Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27660 | 83203;83204;83205 | chr2:178563154;178563153;178563152 | chr2:179427881;179427880;179427879 |
| N2AB | 26019 | 78280;78281;78282 | chr2:178563154;178563153;178563152 | chr2:179427881;179427880;179427879 |
| N2A | 25092 | 75499;75500;75501 | chr2:178563154;178563153;178563152 | chr2:179427881;179427880;179427879 |
| N2B | 18595 | 56008;56009;56010 | chr2:178563154;178563153;178563152 | chr2:179427881;179427880;179427879 |
| Novex-1 | 18720 | 56383;56384;56385 | chr2:178563154;178563153;178563152 | chr2:179427881;179427880;179427879 |
| Novex-2 | 18787 | 56584;56585;56586 | chr2:178563154;178563153;178563152 | chr2:179427881;179427880;179427879 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/P | rs1222575627  |
-1.498 | 0.57 | N | 0.789 | 0.365 | 0.77589158586 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.89E-06 | 0 |
| L/P | rs1222575627 |
-1.498 | 0.57 | N | 0.789 | 0.365 | 0.77589158586 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| L/P | rs1222575627 |
-1.498 | 0.57 | N | 0.789 | 0.365 | 0.77589158586 | gnomAD-4.0.0 | 1.23945E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.69531E-06 | 0 | 0 |
| L/Q | None | None | 0.303 | N | 0.727 | 0.353 | 0.796785688759 | gnomAD-4.0.0 | 6.8424E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 1.65684E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.4297 | ambiguous | 0.4017 | ambiguous | -2.168 | Highly Destabilizing | 0.016 | N | 0.678 | prob.neutral | None | None | None | None | N |
| L/C | 0.5931 | likely_pathogenic | 0.5679 | pathogenic | -1.464 | Destabilizing | 0.869 | D | 0.677 | prob.neutral | None | None | None | None | N |
| L/D | 0.9159 | likely_pathogenic | 0.8908 | pathogenic | -1.895 | Destabilizing | 0.366 | N | 0.791 | deleterious | None | None | None | None | N |
| L/E | 0.7579 | likely_pathogenic | 0.7207 | pathogenic | -1.757 | Destabilizing | 0.366 | N | 0.777 | deleterious | None | None | None | None | N |
| L/F | 0.1922 | likely_benign | 0.191 | benign | -1.299 | Destabilizing | 0.221 | N | 0.782 | deleterious | None | None | None | None | N |
| L/G | 0.7666 | likely_pathogenic | 0.7228 | pathogenic | -2.646 | Highly Destabilizing | 0.366 | N | 0.78 | deleterious | None | None | None | None | N |
| L/H | 0.5649 | likely_pathogenic | 0.5305 | ambiguous | -2.002 | Highly Destabilizing | 0.869 | D | 0.757 | deleterious | None | None | None | None | N |
| L/I | 0.0526 | likely_benign | 0.0543 | benign | -0.845 | Destabilizing | None | N | 0.187 | neutral | N | 0.447589856 | None | None | N |
| L/K | 0.7338 | likely_pathogenic | 0.6853 | pathogenic | -1.635 | Destabilizing | 0.221 | N | 0.746 | deleterious | None | None | None | None | N |
| L/M | 0.1238 | likely_benign | 0.1245 | benign | -0.739 | Destabilizing | 0.007 | N | 0.532 | neutral | None | None | None | None | N |
| L/N | 0.6181 | likely_pathogenic | 0.5726 | pathogenic | -1.689 | Destabilizing | 0.366 | N | 0.779 | deleterious | None | None | None | None | N |
| L/P | 0.5751 | likely_pathogenic | 0.5198 | ambiguous | -1.26 | Destabilizing | 0.57 | D | 0.789 | deleterious | N | 0.472410943 | None | None | N |
| L/Q | 0.5257 | ambiguous | 0.4937 | ambiguous | -1.67 | Destabilizing | 0.303 | N | 0.727 | deleterious | N | 0.491969753 | None | None | N |
| L/R | 0.6638 | likely_pathogenic | 0.5972 | pathogenic | -1.252 | Destabilizing | 0.303 | N | 0.738 | deleterious | N | 0.510074008 | None | None | N |
| L/S | 0.5556 | ambiguous | 0.5081 | ambiguous | -2.402 | Highly Destabilizing | 0.075 | N | 0.714 | prob.delet. | None | None | None | None | N |
| L/T | 0.3567 | ambiguous | 0.3407 | ambiguous | -2.122 | Highly Destabilizing | 0.075 | N | 0.754 | deleterious | None | None | None | None | N |
| L/V | 0.0642 | likely_benign | 0.0652 | benign | -1.26 | Destabilizing | None | N | 0.231 | neutral | N | 0.391947217 | None | None | N |
| L/W | 0.5984 | likely_pathogenic | 0.5674 | pathogenic | -1.55 | Destabilizing | 0.869 | D | 0.722 | deleterious | None | None | None | None | N |
| L/Y | 0.5806 | likely_pathogenic | 0.5539 | ambiguous | -1.28 | Destabilizing | 0.366 | N | 0.779 | 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.