Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15069 | 45430;45431;45432 | chr2:178621619;178621618;178621617 | chr2:179486346;179486345;179486344 |
| N2AB | 13428 | 40507;40508;40509 | chr2:178621619;178621618;178621617 | chr2:179486346;179486345;179486344 |
| N2A | 12501 | 37726;37727;37728 | chr2:178621619;178621618;178621617 | chr2:179486346;179486345;179486344 |
| N2B | 6004 | 18235;18236;18237 | chr2:178621619;178621618;178621617 | chr2:179486346;179486345;179486344 |
| Novex-1 | 6129 | 18610;18611;18612 | chr2:178621619;178621618;178621617 | chr2:179486346;179486345;179486344 |
| Novex-2 | 6196 | 18811;18812;18813 | chr2:178621619;178621618;178621617 | chr2:179486346;179486345;179486344 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| E/V | rs114331773  |
0.317 | 1.0 | N | 0.694 | 0.503 | None | gnomAD-2.1.1 | 6.41614E-03 | None | None | None | None | N | None | 5.5689E-02 | 4.00182E-03 | None | 1.69672E-02 | 0 | None | 2.28833E-04 | None | 0 | 6.68807E-04 | 5.06757E-03 |
| E/V | rs114331773 |
0.317 | 1.0 | N | 0.694 | 0.503 | None | gnomAD-3.1.2 | 1.6895E-02 | None | None | None | None | N | None | 5.52224E-02 | 9.39924E-03 | 0 | 1.50029E-02 | 0 | None | 0 | 1.26582E-02 | 6.92317E-04 | 0 | 1.67785E-02 |
| E/V | rs114331773 |
0.317 | 1.0 | N | 0.694 | 0.503 | None | 1000 genomes | 1.69728E-02 | None | None | None | None | N | None | 6.05E-02 | 7.2E-03 | None | None | 0 | 0 | None | None | None | 0 | None |
| E/V | rs114331773 |
0.317 | 1.0 | N | 0.694 | 0.503 | None | gnomAD-4.0.0 | 3.79652E-03 | None | None | None | None | N | None | 5.59651E-02 | 5.77977E-03 | None | 1.68121E-02 | 0 | None | 3.1249E-05 | 9.41837E-03 | 5.16493E-04 | 2.63568E-04 | 6.34514E-03 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| E/A | 0.2343 | likely_benign | 0.2228 | benign | -0.514 | Destabilizing | 0.999 | D | 0.661 | neutral | N | 0.508426278 | None | None | N |
| E/C | 0.9384 | likely_pathogenic | 0.9467 | pathogenic | -0.474 | Destabilizing | 1.0 | D | 0.67 | neutral | None | None | None | None | N |
| E/D | 0.3316 | likely_benign | 0.3346 | benign | -0.665 | Destabilizing | 0.999 | D | 0.493 | neutral | D | 0.554619169 | None | None | N |
| E/F | 0.9 | likely_pathogenic | 0.9075 | pathogenic | 0.193 | Stabilizing | 1.0 | D | 0.671 | neutral | None | None | None | None | N |
| E/G | 0.3334 | likely_benign | 0.3109 | benign | -0.826 | Destabilizing | 1.0 | D | 0.651 | neutral | D | 0.671656969 | None | None | N |
| E/H | 0.7422 | likely_pathogenic | 0.7491 | pathogenic | 0.435 | Stabilizing | 1.0 | D | 0.629 | neutral | None | None | None | None | N |
| E/I | 0.5066 | ambiguous | 0.5147 | ambiguous | 0.322 | Stabilizing | 1.0 | D | 0.708 | prob.delet. | None | None | None | None | N |
| E/K | 0.2091 | likely_benign | 0.1989 | benign | -0.085 | Destabilizing | 0.999 | D | 0.624 | neutral | N | 0.509815767 | None | None | N |
| E/L | 0.5824 | likely_pathogenic | 0.5946 | pathogenic | 0.322 | Stabilizing | 1.0 | D | 0.707 | prob.neutral | None | None | None | None | N |
| E/M | 0.5918 | likely_pathogenic | 0.5895 | pathogenic | 0.318 | Stabilizing | 1.0 | D | 0.618 | neutral | None | None | None | None | N |
| E/N | 0.4496 | ambiguous | 0.4487 | ambiguous | -0.794 | Destabilizing | 1.0 | D | 0.673 | neutral | None | None | None | None | N |
| E/P | 0.5237 | ambiguous | 0.5557 | ambiguous | 0.064 | Stabilizing | 1.0 | D | 0.675 | prob.neutral | None | None | None | None | N |
| E/Q | 0.2228 | likely_benign | 0.2205 | benign | -0.658 | Destabilizing | 1.0 | D | 0.583 | neutral | D | 0.536781136 | None | None | N |
| E/R | 0.3903 | ambiguous | 0.3893 | ambiguous | 0.369 | Stabilizing | 1.0 | D | 0.672 | neutral | None | None | None | None | N |
| E/S | 0.4139 | ambiguous | 0.4112 | ambiguous | -0.986 | Destabilizing | 0.999 | D | 0.629 | neutral | None | None | None | None | N |
| E/T | 0.3902 | ambiguous | 0.381 | ambiguous | -0.712 | Destabilizing | 1.0 | D | 0.693 | prob.neutral | None | None | None | None | N |
| E/V | 0.3277 | likely_benign | 0.3097 | benign | 0.064 | Stabilizing | 1.0 | D | 0.694 | prob.neutral | N | 0.51125252 | None | None | N |
| E/W | 0.9698 | likely_pathogenic | 0.9703 | pathogenic | 0.49 | Stabilizing | 1.0 | D | 0.673 | neutral | None | None | None | None | N |
| E/Y | 0.8135 | likely_pathogenic | 0.8226 | pathogenic | 0.471 | Stabilizing | 1.0 | D | 0.652 | 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.