Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 8200 | 24823;24824;24825 | chr2:178718508;178718507;178718506 | chr2:179583235;179583234;179583233 |
| N2AB | 7883 | 23872;23873;23874 | chr2:178718508;178718507;178718506 | chr2:179583235;179583234;179583233 |
| N2A | 6956 | 21091;21092;21093 | chr2:178718508;178718507;178718506 | chr2:179583235;179583234;179583233 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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/M | rs2077838172  |
None | 0.267 | N | 0.447 | 0.124 | 0.354183961838 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| I/M | rs2077838172 |
None | 0.267 | N | 0.447 | 0.124 | 0.354183961838 | gnomAD-4.0.0 | 3.04487E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.61479E-06 | 0 | 0 |
| I/T | rs2077838539 |
None | 0.801 | N | 0.658 | 0.326 | 0.658673760821 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/T | rs2077838539 |
None | 0.801 | N | 0.658 | 0.326 | 0.658673760821 | gnomAD-4.0.0 | 6.57168E-06 | None | None | None | None | N | None | 2.41278E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | rs1439095726 |
-1.607 | 0.051 | N | 0.167 | 0.081 | 0.420939154896 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| I/V | rs1439095726 |
-1.607 | 0.051 | N | 0.167 | 0.081 | 0.420939154896 | gnomAD-4.0.0 | 1.59144E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43283E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.7845 | likely_pathogenic | 0.7407 | pathogenic | -2.321 | Highly Destabilizing | 0.688 | D | 0.555 | neutral | None | None | None | None | N |
| I/C | 0.9341 | likely_pathogenic | 0.9118 | pathogenic | -1.824 | Destabilizing | 0.998 | D | 0.633 | neutral | None | None | None | None | N |
| I/D | 0.9916 | likely_pathogenic | 0.989 | pathogenic | -2.289 | Highly Destabilizing | 0.991 | D | 0.737 | prob.delet. | None | None | None | None | N |
| I/E | 0.9821 | likely_pathogenic | 0.9764 | pathogenic | -2.154 | Highly Destabilizing | 0.991 | D | 0.712 | prob.delet. | None | None | None | None | N |
| I/F | 0.5785 | likely_pathogenic | 0.5561 | ambiguous | -1.484 | Destabilizing | 0.934 | D | 0.62 | neutral | N | 0.501759576 | None | None | N |
| I/G | 0.9714 | likely_pathogenic | 0.9636 | pathogenic | -2.78 | Highly Destabilizing | 0.974 | D | 0.718 | prob.delet. | None | None | None | None | N |
| I/H | 0.9732 | likely_pathogenic | 0.9628 | pathogenic | -2.129 | Highly Destabilizing | 0.998 | D | 0.681 | prob.neutral | None | None | None | None | N |
| I/K | 0.9598 | likely_pathogenic | 0.9396 | pathogenic | -1.667 | Destabilizing | 0.974 | D | 0.721 | prob.delet. | None | None | None | None | N |
| I/L | 0.2604 | likely_benign | 0.2518 | benign | -1.044 | Destabilizing | 0.005 | N | 0.133 | neutral | N | 0.506446159 | None | None | N |
| I/M | 0.3404 | ambiguous | 0.3343 | benign | -1.093 | Destabilizing | 0.267 | N | 0.447 | neutral | N | 0.496986636 | None | None | N |
| I/N | 0.9021 | likely_pathogenic | 0.8743 | pathogenic | -1.769 | Destabilizing | 0.989 | D | 0.724 | prob.delet. | N | 0.497493615 | None | None | N |
| I/P | 0.8947 | likely_pathogenic | 0.857 | pathogenic | -1.445 | Destabilizing | 0.991 | D | 0.727 | prob.delet. | None | None | None | None | N |
| I/Q | 0.9605 | likely_pathogenic | 0.9473 | pathogenic | -1.79 | Destabilizing | 0.974 | D | 0.722 | prob.delet. | None | None | None | None | N |
| I/R | 0.9377 | likely_pathogenic | 0.9065 | pathogenic | -1.269 | Destabilizing | 0.974 | D | 0.729 | prob.delet. | None | None | None | None | N |
| I/S | 0.8759 | likely_pathogenic | 0.8441 | pathogenic | -2.474 | Highly Destabilizing | 0.966 | D | 0.691 | prob.neutral | N | 0.490238687 | None | None | N |
| I/T | 0.8385 | likely_pathogenic | 0.798 | pathogenic | -2.205 | Highly Destabilizing | 0.801 | D | 0.658 | neutral | N | 0.496986636 | None | None | N |
| I/V | 0.0808 | likely_benign | 0.0829 | benign | -1.445 | Destabilizing | 0.051 | N | 0.167 | neutral | N | 0.502504564 | None | None | N |
| I/W | 0.9892 | likely_pathogenic | 0.9867 | pathogenic | -1.713 | Destabilizing | 0.998 | D | 0.696 | prob.neutral | None | None | None | None | N |
| I/Y | 0.9379 | likely_pathogenic | 0.9244 | pathogenic | -1.449 | Destabilizing | 0.974 | D | 0.718 | prob.delet. | 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.