Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1869 | 5830;5831;5832 | chr2:178776259;178776258;178776257 | chr2:179640986;179640985;179640984 |
| N2AB | 1869 | 5830;5831;5832 | chr2:178776259;178776258;178776257 | chr2:179640986;179640985;179640984 |
| N2A | 1869 | 5830;5831;5832 | chr2:178776259;178776258;178776257 | chr2:179640986;179640985;179640984 |
| N2B | 1823 | 5692;5693;5694 | chr2:178776259;178776258;178776257 | chr2:179640986;179640985;179640984 |
| Novex-1 | 1823 | 5692;5693;5694 | chr2:178776259;178776258;178776257 | chr2:179640986;179640985;179640984 |
| Novex-2 | 1823 | 5692;5693;5694 | chr2:178776259;178776258;178776257 | chr2:179640986;179640985;179640984 |
| Novex-3 | 1869 | 5830;5831;5832 | chr2:178776259;178776258;178776257 | chr2:179640986;179640985;179640984 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Q/K | None | None | 0.425 | N | 0.283 | 0.167 | 0.187945064343 | gnomAD-4.0.0 | 1.59055E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85657E-06 | 0 | 0 |
| Q/R | rs770347404  |
0.249 | 0.642 | N | 0.285 | 0.265 | 0.202086224978 | gnomAD-2.1.1 | 3.58E-05 | None | None | None | None | I | None | 0 | 2.60221E-04 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| Q/R | rs770347404 |
0.249 | 0.642 | N | 0.285 | 0.265 | 0.202086224978 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | I | None | 0 | 6.54E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 4.77555E-04 |
| Q/R | rs770347404 |
0.249 | 0.642 | N | 0.285 | 0.265 | 0.202086224978 | gnomAD-4.0.0 | 1.66462E-05 | None | None | None | None | I | None | 0 | 2.03314E-04 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 2.84172E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Q/A | 0.1162 | likely_benign | 0.1248 | benign | -0.257 | Destabilizing | 0.004 | N | 0.181 | neutral | None | None | None | None | I |
| Q/C | 0.7325 | likely_pathogenic | 0.7513 | pathogenic | 0.115 | Stabilizing | 0.981 | D | 0.453 | neutral | None | None | None | None | I |
| Q/D | 0.6087 | likely_pathogenic | 0.6298 | pathogenic | -0.022 | Destabilizing | 0.704 | D | 0.27 | neutral | None | None | None | None | I |
| Q/E | 0.1347 | likely_benign | 0.1369 | benign | -0.024 | Destabilizing | 0.425 | N | 0.253 | neutral | N | 0.4771061 | None | None | I |
| Q/F | 0.5625 | ambiguous | 0.5624 | ambiguous | -0.35 | Destabilizing | 0.893 | D | 0.476 | neutral | None | None | None | None | I |
| Q/G | 0.4235 | ambiguous | 0.4417 | ambiguous | -0.476 | Destabilizing | 0.495 | N | 0.423 | neutral | None | None | None | None | I |
| Q/H | 0.2517 | likely_benign | 0.2552 | benign | -0.287 | Destabilizing | 0.006 | N | 0.195 | neutral | N | 0.514463113 | None | None | I |
| Q/I | 0.1994 | likely_benign | 0.2081 | benign | 0.242 | Stabilizing | 0.543 | D | 0.428 | neutral | None | None | None | None | I |
| Q/K | 0.2079 | likely_benign | 0.2044 | benign | -0.109 | Destabilizing | 0.425 | N | 0.283 | neutral | N | 0.446118389 | None | None | I |
| Q/L | 0.069 | likely_benign | 0.0688 | benign | 0.242 | Stabilizing | 0.002 | N | 0.198 | neutral | N | 0.470106442 | None | None | I |
| Q/M | 0.1946 | likely_benign | 0.2015 | benign | 0.318 | Stabilizing | 0.085 | N | 0.196 | neutral | None | None | None | None | I |
| Q/N | 0.2846 | likely_benign | 0.2934 | benign | -0.366 | Destabilizing | 0.704 | D | 0.308 | neutral | None | None | None | None | I |
| Q/P | 0.1096 | likely_benign | 0.1164 | benign | 0.104 | Stabilizing | 0.784 | D | 0.476 | neutral | N | 0.479290853 | None | None | I |
| Q/R | 0.2477 | likely_benign | 0.2517 | benign | 0.055 | Stabilizing | 0.642 | D | 0.285 | neutral | N | 0.486896193 | None | None | I |
| Q/S | 0.171 | likely_benign | 0.187 | benign | -0.372 | Destabilizing | 0.329 | N | 0.214 | neutral | None | None | None | None | I |
| Q/T | 0.1489 | likely_benign | 0.165 | benign | -0.22 | Destabilizing | 0.013 | N | 0.197 | neutral | None | None | None | None | I |
| Q/V | 0.1229 | likely_benign | 0.1326 | benign | 0.104 | Stabilizing | 0.329 | N | 0.347 | neutral | None | None | None | None | I |
| Q/W | 0.709 | likely_pathogenic | 0.7219 | pathogenic | -0.352 | Destabilizing | 0.995 | D | 0.457 | neutral | None | None | None | None | I |
| Q/Y | 0.4616 | ambiguous | 0.4523 | ambiguous | -0.11 | Destabilizing | 0.704 | D | 0.469 | 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.