Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20452 | 61579;61580;61581 | chr2:178590371;178590370;178590369 | chr2:179455098;179455097;179455096 |
| N2AB | 18811 | 56656;56657;56658 | chr2:178590371;178590370;178590369 | chr2:179455098;179455097;179455096 |
| N2A | 17884 | 53875;53876;53877 | chr2:178590371;178590370;178590369 | chr2:179455098;179455097;179455096 |
| N2B | 11387 | 34384;34385;34386 | chr2:178590371;178590370;178590369 | chr2:179455098;179455097;179455096 |
| Novex-1 | 11512 | 34759;34760;34761 | chr2:178590371;178590370;178590369 | chr2:179455098;179455097;179455096 |
| Novex-2 | 11579 | 34960;34961;34962 | chr2:178590371;178590370;178590369 | chr2:179455098;179455097;179455096 |
| 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/N | rs375946418  |
0.012 | 0.996 | N | 0.525 | 0.393 | None | gnomAD-2.1.1 | 8.89E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 4.23E-05 | None | 0 | 9.62E-06 | 0 |
| I/N | rs375946418 |
0.012 | 0.996 | N | 0.525 | 0.393 | None | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| I/N | rs375946418 |
0.012 | 0.996 | N | 0.525 | 0.393 | None | gnomAD-4.0.0 | 1.00986E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.1151E-05 | 1.18265E-05 | 3.27086E-05 |
| I/T | None | None | 0.92 | N | 0.445 | 0.201 | 0.645970908164 | gnomAD-4.0.0 | 6.98158E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.10891E-07 | 0 | 0 |
| I/V | None | None | 0.061 | N | 0.103 | 0.101 | 0.39709148275 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.3048 | likely_benign | 0.2708 | benign | -0.529 | Destabilizing | 0.863 | D | 0.431 | neutral | None | None | None | None | I |
| I/C | 0.7165 | likely_pathogenic | 0.7254 | pathogenic | -0.776 | Destabilizing | 0.999 | D | 0.389 | neutral | None | None | None | None | I |
| I/D | 0.8283 | likely_pathogenic | 0.8152 | pathogenic | -0.071 | Destabilizing | 0.997 | D | 0.53 | neutral | None | None | None | None | I |
| I/E | 0.6845 | likely_pathogenic | 0.631 | pathogenic | -0.159 | Destabilizing | 0.997 | D | 0.521 | neutral | None | None | None | None | I |
| I/F | 0.3396 | likely_benign | 0.3297 | benign | -0.544 | Destabilizing | 0.976 | D | 0.302 | neutral | N | 0.466822881 | None | None | I |
| I/G | 0.7359 | likely_pathogenic | 0.7278 | pathogenic | -0.67 | Destabilizing | 0.991 | D | 0.507 | neutral | None | None | None | None | I |
| I/H | 0.6719 | likely_pathogenic | 0.6541 | pathogenic | 0.071 | Stabilizing | 0.999 | D | 0.488 | neutral | None | None | None | None | I |
| I/K | 0.4692 | ambiguous | 0.4096 | ambiguous | -0.316 | Destabilizing | 0.991 | D | 0.515 | neutral | None | None | None | None | I |
| I/L | 0.1643 | likely_benign | 0.1568 | benign | -0.284 | Destabilizing | 0.31 | N | 0.299 | neutral | N | 0.460086646 | None | None | I |
| I/M | 0.1204 | likely_benign | 0.1205 | benign | -0.458 | Destabilizing | 0.31 | N | 0.175 | neutral | N | 0.441674244 | None | None | I |
| I/N | 0.5243 | ambiguous | 0.4909 | ambiguous | -0.218 | Destabilizing | 0.996 | D | 0.525 | neutral | N | 0.488502611 | None | None | I |
| I/P | 0.8319 | likely_pathogenic | 0.8502 | pathogenic | -0.334 | Destabilizing | 0.997 | D | 0.529 | neutral | None | None | None | None | I |
| I/Q | 0.5367 | ambiguous | 0.4946 | ambiguous | -0.406 | Destabilizing | 0.991 | D | 0.527 | neutral | None | None | None | None | I |
| I/R | 0.3946 | ambiguous | 0.3565 | ambiguous | 0.204 | Stabilizing | 0.991 | D | 0.532 | neutral | None | None | None | None | I |
| I/S | 0.401 | ambiguous | 0.3701 | ambiguous | -0.668 | Destabilizing | 0.959 | D | 0.513 | neutral | N | 0.431225177 | None | None | I |
| I/T | 0.2872 | likely_benign | 0.2484 | benign | -0.645 | Destabilizing | 0.92 | D | 0.445 | neutral | N | 0.461950728 | None | None | I |
| I/V | 0.0941 | likely_benign | 0.09 | benign | -0.334 | Destabilizing | 0.061 | N | 0.103 | neutral | N | 0.470263567 | None | None | I |
| I/W | 0.8645 | likely_pathogenic | 0.8743 | pathogenic | -0.555 | Destabilizing | 0.999 | D | 0.547 | neutral | None | None | None | None | I |
| I/Y | 0.6665 | likely_pathogenic | 0.6668 | pathogenic | -0.314 | Destabilizing | 0.997 | D | 0.419 | 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.