Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 3836 | 11731;11732;11733 | chr2:178741727;178741726;178741725 | chr2:179606454;179606453;179606452 |
| N2AB | 3519 | 10780;10781;10782 | chr2:178741727;178741726;178741725 | chr2:179606454;179606453;179606452 |
| N2A | None | None | chr2:None | chr2:None |
| N2B | 3473 | 10642;10643;10644 | chr2:178741727;178741726;178741725 | chr2:179606454;179606453;179606452 |
| Novex-1 | 3598 | 11017;11018;11019 | chr2:178741727;178741726;178741725 | chr2:179606454;179606453;179606452 |
| Novex-2 | 3665 | 11218;11219;11220 | chr2:178741727;178741726;178741725 | chr2:179606454;179606453;179606452 |
| 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 | None | None | 0.27 | N | 0.288 | 0.089 | None | gnomAD-4.0.0 | 1.59149E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.8586E-06 | 0 | 0 |
| V/M | rs397517825  |
-0.158 | 0.863 | N | 0.409 | 0.115 | None | gnomAD-2.1.1 | 8.50061E-04 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 7.45195E-03 | None | 0 | 6.25E-05 | 2.80741E-04 |
| V/M | rs397517825 |
-0.158 | 0.863 | N | 0.409 | 0.115 | None | gnomAD-3.1.2 | 2.03711E-04 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 6.21633E-03 | 0 |
| V/M | rs397517825 |
-0.158 | 0.863 | N | 0.409 | 0.115 | None | 1000 genomes | 7.98722E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 4.1E-03 | None |
| V/M | rs397517825 |
-0.158 | 0.863 | N | 0.409 | 0.115 | None | gnomAD-4.0.0 | 4.07748E-04 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 1.65017E-04 | 5.93349E-06 | 6.75275E-03 | 5.60251E-04 |
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 | 0.2945 | likely_benign | 0.2696 | benign | -0.884 | Destabilizing | 0.27 | N | 0.288 | neutral | N | 0.432171583 | None | None | N |
| V/C | 0.8994 | likely_pathogenic | 0.8891 | pathogenic | -0.765 | Destabilizing | 0.995 | D | 0.405 | neutral | None | None | None | None | N |
| V/D | 0.658 | likely_pathogenic | 0.6311 | pathogenic | -0.31 | Destabilizing | 0.704 | D | 0.44 | neutral | None | None | None | None | N |
| V/E | 0.5434 | ambiguous | 0.5276 | ambiguous | -0.355 | Destabilizing | 0.642 | D | 0.376 | neutral | N | 0.431028542 | None | None | N |
| V/F | 0.3246 | likely_benign | 0.3036 | benign | -0.706 | Destabilizing | 0.893 | D | 0.456 | neutral | None | None | None | None | N |
| V/G | 0.4772 | ambiguous | 0.444 | ambiguous | -1.134 | Destabilizing | 0.642 | D | 0.417 | neutral | N | 0.446739045 | None | None | N |
| V/H | 0.8551 | likely_pathogenic | 0.8279 | pathogenic | -0.574 | Destabilizing | 0.995 | D | 0.427 | neutral | None | None | None | None | N |
| V/I | 0.1035 | likely_benign | 0.0955 | benign | -0.336 | Destabilizing | 0.007 | N | 0.171 | neutral | None | None | None | None | N |
| V/K | 0.5854 | likely_pathogenic | 0.5611 | ambiguous | -0.712 | Destabilizing | 0.031 | N | 0.345 | neutral | None | None | None | None | N |
| V/L | 0.4544 | ambiguous | 0.4222 | ambiguous | -0.336 | Destabilizing | 0.002 | N | 0.116 | neutral | N | 0.440215935 | None | None | N |
| V/M | 0.2413 | likely_benign | 0.2062 | benign | -0.354 | Destabilizing | 0.863 | D | 0.409 | neutral | N | 0.450390938 | None | None | N |
| V/N | 0.6082 | likely_pathogenic | 0.5544 | ambiguous | -0.482 | Destabilizing | 0.704 | D | 0.46 | neutral | None | None | None | None | N |
| V/P | 0.82 | likely_pathogenic | 0.7903 | pathogenic | -0.481 | Destabilizing | 0.944 | D | 0.449 | neutral | None | None | None | None | N |
| V/Q | 0.6843 | likely_pathogenic | 0.6621 | pathogenic | -0.653 | Destabilizing | 0.893 | D | 0.449 | neutral | None | None | None | None | N |
| V/R | 0.5376 | ambiguous | 0.5338 | ambiguous | -0.217 | Destabilizing | 0.807 | D | 0.463 | neutral | None | None | None | None | N |
| V/S | 0.4549 | ambiguous | 0.4132 | ambiguous | -1.012 | Destabilizing | 0.031 | N | 0.357 | neutral | None | None | None | None | N |
| V/T | 0.2692 | likely_benign | 0.2507 | benign | -0.941 | Destabilizing | 0.013 | N | 0.115 | neutral | None | None | None | None | N |
| V/W | 0.9362 | likely_pathogenic | 0.9289 | pathogenic | -0.821 | Destabilizing | 0.995 | D | 0.491 | neutral | None | None | None | None | N |
| V/Y | 0.798 | likely_pathogenic | 0.7835 | pathogenic | -0.526 | Destabilizing | 0.944 | D | 0.431 | 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.