Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27486 | 82681;82682;82683 | chr2:178563676;178563675;178563674 | chr2:179428403;179428402;179428401 |
| N2AB | 25845 | 77758;77759;77760 | chr2:178563676;178563675;178563674 | chr2:179428403;179428402;179428401 |
| N2A | 24918 | 74977;74978;74979 | chr2:178563676;178563675;178563674 | chr2:179428403;179428402;179428401 |
| N2B | 18421 | 55486;55487;55488 | chr2:178563676;178563675;178563674 | chr2:179428403;179428402;179428401 |
| Novex-1 | 18546 | 55861;55862;55863 | chr2:178563676;178563675;178563674 | chr2:179428403;179428402;179428401 |
| Novex-2 | 18613 | 56062;56063;56064 | chr2:178563676;178563675;178563674 | chr2:179428403;179428402;179428401 |
| 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/L | None | None | 0.007 | N | 0.324 | 0.183 | 0.322230723748 | gnomAD-4.0.0 | 1.59122E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43279E-05 | 0 |
| M/T | rs746435098  |
-1.27 | 0.183 | N | 0.635 | 0.362 | None | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.67094E-04 | None | 0 | None | 0 | 0 | 0 |
| M/T | rs746435098 |
-1.27 | 0.183 | N | 0.635 | 0.362 | None | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 1.93648E-04 | None | 0 | 0 | 0 | 0 | 0 |
| M/T | rs746435098 |
-1.27 | 0.183 | N | 0.635 | 0.362 | None | gnomAD-4.0.0 | 2.3549E-05 | None | None | None | None | N | None | 1.3354E-05 | 0 | None | 0 | 6.24303E-04 | None | 0 | 0 | 5.93332E-06 | 1.09789E-05 | 1.60102E-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 | 0.6904 | likely_pathogenic | 0.6579 | pathogenic | -1.983 | Destabilizing | 0.001 | N | 0.475 | neutral | None | None | None | None | N |
| M/C | 0.8488 | likely_pathogenic | 0.8398 | pathogenic | -2.354 | Highly Destabilizing | 0.836 | D | 0.773 | deleterious | None | None | None | None | N |
| M/D | 0.9992 | likely_pathogenic | 0.9994 | pathogenic | -1.992 | Destabilizing | 0.593 | D | 0.789 | deleterious | None | None | None | None | N |
| M/E | 0.9925 | likely_pathogenic | 0.9938 | pathogenic | -1.718 | Destabilizing | 0.418 | N | 0.761 | deleterious | None | None | None | None | N |
| M/F | 0.8459 | likely_pathogenic | 0.8655 | pathogenic | -0.523 | Destabilizing | 0.418 | N | 0.671 | neutral | None | None | None | None | N |
| M/G | 0.974 | likely_pathogenic | 0.9737 | pathogenic | -2.5 | Highly Destabilizing | 0.129 | N | 0.689 | prob.neutral | None | None | None | None | N |
| M/H | 0.9951 | likely_pathogenic | 0.9962 | pathogenic | -2.345 | Highly Destabilizing | 0.94 | D | 0.776 | deleterious | None | None | None | None | N |
| M/I | 0.7381 | likely_pathogenic | 0.7602 | pathogenic | -0.483 | Destabilizing | None | N | 0.213 | neutral | N | 0.415900647 | None | None | N |
| M/K | 0.9841 | likely_pathogenic | 0.989 | pathogenic | -1.173 | Destabilizing | 0.351 | N | 0.721 | prob.delet. | N | 0.502102657 | None | None | N |
| M/L | 0.4328 | ambiguous | 0.4256 | ambiguous | -0.483 | Destabilizing | 0.007 | N | 0.324 | neutral | N | 0.42715779 | None | None | N |
| M/N | 0.9936 | likely_pathogenic | 0.9943 | pathogenic | -1.695 | Destabilizing | 0.836 | D | 0.805 | deleterious | None | None | None | None | N |
| M/P | 0.9992 | likely_pathogenic | 0.9993 | pathogenic | -0.967 | Destabilizing | 0.593 | D | 0.784 | deleterious | None | None | None | None | N |
| M/Q | 0.9513 | likely_pathogenic | 0.9585 | pathogenic | -1.262 | Destabilizing | 0.593 | D | 0.711 | prob.delet. | None | None | None | None | N |
| M/R | 0.9792 | likely_pathogenic | 0.9842 | pathogenic | -1.55 | Destabilizing | 0.523 | D | 0.791 | deleterious | N | 0.490746352 | None | None | N |
| M/S | 0.9345 | likely_pathogenic | 0.9326 | pathogenic | -2.213 | Highly Destabilizing | 0.129 | N | 0.664 | neutral | None | None | None | None | N |
| M/T | 0.8915 | likely_pathogenic | 0.8834 | pathogenic | -1.794 | Destabilizing | 0.183 | N | 0.635 | neutral | N | 0.483491423 | None | None | N |
| M/V | 0.215 | likely_benign | 0.2175 | benign | -0.967 | Destabilizing | None | N | 0.215 | neutral | N | 0.412436267 | None | None | N |
| M/W | 0.9946 | likely_pathogenic | 0.9955 | pathogenic | -0.896 | Destabilizing | 0.983 | D | 0.756 | deleterious | None | None | None | None | N |
| M/Y | 0.9898 | likely_pathogenic | 0.9917 | pathogenic | -0.837 | Destabilizing | 0.593 | D | 0.811 | 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.