Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16741 | 50446;50447;50448 | chr2:178612304;178612303;178612302 | chr2:179477031;179477030;179477029 |
| N2AB | 15100 | 45523;45524;45525 | chr2:178612304;178612303;178612302 | chr2:179477031;179477030;179477029 |
| N2A | 14173 | 42742;42743;42744 | chr2:178612304;178612303;178612302 | chr2:179477031;179477030;179477029 |
| N2B | 7676 | 23251;23252;23253 | chr2:178612304;178612303;178612302 | chr2:179477031;179477030;179477029 |
| Novex-1 | 7801 | 23626;23627;23628 | chr2:178612304;178612303;178612302 | chr2:179477031;179477030;179477029 |
| Novex-2 | 7868 | 23827;23828;23829 | chr2:178612304;178612303;178612302 | chr2:179477031;179477030;179477029 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/E | rs372658275  |
None | 0.999 | N | 0.503 | 0.159 | 0.258283824007 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | I | None | 4.83E-05 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| D/E | rs372658275 |
None | 0.999 | N | 0.503 | 0.159 | 0.258283824007 | gnomAD-4.0.0 | 3.10078E-06 | None | None | None | None | I | None | 4.00866E-05 | 1.66911E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 1.60292E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.7457 | likely_pathogenic | 0.7645 | pathogenic | 0.059 | Stabilizing | 1.0 | D | 0.717 | prob.delet. | N | 0.500598107 | None | None | I |
| D/C | 0.9748 | likely_pathogenic | 0.9792 | pathogenic | -0.208 | Destabilizing | 1.0 | D | 0.687 | prob.delet. | None | None | None | None | I |
| D/E | 0.537 | ambiguous | 0.5567 | ambiguous | -0.272 | Destabilizing | 0.999 | D | 0.503 | neutral | N | 0.431696693 | None | None | I |
| D/F | 0.9551 | likely_pathogenic | 0.9605 | pathogenic | 0.014 | Stabilizing | 1.0 | D | 0.711 | prob.delet. | None | None | None | None | I |
| D/G | 0.6106 | likely_pathogenic | 0.6261 | pathogenic | -0.058 | Destabilizing | 1.0 | D | 0.75 | deleterious | N | 0.494408467 | None | None | I |
| D/H | 0.8935 | likely_pathogenic | 0.8899 | pathogenic | 0.646 | Stabilizing | 1.0 | D | 0.711 | prob.delet. | D | 0.598351881 | None | None | I |
| D/I | 0.9259 | likely_pathogenic | 0.9408 | pathogenic | 0.3 | Stabilizing | 1.0 | D | 0.699 | prob.delet. | None | None | None | None | I |
| D/K | 0.9051 | likely_pathogenic | 0.9061 | pathogenic | 0.41 | Stabilizing | 1.0 | D | 0.779 | deleterious | None | None | None | None | I |
| D/L | 0.9146 | likely_pathogenic | 0.9264 | pathogenic | 0.3 | Stabilizing | 1.0 | D | 0.733 | deleterious | None | None | None | None | I |
| D/M | 0.9668 | likely_pathogenic | 0.975 | pathogenic | 0.037 | Stabilizing | 1.0 | D | 0.675 | prob.neutral | None | None | None | None | I |
| D/N | 0.4201 | ambiguous | 0.4021 | ambiguous | 0.136 | Stabilizing | 1.0 | D | 0.739 | deleterious | N | 0.493892155 | None | None | I |
| D/P | 0.9676 | likely_pathogenic | 0.9676 | pathogenic | 0.239 | Stabilizing | 1.0 | D | 0.724 | deleterious | None | None | None | None | I |
| D/Q | 0.8835 | likely_pathogenic | 0.895 | pathogenic | 0.15 | Stabilizing | 1.0 | D | 0.695 | prob.delet. | None | None | None | None | I |
| D/R | 0.9241 | likely_pathogenic | 0.9287 | pathogenic | 0.67 | Stabilizing | 1.0 | D | 0.707 | prob.delet. | None | None | None | None | I |
| D/S | 0.608 | likely_pathogenic | 0.6177 | pathogenic | 0.041 | Stabilizing | 1.0 | D | 0.757 | deleterious | None | None | None | None | I |
| D/T | 0.7918 | likely_pathogenic | 0.8128 | pathogenic | 0.142 | Stabilizing | 1.0 | D | 0.779 | deleterious | None | None | None | None | I |
| D/V | 0.8213 | likely_pathogenic | 0.8469 | pathogenic | 0.239 | Stabilizing | 1.0 | D | 0.721 | deleterious | D | 0.541001901 | None | None | I |
| D/W | 0.9902 | likely_pathogenic | 0.9922 | pathogenic | 0.057 | Stabilizing | 1.0 | D | 0.633 | neutral | None | None | None | None | I |
| D/Y | 0.7637 | likely_pathogenic | 0.7876 | pathogenic | 0.24 | Stabilizing | 1.0 | D | 0.707 | prob.delet. | D | 0.638770578 | None | None | I |
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.