Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21077 | 63454;63455;63456 | chr2:178588178;178588177;178588176 | chr2:179452905;179452904;179452903 |
| N2AB | 19436 | 58531;58532;58533 | chr2:178588178;178588177;178588176 | chr2:179452905;179452904;179452903 |
| N2A | 18509 | 55750;55751;55752 | chr2:178588178;178588177;178588176 | chr2:179452905;179452904;179452903 |
| N2B | 12012 | 36259;36260;36261 | chr2:178588178;178588177;178588176 | chr2:179452905;179452904;179452903 |
| Novex-1 | 12137 | 36634;36635;36636 | chr2:178588178;178588177;178588176 | chr2:179452905;179452904;179452903 |
| Novex-2 | 12204 | 36835;36836;36837 | chr2:178588178;178588177;178588176 | chr2:179452905;179452904;179452903 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/I | rs2049450214  |
None | 1.0 | N | 0.761 | 0.445 | 0.468669884856 | 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 |
| T/I | rs2049450214 |
None | 1.0 | N | 0.761 | 0.445 | 0.468669884856 | gnomAD-4.0.0 | 6.25166E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.54942E-06 | 0 | 0 |
| T/N | None | None | 1.0 | N | 0.756 | 0.397 | 0.302459207581 | gnomAD-4.0.0 | 6.90806E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.0768E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.2808 | likely_benign | 0.2891 | benign | -0.641 | Destabilizing | 0.999 | D | 0.473 | neutral | N | 0.465228448 | None | None | N |
| T/C | 0.8287 | likely_pathogenic | 0.827 | pathogenic | -0.612 | Destabilizing | 1.0 | D | 0.687 | prob.neutral | None | None | None | None | N |
| T/D | 0.7313 | likely_pathogenic | 0.7129 | pathogenic | -1.582 | Destabilizing | 1.0 | D | 0.768 | deleterious | None | None | None | None | N |
| T/E | 0.8217 | likely_pathogenic | 0.8077 | pathogenic | -1.531 | Destabilizing | 1.0 | D | 0.775 | deleterious | None | None | None | None | N |
| T/F | 0.9014 | likely_pathogenic | 0.8905 | pathogenic | -0.701 | Destabilizing | 1.0 | D | 0.77 | deleterious | None | None | None | None | N |
| T/G | 0.3304 | likely_benign | 0.3246 | benign | -0.936 | Destabilizing | 1.0 | D | 0.735 | prob.delet. | None | None | None | None | N |
| T/H | 0.7337 | likely_pathogenic | 0.7155 | pathogenic | -1.331 | Destabilizing | 1.0 | D | 0.706 | prob.neutral | None | None | None | None | N |
| T/I | 0.9351 | likely_pathogenic | 0.9349 | pathogenic | 0.066 | Stabilizing | 1.0 | D | 0.761 | deleterious | N | 0.499248139 | None | None | N |
| T/K | 0.7101 | likely_pathogenic | 0.6824 | pathogenic | -0.85 | Destabilizing | 1.0 | D | 0.772 | deleterious | None | None | None | None | N |
| T/L | 0.5864 | likely_pathogenic | 0.5812 | pathogenic | 0.066 | Stabilizing | 0.999 | D | 0.667 | neutral | None | None | None | None | N |
| T/M | 0.4488 | ambiguous | 0.472 | ambiguous | 0.424 | Stabilizing | 1.0 | D | 0.703 | prob.neutral | None | None | None | None | N |
| T/N | 0.3612 | ambiguous | 0.3472 | ambiguous | -1.198 | Destabilizing | 1.0 | D | 0.756 | deleterious | N | 0.460807449 | None | None | N |
| T/P | 0.8157 | likely_pathogenic | 0.8401 | pathogenic | -0.138 | Destabilizing | 1.0 | D | 0.741 | deleterious | N | 0.498487671 | None | None | N |
| T/Q | 0.6556 | likely_pathogenic | 0.6426 | pathogenic | -1.336 | Destabilizing | 1.0 | D | 0.762 | deleterious | None | None | None | None | N |
| T/R | 0.6459 | likely_pathogenic | 0.6359 | pathogenic | -0.646 | Destabilizing | 1.0 | D | 0.749 | deleterious | None | None | None | None | N |
| T/S | 0.1459 | likely_benign | 0.1556 | benign | -1.236 | Destabilizing | 0.999 | D | 0.501 | neutral | N | 0.465326602 | None | None | N |
| T/V | 0.7938 | likely_pathogenic | 0.7891 | pathogenic | -0.138 | Destabilizing | 0.999 | D | 0.568 | neutral | None | None | None | None | N |
| T/W | 0.9676 | likely_pathogenic | 0.966 | pathogenic | -0.811 | Destabilizing | 1.0 | D | 0.697 | prob.neutral | None | None | None | None | N |
| T/Y | 0.8893 | likely_pathogenic | 0.8809 | pathogenic | -0.471 | Destabilizing | 1.0 | D | 0.763 | 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.