Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29998 | 90217;90218;90219 | chr2:178552908;178552907;178552906 | chr2:179417635;179417634;179417633 |
| N2AB | 28357 | 85294;85295;85296 | chr2:178552908;178552907;178552906 | chr2:179417635;179417634;179417633 |
| N2A | 27430 | 82513;82514;82515 | chr2:178552908;178552907;178552906 | chr2:179417635;179417634;179417633 |
| N2B | 20933 | 63022;63023;63024 | chr2:178552908;178552907;178552906 | chr2:179417635;179417634;179417633 |
| Novex-1 | 21058 | 63397;63398;63399 | chr2:178552908;178552907;178552906 | chr2:179417635;179417634;179417633 |
| Novex-2 | 21125 | 63598;63599;63600 | chr2:178552908;178552907;178552906 | chr2:179417635;179417634;179417633 |
| 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/L | rs376543931  |
-0.222 | 0.999 | N | 0.535 | 0.317 | None | gnomAD-2.1.1 | 2.86E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 6.26E-05 | 0 |
| S/L | rs376543931 |
-0.222 | 0.999 | N | 0.535 | 0.317 | None | 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 |
| S/L | rs376543931 |
-0.222 | 0.999 | N | 0.535 | 0.317 | None | gnomAD-4.0.0 | 1.73531E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.28853E-05 | 0 | 1.60097E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.0746 | likely_benign | 0.0784 | benign | -0.621 | Destabilizing | 0.953 | D | 0.469 | neutral | N | 0.454968828 | None | None | N |
| S/C | 0.123 | likely_benign | 0.1314 | benign | -0.384 | Destabilizing | 1.0 | D | 0.629 | neutral | None | None | None | None | N |
| S/D | 0.324 | likely_benign | 0.3359 | benign | 0.59 | Stabilizing | 0.171 | N | 0.163 | neutral | None | None | None | None | N |
| S/E | 0.4295 | ambiguous | 0.4781 | ambiguous | 0.547 | Stabilizing | 0.469 | N | 0.212 | neutral | None | None | None | None | N |
| S/F | 0.2371 | likely_benign | 0.2567 | benign | -1.005 | Destabilizing | 0.999 | D | 0.653 | neutral | None | None | None | None | N |
| S/G | 0.1061 | likely_benign | 0.1079 | benign | -0.8 | Destabilizing | 0.993 | D | 0.421 | neutral | None | None | None | None | N |
| S/H | 0.3406 | ambiguous | 0.3719 | ambiguous | -1.181 | Destabilizing | 1.0 | D | 0.613 | neutral | None | None | None | None | N |
| S/I | 0.1495 | likely_benign | 0.1658 | benign | -0.265 | Destabilizing | 0.999 | D | 0.651 | neutral | None | None | None | None | N |
| S/K | 0.5827 | likely_pathogenic | 0.6488 | pathogenic | -0.355 | Destabilizing | 0.985 | D | 0.413 | neutral | None | None | None | None | N |
| S/L | 0.0809 | likely_benign | 0.082 | benign | -0.265 | Destabilizing | 0.999 | D | 0.535 | neutral | N | 0.468263412 | None | None | N |
| S/M | 0.1756 | likely_benign | 0.1907 | benign | -0.131 | Destabilizing | 1.0 | D | 0.613 | neutral | None | None | None | None | N |
| S/N | 0.1271 | likely_benign | 0.1328 | benign | -0.181 | Destabilizing | 0.985 | D | 0.494 | neutral | None | None | None | None | N |
| S/P | 0.1289 | likely_benign | 0.1339 | benign | -0.352 | Destabilizing | 0.999 | D | 0.581 | neutral | D | 0.524156767 | None | None | N |
| S/Q | 0.4228 | ambiguous | 0.4609 | ambiguous | -0.333 | Destabilizing | 0.996 | D | 0.505 | neutral | None | None | None | None | N |
| S/R | 0.579 | likely_pathogenic | 0.6373 | pathogenic | -0.255 | Destabilizing | 0.996 | D | 0.601 | neutral | None | None | None | None | N |
| S/T | 0.0799 | likely_benign | 0.0771 | benign | -0.327 | Destabilizing | 0.99 | D | 0.443 | neutral | N | 0.413967567 | None | None | N |
| S/V | 0.1485 | likely_benign | 0.1631 | benign | -0.352 | Destabilizing | 0.998 | D | 0.571 | neutral | None | None | None | None | N |
| S/W | 0.3772 | ambiguous | 0.4216 | ambiguous | -0.956 | Destabilizing | 1.0 | D | 0.713 | prob.delet. | D | 0.524676842 | None | None | N |
| S/Y | 0.2276 | likely_benign | 0.2582 | benign | -0.684 | Destabilizing | 0.999 | D | 0.654 | 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.