Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 5393 | 16402;16403;16404 | chr2:178732999;178732998;178732997 | chr2:179597726;179597725;179597724 |
| N2AB | 5076 | 15451;15452;15453 | chr2:178732999;178732998;178732997 | chr2:179597726;179597725;179597724 |
| N2A | 4149 | 12670;12671;12672 | chr2:178732999;178732998;178732997 | chr2:179597726;179597725;179597724 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/E | rs768837104  |
-0.22 | 0.006 | N | 0.195 | 0.093 | 0.0954503805726 | gnomAD-2.1.1 | 8.06E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.78E-05 | 0 |
| D/E | rs768837104 |
-0.22 | 0.006 | N | 0.195 | 0.093 | 0.0954503805726 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| D/E | rs768837104 |
-0.22 | 0.006 | N | 0.195 | 0.093 | 0.0954503805726 | gnomAD-4.0.0 | 7.4378E-06 | None | None | None | None | N | None | 1.33551E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 9.3241E-06 | 0 | 0 |
| D/H | None | None | 0.008 | N | 0.351 | 0.291 | 0.215869574891 | gnomAD-4.0.0 | 6.84316E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99502E-07 | 0 | 0 |
| D/N | rs867980863 |
-0.224 | 0.001 | N | 0.166 | 0.118 | 0.154104182512 | gnomAD-2.1.1 | 8.06E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.12145E-04 | None | 0 | None | 0 | 0 | 0 |
| D/N | rs867980863 |
-0.224 | 0.001 | N | 0.166 | 0.118 | 0.154104182512 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 3.86997E-04 | None | 0 | 0 | 0 | 0 | 0 |
| D/N | rs867980863 |
-0.224 | 0.001 | N | 0.166 | 0.118 | 0.154104182512 | gnomAD-4.0.0 | 1.92135E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 6.92676E-04 | None | 0 | 0 | 0 | 0 | 0 |
| D/Y | None | None | 0.627 | N | 0.495 | 0.344 | 0.29527378943 | gnomAD-4.0.0 | 6.84316E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99502E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.2022 | likely_benign | 0.2221 | benign | -0.463 | Destabilizing | 0.324 | N | 0.429 | neutral | N | 0.489514903 | None | None | N |
| D/C | 0.6354 | likely_pathogenic | 0.6551 | pathogenic | -0.1 | Destabilizing | 0.981 | D | 0.548 | neutral | None | None | None | None | N |
| D/E | 0.2018 | likely_benign | 0.2217 | benign | -0.275 | Destabilizing | 0.006 | N | 0.195 | neutral | N | 0.497559238 | None | None | N |
| D/F | 0.6338 | likely_pathogenic | 0.6796 | pathogenic | -0.181 | Destabilizing | 0.818 | D | 0.484 | neutral | None | None | None | None | N |
| D/G | 0.1267 | likely_benign | 0.138 | benign | -0.696 | Destabilizing | 0.193 | N | 0.387 | neutral | N | 0.506946725 | None | None | N |
| D/H | 0.3206 | likely_benign | 0.3544 | ambiguous | -0.036 | Destabilizing | 0.008 | N | 0.351 | neutral | N | 0.508126137 | None | None | N |
| D/I | 0.6006 | likely_pathogenic | 0.6327 | pathogenic | 0.116 | Stabilizing | 0.818 | D | 0.493 | neutral | None | None | None | None | N |
| D/K | 0.5007 | ambiguous | 0.5393 | ambiguous | 0.22 | Stabilizing | 0.241 | N | 0.375 | neutral | None | None | None | None | N |
| D/L | 0.4962 | ambiguous | 0.5471 | ambiguous | 0.116 | Stabilizing | 0.69 | D | 0.457 | neutral | None | None | None | None | N |
| D/M | 0.6959 | likely_pathogenic | 0.731 | pathogenic | 0.289 | Stabilizing | 0.944 | D | 0.493 | neutral | None | None | None | None | N |
| D/N | 0.0827 | likely_benign | 0.0861 | benign | -0.23 | Destabilizing | 0.001 | N | 0.166 | neutral | N | 0.420402389 | None | None | N |
| D/P | 0.9429 | likely_pathogenic | 0.9465 | pathogenic | -0.055 | Destabilizing | 0.818 | D | 0.431 | neutral | None | None | None | None | N |
| D/Q | 0.3873 | ambiguous | 0.4316 | ambiguous | -0.154 | Destabilizing | 0.019 | N | 0.195 | neutral | None | None | None | None | N |
| D/R | 0.4782 | ambiguous | 0.528 | ambiguous | 0.439 | Stabilizing | 0.527 | D | 0.438 | neutral | None | None | None | None | N |
| D/S | 0.1448 | likely_benign | 0.1535 | benign | -0.346 | Destabilizing | 0.241 | N | 0.349 | neutral | None | None | None | None | N |
| D/T | 0.4197 | ambiguous | 0.4523 | ambiguous | -0.15 | Destabilizing | 0.241 | N | 0.408 | neutral | None | None | None | None | N |
| D/V | 0.3711 | ambiguous | 0.4041 | ambiguous | -0.055 | Destabilizing | 0.773 | D | 0.471 | neutral | N | 0.496858737 | None | None | N |
| D/W | 0.8597 | likely_pathogenic | 0.8796 | pathogenic | 0.04 | Stabilizing | 0.981 | D | 0.587 | neutral | None | None | None | None | N |
| D/Y | 0.2154 | likely_benign | 0.2401 | benign | 0.077 | Stabilizing | 0.627 | D | 0.495 | neutral | N | 0.519735932 | 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.