Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25179 | 75760;75761;75762 | chr2:178570597;178570596;178570595 | chr2:179435324;179435323;179435322 |
| N2AB | 23538 | 70837;70838;70839 | chr2:178570597;178570596;178570595 | chr2:179435324;179435323;179435322 |
| N2A | 22611 | 68056;68057;68058 | chr2:178570597;178570596;178570595 | chr2:179435324;179435323;179435322 |
| N2B | 16114 | 48565;48566;48567 | chr2:178570597;178570596;178570595 | chr2:179435324;179435323;179435322 |
| Novex-1 | 16239 | 48940;48941;48942 | chr2:178570597;178570596;178570595 | chr2:179435324;179435323;179435322 |
| Novex-2 | 16306 | 49141;49142;49143 | chr2:178570597;178570596;178570595 | chr2:179435324;179435323;179435322 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/G | None | None | 0.001 | N | 0.099 | 0.112 | 0.240491677333 | gnomAD-4.0.0 | 1.59201E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.8593E-06 | 0 | 0 |
| S/I | rs1707825779  |
None | 0.939 | N | 0.551 | 0.59 | 0.610263417295 | gnomAD-4.0.0 | 1.59203E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85928E-06 | 0 | 0 |
| S/T | rs1707825779 |
None | 0.815 | D | 0.429 | 0.252 | 0.335661160332 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| S/T | rs1707825779 |
None | 0.815 | D | 0.429 | 0.252 | 0.335661160332 | gnomAD-4.0.0 | 6.57428E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.47067E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.1274 | likely_benign | 0.1374 | benign | -0.753 | Destabilizing | 0.373 | N | 0.395 | neutral | None | None | None | None | N |
| S/C | 0.1565 | likely_benign | 0.1686 | benign | -0.486 | Destabilizing | 0.994 | D | 0.472 | neutral | N | 0.519729382 | None | None | N |
| S/D | 0.7754 | likely_pathogenic | 0.8447 | pathogenic | 0.066 | Stabilizing | 0.742 | D | 0.401 | neutral | None | None | None | None | N |
| S/E | 0.8589 | likely_pathogenic | 0.9111 | pathogenic | 0.075 | Stabilizing | 0.742 | D | 0.407 | neutral | None | None | None | None | N |
| S/F | 0.7041 | likely_pathogenic | 0.752 | pathogenic | -0.945 | Destabilizing | 0.953 | D | 0.56 | neutral | None | None | None | None | N |
| S/G | 0.0652 | likely_benign | 0.0668 | benign | -1.007 | Destabilizing | 0.001 | N | 0.099 | neutral | N | 0.463797034 | None | None | N |
| S/H | 0.6673 | likely_pathogenic | 0.7453 | pathogenic | -1.417 | Destabilizing | 0.02 | N | 0.285 | neutral | None | None | None | None | N |
| S/I | 0.6582 | likely_pathogenic | 0.7248 | pathogenic | -0.184 | Destabilizing | 0.939 | D | 0.551 | neutral | N | 0.519222403 | None | None | N |
| S/K | 0.9 | likely_pathogenic | 0.9423 | pathogenic | -0.538 | Destabilizing | 0.742 | D | 0.395 | neutral | None | None | None | None | N |
| S/L | 0.3797 | ambiguous | 0.4104 | ambiguous | -0.184 | Destabilizing | 0.742 | D | 0.519 | neutral | None | None | None | None | N |
| S/M | 0.4474 | ambiguous | 0.4944 | ambiguous | 0.04 | Stabilizing | 0.996 | D | 0.465 | neutral | None | None | None | None | N |
| S/N | 0.343 | ambiguous | 0.4053 | ambiguous | -0.544 | Destabilizing | 0.684 | D | 0.429 | neutral | D | 0.52479181 | None | None | N |
| S/P | 0.9572 | likely_pathogenic | 0.9708 | pathogenic | -0.34 | Destabilizing | 0.984 | D | 0.49 | neutral | None | None | None | None | N |
| S/Q | 0.7749 | likely_pathogenic | 0.8436 | pathogenic | -0.648 | Destabilizing | 0.91 | D | 0.431 | neutral | None | None | None | None | N |
| S/R | 0.8191 | likely_pathogenic | 0.8837 | pathogenic | -0.489 | Destabilizing | 0.884 | D | 0.493 | neutral | N | 0.487760379 | None | None | N |
| S/T | 0.1031 | likely_benign | 0.1101 | benign | -0.597 | Destabilizing | 0.815 | D | 0.429 | neutral | D | 0.522535906 | None | None | N |
| S/V | 0.615 | likely_pathogenic | 0.6806 | pathogenic | -0.34 | Destabilizing | 0.953 | D | 0.553 | neutral | None | None | None | None | N |
| S/W | 0.7998 | likely_pathogenic | 0.8459 | pathogenic | -0.908 | Destabilizing | 0.996 | D | 0.606 | neutral | None | None | None | None | N |
| S/Y | 0.6083 | likely_pathogenic | 0.6849 | pathogenic | -0.632 | Destabilizing | 0.835 | D | 0.55 | 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.