Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 9770 | 29533;29534;29535 | chr2:178706566;178706565;178706564 | chr2:179571293;179571292;179571291 |
| N2AB | 9453 | 28582;28583;28584 | chr2:178706566;178706565;178706564 | chr2:179571293;179571292;179571291 |
| N2A | 8526 | 25801;25802;25803 | chr2:178706566;178706565;178706564 | chr2:179571293;179571292;179571291 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/L | None | None | 0.975 | None | 0.571 | 0.379 | 0.507093260865 | gnomAD-4.0.0 | 6.84163E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 1.7337E-04 | 0 | 0 | 0 |
| R/Q | rs368309068  |
-1.497 | 0.997 | None | 0.486 | 0.274 | None | gnomAD-2.1.1 | 5.22E-05 | None | None | None | None | I | None | 1.29166E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 9.74E-05 | 0 |
| R/Q | rs368309068 |
-1.497 | 0.997 | None | 0.486 | 0.274 | None | gnomAD-3.1.2 | 6.57E-05 | None | None | None | None | I | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.02899E-04 | 2.07383E-04 | 0 |
| R/Q | rs368309068 |
-1.497 | 0.997 | None | 0.486 | 0.274 | None | gnomAD-4.0.0 | 8.05513E-05 | None | None | None | None | I | None | 6.66453E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 9.40802E-05 | 3.29431E-05 | 1.76045E-04 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.9737 | likely_pathogenic | 0.9063 | pathogenic | -1.525 | Destabilizing | 0.953 | D | 0.461 | neutral | None | None | None | None | I |
| R/C | 0.7345 | likely_pathogenic | 0.4595 | ambiguous | -1.853 | Destabilizing | 0.999 | D | 0.677 | prob.neutral | None | None | None | None | I |
| R/D | 0.9954 | likely_pathogenic | 0.986 | pathogenic | -1.112 | Destabilizing | 0.986 | D | 0.632 | neutral | None | None | None | None | I |
| R/E | 0.9611 | likely_pathogenic | 0.8913 | pathogenic | -1.033 | Destabilizing | 0.91 | D | 0.415 | neutral | None | None | None | None | I |
| R/F | 0.9866 | likely_pathogenic | 0.9357 | pathogenic | -1.78 | Destabilizing | 0.998 | D | 0.702 | prob.neutral | None | None | None | None | I |
| R/G | 0.9447 | likely_pathogenic | 0.8174 | pathogenic | -1.745 | Destabilizing | 0.975 | D | 0.571 | neutral | None | None | None | None | I |
| R/H | 0.4377 | ambiguous | 0.2392 | benign | -1.569 | Destabilizing | 0.998 | D | 0.535 | neutral | None | None | None | None | I |
| R/I | 0.906 | likely_pathogenic | 0.7314 | pathogenic | -0.937 | Destabilizing | 0.993 | D | 0.706 | prob.neutral | None | None | None | None | I |
| R/K | 0.3551 | ambiguous | 0.2348 | benign | -1.696 | Destabilizing | 0.06 | N | 0.267 | neutral | None | None | None | None | I |
| R/L | 0.8902 | likely_pathogenic | 0.7213 | pathogenic | -0.937 | Destabilizing | 0.975 | D | 0.571 | neutral | None | None | None | None | I |
| R/M | 0.9465 | likely_pathogenic | 0.813 | pathogenic | -0.987 | Destabilizing | 0.999 | D | 0.605 | neutral | None | None | None | None | I |
| R/N | 0.9834 | likely_pathogenic | 0.9514 | pathogenic | -1.197 | Destabilizing | 0.986 | D | 0.489 | neutral | None | None | None | None | I |
| R/P | 0.999 | likely_pathogenic | 0.9963 | pathogenic | -1.118 | Destabilizing | 0.996 | D | 0.645 | neutral | None | None | None | None | I |
| R/Q | 0.4792 | ambiguous | 0.2638 | benign | -1.579 | Destabilizing | 0.997 | D | 0.486 | neutral | None | None | None | None | I |
| R/S | 0.9671 | likely_pathogenic | 0.8914 | pathogenic | -2.009 | Highly Destabilizing | 0.953 | D | 0.523 | neutral | None | None | None | None | I |
| R/T | 0.9084 | likely_pathogenic | 0.7311 | pathogenic | -1.785 | Destabilizing | 0.986 | D | 0.583 | neutral | None | None | None | None | I |
| R/V | 0.9303 | likely_pathogenic | 0.8009 | pathogenic | -1.118 | Destabilizing | 0.993 | D | 0.671 | neutral | None | None | None | None | I |
| R/W | 0.863 | likely_pathogenic | 0.5982 | pathogenic | -1.398 | Destabilizing | 0.999 | D | 0.641 | neutral | None | None | None | None | I |
| R/Y | 0.9563 | likely_pathogenic | 0.8514 | pathogenic | -1.055 | Destabilizing | 0.998 | D | 0.673 | 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.