Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1582 | 4969;4970;4971 | chr2:178777219;178777218;178777217 | chr2:179641946;179641945;179641944 |
| N2AB | 1582 | 4969;4970;4971 | chr2:178777219;178777218;178777217 | chr2:179641946;179641945;179641944 |
| N2A | 1582 | 4969;4970;4971 | chr2:178777219;178777218;178777217 | chr2:179641946;179641945;179641944 |
| N2B | 1536 | 4831;4832;4833 | chr2:178777219;178777218;178777217 | chr2:179641946;179641945;179641944 |
| Novex-1 | 1536 | 4831;4832;4833 | chr2:178777219;178777218;178777217 | chr2:179641946;179641945;179641944 |
| Novex-2 | 1536 | 4831;4832;4833 | chr2:178777219;178777218;178777217 | chr2:179641946;179641945;179641944 |
| Novex-3 | 1582 | 4969;4970;4971 | chr2:178777219;178777218;178777217 | chr2:179641946;179641945;179641944 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/D | None | None | 0.999 | N | 0.687 | 0.483 | 0.349647731962 | gnomAD-4.0.0 | 1.36819E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79864E-06 | 0 | 0 |
| N/K | rs1183874678  |
0.461 | 1.0 | N | 0.747 | 0.356 | 0.292062946507 | gnomAD-2.1.1 | 3.98E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| N/K | rs1183874678 |
0.461 | 1.0 | N | 0.747 | 0.356 | 0.292062946507 | gnomAD-4.0.0 | 3.42047E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 1.7337E-04 | 2.69796E-06 | 1.15931E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/A | 0.3812 | ambiguous | 0.3027 | benign | -0.085 | Destabilizing | 1.0 | D | 0.679 | prob.neutral | None | None | None | None | I |
| N/C | 0.452 | ambiguous | 0.3861 | ambiguous | 0.118 | Stabilizing | 1.0 | D | 0.787 | deleterious | None | None | None | None | I |
| N/D | 0.2543 | likely_benign | 0.2083 | benign | -0.044 | Destabilizing | 0.999 | D | 0.687 | prob.neutral | N | 0.486309282 | None | None | I |
| N/E | 0.5367 | ambiguous | 0.4388 | ambiguous | -0.113 | Destabilizing | 0.999 | D | 0.738 | prob.delet. | None | None | None | None | I |
| N/F | 0.4964 | ambiguous | 0.4168 | ambiguous | -0.715 | Destabilizing | 1.0 | D | 0.741 | deleterious | None | None | None | None | I |
| N/G | 0.6583 | likely_pathogenic | 0.5608 | ambiguous | -0.158 | Destabilizing | 0.999 | D | 0.611 | neutral | None | None | None | None | I |
| N/H | 0.1433 | likely_benign | 0.1241 | benign | -0.182 | Destabilizing | 1.0 | D | 0.744 | deleterious | N | 0.507620127 | None | None | I |
| N/I | 0.1746 | likely_benign | 0.1438 | benign | 0.01 | Stabilizing | 1.0 | D | 0.753 | deleterious | N | 0.51334847 | None | None | I |
| N/K | 0.4284 | ambiguous | 0.3322 | benign | 0.041 | Stabilizing | 1.0 | D | 0.747 | deleterious | N | 0.507483953 | None | None | I |
| N/L | 0.2653 | likely_benign | 0.2149 | benign | 0.01 | Stabilizing | 1.0 | D | 0.725 | prob.delet. | None | None | None | None | I |
| N/M | 0.3293 | likely_benign | 0.2795 | benign | 0.059 | Stabilizing | 1.0 | D | 0.737 | prob.delet. | None | None | None | None | I |
| N/P | 0.9564 | likely_pathogenic | 0.9419 | pathogenic | -0.001 | Destabilizing | 1.0 | D | 0.753 | deleterious | None | None | None | None | I |
| N/Q | 0.4167 | ambiguous | 0.3395 | benign | -0.257 | Destabilizing | 1.0 | D | 0.756 | deleterious | None | None | None | None | I |
| N/R | 0.4891 | ambiguous | 0.3972 | ambiguous | 0.127 | Stabilizing | 1.0 | D | 0.769 | deleterious | None | None | None | None | I |
| N/S | 0.1127 | likely_benign | 0.0998 | benign | -0.033 | Destabilizing | 0.999 | D | 0.615 | neutral | N | 0.508514756 | None | None | I |
| N/T | 0.1848 | likely_benign | 0.1523 | benign | -0.004 | Destabilizing | 0.999 | D | 0.74 | deleterious | N | 0.508862917 | None | None | I |
| N/V | 0.2191 | likely_benign | 0.1817 | benign | -0.001 | Destabilizing | 1.0 | D | 0.723 | prob.delet. | None | None | None | None | I |
| N/W | 0.8659 | likely_pathogenic | 0.8152 | pathogenic | -0.876 | Destabilizing | 1.0 | D | 0.786 | deleterious | None | None | None | None | I |
| N/Y | 0.172 | likely_benign | 0.1433 | benign | -0.548 | Destabilizing | 1.0 | D | 0.741 | deleterious | N | 0.512059767 | 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.