Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 7810 | 23653;23654;23655 | chr2:178720214;178720213;178720212 | chr2:179584941;179584940;179584939 |
| N2AB | 7493 | 22702;22703;22704 | chr2:178720214;178720213;178720212 | chr2:179584941;179584940;179584939 |
| N2A | 6566 | 19921;19922;19923 | chr2:178720214;178720213;178720212 | chr2:179584941;179584940;179584939 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/G | rs375392021  |
-0.193 | 0.324 | N | 0.365 | 0.187 | 0.110078149338 | 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 |
| D/H | rs2078129851 |
None | 0.773 | N | 0.331 | 0.252 | 0.163833314356 | gnomAD-4.0.0 | 3.18334E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.71798E-06 | 0 | 0 |
| D/V | rs375392021 |
0.227 | 0.324 | N | 0.413 | 0.245 | None | gnomAD-2.1.1 | 2.15E-05 | None | None | None | None | I | None | 2.48221E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| D/V | rs375392021 |
0.227 | 0.324 | N | 0.413 | 0.245 | None | gnomAD-3.1.2 | 4.6E-05 | None | None | None | None | I | None | 1.6887E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| D/V | rs375392021 |
0.227 | 0.324 | N | 0.413 | 0.245 | None | gnomAD-4.0.0 | 9.13472E-06 | None | None | None | None | I | None | 1.57238E-04 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| D/Y | None | None | 0.912 | N | 0.371 | 0.265 | 0.423480098753 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 1.92901E-04 | None | 0 | 0 | 0 | 0 | 0 |
| D/Y | None | None | 0.912 | N | 0.371 | 0.265 | 0.423480098753 | gnomAD-4.0.0 | 6.57194E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 1.92901E-04 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.1417 | likely_benign | 0.1364 | benign | -0.435 | Destabilizing | 0.09 | N | 0.376 | neutral | N | 0.500866115 | None | None | I |
| D/C | 0.5821 | likely_pathogenic | 0.5514 | ambiguous | -0.044 | Destabilizing | 0.981 | D | 0.368 | neutral | None | None | None | None | I |
| D/E | 0.0962 | likely_benign | 0.0974 | benign | -0.43 | Destabilizing | 0.001 | N | 0.159 | neutral | N | 0.397754816 | None | None | I |
| D/F | 0.5378 | ambiguous | 0.5072 | ambiguous | -0.272 | Destabilizing | 0.932 | D | 0.365 | neutral | None | None | None | None | I |
| D/G | 0.1395 | likely_benign | 0.1369 | benign | -0.671 | Destabilizing | 0.324 | N | 0.365 | neutral | N | 0.481240204 | None | None | I |
| D/H | 0.1974 | likely_benign | 0.1923 | benign | -0.239 | Destabilizing | 0.773 | D | 0.331 | neutral | N | 0.472950676 | None | None | I |
| D/I | 0.3291 | likely_benign | 0.3033 | benign | 0.151 | Stabilizing | 0.818 | D | 0.381 | neutral | None | None | None | None | I |
| D/K | 0.1832 | likely_benign | 0.1841 | benign | 0.198 | Stabilizing | 0.004 | N | 0.169 | neutral | None | None | None | None | I |
| D/L | 0.3361 | likely_benign | 0.3252 | benign | 0.151 | Stabilizing | 0.388 | N | 0.447 | neutral | None | None | None | None | I |
| D/M | 0.5065 | ambiguous | 0.4901 | ambiguous | 0.369 | Stabilizing | 0.981 | D | 0.352 | neutral | None | None | None | None | I |
| D/N | 0.0873 | likely_benign | 0.081 | benign | -0.211 | Destabilizing | 0.324 | N | 0.342 | neutral | N | 0.467926977 | None | None | I |
| D/P | 0.7011 | likely_pathogenic | 0.7016 | pathogenic | -0.022 | Destabilizing | 0.818 | D | 0.367 | neutral | None | None | None | None | I |
| D/Q | 0.1899 | likely_benign | 0.1879 | benign | -0.158 | Destabilizing | 0.024 | N | 0.251 | neutral | None | None | None | None | I |
| D/R | 0.2279 | likely_benign | 0.2302 | benign | 0.358 | Stabilizing | 0.002 | N | 0.267 | neutral | None | None | None | None | I |
| D/S | 0.1028 | likely_benign | 0.0995 | benign | -0.321 | Destabilizing | 0.116 | N | 0.319 | neutral | None | None | None | None | I |
| D/T | 0.1864 | likely_benign | 0.1822 | benign | -0.132 | Destabilizing | 0.388 | N | 0.363 | neutral | None | None | None | None | I |
| D/V | 0.1944 | likely_benign | 0.1799 | benign | -0.022 | Destabilizing | 0.324 | N | 0.413 | neutral | N | 0.473711145 | None | None | I |
| D/W | 0.822 | likely_pathogenic | 0.8131 | pathogenic | -0.093 | Destabilizing | 0.981 | D | 0.477 | neutral | None | None | None | None | I |
| D/Y | 0.2137 | likely_benign | 0.1994 | benign | -0.024 | Destabilizing | 0.912 | D | 0.371 | neutral | N | 0.516008926 | 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.