gnomAD-2.1.1 | 8.25E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.8E-05 | 0 |
| S/A | rs367822879 |
-0.662 | 0.997 | N | 0.609 | 0.281 | None | 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 |
| S/A | rs367822879 |
-0.662 | 0.997 | N | 0.609 | 0.281 | None | gnomAD-4.0.0 | 9.95087E-06 | None | None | None | None | I | None | 6.71899E-05 | 0 | None | 0 | 0 | None | 0 | 4.94723E-04 | 3.394E-06 | 0 | 6.42405E-05 |
| S/T | None | None | 0.999 | N | 0.615 | 0.307 | 0.293502639404 | gnomAD-4.0.0 | 6.86815E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.0043E-07 | 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 | 0.1541 | likely_benign | 0.1515 | benign | -0.614 | Destabilizing | 0.997 | D | 0.609 | neutral | N | 0.511939619 | None | None | I |
| S/C | 0.119 | likely_benign | 0.1124 | benign | -0.445 | Destabilizing | 1.0 | D | 0.772 | deleterious | N | 0.482577414 | None | None | I |
| S/D | 0.903 | likely_pathogenic | 0.8907 | pathogenic | -0.432 | Destabilizing | 0.999 | D | 0.785 | deleterious | None | None | None | None | I |
| S/E | 0.9252 | likely_pathogenic | 0.9142 | pathogenic | -0.498 | Destabilizing | 0.999 | D | 0.758 | deleterious | None | None | None | None | I |
| S/F | 0.5451 | ambiguous | 0.5422 | ambiguous | -1.144 | Destabilizing | 1.0 | D | 0.829 | deleterious | N | 0.507923371 | None | None | I |
| S/G | 0.1507 | likely_benign | 0.1302 | benign | -0.763 | Destabilizing | 0.999 | D | 0.605 | neutral | None | None | None | None | I |
| S/H | 0.7469 | likely_pathogenic | 0.7085 | pathogenic | -1.363 | Destabilizing | 1.0 | D | 0.781 | deleterious | None | None | None | None | I |
| S/I | 0.7505 | likely_pathogenic | 0.7408 | pathogenic | -0.339 | Destabilizing | 1.0 | D | 0.831 | deleterious | None | None | None | None | I |
| S/K | 0.9769 | likely_pathogenic | 0.9707 | pathogenic | -0.641 | Destabilizing | 0.999 | D | 0.771 | deleterious | None | None | None | None | I |
| S/L | 0.3659 | ambiguous | 0.3181 | benign | -0.339 | Destabilizing | 1.0 | D | 0.805 | deleterious | None | None | None | None | I |
| S/M | 0.4865 | ambiguous | 0.4921 | ambiguous | 0.138 | Stabilizing | 1.0 | D | 0.78 | deleterious | None | None | None | None | I |
| S/N | 0.5673 | likely_pathogenic | 0.5467 | ambiguous | -0.496 | Destabilizing | 0.999 | D | 0.765 | deleterious | None | None | None | None | I |
| S/P | 0.9873 | likely_pathogenic | 0.983 | pathogenic | -0.402 | Destabilizing | 1.0 | D | 0.798 | deleterious | D | 0.525774136 | None | None | I |
| S/Q | 0.8478 | likely_pathogenic | 0.8421 | pathogenic | -0.825 | Destabilizing | 1.0 | D | 0.819 | deleterious | None | None | None | None | I |
| S/R | 0.9567 | likely_pathogenic | 0.9479 | pathogenic | -0.404 | Destabilizing | 1.0 | D | 0.792 | deleterious | None | None | None | None | I |
| S/T | 0.3403 | ambiguous | 0.3402 | ambiguous | -0.552 | Destabilizing | 0.999 | D | 0.615 | neutral | N | 0.479410635 | None | None | I |
| S/V | 0.6588 | likely_pathogenic | 0.6558 | pathogenic | -0.402 | Destabilizing | 1.0 | D | 0.833 | deleterious | None | None | None | None | I |
| S/W | 0.6839 | likely_pathogenic | 0.6627 | pathogenic | -1.095 | Destabilizing | 1.0 | D | 0.84 | deleterious | None | None | None | None | I |
| S/Y | 0.5255 | ambiguous | 0.4752 | ambiguous | -0.826 | Destabilizing | 1.0 | D | 0.836 | deleterious | D | 0.525774136 | 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.