Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28972 | 87139;87140;87141 | chr2:178558545;178558544;178558543 | chr2:179423272;179423271;179423270 |
| N2AB | 27331 | 82216;82217;82218 | chr2:178558545;178558544;178558543 | chr2:179423272;179423271;179423270 |
| N2A | 26404 | 79435;79436;79437 | chr2:178558545;178558544;178558543 | chr2:179423272;179423271;179423270 |
| N2B | 19907 | 59944;59945;59946 | chr2:178558545;178558544;178558543 | chr2:179423272;179423271;179423270 |
| Novex-1 | 20032 | 60319;60320;60321 | chr2:178558545;178558544;178558543 | chr2:179423272;179423271;179423270 |
| Novex-2 | 20099 | 60520;60521;60522 | chr2:178558545;178558544;178558543 | chr2:179423272;179423271;179423270 |
| 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/N | None | None | 0.997 | N | 0.713 | 0.326 | 0.340992353424 | gnomAD-4.0.0 | 1.36848E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79892E-06 | 0 | 0 |
| S/R | rs373312389  |
-0.294 | 1.0 | N | 0.755 | 0.556 | 0.386558576397 | gnomAD-2.1.1 | 8.06E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.78E-05 | 0 |
| S/R | rs373312389 |
-0.294 | 1.0 | N | 0.755 | 0.556 | 0.386558576397 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| S/R | rs373312389 |
-0.294 | 1.0 | N | 0.755 | 0.556 | 0.386558576397 | gnomAD-4.0.0 | 3.16044E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.23796E-05 | 0 | 1.60123E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.2133 | likely_benign | 0.1977 | benign | -0.487 | Destabilizing | 0.997 | D | 0.595 | neutral | None | None | None | None | I |
| S/C | 0.1937 | likely_benign | 0.167 | benign | -0.265 | Destabilizing | 1.0 | D | 0.756 | deleterious | N | 0.480931572 | None | None | I |
| S/D | 0.9092 | likely_pathogenic | 0.9246 | pathogenic | -0.297 | Destabilizing | 1.0 | D | 0.736 | prob.delet. | None | None | None | None | I |
| S/E | 0.9487 | likely_pathogenic | 0.9554 | pathogenic | -0.37 | Destabilizing | 1.0 | D | 0.705 | prob.neutral | None | None | None | None | I |
| S/F | 0.6482 | likely_pathogenic | 0.6715 | pathogenic | -0.95 | Destabilizing | 1.0 | D | 0.803 | deleterious | None | None | None | None | I |
| S/G | 0.3128 | likely_benign | 0.3076 | benign | -0.648 | Destabilizing | 1.0 | D | 0.574 | neutral | N | 0.467033009 | None | None | I |
| S/H | 0.8205 | likely_pathogenic | 0.8353 | pathogenic | -1.224 | Destabilizing | 1.0 | D | 0.761 | deleterious | None | None | None | None | I |
| S/I | 0.7855 | likely_pathogenic | 0.7629 | pathogenic | -0.182 | Destabilizing | 1.0 | D | 0.792 | deleterious | N | 0.50056631 | None | None | I |
| S/K | 0.9867 | likely_pathogenic | 0.9882 | pathogenic | -0.661 | Destabilizing | 1.0 | D | 0.724 | prob.delet. | None | None | None | None | I |
| S/L | 0.3679 | ambiguous | 0.3649 | ambiguous | -0.182 | Destabilizing | 1.0 | D | 0.777 | deleterious | None | None | None | None | I |
| S/M | 0.5626 | ambiguous | 0.5524 | ambiguous | 0.255 | Stabilizing | 1.0 | D | 0.761 | deleterious | None | None | None | None | I |
| S/N | 0.5674 | likely_pathogenic | 0.5734 | pathogenic | -0.426 | Destabilizing | 0.997 | D | 0.713 | prob.delet. | N | 0.49579337 | None | None | I |
| S/P | 0.9924 | likely_pathogenic | 0.9928 | pathogenic | -0.253 | Destabilizing | 1.0 | D | 0.761 | deleterious | None | None | None | None | I |
| S/Q | 0.9074 | likely_pathogenic | 0.9102 | pathogenic | -0.719 | Destabilizing | 1.0 | D | 0.789 | deleterious | None | None | None | None | I |
| S/R | 0.9768 | likely_pathogenic | 0.9782 | pathogenic | -0.418 | Destabilizing | 1.0 | D | 0.755 | deleterious | N | 0.474344526 | None | None | I |
| S/T | 0.2586 | likely_benign | 0.2572 | benign | -0.483 | Destabilizing | 0.981 | D | 0.591 | neutral | N | 0.479410635 | None | None | I |
| S/V | 0.6791 | likely_pathogenic | 0.6513 | pathogenic | -0.253 | Destabilizing | 1.0 | D | 0.802 | deleterious | None | None | None | None | I |
| S/W | 0.8078 | likely_pathogenic | 0.8194 | pathogenic | -0.931 | Destabilizing | 1.0 | D | 0.827 | deleterious | None | None | None | None | I |
| S/Y | 0.6512 | likely_pathogenic | 0.6784 | pathogenic | -0.67 | Destabilizing | 1.0 | D | 0.81 | deleterious | 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.