Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29089 | 87490;87491;87492 | chr2:178558089;178558088;178558087 | chr2:179422816;179422815;179422814 |
| N2AB | 27448 | 82567;82568;82569 | chr2:178558089;178558088;178558087 | chr2:179422816;179422815;179422814 |
| N2A | 26521 | 79786;79787;79788 | chr2:178558089;178558088;178558087 | chr2:179422816;179422815;179422814 |
| N2B | 20024 | 60295;60296;60297 | chr2:178558089;178558088;178558087 | chr2:179422816;179422815;179422814 |
| Novex-1 | 20149 | 60670;60671;60672 | chr2:178558089;178558088;178558087 | chr2:179422816;179422815;179422814 |
| Novex-2 | 20216 | 60871;60872;60873 | chr2:178558089;178558088;178558087 | chr2:179422816;179422815;179422814 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/K | None | None | 0.891 | N | 0.39 | 0.329 | 0.41441075005 | gnomAD-4.0.0 | 6.87474E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.04632E-07 | 0 | 0 |
| M/R | None | None | 0.966 | N | 0.373 | 0.368 | 0.465464902746 | gnomAD-4.0.0 | 7.58752E-04 | None | None | None | None | N | None | 5.11494E-04 | 0 | None | 2.68797E-04 | 1.26199E-04 | None | 0 | 1.74459E-04 | 9.12091E-04 | 2.56046E-04 | 7.34656E-04 |
| M/T | rs185467126  |
0.812 | 0.891 | N | 0.359 | 0.271 | None | gnomAD-2.1.1 | 4.29E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 6.15195E-04 | None | 0 | None | 0 | 0 | 0 |
| M/T | rs185467126 |
0.812 | 0.891 | N | 0.359 | 0.271 | None | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 7.71605E-04 | None | 0 | 0 | 0 | 0 | 0 |
| M/T | rs185467126 |
0.812 | 0.891 | N | 0.359 | 0.271 | None | 1000 genomes | 3.99361E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 2E-03 | 0 | None | None | None | 0 | None |
| M/T | rs185467126 |
0.812 | 0.891 | N | 0.359 | 0.271 | None | gnomAD-4.0.0 | 1.24467E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 4.01589E-04 | None | 0 | 0 | 8.52194E-07 | 1.10009E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.2917 | likely_benign | 0.2635 | benign | -0.066 | Destabilizing | 0.688 | D | 0.372 | neutral | None | None | None | None | N |
| M/C | 0.8152 | likely_pathogenic | 0.779 | pathogenic | -0.212 | Destabilizing | 0.998 | D | 0.372 | neutral | None | None | None | None | N |
| M/D | 0.798 | likely_pathogenic | 0.8066 | pathogenic | 0.5 | Stabilizing | 0.991 | D | 0.392 | neutral | None | None | None | None | N |
| M/E | 0.5454 | ambiguous | 0.5682 | pathogenic | 0.434 | Stabilizing | 0.991 | D | 0.377 | neutral | None | None | None | None | N |
| M/F | 0.5011 | ambiguous | 0.4448 | ambiguous | -0.073 | Destabilizing | 0.842 | D | 0.366 | neutral | None | None | None | None | N |
| M/G | 0.5048 | ambiguous | 0.4637 | ambiguous | -0.157 | Destabilizing | 0.991 | D | 0.391 | neutral | None | None | None | None | N |
| M/H | 0.5933 | likely_pathogenic | 0.5611 | ambiguous | 0.456 | Stabilizing | 0.998 | D | 0.389 | neutral | None | None | None | None | N |
| M/I | 0.3757 | ambiguous | 0.3555 | ambiguous | 0.07 | Stabilizing | 0.454 | N | 0.396 | neutral | N | 0.475716954 | None | None | N |
| M/K | 0.2369 | likely_benign | 0.2376 | benign | 0.559 | Stabilizing | 0.891 | D | 0.39 | neutral | N | 0.390924844 | None | None | N |
| M/L | 0.1189 | likely_benign | 0.1085 | benign | 0.07 | Stabilizing | 0.005 | N | 0.163 | neutral | N | 0.445914122 | None | None | N |
| M/N | 0.4891 | ambiguous | 0.4775 | ambiguous | 0.704 | Stabilizing | 0.991 | D | 0.393 | neutral | None | None | None | None | N |
| M/P | 0.4762 | ambiguous | 0.4141 | ambiguous | 0.048 | Stabilizing | 0.991 | D | 0.392 | neutral | None | None | None | None | N |
| M/Q | 0.26 | likely_benign | 0.2498 | benign | 0.558 | Stabilizing | 0.991 | D | 0.358 | neutral | None | None | None | None | N |
| M/R | 0.278 | likely_benign | 0.2728 | benign | 0.944 | Stabilizing | 0.966 | D | 0.373 | neutral | N | 0.474503446 | None | None | N |
| M/S | 0.3304 | likely_benign | 0.3058 | benign | 0.3 | Stabilizing | 0.915 | D | 0.392 | neutral | None | None | None | None | N |
| M/T | 0.1701 | likely_benign | 0.1636 | benign | 0.324 | Stabilizing | 0.891 | D | 0.359 | neutral | N | 0.396832096 | None | None | N |
| M/V | 0.0776 | likely_benign | 0.0741 | benign | 0.048 | Stabilizing | 0.454 | N | 0.367 | neutral | N | 0.456688476 | None | None | N |
| M/W | 0.7253 | likely_pathogenic | 0.6725 | pathogenic | -0.11 | Destabilizing | 0.998 | D | 0.411 | neutral | None | None | None | None | N |
| M/Y | 0.6792 | likely_pathogenic | 0.655 | pathogenic | 0.114 | Stabilizing | 0.991 | D | 0.369 | 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.