Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24541 | 73846;73847;73848 | chr2:178572511;178572510;178572509 | chr2:179437238;179437237;179437236 |
| N2AB | 22900 | 68923;68924;68925 | chr2:178572511;178572510;178572509 | chr2:179437238;179437237;179437236 |
| N2A | 21973 | 66142;66143;66144 | chr2:178572511;178572510;178572509 | chr2:179437238;179437237;179437236 |
| N2B | 15476 | 46651;46652;46653 | chr2:178572511;178572510;178572509 | chr2:179437238;179437237;179437236 |
| Novex-1 | 15601 | 47026;47027;47028 | chr2:178572511;178572510;178572509 | chr2:179437238;179437237;179437236 |
| Novex-2 | 15668 | 47227;47228;47229 | chr2:178572511;178572510;178572509 | chr2:179437238;179437237;179437236 |
| 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/E | None | None | None | N | 0.237 | 0.046 | 0.0716867268079 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| D/H | None | None | 0.953 | N | 0.724 | 0.289 | 0.359963025489 | gnomAD-4.0.0 | 6.84369E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99594E-07 | 0 | 0 |
| D/N | rs868185177  |
None | 0.2 | N | 0.54 | 0.174 | 0.216624796971 | gnomAD-4.0.0 | 1.36874E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99594E-07 | 0 | 1.65706E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.1097 | likely_benign | 0.1009 | benign | -0.369 | Destabilizing | 0.22 | N | 0.604 | neutral | N | 0.477288327 | None | None | N |
| D/C | 0.4861 | ambiguous | 0.4303 | ambiguous | -0.155 | Destabilizing | 0.946 | D | 0.746 | deleterious | None | None | None | None | N |
| D/E | 0.059 | likely_benign | 0.0565 | benign | -0.862 | Destabilizing | None | N | 0.237 | neutral | N | 0.403481215 | None | None | N |
| D/F | 0.4979 | ambiguous | 0.4446 | ambiguous | -0.31 | Destabilizing | 0.983 | D | 0.781 | deleterious | None | None | None | None | N |
| D/G | 0.1736 | likely_benign | 0.1479 | benign | -0.694 | Destabilizing | 0.289 | N | 0.603 | neutral | N | 0.470002886 | None | None | N |
| D/H | 0.2655 | likely_benign | 0.2185 | benign | -0.743 | Destabilizing | 0.953 | D | 0.724 | prob.delet. | N | 0.473294569 | None | None | N |
| D/I | 0.2018 | likely_benign | 0.1827 | benign | 0.475 | Stabilizing | 0.95 | D | 0.78 | deleterious | None | None | None | None | N |
| D/K | 0.2486 | likely_benign | 0.2179 | benign | -0.512 | Destabilizing | 0.572 | D | 0.559 | neutral | None | None | None | None | N |
| D/L | 0.2077 | likely_benign | 0.1791 | benign | 0.475 | Stabilizing | 0.904 | D | 0.772 | deleterious | None | None | None | None | N |
| D/M | 0.3156 | likely_benign | 0.2764 | benign | 0.92 | Stabilizing | 0.988 | D | 0.778 | deleterious | None | None | None | None | N |
| D/N | 0.085 | likely_benign | 0.0839 | benign | -0.8 | Destabilizing | 0.2 | N | 0.54 | neutral | N | 0.472727869 | None | None | N |
| D/P | 0.9247 | likely_pathogenic | 0.8931 | pathogenic | 0.219 | Stabilizing | 0.273 | N | 0.728 | prob.delet. | None | None | None | None | N |
| D/Q | 0.1722 | likely_benign | 0.1472 | benign | -0.669 | Destabilizing | 0.637 | D | 0.579 | neutral | None | None | None | None | N |
| D/R | 0.377 | ambiguous | 0.3169 | benign | -0.435 | Destabilizing | 0.824 | D | 0.769 | deleterious | None | None | None | None | N |
| D/S | 0.0977 | likely_benign | 0.0919 | benign | -1.018 | Destabilizing | 0.272 | N | 0.45 | neutral | None | None | None | None | N |
| D/T | 0.1436 | likely_benign | 0.1331 | benign | -0.764 | Destabilizing | 0.538 | D | 0.684 | prob.neutral | None | None | None | None | N |
| D/V | 0.128 | likely_benign | 0.1132 | benign | 0.219 | Stabilizing | 0.553 | D | 0.764 | deleterious | N | 0.505379006 | None | None | N |
| D/W | 0.8816 | likely_pathogenic | 0.825 | pathogenic | -0.293 | Destabilizing | 0.995 | D | 0.719 | prob.delet. | None | None | None | None | N |
| D/Y | 0.2421 | likely_benign | 0.197 | benign | -0.13 | Destabilizing | 0.978 | D | 0.781 | deleterious | N | 0.470256376 | 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.