Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 7808 | 23647;23648;23649 | chr2:178720220;178720219;178720218 | chr2:179584947;179584946;179584945 |
| N2AB | 7491 | 22696;22697;22698 | chr2:178720220;178720219;178720218 | chr2:179584947;179584946;179584945 |
| N2A | 6564 | 19915;19916;19917 | chr2:178720220;178720219;178720218 | chr2:179584947;179584946;179584945 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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/F | rs780407852  |
-0.468 | 0.171 | N | 0.261 | 0.039 | None | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| I/F | rs780407852 |
-0.468 | 0.171 | N | 0.261 | 0.039 | None | gnomAD-4.0.0 | 1.23958E-06 | None | None | None | None | I | None | 1.33518E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 8.4769E-07 | 0 | 0 |
| I/T | rs1401488041 |
-0.212 | 0.001 | N | 0.241 | 0.09 | 0.36056563 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/T | rs1401488041 |
-0.212 | 0.001 | N | 0.241 | 0.09 | 0.36056563 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 9.42E-05 | 0 | 0 | 0 | 0 |
| I/T | rs1401488041 |
-0.212 | 0.001 | N | 0.241 | 0.09 | 0.36056563 | gnomAD-4.0.0 | 5.57796E-06 | None | None | None | None | I | None | 0 | 1.66706E-05 | None | 0 | 0 | None | 1.56299E-05 | 0 | 3.39076E-06 | 2.19664E-05 | 1.60123E-05 |
| I/V | rs780407852 |
0.021 | None | N | 0.137 | 0.025 | 0.07168673 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.93E-06 | 0 |
| I/V | rs780407852 |
0.021 | None | N | 0.137 | 0.025 | 0.07168673 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| I/V | rs780407852 |
0.021 | None | N | 0.137 | 0.025 | 0.07168673 | gnomAD-4.0.0 | 1.23958E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.69538E-06 | 0 | 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 | 0.1017 | likely_benign | 0.0986 | benign | -1.267 | Destabilizing | None | N | 0.147 | neutral | None | None | None | None | I |
| I/C | 0.6286 | likely_pathogenic | 0.5811 | pathogenic | -0.816 | Destabilizing | 0.356 | N | 0.263 | neutral | None | None | None | None | I |
| I/D | 0.5044 | ambiguous | 0.4606 | ambiguous | -0.64 | Destabilizing | 0.356 | N | 0.295 | neutral | None | None | None | None | I |
| I/E | 0.331 | likely_benign | 0.3117 | benign | -0.693 | Destabilizing | 0.072 | N | 0.295 | neutral | None | None | None | None | I |
| I/F | 0.1645 | likely_benign | 0.1488 | benign | -0.991 | Destabilizing | 0.171 | N | 0.261 | neutral | N | 0.49516952 | None | None | I |
| I/G | 0.4094 | ambiguous | 0.3844 | ambiguous | -1.52 | Destabilizing | 0.038 | N | 0.327 | neutral | None | None | None | None | I |
| I/H | 0.3914 | ambiguous | 0.3698 | ambiguous | -0.698 | Destabilizing | 0.864 | D | 0.241 | neutral | None | None | None | None | I |
| I/K | 0.2401 | likely_benign | 0.235 | benign | -0.795 | Destabilizing | 0.072 | N | 0.301 | neutral | None | None | None | None | I |
| I/L | 0.0961 | likely_benign | 0.0947 | benign | -0.685 | Destabilizing | None | N | 0.119 | neutral | N | 0.41765007 | None | None | I |
| I/M | 0.094 | likely_benign | 0.0927 | benign | -0.523 | Destabilizing | 0.171 | N | 0.263 | neutral | N | 0.45741364 | None | None | I |
| I/N | 0.2227 | likely_benign | 0.2075 | benign | -0.558 | Destabilizing | 0.295 | N | 0.283 | neutral | N | 0.4689457 | None | None | I |
| I/P | 0.3633 | ambiguous | 0.3315 | benign | -0.845 | Destabilizing | 0.356 | N | 0.29 | neutral | None | None | None | None | I |
| I/Q | 0.2715 | likely_benign | 0.2652 | benign | -0.801 | Destabilizing | 0.356 | N | 0.266 | neutral | None | None | None | None | I |
| I/R | 0.159 | likely_benign | 0.1528 | benign | -0.158 | Destabilizing | 0.214 | N | 0.286 | neutral | None | None | None | None | I |
| I/S | 0.142 | likely_benign | 0.1353 | benign | -1.123 | Destabilizing | 0.029 | N | 0.329 | neutral | N | 0.4496665 | None | None | I |
| I/T | 0.0739 | likely_benign | 0.0716 | benign | -1.065 | Destabilizing | 0.001 | N | 0.241 | neutral | N | 0.4574779 | None | None | I |
| I/V | 0.0708 | likely_benign | 0.0681 | benign | -0.845 | Destabilizing | None | N | 0.137 | neutral | N | 0.34344032 | None | None | I |
| I/W | 0.6949 | likely_pathogenic | 0.6551 | pathogenic | -0.988 | Destabilizing | 0.864 | D | 0.269 | neutral | None | None | None | None | I |
| I/Y | 0.4879 | ambiguous | 0.462 | ambiguous | -0.771 | Destabilizing | 0.356 | N | 0.276 | neutral | None | None | 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.