Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27775 | 83548;83549;83550 | chr2:178562809;178562808;178562807 | chr2:179427536;179427535;179427534 |
| N2AB | 26134 | 78625;78626;78627 | chr2:178562809;178562808;178562807 | chr2:179427536;179427535;179427534 |
| N2A | 25207 | 75844;75845;75846 | chr2:178562809;178562808;178562807 | chr2:179427536;179427535;179427534 |
| N2B | 18710 | 56353;56354;56355 | chr2:178562809;178562808;178562807 | chr2:179427536;179427535;179427534 |
| Novex-1 | 18835 | 56728;56729;56730 | chr2:178562809;178562808;178562807 | chr2:179427536;179427535;179427534 |
| Novex-2 | 18902 | 56929;56930;56931 | chr2:178562809;178562808;178562807 | chr2:179427536;179427535;179427534 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/T | rs769577217  |
-2.119 | 0.062 | N | 0.557 | 0.289 | 0.680912940599 | gnomAD-2.1.1 | 1.62E-05 | None | None | None | None | N | None | 0 | 2.91E-05 | None | 0 | 0 | None | 0 | None | 0 | 2.68E-05 | 0 |
| I/T | rs769577217 |
-2.119 | 0.062 | N | 0.557 | 0.289 | 0.680912940599 | gnomAD-4.0.0 | 2.94319E-05 | None | None | None | None | N | None | 0 | 2.23874E-05 | None | 0 | 0 | None | 0 | 0 | 3.77843E-05 | 0 | 0 |
| I/V | rs3829746 |
-1.001 | None | N | 0.149 | 0.117 | None | gnomAD-2.1.1 | 3.51982E-01 | None | None | None | None | N | None | 5.42802E-01 | 4.25661E-01 | None | 2.79934E-01 | 7.02859E-01 | None | 5.1526E-01 | None | 2.76192E-01 | 2.26316E-01 | 3.0741E-01 |
| I/V | rs3829746 |
-1.001 | None | N | 0.149 | 0.117 | None | gnomAD-3.1.2 | 3.61673E-01 | None | None | None | None | N | None | 5.41417E-01 | 3.84141E-01 | 5.6044E-01 | 2.84314E-01 | 7.00233E-01 | None | 2.85471E-01 | 2.75316E-01 | 2.25397E-01 | 5.15748E-01 | 3.2808E-01 |
| I/V | rs3829746 |
-1.001 | None | N | 0.149 | 0.117 | None | 1000 genomes | 5.08387E-01 | None | None | None | None | N | None | 5.658E-01 | 4.078E-01 | None | None | 7.153E-01 | 2.535E-01 | None | None | None | 5.511E-01 | None |
| I/V | rs3829746 |
-1.001 | None | N | 0.149 | 0.117 | None | gnomAD-4.0.0 | 2.77343E-01 | None | None | None | None | N | None | 5.48296E-01 | 4.14713E-01 | None | 2.80185E-01 | 6.94595E-01 | None | 2.78413E-01 | 3.06005E-01 | 2.17918E-01 | 5.04415E-01 | 3.04211E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.2617 | likely_benign | 0.2804 | benign | -1.68 | Destabilizing | 0.035 | N | 0.396 | neutral | None | None | None | None | N |
| I/C | 0.5401 | ambiguous | 0.5566 | ambiguous | -1.334 | Destabilizing | 0.824 | D | 0.62 | neutral | None | None | None | None | N |
| I/D | 0.8436 | likely_pathogenic | 0.8556 | pathogenic | -0.814 | Destabilizing | 0.555 | D | 0.691 | prob.neutral | None | None | None | None | N |
| I/E | 0.748 | likely_pathogenic | 0.7564 | pathogenic | -0.763 | Destabilizing | 0.555 | D | 0.693 | prob.neutral | None | None | None | None | N |
| I/F | 0.1742 | likely_benign | 0.1844 | benign | -1.034 | Destabilizing | 0.38 | N | 0.579 | neutral | None | None | None | None | N |
| I/G | 0.5934 | likely_pathogenic | 0.6005 | pathogenic | -2.045 | Highly Destabilizing | 0.262 | N | 0.686 | prob.neutral | None | None | None | None | N |
| I/H | 0.6996 | likely_pathogenic | 0.725 | pathogenic | -1.098 | Destabilizing | 0.935 | D | 0.681 | prob.neutral | None | None | None | None | N |
| I/K | 0.6568 | likely_pathogenic | 0.6792 | pathogenic | -1.216 | Destabilizing | 0.484 | N | 0.695 | prob.neutral | N | 0.488805157 | None | None | N |
| I/L | 0.1188 | likely_benign | 0.1124 | benign | -0.734 | Destabilizing | 0.005 | N | 0.369 | neutral | N | 0.48477166 | None | None | N |
| I/M | 0.1249 | likely_benign | 0.129 | benign | -0.75 | Destabilizing | 0.317 | N | 0.572 | neutral | N | 0.482702318 | None | None | N |
| I/N | 0.4788 | ambiguous | 0.5052 | ambiguous | -1.169 | Destabilizing | 0.791 | D | 0.693 | prob.neutral | None | None | None | None | N |
| I/P | 0.5161 | ambiguous | 0.4978 | ambiguous | -1.019 | Destabilizing | 0.555 | D | 0.691 | prob.neutral | None | None | None | None | N |
| I/Q | 0.623 | likely_pathogenic | 0.6491 | pathogenic | -1.23 | Destabilizing | 0.791 | D | 0.701 | prob.neutral | None | None | None | None | N |
| I/R | 0.5848 | likely_pathogenic | 0.6191 | pathogenic | -0.7 | Destabilizing | 0.484 | N | 0.699 | prob.neutral | N | 0.515303203 | None | None | N |
| I/S | 0.3528 | ambiguous | 0.3981 | ambiguous | -1.88 | Destabilizing | 0.149 | N | 0.624 | neutral | None | None | None | None | N |
| I/T | 0.2546 | likely_benign | 0.2772 | benign | -1.686 | Destabilizing | 0.062 | N | 0.557 | neutral | N | 0.477030778 | None | None | N |
| I/V | 0.0516 | likely_benign | 0.0541 | benign | -1.019 | Destabilizing | None | N | 0.149 | neutral | N | 0.382623153 | None | None | N |
| I/W | 0.8361 | likely_pathogenic | 0.8343 | pathogenic | -1.076 | Destabilizing | 0.935 | D | 0.702 | prob.neutral | None | None | None | None | N |
| I/Y | 0.5789 | likely_pathogenic | 0.5968 | pathogenic | -0.871 | Destabilizing | 0.555 | D | 0.625 | 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.