Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 34173 | 102742;102743;102744 | chr2:178534098;178534097;178534096 | chr2:179398825;179398824;179398823 |
| N2AB | 32532 | 97819;97820;97821 | chr2:178534098;178534097;178534096 | chr2:179398825;179398824;179398823 |
| N2A | 31605 | 95038;95039;95040 | chr2:178534098;178534097;178534096 | chr2:179398825;179398824;179398823 |
| N2B | 25108 | 75547;75548;75549 | chr2:178534098;178534097;178534096 | chr2:179398825;179398824;179398823 |
| Novex-1 | 25233 | 75922;75923;75924 | chr2:178534098;178534097;178534096 | chr2:179398825;179398824;179398823 |
| Novex-2 | 25300 | 76123;76124;76125 | chr2:178534098;178534097;178534096 | chr2:179398825;179398824;179398823 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| G/D | rs752184554  |
0.377 | 1.0 | N | 0.676 | 0.487 | 0.376570364461 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.66E-05 | 0 |
| G/D | rs752184554 |
0.377 | 1.0 | N | 0.676 | 0.487 | 0.376570364461 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| G/D | rs752184554 |
0.377 | 1.0 | N | 0.676 | 0.487 | 0.376570364461 | gnomAD-4.0.0 | 2.97435E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.06832E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| G/A | 0.5838 | likely_pathogenic | 0.6659 | pathogenic | -0.077 | Destabilizing | 1.0 | D | 0.59 | neutral | N | 0.457137372 | None | None | I |
| G/C | 0.8172 | likely_pathogenic | 0.8974 | pathogenic | -0.39 | Destabilizing | 1.0 | D | 0.633 | neutral | N | 0.46992571 | None | None | I |
| G/D | 0.8544 | likely_pathogenic | 0.8952 | pathogenic | 0.045 | Stabilizing | 1.0 | D | 0.676 | prob.neutral | N | 0.429672447 | None | None | I |
| G/E | 0.9099 | likely_pathogenic | 0.9429 | pathogenic | 0.028 | Stabilizing | 1.0 | D | 0.665 | neutral | None | None | None | None | I |
| G/F | 0.9821 | likely_pathogenic | 0.9882 | pathogenic | -0.334 | Destabilizing | 1.0 | D | 0.598 | neutral | None | None | None | None | I |
| G/H | 0.937 | likely_pathogenic | 0.9615 | pathogenic | -0.603 | Destabilizing | 1.0 | D | 0.603 | neutral | None | None | None | None | I |
| G/I | 0.9722 | likely_pathogenic | 0.9827 | pathogenic | 0.341 | Stabilizing | 1.0 | D | 0.609 | neutral | None | None | None | None | I |
| G/K | 0.9589 | likely_pathogenic | 0.9745 | pathogenic | -0.496 | Destabilizing | 1.0 | D | 0.667 | neutral | None | None | None | None | I |
| G/L | 0.9424 | likely_pathogenic | 0.9603 | pathogenic | 0.341 | Stabilizing | 1.0 | D | 0.655 | neutral | None | None | None | None | I |
| G/M | 0.9659 | likely_pathogenic | 0.9793 | pathogenic | 0.06 | Stabilizing | 1.0 | D | 0.621 | neutral | None | None | None | None | I |
| G/N | 0.8608 | likely_pathogenic | 0.8975 | pathogenic | -0.315 | Destabilizing | 1.0 | D | 0.64 | neutral | None | None | None | None | I |
| G/P | 0.9899 | likely_pathogenic | 0.9925 | pathogenic | 0.244 | Stabilizing | 1.0 | D | 0.647 | neutral | None | None | None | None | I |
| G/Q | 0.9141 | likely_pathogenic | 0.9408 | pathogenic | -0.341 | Destabilizing | 1.0 | D | 0.636 | neutral | None | None | None | None | I |
| G/R | 0.9 | likely_pathogenic | 0.9359 | pathogenic | -0.41 | Destabilizing | 1.0 | D | 0.64 | neutral | N | 0.468911752 | None | None | I |
| G/S | 0.4325 | ambiguous | 0.4958 | ambiguous | -0.651 | Destabilizing | 1.0 | D | 0.644 | neutral | N | 0.456630393 | None | None | I |
| G/T | 0.8495 | likely_pathogenic | 0.8901 | pathogenic | -0.558 | Destabilizing | 1.0 | D | 0.664 | neutral | None | None | None | None | I |
| G/V | 0.9415 | likely_pathogenic | 0.9623 | pathogenic | 0.244 | Stabilizing | 1.0 | D | 0.663 | neutral | N | 0.498769959 | None | None | I |
| G/W | 0.9591 | likely_pathogenic | 0.9742 | pathogenic | -0.783 | Destabilizing | 1.0 | D | 0.628 | neutral | None | None | None | None | I |
| G/Y | 0.9668 | likely_pathogenic | 0.9795 | pathogenic | -0.249 | Destabilizing | 1.0 | D | 0.592 | 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.