Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21403 | 64432;64433;64434 | chr2:178586694;178586693;178586692 | chr2:179451421;179451420;179451419 |
| N2AB | 19762 | 59509;59510;59511 | chr2:178586694;178586693;178586692 | chr2:179451421;179451420;179451419 |
| N2A | 18835 | 56728;56729;56730 | chr2:178586694;178586693;178586692 | chr2:179451421;179451420;179451419 |
| N2B | 12338 | 37237;37238;37239 | chr2:178586694;178586693;178586692 | chr2:179451421;179451420;179451419 |
| Novex-1 | 12463 | 37612;37613;37614 | chr2:178586694;178586693;178586692 | chr2:179451421;179451420;179451419 |
| Novex-2 | 12530 | 37813;37814;37815 | chr2:178586694;178586693;178586692 | chr2:179451421;179451420;179451419 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/I | rs2042996  |
0.672 | None | N | 0.357 | 0.201 | None | gnomAD-2.1.1 | 3.50373E-01 | None | None | None | None | N | None | 5.27651E-01 | 4.25999E-01 | None | 2.83546E-01 | 7.07715E-01 | None | 5.18502E-01 | None | 2.76192E-01 | 2.24116E-01 | 3.05001E-01 |
| T/I | rs2042996 |
0.672 | None | N | 0.357 | 0.201 | None | gnomAD-3.1.2 | 3.56988E-01 | None | None | None | None | N | None | 5.27969E-01 | 3.79627E-01 | 5.60307E-01 | 2.87651E-01 | 7.06123E-01 | None | 2.85971E-01 | 2.75316E-01 | 2.23166E-01 | 5.20175E-01 | 3.26462E-01 |
| T/I | rs2042996 |
0.672 | None | N | 0.357 | 0.201 | None | 1000 genomes | 5.07588E-01 | None | None | None | None | N | None | 5.582E-01 | 4.078E-01 | None | None | 7.212E-01 | 2.485E-01 | None | None | None | 5.562E-01 | None |
| T/I | rs2042996 |
0.672 | None | N | 0.357 | 0.201 | None | gnomAD-4.0.0 | 2.75244E-01 | None | None | None | None | N | None | 5.3375E-01 | 4.13419E-01 | None | 2.85637E-01 | 6.9729E-01 | None | 2.77941E-01 | 3.05785E-01 | 2.15615E-01 | 5.08019E-01 | 3.02332E-01 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.0986 | likely_benign | 0.0855 | benign | -1.193 | Destabilizing | None | N | 0.225 | neutral | N | 0.418354667 | None | None | N |
| T/C | 0.3504 | ambiguous | 0.3048 | benign | -0.773 | Destabilizing | 0.018 | N | 0.576 | neutral | None | None | None | None | N |
| T/D | 0.9721 | likely_pathogenic | 0.9713 | pathogenic | -2.08 | Highly Destabilizing | 0.003 | N | 0.524 | neutral | None | None | None | None | N |
| T/E | 0.9376 | likely_pathogenic | 0.9272 | pathogenic | -1.739 | Destabilizing | 0.003 | N | 0.535 | neutral | None | None | None | None | N |
| T/F | 0.3699 | ambiguous | 0.3463 | ambiguous | -0.794 | Destabilizing | 0.002 | N | 0.569 | neutral | None | None | None | None | N |
| T/G | 0.5818 | likely_pathogenic | 0.528 | ambiguous | -1.679 | Destabilizing | 0.003 | N | 0.567 | neutral | None | None | None | None | N |
| T/H | 0.8958 | likely_pathogenic | 0.8882 | pathogenic | -1.59 | Destabilizing | 0.116 | N | 0.63 | neutral | None | None | None | None | N |
| T/I | 0.0302 | likely_benign | 0.0273 | benign | 0.149 | Stabilizing | None | N | 0.357 | neutral | N | 0.227330808 | None | None | N |
| T/K | 0.9254 | likely_pathogenic | 0.9225 | pathogenic | 0.01 | Stabilizing | 0.003 | N | 0.533 | neutral | None | None | None | None | N |
| T/L | 0.0436 | likely_benign | 0.0428 | benign | 0.149 | Stabilizing | None | N | 0.365 | neutral | None | None | None | None | N |
| T/M | 0.0926 | likely_benign | 0.0849 | benign | -0.236 | Destabilizing | 0.002 | N | 0.511 | neutral | None | None | None | None | N |
| T/N | 0.7449 | likely_pathogenic | 0.7434 | pathogenic | -1.235 | Destabilizing | 0.018 | N | 0.431 | neutral | N | 0.4190481 | None | None | N |
| T/P | 0.6201 | likely_pathogenic | 0.634 | pathogenic | -0.272 | Destabilizing | 0.008 | N | 0.515 | neutral | N | 0.400462339 | None | None | N |
| T/Q | 0.8863 | likely_pathogenic | 0.8755 | pathogenic | -0.684 | Destabilizing | 0.023 | N | 0.543 | neutral | None | None | None | None | N |
| T/R | 0.8841 | likely_pathogenic | 0.8794 | pathogenic | -0.649 | Destabilizing | 0.008 | N | 0.531 | neutral | None | None | None | None | N |
| T/S | 0.3684 | ambiguous | 0.3256 | benign | -1.415 | Destabilizing | 0.001 | N | 0.367 | neutral | N | 0.418874742 | None | None | N |
| T/V | 0.0283 | likely_benign | 0.0284 | benign | -0.272 | Destabilizing | None | N | 0.225 | neutral | None | None | None | None | N |
| T/W | 0.9576 | likely_pathogenic | 0.9507 | pathogenic | -1.048 | Destabilizing | 0.316 | N | 0.697 | prob.neutral | None | None | None | None | N |
| T/Y | 0.804 | likely_pathogenic | 0.7797 | pathogenic | -0.602 | Destabilizing | 0.003 | N | 0.581 | neutral | 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.