Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21821 | 65686;65687;65688 | chr2:178583721;178583720;178583719 | chr2:179448448;179448447;179448446 |
| N2AB | 20180 | 60763;60764;60765 | chr2:178583721;178583720;178583719 | chr2:179448448;179448447;179448446 |
| N2A | 19253 | 57982;57983;57984 | chr2:178583721;178583720;178583719 | chr2:179448448;179448447;179448446 |
| N2B | 12756 | 38491;38492;38493 | chr2:178583721;178583720;178583719 | chr2:179448448;179448447;179448446 |
| Novex-1 | 12881 | 38866;38867;38868 | chr2:178583721;178583720;178583719 | chr2:179448448;179448447;179448446 |
| Novex-2 | 12948 | 39067;39068;39069 | chr2:178583721;178583720;178583719 | chr2:179448448;179448447;179448446 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/P | None | None | 0.667 | N | 0.838 | 0.339 | 0.344945010812 | gnomAD-4.0.0 | 1.59462E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86277E-06 | 0 | 0 |
| A/T | rs2048299727  |
None | 0.124 | N | 0.687 | 0.162 | 0.225902525712 | gnomAD-4.0.0 | 1.59462E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.03269E-05 |
| A/V | rs1398162885 |
None | None | N | 0.293 | 0.118 | 0.119812018005 | 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 |
| A/V | rs1398162885 |
None | None | N | 0.293 | 0.118 | 0.119812018005 | gnomAD-4.0.0 | 6.09034E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 7.22993E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.4161 | ambiguous | 0.4055 | ambiguous | -0.968 | Destabilizing | 0.909 | D | 0.724 | prob.delet. | None | None | None | None | N |
| A/D | 0.9231 | likely_pathogenic | 0.9001 | pathogenic | -0.857 | Destabilizing | 0.667 | D | 0.902 | deleterious | N | 0.456046263 | None | None | N |
| A/E | 0.8351 | likely_pathogenic | 0.809 | pathogenic | -0.739 | Destabilizing | 0.726 | D | 0.843 | deleterious | None | None | None | None | N |
| A/F | 0.5558 | ambiguous | 0.4739 | ambiguous | -0.669 | Destabilizing | 0.567 | D | 0.905 | deleterious | None | None | None | None | N |
| A/G | 0.4454 | ambiguous | 0.4009 | ambiguous | -1.204 | Destabilizing | 0.364 | N | 0.687 | prob.neutral | N | 0.470368053 | None | None | N |
| A/H | 0.897 | likely_pathogenic | 0.8746 | pathogenic | -1.473 | Destabilizing | 0.968 | D | 0.891 | deleterious | None | None | None | None | N |
| A/I | 0.1707 | likely_benign | 0.1388 | benign | 0.263 | Stabilizing | 0.06 | N | 0.778 | deleterious | None | None | None | None | N |
| A/K | 0.9102 | likely_pathogenic | 0.8994 | pathogenic | -0.848 | Destabilizing | 0.726 | D | 0.835 | deleterious | None | None | None | None | N |
| A/L | 0.2291 | likely_benign | 0.1893 | benign | 0.263 | Stabilizing | 0.072 | N | 0.773 | deleterious | None | None | None | None | N |
| A/M | 0.3219 | likely_benign | 0.2741 | benign | 0.011 | Stabilizing | 0.567 | D | 0.824 | deleterious | None | None | None | None | N |
| A/N | 0.825 | likely_pathogenic | 0.7717 | pathogenic | -0.892 | Destabilizing | 0.89 | D | 0.901 | deleterious | None | None | None | None | N |
| A/P | 0.801 | likely_pathogenic | 0.7761 | pathogenic | -0.041 | Destabilizing | 0.667 | D | 0.838 | deleterious | N | 0.495623372 | None | None | N |
| A/Q | 0.8015 | likely_pathogenic | 0.7888 | pathogenic | -0.771 | Destabilizing | 0.89 | D | 0.815 | deleterious | None | None | None | None | N |
| A/R | 0.8559 | likely_pathogenic | 0.8567 | pathogenic | -0.915 | Destabilizing | 0.726 | D | 0.829 | deleterious | None | None | None | None | N |
| A/S | 0.2516 | likely_benign | 0.218 | benign | -1.435 | Destabilizing | 0.22 | N | 0.681 | prob.neutral | N | 0.489177402 | None | None | N |
| A/T | 0.14 | likely_benign | 0.1267 | benign | -1.165 | Destabilizing | 0.124 | N | 0.687 | prob.neutral | N | 0.495276655 | None | None | N |
| A/V | 0.0691 | likely_benign | 0.0617 | benign | -0.041 | Destabilizing | None | N | 0.293 | neutral | N | 0.325457575 | None | None | N |
| A/W | 0.9452 | likely_pathogenic | 0.9325 | pathogenic | -1.19 | Destabilizing | 0.968 | D | 0.867 | deleterious | None | None | None | None | N |
| A/Y | 0.8156 | likely_pathogenic | 0.7652 | pathogenic | -0.639 | Destabilizing | 0.726 | D | 0.903 | deleterious | 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.