Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14905 | 44938;44939;44940 | chr2:178624567;178624566;178624565 | chr2:179489294;179489293;179489292 |
| N2AB | 13264 | 40015;40016;40017 | chr2:178624567;178624566;178624565 | chr2:179489294;179489293;179489292 |
| N2A | 12337 | 37234;37235;37236 | chr2:178624567;178624566;178624565 | chr2:179489294;179489293;179489292 |
| N2B | 5840 | 17743;17744;17745 | chr2:178624567;178624566;178624565 | chr2:179489294;179489293;179489292 |
| Novex-1 | 5965 | 18118;18119;18120 | chr2:178624567;178624566;178624565 | chr2:179489294;179489293;179489292 |
| Novex-2 | 6032 | 18319;18320;18321 | chr2:178624567;178624566;178624565 | chr2:179489294;179489293;179489292 |
| 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 | None | None | 0.549 | N | 0.499 | 0.274 | 0.455448229734 | gnomAD-4.0.0 | 1.5934E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.4332E-05 | 0 |
| R/K | None | None | 0.004 | N | 0.141 | 0.135 | 0.266843984389 | 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 |
| R/S | rs1279690538  |
None | 0.379 | N | 0.399 | 0.27 | 0.262175524916 | gnomAD-3.1.2 | 6.59E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/S | rs1279690538 |
None | 0.379 | N | 0.399 | 0.27 | 0.262175524916 | gnomAD-4.0.0 | 6.58527E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.47249E-05 | 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 | 0.496 | ambiguous | 0.6775 | pathogenic | -0.976 | Destabilizing | 0.25 | N | 0.377 | neutral | None | None | None | None | N |
| R/C | 0.2647 | likely_benign | 0.3995 | ambiguous | -0.965 | Destabilizing | 0.005 | N | 0.369 | neutral | None | None | None | None | N |
| R/D | 0.7614 | likely_pathogenic | 0.8781 | pathogenic | -0.23 | Destabilizing | 0.85 | D | 0.483 | neutral | None | None | None | None | N |
| R/E | 0.5282 | ambiguous | 0.6754 | pathogenic | -0.145 | Destabilizing | 0.447 | N | 0.381 | neutral | None | None | None | None | N |
| R/F | 0.6447 | likely_pathogenic | 0.7841 | pathogenic | -1.042 | Destabilizing | 0.739 | D | 0.519 | neutral | None | None | None | None | N |
| R/G | 0.3569 | ambiguous | 0.533 | ambiguous | -1.231 | Destabilizing | 0.549 | D | 0.499 | neutral | N | 0.464684471 | None | None | N |
| R/H | 0.1617 | likely_benign | 0.2289 | benign | -1.406 | Destabilizing | 0.92 | D | 0.453 | neutral | None | None | None | None | N |
| R/I | 0.3614 | ambiguous | 0.549 | ambiguous | -0.303 | Destabilizing | 0.92 | D | 0.504 | neutral | None | None | None | None | N |
| R/K | 0.124 | likely_benign | 0.1464 | benign | -1.034 | Destabilizing | 0.004 | N | 0.141 | neutral | N | 0.482393141 | None | None | N |
| R/L | 0.3307 | likely_benign | 0.4224 | ambiguous | -0.303 | Destabilizing | 0.617 | D | 0.447 | neutral | None | None | None | None | N |
| R/M | 0.3578 | ambiguous | 0.4614 | ambiguous | -0.452 | Destabilizing | 0.963 | D | 0.454 | neutral | D | 0.55019656 | None | None | N |
| R/N | 0.6049 | likely_pathogenic | 0.7166 | pathogenic | -0.397 | Destabilizing | 0.85 | D | 0.43 | neutral | None | None | None | None | N |
| R/P | 0.5467 | ambiguous | 0.7729 | pathogenic | -0.508 | Destabilizing | 0.92 | D | 0.511 | neutral | None | None | None | None | N |
| R/Q | 0.161 | likely_benign | 0.2169 | benign | -0.703 | Destabilizing | 0.739 | D | 0.461 | neutral | None | None | None | None | N |
| R/S | 0.6084 | likely_pathogenic | 0.7765 | pathogenic | -1.211 | Destabilizing | 0.379 | N | 0.399 | neutral | N | 0.482629843 | None | None | N |
| R/T | 0.3339 | likely_benign | 0.4677 | ambiguous | -0.969 | Destabilizing | 0.549 | D | 0.451 | neutral | N | 0.451106007 | None | None | N |
| R/V | 0.4801 | ambiguous | 0.6364 | pathogenic | -0.508 | Destabilizing | 0.617 | D | 0.499 | neutral | None | None | None | None | N |
| R/W | 0.3163 | likely_benign | 0.3911 | ambiguous | -0.695 | Destabilizing | 0.99 | D | 0.517 | neutral | D | 0.61637989 | None | None | N |
| R/Y | 0.5528 | ambiguous | 0.6815 | pathogenic | -0.392 | Destabilizing | 0.048 | N | 0.315 | 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.