Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28113 | 84562;84563;84564 | chr2:178561795;178561794;178561793 | chr2:179426522;179426521;179426520 |
| N2AB | 26472 | 79639;79640;79641 | chr2:178561795;178561794;178561793 | chr2:179426522;179426521;179426520 |
| N2A | 25545 | 76858;76859;76860 | chr2:178561795;178561794;178561793 | chr2:179426522;179426521;179426520 |
| N2B | 19048 | 57367;57368;57369 | chr2:178561795;178561794;178561793 | chr2:179426522;179426521;179426520 |
| Novex-1 | 19173 | 57742;57743;57744 | chr2:178561795;178561794;178561793 | chr2:179426522;179426521;179426520 |
| Novex-2 | 19240 | 57943;57944;57945 | chr2:178561795;178561794;178561793 | chr2:179426522;179426521;179426520 |
| 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/F | rs753201539  |
-0.862 | 0.994 | N | 0.733 | 0.454 | 0.65667953858 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 1.66168E-04 |
| S/F | rs753201539 |
-0.862 | 0.994 | N | 0.733 | 0.454 | 0.65667953858 | gnomAD-4.0.0 | 1.02644E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.34926E-05 | 0 | 0 |
| S/T | None | None | 0.944 | N | 0.472 | 0.279 | 0.238705975628 | gnomAD-4.0.0 | 1.59172E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.0248E-05 |
| S/Y | rs753201539 |
-0.514 | 0.994 | N | 0.733 | 0.44 | 0.657976263744 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.6E-05 | None | 0 | None | 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 | 0.0913 | likely_benign | 0.092 | benign | -0.736 | Destabilizing | 0.63 | D | 0.429 | neutral | N | 0.471221108 | None | None | N |
| S/C | 0.1179 | likely_benign | 0.1317 | benign | -0.364 | Destabilizing | 0.999 | D | 0.707 | prob.neutral | N | 0.481731721 | None | None | N |
| S/D | 0.6904 | likely_pathogenic | 0.6756 | pathogenic | -0.085 | Destabilizing | 0.916 | D | 0.564 | neutral | None | None | None | None | N |
| S/E | 0.748 | likely_pathogenic | 0.7239 | pathogenic | 0.012 | Stabilizing | 0.957 | D | 0.563 | neutral | None | None | None | None | N |
| S/F | 0.3187 | likely_benign | 0.3225 | benign | -0.792 | Destabilizing | 0.994 | D | 0.733 | prob.delet. | N | 0.484503198 | None | None | N |
| S/G | 0.133 | likely_benign | 0.1267 | benign | -1.07 | Destabilizing | 0.014 | N | 0.312 | neutral | None | None | None | None | N |
| S/H | 0.4817 | ambiguous | 0.49 | ambiguous | -1.426 | Destabilizing | 0.999 | D | 0.713 | prob.delet. | None | None | None | None | N |
| S/I | 0.2894 | likely_benign | 0.3081 | benign | 0.071 | Stabilizing | 0.996 | D | 0.703 | prob.neutral | None | None | None | None | N |
| S/K | 0.8155 | likely_pathogenic | 0.7904 | pathogenic | -0.158 | Destabilizing | 0.916 | D | 0.591 | neutral | None | None | None | None | N |
| S/L | 0.1554 | likely_benign | 0.1555 | benign | 0.071 | Stabilizing | 0.987 | D | 0.631 | neutral | None | None | None | None | N |
| S/M | 0.2325 | likely_benign | 0.2323 | benign | 0.081 | Stabilizing | 0.999 | D | 0.709 | prob.delet. | None | None | None | None | N |
| S/N | 0.2004 | likely_benign | 0.2018 | benign | -0.436 | Destabilizing | 0.916 | D | 0.579 | neutral | None | None | None | None | N |
| S/P | 0.9443 | likely_pathogenic | 0.9369 | pathogenic | -0.163 | Destabilizing | 0.994 | D | 0.694 | prob.neutral | N | 0.49454283 | None | None | N |
| S/Q | 0.606 | likely_pathogenic | 0.6056 | pathogenic | -0.363 | Destabilizing | 0.996 | D | 0.637 | neutral | None | None | None | None | N |
| S/R | 0.7611 | likely_pathogenic | 0.7378 | pathogenic | -0.352 | Destabilizing | 0.987 | D | 0.689 | prob.neutral | None | None | None | None | N |
| S/T | 0.0801 | likely_benign | 0.082 | benign | -0.368 | Destabilizing | 0.944 | D | 0.472 | neutral | N | 0.418376096 | None | None | N |
| S/V | 0.2462 | likely_benign | 0.2653 | benign | -0.163 | Destabilizing | 0.987 | D | 0.659 | neutral | None | None | None | None | N |
| S/W | 0.5567 | ambiguous | 0.5349 | ambiguous | -0.85 | Destabilizing | 0.999 | D | 0.724 | prob.delet. | None | None | None | None | N |
| S/Y | 0.3031 | likely_benign | 0.2898 | benign | -0.48 | Destabilizing | 0.994 | D | 0.733 | prob.delet. | N | 0.484756687 | 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.