Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30515 | 91768;91769;91770 | chr2:178550988;178550987;178550986 | chr2:179415715;179415714;179415713 |
| N2AB | 28874 | 86845;86846;86847 | chr2:178550988;178550987;178550986 | chr2:179415715;179415714;179415713 |
| N2A | 27947 | 84064;84065;84066 | chr2:178550988;178550987;178550986 | chr2:179415715;179415714;179415713 |
| N2B | 21450 | 64573;64574;64575 | chr2:178550988;178550987;178550986 | chr2:179415715;179415714;179415713 |
| Novex-1 | 21575 | 64948;64949;64950 | chr2:178550988;178550987;178550986 | chr2:179415715;179415714;179415713 |
| Novex-2 | 21642 | 65149;65150;65151 | chr2:178550988;178550987;178550986 | chr2:179415715;179415714;179415713 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/M | None | None | 0.062 | N | 0.329 | 0.215 | 0.204665344411 | gnomAD-4.0.0 | 1.59315E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43382E-05 | 0 |
| I/T | rs2154150025  |
None | 0.682 | N | 0.716 | 0.402 | 0.6104159791 | gnomAD-4.0.0 | 1.59299E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43365E-05 | 0 |
| I/V | rs1699213843 |
None | 0.162 | N | 0.391 | 0.138 | 0.526539220858 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | rs1699213843 |
None | 0.162 | N | 0.391 | 0.138 | 0.526539220858 | gnomAD-4.0.0 | 2.0299E-06 | None | None | None | None | N | None | 0 | 6.1546E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 4.6966E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.897 | likely_pathogenic | 0.8989 | pathogenic | -2.056 | Highly Destabilizing | 0.587 | D | 0.585 | neutral | None | None | None | None | N |
| I/C | 0.9306 | likely_pathogenic | 0.9303 | pathogenic | -1.252 | Destabilizing | 0.996 | D | 0.664 | prob.neutral | None | None | None | None | N |
| I/D | 0.9962 | likely_pathogenic | 0.996 | pathogenic | -2.26 | Highly Destabilizing | 0.984 | D | 0.825 | deleterious | None | None | None | None | N |
| I/E | 0.9833 | likely_pathogenic | 0.9811 | pathogenic | -1.979 | Destabilizing | 0.953 | D | 0.814 | deleterious | None | None | None | None | N |
| I/F | 0.5819 | likely_pathogenic | 0.5914 | pathogenic | -1.188 | Destabilizing | 0.883 | D | 0.637 | neutral | N | 0.467971289 | None | None | N |
| I/G | 0.9839 | likely_pathogenic | 0.9841 | pathogenic | -2.624 | Highly Destabilizing | 0.953 | D | 0.799 | deleterious | None | None | None | None | N |
| I/H | 0.9634 | likely_pathogenic | 0.9614 | pathogenic | -2.168 | Highly Destabilizing | 0.996 | D | 0.805 | deleterious | None | None | None | None | N |
| I/K | 0.9461 | likely_pathogenic | 0.9414 | pathogenic | -1.448 | Destabilizing | 0.909 | D | 0.8 | deleterious | None | None | None | None | N |
| I/L | 0.2902 | likely_benign | 0.2809 | benign | -0.396 | Destabilizing | 0.062 | N | 0.363 | neutral | N | 0.512723478 | None | None | N |
| I/M | 0.3147 | likely_benign | 0.3288 | benign | -0.409 | Destabilizing | 0.062 | N | 0.329 | neutral | N | 0.479327594 | None | None | N |
| I/N | 0.939 | likely_pathogenic | 0.9386 | pathogenic | -1.963 | Destabilizing | 0.938 | D | 0.831 | deleterious | N | 0.497685339 | None | None | N |
| I/P | 0.9916 | likely_pathogenic | 0.9919 | pathogenic | -0.933 | Destabilizing | 0.984 | D | 0.828 | deleterious | None | None | None | None | N |
| I/Q | 0.9477 | likely_pathogenic | 0.9418 | pathogenic | -1.677 | Destabilizing | 0.953 | D | 0.82 | deleterious | None | None | None | None | N |
| I/R | 0.9203 | likely_pathogenic | 0.9127 | pathogenic | -1.506 | Destabilizing | 0.909 | D | 0.828 | deleterious | None | None | None | None | N |
| I/S | 0.9282 | likely_pathogenic | 0.9353 | pathogenic | -2.638 | Highly Destabilizing | 0.883 | D | 0.717 | prob.delet. | N | 0.49692487 | None | None | N |
| I/T | 0.8057 | likely_pathogenic | 0.8169 | pathogenic | -2.187 | Highly Destabilizing | 0.682 | D | 0.716 | prob.delet. | N | 0.474764783 | None | None | N |
| I/V | 0.1187 | likely_benign | 0.1206 | benign | -0.933 | Destabilizing | 0.162 | N | 0.391 | neutral | N | 0.423584341 | None | None | N |
| I/W | 0.9798 | likely_pathogenic | 0.9807 | pathogenic | -1.547 | Destabilizing | 0.996 | D | 0.795 | deleterious | None | None | None | None | N |
| I/Y | 0.9318 | likely_pathogenic | 0.9265 | pathogenic | -1.196 | Destabilizing | 0.953 | D | 0.683 | 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.