Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15175 | 45748;45749;45750 | chr2:178621195;178621194;178621193 | chr2:179485922;179485921;179485920 |
| N2AB | 13534 | 40825;40826;40827 | chr2:178621195;178621194;178621193 | chr2:179485922;179485921;179485920 |
| N2A | 12607 | 38044;38045;38046 | chr2:178621195;178621194;178621193 | chr2:179485922;179485921;179485920 |
| N2B | 6110 | 18553;18554;18555 | chr2:178621195;178621194;178621193 | chr2:179485922;179485921;179485920 |
| Novex-1 | 6235 | 18928;18929;18930 | chr2:178621195;178621194;178621193 | chr2:179485922;179485921;179485920 |
| Novex-2 | 6302 | 19129;19130;19131 | chr2:178621195;178621194;178621193 | chr2:179485922;179485921;179485920 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | rs773388033  |
-2.059 | 0.027 | N | 0.445 | 0.073 | 0.34854441366 | gnomAD-2.1.1 | 7.17E-06 | None | None | None | None | N | None | 4.14E-05 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| V/A | rs773388033 |
-2.059 | 0.027 | N | 0.445 | 0.073 | 0.34854441366 | gnomAD-3.1.2 | 6.59E-06 | None | None | None | None | N | None | 2.42E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/A | rs773388033 |
-2.059 | 0.027 | N | 0.445 | 0.073 | 0.34854441366 | gnomAD-4.0.0 | 1.24049E-06 | None | None | None | None | N | None | 1.33772E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.09859E-05 | 0 |
| V/F | rs1331081266 |
None | 0.317 | N | 0.619 | 0.129 | 0.31411915649 | gnomAD-3.1.2 | 6.59E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| V/F | rs1331081266 |
None | 0.317 | N | 0.619 | 0.129 | 0.31411915649 | gnomAD-4.0.0 | 6.58796E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.47332E-05 | 0 | 0 |
| V/I | rs1331081266 |
-0.275 | None | N | 0.229 | 0.109 | 0.0920862733494 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.64E-05 | None | 0 | None | 0 | 0 | 0 |
| V/I | rs1331081266 |
-0.275 | None | N | 0.229 | 0.109 | 0.0920862733494 | gnomAD-4.0.0 | 1.59387E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.78909E-05 | None | 0 | 0 | 0 | 0 | 0 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.2917 | likely_benign | 0.2171 | benign | -2.125 | Highly Destabilizing | 0.027 | N | 0.445 | neutral | N | 0.493261606 | None | None | N |
| V/C | 0.7706 | likely_pathogenic | 0.5879 | pathogenic | -1.441 | Destabilizing | 0.935 | D | 0.614 | neutral | None | None | None | None | N |
| V/D | 0.7398 | likely_pathogenic | 0.6325 | pathogenic | -3.015 | Highly Destabilizing | 0.117 | N | 0.659 | neutral | D | 0.590809505 | None | None | N |
| V/E | 0.5003 | ambiguous | 0.4209 | ambiguous | -2.783 | Highly Destabilizing | 0.149 | N | 0.6 | neutral | None | None | None | None | N |
| V/F | 0.1876 | likely_benign | 0.1243 | benign | -1.293 | Destabilizing | 0.317 | N | 0.619 | neutral | N | 0.510265871 | None | None | N |
| V/G | 0.4412 | ambiguous | 0.3527 | ambiguous | -2.646 | Highly Destabilizing | 0.117 | N | 0.609 | neutral | N | 0.498263341 | None | None | N |
| V/H | 0.6258 | likely_pathogenic | 0.4641 | ambiguous | -2.534 | Highly Destabilizing | 0.935 | D | 0.685 | prob.neutral | None | None | None | None | N |
| V/I | 0.0703 | likely_benign | 0.0565 | benign | -0.652 | Destabilizing | None | N | 0.229 | neutral | N | 0.471180281 | None | None | N |
| V/K | 0.4301 | ambiguous | 0.325 | benign | -1.905 | Destabilizing | 0.149 | N | 0.603 | neutral | None | None | None | None | N |
| V/L | 0.1765 | likely_benign | 0.1128 | benign | -0.652 | Destabilizing | 0.009 | N | 0.439 | neutral | N | 0.507284971 | None | None | N |
| V/M | 0.1129 | likely_benign | 0.0978 | benign | -0.589 | Destabilizing | 0.38 | N | 0.617 | neutral | None | None | None | None | N |
| V/N | 0.4507 | ambiguous | 0.3045 | benign | -2.279 | Highly Destabilizing | 0.38 | N | 0.665 | neutral | None | None | None | None | N |
| V/P | 0.9863 | likely_pathogenic | 0.9692 | pathogenic | -1.119 | Destabilizing | 0.555 | D | 0.626 | neutral | None | None | None | None | N |
| V/Q | 0.415 | ambiguous | 0.3295 | benign | -2.096 | Highly Destabilizing | 0.555 | D | 0.635 | neutral | None | None | None | None | N |
| V/R | 0.388 | ambiguous | 0.2683 | benign | -1.717 | Destabilizing | 0.38 | N | 0.675 | neutral | None | None | None | None | N |
| V/S | 0.3326 | likely_benign | 0.2272 | benign | -2.797 | Highly Destabilizing | 0.007 | N | 0.514 | neutral | None | None | None | None | N |
| V/T | 0.2228 | likely_benign | 0.1616 | benign | -2.439 | Highly Destabilizing | None | N | 0.234 | neutral | None | None | None | None | N |
| V/W | 0.848 | likely_pathogenic | 0.6961 | pathogenic | -1.941 | Destabilizing | 0.935 | D | 0.709 | prob.delet. | None | None | None | None | N |
| V/Y | 0.5808 | likely_pathogenic | 0.4217 | ambiguous | -1.533 | Destabilizing | 0.555 | D | 0.615 | 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.