Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18521 | 55786;55787;55788 | chr2:178601436;178601435;178601434 | chr2:179466163;179466162;179466161 |
| N2AB | 16880 | 50863;50864;50865 | chr2:178601436;178601435;178601434 | chr2:179466163;179466162;179466161 |
| N2A | 15953 | 48082;48083;48084 | chr2:178601436;178601435;178601434 | chr2:179466163;179466162;179466161 |
| N2B | 9456 | 28591;28592;28593 | chr2:178601436;178601435;178601434 | chr2:179466163;179466162;179466161 |
| Novex-1 | 9581 | 28966;28967;28968 | chr2:178601436;178601435;178601434 | chr2:179466163;179466162;179466161 |
| Novex-2 | 9648 | 29167;29168;29169 | chr2:178601436;178601435;178601434 | chr2:179466163;179466162;179466161 |
| 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/M | rs887160734  |
None | 0.627 | N | 0.461 | 0.095 | 0.286081765059 | gnomAD-4.0.0 | 6.84541E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 1.65755E-05 |
| I/T | rs538872534 |
-1.582 | 0.324 | N | 0.379 | 0.271 | None | gnomAD-2.1.1 | 1.61E-05 | None | None | None | None | N | None | 6.47E-05 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 1.78E-05 | 0 |
| I/T | rs538872534 |
-1.582 | 0.324 | N | 0.379 | 0.271 | None | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | N | None | 2.42E-05 | 1.97031E-04 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/T | rs538872534 |
-1.582 | 0.324 | N | 0.379 | 0.271 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 1.4E-03 | None | None | 0 | 0 | None | None | None | 0 | None |
| I/T | rs538872534 |
-1.582 | 0.324 | N | 0.379 | 0.271 | None | gnomAD-4.0.0 | 9.92036E-06 | None | None | None | None | N | None | 4.00331E-05 | 5.00734E-05 | None | 0 | 2.23834E-05 | None | 0 | 1.65125E-04 | 5.93559E-06 | 0 | 1.60149E-05 |
| I/V | None | None | None | N | 0.138 | 0.041 | 0.210429274316 | gnomAD-4.0.0 | 1.5931E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86144E-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 | 0.1237 | likely_benign | 0.1439 | benign | -1.506 | Destabilizing | 0.116 | N | 0.393 | neutral | None | None | None | None | N |
| I/C | 0.622 | likely_pathogenic | 0.6827 | pathogenic | -0.927 | Destabilizing | 0.944 | D | 0.437 | neutral | None | None | None | None | N |
| I/D | 0.6768 | likely_pathogenic | 0.7455 | pathogenic | -0.622 | Destabilizing | 0.818 | D | 0.558 | neutral | None | None | None | None | N |
| I/E | 0.5068 | ambiguous | 0.5689 | pathogenic | -0.607 | Destabilizing | 0.818 | D | 0.541 | neutral | None | None | None | None | N |
| I/F | 0.2349 | likely_benign | 0.2815 | benign | -0.961 | Destabilizing | 0.627 | D | 0.409 | neutral | N | 0.492199065 | None | None | N |
| I/G | 0.4559 | ambiguous | 0.5302 | ambiguous | -1.838 | Destabilizing | 0.818 | D | 0.52 | neutral | None | None | None | None | N |
| I/H | 0.5661 | likely_pathogenic | 0.6558 | pathogenic | -0.881 | Destabilizing | 0.981 | D | 0.545 | neutral | None | None | None | None | N |
| I/K | 0.3979 | ambiguous | 0.4929 | ambiguous | -0.888 | Destabilizing | 0.818 | D | 0.529 | neutral | None | None | None | None | N |
| I/L | 0.1126 | likely_benign | 0.1302 | benign | -0.673 | Destabilizing | 0.001 | N | 0.116 | neutral | N | 0.429763739 | None | None | N |
| I/M | 0.0927 | likely_benign | 0.1043 | benign | -0.588 | Destabilizing | 0.627 | D | 0.461 | neutral | N | 0.482790147 | None | None | N |
| I/N | 0.3168 | likely_benign | 0.3837 | ambiguous | -0.707 | Destabilizing | 0.912 | D | 0.553 | neutral | N | 0.449563008 | None | None | N |
| I/P | 0.4388 | ambiguous | 0.5067 | ambiguous | -0.918 | Destabilizing | 0.932 | D | 0.559 | neutral | None | None | None | None | N |
| I/Q | 0.4165 | ambiguous | 0.4985 | ambiguous | -0.85 | Destabilizing | 0.932 | D | 0.549 | neutral | None | None | None | None | N |
| I/R | 0.346 | ambiguous | 0.4445 | ambiguous | -0.314 | Destabilizing | 0.818 | D | 0.551 | neutral | None | None | None | None | N |
| I/S | 0.188 | likely_benign | 0.2246 | benign | -1.39 | Destabilizing | 0.627 | D | 0.498 | neutral | N | 0.403193213 | None | None | N |
| I/T | 0.0886 | likely_benign | 0.103 | benign | -1.247 | Destabilizing | 0.324 | N | 0.379 | neutral | N | 0.425203281 | None | None | N |
| I/V | 0.0577 | likely_benign | 0.0581 | benign | -0.918 | Destabilizing | None | N | 0.138 | neutral | N | 0.369368641 | None | None | N |
| I/W | 0.791 | likely_pathogenic | 0.8553 | pathogenic | -0.983 | Destabilizing | 0.981 | D | 0.607 | neutral | None | None | None | None | N |
| I/Y | 0.6147 | likely_pathogenic | 0.6859 | pathogenic | -0.774 | Destabilizing | 0.818 | D | 0.455 | 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.