Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24008 | 72247;72248;72249 | chr2:178574110;178574109;178574108 | chr2:179438837;179438836;179438835 |
| N2AB | 22367 | 67324;67325;67326 | chr2:178574110;178574109;178574108 | chr2:179438837;179438836;179438835 |
| N2A | 21440 | 64543;64544;64545 | chr2:178574110;178574109;178574108 | chr2:179438837;179438836;179438835 |
| N2B | 14943 | 45052;45053;45054 | chr2:178574110;178574109;178574108 | chr2:179438837;179438836;179438835 |
| Novex-1 | 15068 | 45427;45428;45429 | chr2:178574110;178574109;178574108 | chr2:179438837;179438836;179438835 |
| Novex-2 | 15135 | 45628;45629;45630 | chr2:178574110;178574109;178574108 | chr2:179438837;179438836;179438835 |
| 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/V | rs1288081911  |
-0.451 | None | N | 0.205 | 0.097 | 0.107399877778 | gnomAD-2.1.1 | 8.05E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 5.58E-05 | None | 3.27E-05 | None | 0 | 0 | 0 |
| I/V | rs1288081911 |
-0.451 | None | N | 0.205 | 0.097 | 0.107399877778 | gnomAD-4.0.0 | 3.18329E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 2.77546E-05 | None | 0 | 0 | 0 | 1.43303E-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 | 0.1873 | likely_benign | 0.3378 | benign | -1.277 | Destabilizing | None | N | 0.318 | neutral | None | None | None | None | I |
| I/C | 0.5312 | ambiguous | 0.6767 | pathogenic | -0.85 | Destabilizing | 0.356 | N | 0.595 | neutral | None | None | None | None | I |
| I/D | 0.5445 | ambiguous | 0.7628 | pathogenic | -0.506 | Destabilizing | 0.214 | N | 0.671 | neutral | None | None | None | None | I |
| I/E | 0.4607 | ambiguous | 0.6665 | pathogenic | -0.541 | Destabilizing | 0.072 | N | 0.657 | neutral | None | None | None | None | I |
| I/F | 0.1049 | likely_benign | 0.143 | benign | -0.928 | Destabilizing | 0.029 | N | 0.589 | neutral | N | 0.469860923 | None | None | I |
| I/G | 0.4417 | ambiguous | 0.6752 | pathogenic | -1.543 | Destabilizing | 0.072 | N | 0.621 | neutral | None | None | None | None | I |
| I/H | 0.3877 | ambiguous | 0.5836 | pathogenic | -0.677 | Destabilizing | 0.864 | D | 0.652 | neutral | None | None | None | None | I |
| I/K | 0.3358 | likely_benign | 0.5306 | ambiguous | -0.81 | Destabilizing | 0.072 | N | 0.653 | neutral | None | None | None | None | I |
| I/L | 0.0851 | likely_benign | 0.1048 | benign | -0.65 | Destabilizing | None | N | 0.225 | neutral | N | 0.439634016 | None | None | I |
| I/M | 0.0926 | likely_benign | 0.1232 | benign | -0.534 | Destabilizing | 0.005 | N | 0.307 | neutral | N | 0.496951523 | None | None | I |
| I/N | 0.1925 | likely_benign | 0.3506 | ambiguous | -0.622 | Destabilizing | 0.171 | N | 0.683 | prob.neutral | N | 0.476088818 | None | None | I |
| I/P | 0.5765 | likely_pathogenic | 0.7447 | pathogenic | -0.826 | Destabilizing | 0.356 | N | 0.675 | prob.neutral | None | None | None | None | I |
| I/Q | 0.3395 | likely_benign | 0.5216 | ambiguous | -0.819 | Destabilizing | 0.356 | N | 0.677 | prob.neutral | None | None | None | None | I |
| I/R | 0.268 | likely_benign | 0.4557 | ambiguous | -0.198 | Destabilizing | 0.214 | N | 0.681 | prob.neutral | None | None | None | None | I |
| I/S | 0.1718 | likely_benign | 0.3108 | benign | -1.219 | Destabilizing | 0.029 | N | 0.608 | neutral | N | 0.429475738 | None | None | I |
| I/T | 0.1304 | likely_benign | 0.2546 | benign | -1.137 | Destabilizing | None | N | 0.345 | neutral | N | 0.496007374 | None | None | I |
| I/V | 0.0564 | likely_benign | 0.0626 | benign | -0.826 | Destabilizing | None | N | 0.205 | neutral | N | 0.401462417 | None | None | I |
| I/W | 0.6619 | likely_pathogenic | 0.7849 | pathogenic | -0.94 | Destabilizing | 0.864 | D | 0.661 | neutral | None | None | None | None | I |
| I/Y | 0.3653 | ambiguous | 0.4883 | ambiguous | -0.724 | Destabilizing | 0.356 | N | 0.622 | neutral | None | None | None | None | I |
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.