Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23740 | 71443;71444;71445 | chr2:178574914;178574913;178574912 | chr2:179439641;179439640;179439639 |
| N2AB | 22099 | 66520;66521;66522 | chr2:178574914;178574913;178574912 | chr2:179439641;179439640;179439639 |
| N2A | 21172 | 63739;63740;63741 | chr2:178574914;178574913;178574912 | chr2:179439641;179439640;179439639 |
| N2B | 14675 | 44248;44249;44250 | chr2:178574914;178574913;178574912 | chr2:179439641;179439640;179439639 |
| Novex-1 | 14800 | 44623;44624;44625 | chr2:178574914;178574913;178574912 | chr2:179439641;179439640;179439639 |
| Novex-2 | 14867 | 44824;44825;44826 | chr2:178574914;178574913;178574912 | chr2:179439641;179439640;179439639 |
| 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 | rs757597284  |
-0.147 | 0.805 | N | 0.573 | 0.434 | 0.531727546574 | gnomAD-2.1.1 | 1.62E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.31105E-04 | None | 0 | 0 | 0 |
| S/L | rs757597284 |
-0.147 | 0.805 | N | 0.573 | 0.434 | 0.531727546574 | 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 | rs757597284 |
-0.147 | 0.805 | N | 0.573 | 0.434 | 0.531727546574 | gnomAD-4.0.0 | 8.06087E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.47884E-07 | 1.20874E-04 | 1.60241E-05 |
| S/P | rs779202830 |
-0.744 | 0.983 | N | 0.643 | 0.393 | 0.378498632473 | gnomAD-2.1.1 | 4.06E-06 | None | None | None | None | N | None | 0 | 2.91E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| S/P | rs779202830 |
-0.744 | 0.983 | N | 0.643 | 0.393 | 0.378498632473 | gnomAD-4.0.0 | 1.59345E-06 | None | None | None | None | N | None | 0 | 2.2899E-05 | None | 0 | 0 | None | 0 | 0 | 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 | 0.1751 | likely_benign | 0.1898 | benign | -0.875 | Destabilizing | 0.63 | D | 0.403 | neutral | N | 0.510267537 | None | None | N |
| S/C | 0.1986 | likely_benign | 0.1913 | benign | -0.646 | Destabilizing | 0.999 | D | 0.595 | neutral | None | None | None | None | N |
| S/D | 0.7716 | likely_pathogenic | 0.8072 | pathogenic | -1.267 | Destabilizing | 0.916 | D | 0.545 | neutral | None | None | None | None | N |
| S/E | 0.9208 | likely_pathogenic | 0.9347 | pathogenic | -1.129 | Destabilizing | 0.916 | D | 0.549 | neutral | None | None | None | None | N |
| S/F | 0.6671 | likely_pathogenic | 0.6852 | pathogenic | -0.708 | Destabilizing | 0.987 | D | 0.655 | neutral | None | None | None | None | N |
| S/G | 0.149 | likely_benign | 0.1612 | benign | -1.218 | Destabilizing | 0.916 | D | 0.431 | neutral | None | None | None | None | N |
| S/H | 0.7059 | likely_pathogenic | 0.7209 | pathogenic | -1.569 | Destabilizing | 0.999 | D | 0.594 | neutral | None | None | None | None | N |
| S/I | 0.7722 | likely_pathogenic | 0.7676 | pathogenic | -0.025 | Destabilizing | 0.975 | D | 0.661 | neutral | None | None | None | None | N |
| S/K | 0.9466 | likely_pathogenic | 0.9536 | pathogenic | -0.555 | Destabilizing | 0.916 | D | 0.547 | neutral | None | None | None | None | N |
| S/L | 0.3643 | ambiguous | 0.3628 | ambiguous | -0.025 | Destabilizing | 0.805 | D | 0.573 | neutral | N | 0.477221816 | None | None | N |
| S/M | 0.5275 | ambiguous | 0.5299 | ambiguous | -0.065 | Destabilizing | 0.999 | D | 0.597 | neutral | None | None | None | None | N |
| S/N | 0.4079 | ambiguous | 0.4089 | ambiguous | -0.997 | Destabilizing | 0.916 | D | 0.555 | neutral | None | None | None | None | N |
| S/P | 0.9783 | likely_pathogenic | 0.9783 | pathogenic | -0.275 | Destabilizing | 0.983 | D | 0.643 | neutral | N | 0.497478891 | None | None | N |
| S/Q | 0.8392 | likely_pathogenic | 0.863 | pathogenic | -0.88 | Destabilizing | 0.987 | D | 0.632 | neutral | None | None | None | None | N |
| S/R | 0.9155 | likely_pathogenic | 0.9274 | pathogenic | -0.761 | Destabilizing | 0.975 | D | 0.652 | neutral | None | None | None | None | N |
| S/T | 0.1467 | likely_benign | 0.1239 | benign | -0.742 | Destabilizing | 0.025 | N | 0.35 | neutral | N | 0.424048488 | None | None | N |
| S/V | 0.6783 | likely_pathogenic | 0.6823 | pathogenic | -0.275 | Destabilizing | 0.95 | D | 0.614 | neutral | None | None | None | None | N |
| S/W | 0.8087 | likely_pathogenic | 0.82 | pathogenic | -0.903 | Destabilizing | 0.999 | D | 0.601 | neutral | None | None | None | None | N |
| S/Y | 0.5708 | likely_pathogenic | 0.5981 | pathogenic | -0.515 | Destabilizing | 0.996 | D | 0.653 | 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.