Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21209 | 63850;63851;63852 | chr2:178587684;178587683;178587682 | chr2:179452411;179452410;179452409 |
| N2AB | 19568 | 58927;58928;58929 | chr2:178587684;178587683;178587682 | chr2:179452411;179452410;179452409 |
| N2A | 18641 | 56146;56147;56148 | chr2:178587684;178587683;178587682 | chr2:179452411;179452410;179452409 |
| N2B | 12144 | 36655;36656;36657 | chr2:178587684;178587683;178587682 | chr2:179452411;179452410;179452409 |
| Novex-1 | 12269 | 37030;37031;37032 | chr2:178587684;178587683;178587682 | chr2:179452411;179452410;179452409 |
| Novex-2 | 12336 | 37231;37232;37233 | chr2:178587684;178587683;178587682 | chr2:179452411;179452410;179452409 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/Q | rs148684589  |
-0.989 | 0.98 | N | 0.536 | 0.187 | None | gnomAD-2.1.1 | 1.00297E-04 | None | None | None | None | I | None | 5.37768E-04 | 0 | None | 0 | 5.19E-05 | None | 3.27E-05 | None | 0 | 7.84E-05 | 4.2337E-04 |
| R/Q | rs148684589 |
-0.989 | 0.98 | N | 0.536 | 0.187 | None | gnomAD-3.1.2 | 1.51344E-04 | None | None | None | None | I | None | 4.3472E-04 | 6.56E-05 | 0 | 0 | 0 | None | 0 | 0 | 5.89E-05 | 0 | 0 |
| R/Q | rs148684589 |
-0.989 | 0.98 | N | 0.536 | 0.187 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | I | None | 8E-04 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| R/Q | rs148684589 |
-0.989 | 0.98 | N | 0.536 | 0.187 | None | gnomAD-4.0.0 | 7.37808E-05 | None | None | None | None | I | None | 3.73543E-04 | 5.00501E-05 | None | 0 | 2.46537E-04 | None | 0 | 0 | 5.68085E-05 | 7.68893E-05 | 4.80523E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.6683 | likely_pathogenic | 0.646 | pathogenic | -0.769 | Destabilizing | 0.919 | D | 0.599 | neutral | None | None | None | None | I |
| R/C | 0.2555 | likely_benign | 0.2468 | benign | -0.641 | Destabilizing | 0.999 | D | 0.711 | prob.delet. | None | None | None | None | I |
| R/D | 0.8743 | likely_pathogenic | 0.8602 | pathogenic | -0.149 | Destabilizing | 0.976 | D | 0.669 | neutral | None | None | None | None | I |
| R/E | 0.512 | ambiguous | 0.4766 | ambiguous | -0.077 | Destabilizing | 0.851 | D | 0.523 | neutral | None | None | None | None | I |
| R/F | 0.8064 | likely_pathogenic | 0.796 | pathogenic | -0.918 | Destabilizing | 0.996 | D | 0.718 | prob.delet. | None | None | None | None | I |
| R/G | 0.4759 | ambiguous | 0.4427 | ambiguous | -1.011 | Destabilizing | 0.956 | D | 0.651 | neutral | N | 0.483856435 | None | None | I |
| R/H | 0.1436 | likely_benign | 0.1328 | benign | -1.3 | Destabilizing | 0.996 | D | 0.592 | neutral | None | None | None | None | I |
| R/I | 0.5401 | ambiguous | 0.5066 | ambiguous | -0.142 | Destabilizing | 0.988 | D | 0.719 | prob.delet. | None | None | None | None | I |
| R/K | 0.1066 | likely_benign | 0.108 | benign | -0.719 | Destabilizing | 0.015 | N | 0.196 | neutral | None | None | None | None | I |
| R/L | 0.4436 | ambiguous | 0.4275 | ambiguous | -0.142 | Destabilizing | 0.956 | D | 0.651 | neutral | N | 0.440332157 | None | None | I |
| R/M | 0.4326 | ambiguous | 0.4081 | ambiguous | -0.234 | Destabilizing | 0.999 | D | 0.704 | prob.neutral | None | None | None | None | I |
| R/N | 0.7488 | likely_pathogenic | 0.7209 | pathogenic | -0.088 | Destabilizing | 0.919 | D | 0.529 | neutral | None | None | None | None | I |
| R/P | 0.9722 | likely_pathogenic | 0.9759 | pathogenic | -0.332 | Destabilizing | 0.994 | D | 0.713 | prob.delet. | N | 0.461603916 | None | None | I |
| R/Q | 0.1198 | likely_benign | 0.1129 | benign | -0.41 | Destabilizing | 0.98 | D | 0.536 | neutral | N | 0.458824705 | None | None | I |
| R/S | 0.6812 | likely_pathogenic | 0.6438 | pathogenic | -0.838 | Destabilizing | 0.919 | D | 0.59 | neutral | None | None | None | None | I |
| R/T | 0.3917 | ambiguous | 0.344 | ambiguous | -0.615 | Destabilizing | 0.919 | D | 0.649 | neutral | None | None | None | None | I |
| R/V | 0.588 | likely_pathogenic | 0.5697 | pathogenic | -0.332 | Destabilizing | 0.988 | D | 0.67 | neutral | None | None | None | None | I |
| R/W | 0.3553 | ambiguous | 0.3374 | benign | -0.643 | Destabilizing | 0.999 | D | 0.691 | prob.neutral | None | None | None | None | I |
| R/Y | 0.6377 | likely_pathogenic | 0.6228 | pathogenic | -0.305 | Destabilizing | 0.996 | D | 0.727 | prob.delet. | 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.