Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 9708 | 29347;29348;29349 | chr2:178706874;178706873;178706872 | chr2:179571601;179571600;179571599 |
| N2AB | 9391 | 28396;28397;28398 | chr2:178706874;178706873;178706872 | chr2:179571601;179571600;179571599 |
| N2A | 8464 | 25615;25616;25617 | chr2:178706874;178706873;178706872 | chr2:179571601;179571600;179571599 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/G | rs1274452311  |
None | 0.642 | None | 0.468 | 0.256 | 0.466059976078 | gnomAD-4.0.0 | 3.42508E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.50058E-06 | 0 | 0 |
| R/K | None | None | 0.002 | None | 0.226 | 0.153 | 0.311387274539 | gnomAD-4.0.0 | 6.84982E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 1.65854E-05 |
| R/T | rs969965309 |
0.136 | 0.023 | None | 0.298 | 0.223 | 0.286848849266 | gnomAD-2.1.1 | 4.07E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 9.01E-06 | 0 |
| R/T | rs969965309 |
0.136 | 0.023 | None | 0.298 | 0.223 | 0.286848849266 | 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 |
| R/T | rs969965309 |
0.136 | 0.023 | None | 0.298 | 0.223 | 0.286848849266 | gnomAD-4.0.0 | 2.48124E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.39264E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.6318 | likely_pathogenic | 0.4515 | ambiguous | -0.267 | Destabilizing | 0.329 | N | 0.452 | neutral | None | None | None | None | I |
| R/C | 0.3484 | ambiguous | 0.2536 | benign | -0.316 | Destabilizing | 0.995 | D | 0.386 | neutral | None | None | None | None | I |
| R/D | 0.892 | likely_pathogenic | 0.7797 | pathogenic | -0.098 | Destabilizing | 0.704 | D | 0.505 | neutral | None | None | None | None | I |
| R/E | 0.5927 | likely_pathogenic | 0.437 | ambiguous | -0.018 | Destabilizing | 0.329 | N | 0.436 | neutral | None | None | None | None | I |
| R/F | 0.8368 | likely_pathogenic | 0.6802 | pathogenic | -0.354 | Destabilizing | 0.944 | D | 0.429 | neutral | None | None | None | None | I |
| R/G | 0.5855 | likely_pathogenic | 0.3612 | ambiguous | -0.505 | Destabilizing | 0.642 | D | 0.468 | neutral | None | None | None | None | I |
| R/H | 0.1333 | likely_benign | 0.1196 | benign | -0.923 | Destabilizing | 0.007 | N | 0.243 | neutral | None | None | None | None | I |
| R/I | 0.517 | ambiguous | 0.3319 | benign | 0.339 | Stabilizing | 0.863 | D | 0.45 | neutral | None | None | None | None | I |
| R/K | 0.1267 | likely_benign | 0.1146 | benign | -0.366 | Destabilizing | 0.002 | N | 0.226 | neutral | None | None | None | None | I |
| R/L | 0.4881 | ambiguous | 0.3461 | ambiguous | 0.339 | Stabilizing | 0.543 | D | 0.464 | neutral | None | None | None | None | I |
| R/M | 0.4944 | ambiguous | 0.3362 | benign | -0.028 | Destabilizing | 0.981 | D | 0.45 | neutral | None | None | None | None | I |
| R/N | 0.7683 | likely_pathogenic | 0.6364 | pathogenic | 0.01 | Stabilizing | 0.704 | D | 0.413 | neutral | None | None | None | None | I |
| R/P | 0.9464 | likely_pathogenic | 0.8348 | pathogenic | 0.158 | Stabilizing | 0.944 | D | 0.475 | neutral | None | None | None | None | I |
| R/Q | 0.1539 | likely_benign | 0.1281 | benign | -0.138 | Destabilizing | 0.704 | D | 0.469 | neutral | None | None | None | None | I |
| R/S | 0.6611 | likely_pathogenic | 0.5001 | ambiguous | -0.482 | Destabilizing | 0.27 | N | 0.457 | neutral | None | None | None | None | I |
| R/T | 0.3326 | likely_benign | 0.2253 | benign | -0.253 | Destabilizing | 0.023 | N | 0.298 | neutral | None | None | None | None | I |
| R/V | 0.5728 | likely_pathogenic | 0.4248 | ambiguous | 0.158 | Stabilizing | 0.543 | D | 0.5 | neutral | None | None | None | None | I |
| R/W | 0.3926 | ambiguous | 0.2481 | benign | -0.259 | Destabilizing | 0.995 | D | 0.397 | neutral | None | None | None | None | I |
| R/Y | 0.6969 | likely_pathogenic | 0.537 | ambiguous | 0.103 | Stabilizing | 0.893 | D | 0.468 | 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.