Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16362 | 49309;49310;49311 | chr2:178614313;178614312;178614311 | chr2:179479040;179479039;179479038 |
| N2AB | 14721 | 44386;44387;44388 | chr2:178614313;178614312;178614311 | chr2:179479040;179479039;179479038 |
| N2A | 13794 | 41605;41606;41607 | chr2:178614313;178614312;178614311 | chr2:179479040;179479039;179479038 |
| N2B | 7297 | 22114;22115;22116 | chr2:178614313;178614312;178614311 | chr2:179479040;179479039;179479038 |
| Novex-1 | 7422 | 22489;22490;22491 | chr2:178614313;178614312;178614311 | chr2:179479040;179479039;179479038 |
| Novex-2 | 7489 | 22690;22691;22692 | chr2:178614313;178614312;178614311 | chr2:179479040;179479039;179479038 |
| 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/A | rs1380942594  |
None | 0.027 | N | 0.301 | 0.274 | 0.295974979623 | 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/A | rs1380942594 |
None | 0.027 | N | 0.301 | 0.274 | 0.295974979623 | gnomAD-4.0.0 | 2.03042E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.41018E-06 | 0 | 0 |
| D/E | None | None | None | N | 0.055 | 0.13 | 0.0297737177859 | gnomAD-4.0.0 | 6.8459E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.9981E-07 | 0 | 0 |
| D/V | None | None | 0.117 | D | 0.379 | 0.364 | 0.351614576976 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.1577 | likely_benign | 0.1416 | benign | -0.308 | Destabilizing | 0.027 | N | 0.301 | neutral | N | 0.508434018 | None | None | N |
| D/C | 0.6295 | likely_pathogenic | 0.6312 | pathogenic | 0.061 | Stabilizing | 0.935 | D | 0.423 | neutral | None | None | None | None | N |
| D/E | 0.0927 | likely_benign | 0.0888 | benign | -0.333 | Destabilizing | None | N | 0.055 | neutral | N | 0.434093168 | None | None | N |
| D/F | 0.7182 | likely_pathogenic | 0.7309 | pathogenic | -0.267 | Destabilizing | 0.791 | D | 0.395 | neutral | None | None | None | None | N |
| D/G | 0.2006 | likely_benign | 0.1857 | benign | -0.515 | Destabilizing | 0.052 | N | 0.271 | neutral | D | 0.534828087 | None | None | N |
| D/H | 0.3727 | ambiguous | 0.373 | ambiguous | -0.206 | Destabilizing | 0.484 | N | 0.353 | neutral | D | 0.556230778 | None | None | N |
| D/I | 0.4983 | ambiguous | 0.4997 | ambiguous | 0.191 | Stabilizing | 0.555 | D | 0.416 | neutral | None | None | None | None | N |
| D/K | 0.3769 | ambiguous | 0.3658 | ambiguous | 0.266 | Stabilizing | 0.035 | N | 0.278 | neutral | None | None | None | None | N |
| D/L | 0.454 | ambiguous | 0.4338 | ambiguous | 0.191 | Stabilizing | 0.149 | N | 0.392 | neutral | None | None | None | None | N |
| D/M | 0.5838 | likely_pathogenic | 0.5734 | pathogenic | 0.378 | Stabilizing | 0.935 | D | 0.383 | neutral | None | None | None | None | N |
| D/N | 0.1162 | likely_benign | 0.1123 | benign | -0.014 | Destabilizing | 0.002 | N | 0.061 | neutral | N | 0.480582928 | None | None | N |
| D/P | 0.9153 | likely_pathogenic | 0.9169 | pathogenic | 0.047 | Stabilizing | 0.555 | D | 0.357 | neutral | None | None | None | None | N |
| D/Q | 0.3018 | likely_benign | 0.2867 | benign | 0.016 | Stabilizing | 0.081 | N | 0.215 | neutral | None | None | None | None | N |
| D/R | 0.4692 | ambiguous | 0.4679 | ambiguous | 0.396 | Stabilizing | 0.081 | N | 0.347 | neutral | None | None | None | None | N |
| D/S | 0.1287 | likely_benign | 0.1204 | benign | -0.131 | Destabilizing | 0.035 | N | 0.235 | neutral | None | None | None | None | N |
| D/T | 0.2522 | likely_benign | 0.2389 | benign | 0.028 | Stabilizing | 0.149 | N | 0.28 | neutral | None | None | None | None | N |
| D/V | 0.2881 | likely_benign | 0.2873 | benign | 0.047 | Stabilizing | 0.117 | N | 0.379 | neutral | D | 0.590596778 | None | None | N |
| D/W | 0.9113 | likely_pathogenic | 0.921 | pathogenic | -0.142 | Destabilizing | 0.935 | D | 0.507 | neutral | None | None | None | None | N |
| D/Y | 0.373 | ambiguous | 0.3853 | ambiguous | -0.033 | Destabilizing | 0.741 | D | 0.401 | neutral | D | 0.672230744 | 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.