Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 13841 | 41746;41747;41748 | chr2:178636050;178636049;178636048 | chr2:179500777;179500776;179500775 |
| N2AB | 12200 | 36823;36824;36825 | chr2:178636050;178636049;178636048 | chr2:179500777;179500776;179500775 |
| N2A | 11273 | 34042;34043;34044 | chr2:178636050;178636049;178636048 | chr2:179500777;179500776;179500775 |
| N2B | 4776 | 14551;14552;14553 | chr2:178636050;178636049;178636048 | chr2:179500777;179500776;179500775 |
| Novex-1 | 4901 | 14926;14927;14928 | chr2:178636050;178636049;178636048 | chr2:179500777;179500776;179500775 |
| Novex-2 | 4968 | 15127;15128;15129 | chr2:178636050;178636049;178636048 | chr2:179500777;179500776;179500775 |
| 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/N | rs201257644  |
0.121 | 0.612 | N | 0.197 | 0.144 | None | gnomAD-2.1.1 | 3.46922E-04 | None | None | None | None | N | None | 2.48201E-04 | 1.13186E-04 | None | 0 | 0 | None | 0 | None | 0 | 6.81231E-04 | 0 |
| D/N | rs201257644 |
0.121 | 0.612 | N | 0.197 | 0.144 | None | gnomAD-3.1.2 | 4.07793E-04 | None | None | None | None | N | None | 2.89631E-04 | 2.62295E-04 | 0 | 0 | 0 | None | 0 | 0 | 6.76709E-04 | 0 | 0 |
| D/N | rs201257644 |
0.121 | 0.612 | N | 0.197 | 0.144 | None | 1000 genomes | 3.99361E-04 | None | None | None | None | N | None | 8E-04 | 0 | None | None | 0 | 1E-03 | None | None | None | 0 | None |
| D/N | rs201257644 |
0.121 | 0.612 | N | 0.197 | 0.144 | None | gnomAD-4.0.0 | 6.366E-04 | None | None | None | None | N | None | 1.86682E-04 | 1.00037E-04 | None | 0 | 0 | None | 0 | 0 | 8.32562E-04 | 0 | 4.00269E-04 |
| D/Y | None | None | 1.0 | N | 0.621 | 0.269 | 0.347659731818 | gnomAD-4.0.0 | 6.84415E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99666E-07 | 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 | 0.3838 | ambiguous | 0.4929 | ambiguous | -0.076 | Destabilizing | 0.98 | D | 0.523 | neutral | N | 0.339423322 | None | None | N |
| D/C | 0.8612 | likely_pathogenic | 0.9014 | pathogenic | 0.337 | Stabilizing | 1.0 | D | 0.686 | prob.delet. | None | None | None | None | N |
| D/E | 0.3215 | likely_benign | 0.4069 | ambiguous | -0.426 | Destabilizing | 0.98 | D | 0.437 | neutral | N | 0.334699857 | None | None | N |
| D/F | 0.8061 | likely_pathogenic | 0.864 | pathogenic | -0.445 | Destabilizing | 0.999 | D | 0.628 | neutral | None | None | None | None | N |
| D/G | 0.321 | likely_benign | 0.3834 | ambiguous | -0.276 | Destabilizing | 0.061 | N | 0.345 | neutral | N | 0.331918454 | None | None | N |
| D/H | 0.5188 | ambiguous | 0.6491 | pathogenic | -0.704 | Destabilizing | 0.999 | D | 0.385 | neutral | N | 0.340497001 | None | None | N |
| D/I | 0.7647 | likely_pathogenic | 0.8557 | pathogenic | 0.395 | Stabilizing | 0.999 | D | 0.626 | neutral | None | None | None | None | N |
| D/K | 0.6847 | likely_pathogenic | 0.8135 | pathogenic | 0.247 | Stabilizing | 0.985 | D | 0.481 | neutral | None | None | None | None | N |
| D/L | 0.7146 | likely_pathogenic | 0.7996 | pathogenic | 0.395 | Stabilizing | 0.998 | D | 0.685 | prob.delet. | None | None | None | None | N |
| D/M | 0.8706 | likely_pathogenic | 0.912 | pathogenic | 0.76 | Stabilizing | 1.0 | D | 0.628 | neutral | None | None | None | None | N |
| D/N | 0.1315 | likely_benign | 0.1559 | benign | 0.145 | Stabilizing | 0.612 | D | 0.197 | neutral | N | 0.346528802 | None | None | N |
| D/P | 0.9619 | likely_pathogenic | 0.9789 | pathogenic | 0.262 | Stabilizing | 0.999 | D | 0.46 | neutral | None | None | None | None | N |
| D/Q | 0.6182 | likely_pathogenic | 0.7337 | pathogenic | 0.161 | Stabilizing | 0.998 | D | 0.451 | neutral | None | None | None | None | N |
| D/R | 0.6858 | likely_pathogenic | 0.8069 | pathogenic | 0.149 | Stabilizing | 0.998 | D | 0.617 | neutral | None | None | None | None | N |
| D/S | 0.2334 | likely_benign | 0.291 | benign | 0.025 | Stabilizing | 0.985 | D | 0.383 | neutral | None | None | None | None | N |
| D/T | 0.5174 | ambiguous | 0.6098 | pathogenic | 0.169 | Stabilizing | 0.985 | D | 0.505 | neutral | None | None | None | None | N |
| D/V | 0.5551 | ambiguous | 0.684 | pathogenic | 0.262 | Stabilizing | 0.999 | D | 0.691 | prob.delet. | N | 0.342102352 | None | None | N |
| D/W | 0.968 | likely_pathogenic | 0.9802 | pathogenic | -0.501 | Destabilizing | 1.0 | D | 0.65 | prob.neutral | None | None | None | None | N |
| D/Y | 0.4109 | ambiguous | 0.5165 | ambiguous | -0.26 | Destabilizing | 1.0 | D | 0.621 | neutral | N | 0.35219318 | 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.