Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31934 | 96025;96026;96027 | chr2:178544429;178544428;178544427 | chr2:179409156;179409155;179409154 |
| N2AB | 30293 | 91102;91103;91104 | chr2:178544429;178544428;178544427 | chr2:179409156;179409155;179409154 |
| N2A | 29366 | 88321;88322;88323 | chr2:178544429;178544428;178544427 | chr2:179409156;179409155;179409154 |
| N2B | 22869 | 68830;68831;68832 | chr2:178544429;178544428;178544427 | chr2:179409156;179409155;179409154 |
| Novex-1 | 22994 | 69205;69206;69207 | chr2:178544429;178544428;178544427 | chr2:179409156;179409155;179409154 |
| Novex-2 | 23061 | 69406;69407;69408 | chr2:178544429;178544428;178544427 | chr2:179409156;179409155;179409154 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/I | rs1365026291  |
0.441 | 0.012 | N | 0.379 | 0.115 | 0.241664281697 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.88E-06 | 0 |
| M/I | rs1365026291 |
0.441 | 0.012 | N | 0.379 | 0.115 | 0.241664281697 | gnomAD-4.0.0 | 6.36576E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.14359E-05 | 0 | 0 |
| M/T | None | None | None | N | 0.174 | 0.112 | 0.3349148499 | gnomAD-4.0.0 | 7.52664E-06 | None | None | None | None | I | None | 0 | 2.23614E-05 | None | 0 | 0 | None | 0 | 0 | 8.09581E-06 | 0 | 1.65651E-05 |
| M/V | rs1696075318 |
None | 0.005 | N | 0.213 | 0.086 | 0.292787519742 | gnomAD-4.0.0 | 1.59144E-06 | None | None | None | None | I | None | 0 | 0 | None | 4.76735E-05 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.241 | likely_benign | 0.1475 | benign | -0.172 | Destabilizing | None | N | 0.182 | neutral | None | None | None | None | I |
| M/C | 0.6792 | likely_pathogenic | 0.5992 | pathogenic | -0.548 | Destabilizing | 0.356 | N | 0.324 | neutral | None | None | None | None | I |
| M/D | 0.8002 | likely_pathogenic | 0.6459 | pathogenic | 0.318 | Stabilizing | 0.072 | N | 0.401 | neutral | None | None | None | None | I |
| M/E | 0.5512 | ambiguous | 0.3623 | ambiguous | 0.26 | Stabilizing | 0.072 | N | 0.45 | neutral | None | None | None | None | I |
| M/F | 0.4143 | ambiguous | 0.3275 | benign | -0.151 | Destabilizing | 0.038 | N | 0.331 | neutral | None | None | None | None | I |
| M/G | 0.4836 | ambiguous | 0.3374 | benign | -0.255 | Destabilizing | 0.038 | N | 0.413 | neutral | None | None | None | None | I |
| M/H | 0.5387 | ambiguous | 0.423 | ambiguous | 0.43 | Stabilizing | 0.864 | D | 0.298 | neutral | None | None | None | None | I |
| M/I | 0.2936 | likely_benign | 0.2049 | benign | -0.05 | Destabilizing | 0.012 | N | 0.379 | neutral | N | 0.399211546 | None | None | I |
| M/K | 0.2789 | likely_benign | 0.1821 | benign | 0.359 | Stabilizing | 0.055 | N | 0.442 | neutral | N | 0.36905921 | None | None | I |
| M/L | 0.1057 | likely_benign | 0.0893 | benign | -0.05 | Destabilizing | None | N | 0.127 | neutral | N | 0.384799454 | None | None | I |
| M/N | 0.4693 | ambiguous | 0.3347 | benign | 0.428 | Stabilizing | 0.214 | N | 0.404 | neutral | None | None | None | None | I |
| M/P | 0.5585 | ambiguous | 0.4123 | ambiguous | -0.069 | Destabilizing | 0.356 | N | 0.402 | neutral | None | None | None | None | I |
| M/Q | 0.2751 | likely_benign | 0.1983 | benign | 0.294 | Stabilizing | 0.356 | N | 0.317 | neutral | None | None | None | None | I |
| M/R | 0.2921 | likely_benign | 0.1815 | benign | 0.769 | Stabilizing | 0.055 | N | 0.393 | neutral | N | 0.386164891 | None | None | I |
| M/S | 0.3103 | likely_benign | 0.1863 | benign | 0.041 | Stabilizing | 0.016 | N | 0.367 | neutral | None | None | None | None | I |
| M/T | 0.1758 | likely_benign | 0.0884 | benign | 0.068 | Stabilizing | None | N | 0.174 | neutral | N | 0.355823341 | None | None | I |
| M/V | 0.074 | likely_benign | 0.0575 | benign | -0.069 | Destabilizing | 0.005 | N | 0.213 | neutral | N | 0.351919031 | None | None | I |
| M/W | 0.7285 | likely_pathogenic | 0.6308 | pathogenic | -0.179 | Destabilizing | 0.864 | D | 0.32 | neutral | None | None | None | None | I |
| M/Y | 0.6269 | likely_pathogenic | 0.5503 | ambiguous | 0.02 | Stabilizing | 0.356 | N | 0.353 | 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.