Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29989 | 90190;90191;90192 | chr2:178552935;178552934;178552933 | chr2:179417662;179417661;179417660 |
| N2AB | 28348 | 85267;85268;85269 | chr2:178552935;178552934;178552933 | chr2:179417662;179417661;179417660 |
| N2A | 27421 | 82486;82487;82488 | chr2:178552935;178552934;178552933 | chr2:179417662;179417661;179417660 |
| N2B | 20924 | 62995;62996;62997 | chr2:178552935;178552934;178552933 | chr2:179417662;179417661;179417660 |
| Novex-1 | 21049 | 63370;63371;63372 | chr2:178552935;178552934;178552933 | chr2:179417662;179417661;179417660 |
| Novex-2 | 21116 | 63571;63572;63573 | chr2:178552935;178552934;178552933 | chr2:179417662;179417661;179417660 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/G | rs1225946550  |
None | None | N | 0.071 | 0.074 | None | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 4.41E-05 | 0 | 0 |
| S/G | rs1225946550 |
None | None | N | 0.071 | 0.074 | None | gnomAD-4.0.0 | 7.43666E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.32336E-06 | 0 | 1.60092E-05 |
| S/T | None | None | 0.012 | N | 0.247 | 0.051 | 0.124217242631 | gnomAD-4.0.0 | 1.59153E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.88743E-05 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.0806 | likely_benign | 0.0766 | benign | -0.766 | Destabilizing | 0.007 | N | 0.163 | neutral | None | None | None | None | N |
| S/C | 0.1069 | likely_benign | 0.0934 | benign | -0.474 | Destabilizing | 0.828 | D | 0.291 | neutral | N | 0.492969856 | None | None | N |
| S/D | 0.3449 | ambiguous | 0.2825 | benign | 0.418 | Stabilizing | 0.016 | N | 0.183 | neutral | None | None | None | None | N |
| S/E | 0.4876 | ambiguous | 0.428 | ambiguous | 0.418 | Stabilizing | 0.016 | N | 0.196 | neutral | None | None | None | None | N |
| S/F | 0.2388 | likely_benign | 0.2324 | benign | -1.203 | Destabilizing | 0.214 | N | 0.391 | neutral | None | None | None | None | N |
| S/G | 0.079 | likely_benign | 0.0636 | benign | -0.962 | Destabilizing | None | N | 0.071 | neutral | N | 0.413970354 | None | None | N |
| S/H | 0.2207 | likely_benign | 0.197 | benign | -1.161 | Destabilizing | None | N | 0.194 | neutral | None | None | None | None | N |
| S/I | 0.1749 | likely_benign | 0.1551 | benign | -0.352 | Destabilizing | 0.295 | N | 0.429 | neutral | N | 0.487427963 | None | None | N |
| S/K | 0.4927 | ambiguous | 0.4391 | ambiguous | -0.263 | Destabilizing | 0.016 | N | 0.221 | neutral | None | None | None | None | N |
| S/L | 0.1218 | likely_benign | 0.1238 | benign | -0.352 | Destabilizing | 0.072 | N | 0.293 | neutral | None | None | None | None | N |
| S/M | 0.1914 | likely_benign | 0.1871 | benign | -0.337 | Destabilizing | 0.356 | N | 0.324 | neutral | None | None | None | None | N |
| S/N | 0.0886 | likely_benign | 0.0765 | benign | -0.302 | Destabilizing | None | N | 0.075 | neutral | N | 0.43157468 | None | None | N |
| S/P | 0.5462 | ambiguous | 0.5283 | ambiguous | -0.46 | Destabilizing | 0.136 | N | 0.362 | neutral | None | None | None | None | N |
| S/Q | 0.3571 | ambiguous | 0.3138 | benign | -0.345 | Destabilizing | 0.001 | N | 0.123 | neutral | None | None | None | None | N |
| S/R | 0.4528 | ambiguous | 0.4005 | ambiguous | -0.166 | Destabilizing | 0.029 | N | 0.286 | neutral | N | 0.379529707 | None | None | N |
| S/T | 0.0715 | likely_benign | 0.0735 | benign | -0.388 | Destabilizing | 0.012 | N | 0.247 | neutral | N | 0.42329634 | None | None | N |
| S/V | 0.1664 | likely_benign | 0.1498 | benign | -0.46 | Destabilizing | 0.136 | N | 0.329 | neutral | None | None | None | None | N |
| S/W | 0.4692 | ambiguous | 0.4464 | ambiguous | -1.2 | Destabilizing | 0.864 | D | 0.374 | neutral | None | None | None | None | N |
| S/Y | 0.2153 | likely_benign | 0.1957 | benign | -0.89 | Destabilizing | 0.12 | N | 0.424 | 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.