Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16590 | 49993;49994;49995 | chr2:178612953;178612952;178612951 | chr2:179477680;179477679;179477678 |
| N2AB | 14949 | 45070;45071;45072 | chr2:178612953;178612952;178612951 | chr2:179477680;179477679;179477678 |
| N2A | 14022 | 42289;42290;42291 | chr2:178612953;178612952;178612951 | chr2:179477680;179477679;179477678 |
| N2B | 7525 | 22798;22799;22800 | chr2:178612953;178612952;178612951 | chr2:179477680;179477679;179477678 |
| Novex-1 | 7650 | 23173;23174;23175 | chr2:178612953;178612952;178612951 | chr2:179477680;179477679;179477678 |
| Novex-2 | 7717 | 23374;23375;23376 | chr2:178612953;178612952;178612951 | chr2:179477680;179477679;179477678 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/I | rs774495753  |
0.901 | 0.047 | N | 0.355 | 0.069 | 0.381409048467 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.67E-05 | 0 |
| M/I | rs774495753 |
0.901 | 0.047 | N | 0.355 | 0.069 | 0.381409048467 | 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 |
| M/I | rs774495753 |
0.901 | 0.047 | N | 0.355 | 0.069 | 0.381409048467 | gnomAD-4.0.0 | 2.1084E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.62874E-05 | 0 | 4.80831E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.8624 | likely_pathogenic | 0.8817 | pathogenic | -1.195 | Destabilizing | 0.228 | N | 0.533 | neutral | None | None | None | None | N |
| M/C | 0.8618 | likely_pathogenic | 0.8581 | pathogenic | -1.428 | Destabilizing | 0.94 | D | 0.701 | prob.neutral | None | None | None | None | N |
| M/D | 0.997 | likely_pathogenic | 0.9978 | pathogenic | -1.539 | Destabilizing | 0.94 | D | 0.747 | deleterious | None | None | None | None | N |
| M/E | 0.9643 | likely_pathogenic | 0.9751 | pathogenic | -1.26 | Destabilizing | 0.593 | D | 0.681 | prob.neutral | None | None | None | None | N |
| M/F | 0.4987 | ambiguous | 0.4969 | ambiguous | -0.073 | Destabilizing | 0.264 | N | 0.582 | neutral | None | None | None | None | N |
| M/G | 0.9473 | likely_pathogenic | 0.9594 | pathogenic | -1.695 | Destabilizing | 0.593 | D | 0.681 | prob.neutral | None | None | None | None | N |
| M/H | 0.9154 | likely_pathogenic | 0.9312 | pathogenic | -1.798 | Destabilizing | 0.983 | D | 0.724 | prob.delet. | None | None | None | None | N |
| M/I | 0.7313 | likely_pathogenic | 0.7404 | pathogenic | 0.253 | Stabilizing | 0.047 | N | 0.355 | neutral | N | 0.475124249 | None | None | N |
| M/K | 0.6467 | likely_pathogenic | 0.7115 | pathogenic | -0.612 | Destabilizing | 0.523 | D | 0.648 | neutral | N | 0.448565777 | None | None | N |
| M/L | 0.2114 | likely_benign | 0.2154 | benign | 0.253 | Stabilizing | None | N | 0.19 | neutral | N | 0.460597052 | None | None | N |
| M/N | 0.9645 | likely_pathogenic | 0.9702 | pathogenic | -1.229 | Destabilizing | 0.94 | D | 0.719 | prob.delet. | None | None | None | None | N |
| M/P | 0.9992 | likely_pathogenic | 0.9994 | pathogenic | -0.213 | Destabilizing | 0.94 | D | 0.721 | prob.delet. | None | None | None | None | N |
| M/Q | 0.756 | likely_pathogenic | 0.8002 | pathogenic | -0.748 | Destabilizing | 0.94 | D | 0.636 | neutral | None | None | None | None | N |
| M/R | 0.7216 | likely_pathogenic | 0.7934 | pathogenic | -1.15 | Destabilizing | 0.523 | D | 0.679 | prob.neutral | N | 0.469713964 | None | None | N |
| M/S | 0.9318 | likely_pathogenic | 0.9405 | pathogenic | -1.609 | Destabilizing | 0.593 | D | 0.629 | neutral | None | None | None | None | N |
| M/T | 0.8496 | likely_pathogenic | 0.8785 | pathogenic | -1.189 | Destabilizing | 0.351 | N | 0.619 | neutral | N | 0.477388176 | None | None | N |
| M/V | 0.3268 | likely_benign | 0.3385 | benign | -0.213 | Destabilizing | 0.047 | N | 0.362 | neutral | N | 0.475002664 | None | None | N |
| M/W | 0.9048 | likely_pathogenic | 0.9211 | pathogenic | -0.544 | Destabilizing | 0.983 | D | 0.695 | prob.neutral | None | None | None | None | N |
| M/Y | 0.7453 | likely_pathogenic | 0.7551 | pathogenic | -0.355 | Destabilizing | 0.836 | D | 0.703 | prob.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.