Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24525 | 73798;73799;73800 | chr2:178572559;178572558;178572557 | chr2:179437286;179437285;179437284 |
| N2AB | 22884 | 68875;68876;68877 | chr2:178572559;178572558;178572557 | chr2:179437286;179437285;179437284 |
| N2A | 21957 | 66094;66095;66096 | chr2:178572559;178572558;178572557 | chr2:179437286;179437285;179437284 |
| N2B | 15460 | 46603;46604;46605 | chr2:178572559;178572558;178572557 | chr2:179437286;179437285;179437284 |
| Novex-1 | 15585 | 46978;46979;46980 | chr2:178572559;178572558;178572557 | chr2:179437286;179437285;179437284 |
| Novex-2 | 15652 | 47179;47180;47181 | chr2:178572559;178572558;178572557 | chr2:179437286;179437285;179437284 |
| 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 | rs1039373351  |
None | 0.001 | N | 0.341 | 0.065 | 0.162503812791 | gnomAD-4.0.0 | 2.053E-06 | None | None | None | None | I | None | 2.98918E-05 | 4.47287E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| D/N | rs1273296080 |
None | None | N | 0.093 | 0.081 | 0.0401082797425 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| D/N | rs1273296080 |
None | None | N | 0.093 | 0.081 | 0.0401082797425 | gnomAD-4.0.0 | 1.85953E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.5432E-06 | 0 | 0 |
| D/V | None | None | 0.011 | N | 0.39 | 0.176 | 0.370608029945 | gnomAD-4.0.0 | 1.59195E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.02608E-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 | 0.1195 | likely_benign | 0.0996 | benign | -0.384 | Destabilizing | None | N | 0.157 | neutral | N | 0.442810394 | None | None | I |
| D/C | 0.3452 | ambiguous | 0.3075 | benign | -0.045 | Destabilizing | 0.271 | N | 0.285 | neutral | None | None | None | None | I |
| D/E | 0.112 | likely_benign | 0.1087 | benign | -0.388 | Destabilizing | 0.001 | N | 0.341 | neutral | N | 0.479808557 | None | None | I |
| D/F | 0.3714 | ambiguous | 0.3403 | ambiguous | -0.32 | Destabilizing | 0.233 | N | 0.399 | neutral | None | None | None | None | I |
| D/G | 0.1181 | likely_benign | 0.1018 | benign | -0.588 | Destabilizing | 0.005 | N | 0.332 | neutral | N | 0.462337517 | None | None | I |
| D/H | 0.1577 | likely_benign | 0.1427 | benign | -0.218 | Destabilizing | 0.146 | N | 0.361 | neutral | N | 0.484523731 | None | None | I |
| D/I | 0.2477 | likely_benign | 0.2026 | benign | 0.11 | Stabilizing | 0.377 | N | 0.401 | neutral | None | None | None | None | I |
| D/K | 0.2846 | likely_benign | 0.2219 | benign | 0.155 | Stabilizing | 0.08 | N | 0.337 | neutral | None | None | None | None | I |
| D/L | 0.2443 | likely_benign | 0.2074 | benign | 0.11 | Stabilizing | 0.08 | N | 0.357 | neutral | None | None | None | None | I |
| D/M | 0.3578 | ambiguous | 0.3455 | ambiguous | 0.28 | Stabilizing | 0.583 | D | 0.291 | neutral | None | None | None | None | I |
| D/N | 0.0516 | likely_benign | 0.0543 | benign | -0.127 | Destabilizing | None | N | 0.093 | neutral | N | 0.3541084 | None | None | I |
| D/P | 0.7693 | likely_pathogenic | 0.6362 | pathogenic | -0.032 | Destabilizing | 0.007 | N | 0.421 | neutral | None | None | None | None | I |
| D/Q | 0.1945 | likely_benign | 0.1775 | benign | -0.097 | Destabilizing | 0.061 | N | 0.356 | neutral | None | None | None | None | I |
| D/R | 0.321 | likely_benign | 0.2577 | benign | 0.327 | Stabilizing | 0.147 | N | 0.373 | neutral | None | None | None | None | I |
| D/S | 0.0873 | likely_benign | 0.0829 | benign | -0.243 | Destabilizing | 0.01 | N | 0.337 | neutral | None | None | None | None | I |
| D/T | 0.1757 | likely_benign | 0.1489 | benign | -0.087 | Destabilizing | 0.004 | N | 0.327 | neutral | None | None | None | None | I |
| D/V | 0.1648 | likely_benign | 0.1279 | benign | -0.032 | Destabilizing | 0.011 | N | 0.39 | neutral | N | 0.505976438 | None | None | I |
| D/W | 0.7972 | likely_pathogenic | 0.7623 | pathogenic | -0.181 | Destabilizing | 0.934 | D | 0.298 | neutral | None | None | None | None | I |
| D/Y | 0.1392 | likely_benign | 0.1182 | benign | -0.09 | Destabilizing | 0.002 | N | 0.221 | neutral | N | 0.493400287 | 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.