Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32371 | 97336;97337;97338 | chr2:178542743;178542742;178542741 | chr2:179407470;179407469;179407468 |
| N2AB | 30730 | 92413;92414;92415 | chr2:178542743;178542742;178542741 | chr2:179407470;179407469;179407468 |
| N2A | 29803 | 89632;89633;89634 | chr2:178542743;178542742;178542741 | chr2:179407470;179407469;179407468 |
| N2B | 23306 | 70141;70142;70143 | chr2:178542743;178542742;178542741 | chr2:179407470;179407469;179407468 |
| Novex-1 | 23431 | 70516;70517;70518 | chr2:178542743;178542742;178542741 | chr2:179407470;179407469;179407468 |
| Novex-2 | 23498 | 70717;70718;70719 | chr2:178542743;178542742;178542741 | chr2:179407470;179407469;179407468 |
| 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/S | rs748682168  |
-0.099 | 1.0 | N | 0.589 | 0.451 | 0.574808824563 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.89E-06 | 0 |
| I/S | rs748682168 |
-0.099 | 1.0 | N | 0.589 | 0.451 | 0.574808824563 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| I/S | rs748682168 |
-0.099 | 1.0 | N | 0.589 | 0.451 | 0.574808824563 | gnomAD-4.0.0 | 3.22242E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.40757E-05 | 0 | 0 |
| I/V | rs397517766 |
0.028 | 0.993 | N | 0.268 | 0.214 | None | gnomAD-2.1.1 | 1.07E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.34E-05 | 0 |
| I/V | rs397517766 |
0.028 | 0.993 | N | 0.268 | 0.214 | None | gnomAD-3.1.2 | 3.94E-05 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 7.35E-05 | 0 | 0 |
| I/V | rs397517766 |
0.028 | 0.993 | N | 0.268 | 0.214 | None | gnomAD-4.0.0 | 6.63056E-05 | None | None | None | None | I | None | 4.00363E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 8.56098E-05 | 0 | 4.80354E-05 |
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 | 0.3562 | ambiguous | 0.3238 | benign | -0.662 | Destabilizing | 0.999 | D | 0.438 | neutral | None | None | None | None | I |
| I/C | 0.7598 | likely_pathogenic | 0.7297 | pathogenic | -0.586 | Destabilizing | 1.0 | D | 0.582 | neutral | None | None | None | None | I |
| I/D | 0.8212 | likely_pathogenic | 0.797 | pathogenic | -0.187 | Destabilizing | 1.0 | D | 0.647 | neutral | None | None | None | None | I |
| I/E | 0.6915 | likely_pathogenic | 0.6701 | pathogenic | -0.283 | Destabilizing | 1.0 | D | 0.649 | neutral | None | None | None | None | I |
| I/F | 0.2721 | likely_benign | 0.2242 | benign | -0.669 | Destabilizing | 1.0 | D | 0.549 | neutral | N | 0.459363422 | None | None | I |
| I/G | 0.654 | likely_pathogenic | 0.6029 | pathogenic | -0.829 | Destabilizing | 1.0 | D | 0.645 | neutral | None | None | None | None | I |
| I/H | 0.6045 | likely_pathogenic | 0.5561 | ambiguous | -0.108 | Destabilizing | 1.0 | D | 0.653 | neutral | None | None | None | None | I |
| I/K | 0.4442 | ambiguous | 0.4102 | ambiguous | -0.352 | Destabilizing | 1.0 | D | 0.648 | neutral | None | None | None | None | I |
| I/L | 0.1225 | likely_benign | 0.1101 | benign | -0.346 | Destabilizing | 0.993 | D | 0.265 | neutral | N | 0.422266472 | None | None | I |
| I/M | 0.1425 | likely_benign | 0.1284 | benign | -0.345 | Destabilizing | 1.0 | D | 0.565 | neutral | N | 0.470580494 | None | None | I |
| I/N | 0.4059 | ambiguous | 0.3589 | ambiguous | -0.137 | Destabilizing | 1.0 | D | 0.661 | neutral | N | 0.470753852 | None | None | I |
| I/P | 0.5826 | likely_pathogenic | 0.5894 | pathogenic | -0.418 | Destabilizing | 1.0 | D | 0.665 | neutral | None | None | None | None | I |
| I/Q | 0.4982 | ambiguous | 0.48 | ambiguous | -0.377 | Destabilizing | 1.0 | D | 0.642 | neutral | None | None | None | None | I |
| I/R | 0.3267 | likely_benign | 0.3029 | benign | 0.225 | Stabilizing | 1.0 | D | 0.661 | neutral | None | None | None | None | I |
| I/S | 0.3594 | ambiguous | 0.322 | benign | -0.597 | Destabilizing | 1.0 | D | 0.589 | neutral | N | 0.459016706 | None | None | I |
| I/T | 0.3675 | ambiguous | 0.315 | benign | -0.584 | Destabilizing | 1.0 | D | 0.496 | neutral | N | 0.459016706 | None | None | I |
| I/V | 0.0893 | likely_benign | 0.0815 | benign | -0.418 | Destabilizing | 0.993 | D | 0.268 | neutral | N | 0.417111368 | None | None | I |
| I/W | 0.8186 | likely_pathogenic | 0.7977 | pathogenic | -0.678 | Destabilizing | 1.0 | D | 0.684 | prob.neutral | None | None | None | None | I |
| I/Y | 0.605 | likely_pathogenic | 0.5813 | pathogenic | -0.429 | Destabilizing | 1.0 | D | 0.584 | 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.