Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23383 | 70372;70373;70374 | chr2:178575985;178575984;178575983 | chr2:179440712;179440711;179440710 |
| N2AB | 21742 | 65449;65450;65451 | chr2:178575985;178575984;178575983 | chr2:179440712;179440711;179440710 |
| N2A | 20815 | 62668;62669;62670 | chr2:178575985;178575984;178575983 | chr2:179440712;179440711;179440710 |
| N2B | 14318 | 43177;43178;43179 | chr2:178575985;178575984;178575983 | chr2:179440712;179440711;179440710 |
| Novex-1 | 14443 | 43552;43553;43554 | chr2:178575985;178575984;178575983 | chr2:179440712;179440711;179440710 |
| Novex-2 | 14510 | 43753;43754;43755 | chr2:178575985;178575984;178575983 | chr2:179440712;179440711;179440710 |
| 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/M | None | None | 0.171 | N | 0.244 | 0.043 | 0.232513804876 | gnomAD-4.0.0 | 1.59681E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.03085E-05 |
| I/N | rs1197503879  |
None | 0.055 | N | 0.441 | 0.163 | 0.66259775642 | 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 |
| I/N | rs1197503879 |
None | 0.055 | N | 0.441 | 0.163 | 0.66259775642 | gnomAD-4.0.0 | 1.24111E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.69767E-06 | 0 | 0 |
| I/T | None | None | None | N | 0.142 | 0.142 | 0.459282285925 | gnomAD-4.0.0 | 6.85202E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.00817E-07 | 0 | 0 |
| I/V | rs773301754 |
-0.157 | None | N | 0.142 | 0.052 | 0.130388298395 | gnomAD-2.1.1 | 8.05E-06 | None | None | None | None | I | None | 0 | 5.8E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/V | rs773301754 |
-0.157 | None | N | 0.142 | 0.052 | 0.130388298395 | gnomAD-4.0.0 | 3.19286E-06 | None | None | None | None | I | None | 0 | 4.57624E-05 | None | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.1413 | likely_benign | 0.1858 | benign | -0.724 | Destabilizing | None | N | 0.157 | neutral | None | None | None | None | I |
| I/C | 0.3437 | ambiguous | 0.4168 | ambiguous | -0.557 | Destabilizing | 0.356 | N | 0.315 | neutral | None | None | None | None | I |
| I/D | 0.3338 | likely_benign | 0.3998 | ambiguous | -0.283 | Destabilizing | 0.072 | N | 0.441 | neutral | None | None | None | None | I |
| I/E | 0.27 | likely_benign | 0.3168 | benign | -0.382 | Destabilizing | 0.072 | N | 0.404 | neutral | None | None | None | None | I |
| I/F | 0.119 | likely_benign | 0.157 | benign | -0.783 | Destabilizing | 0.055 | N | 0.253 | neutral | N | 0.486863108 | None | None | I |
| I/G | 0.2623 | likely_benign | 0.3298 | benign | -0.893 | Destabilizing | 0.031 | N | 0.374 | neutral | None | None | None | None | I |
| I/H | 0.263 | likely_benign | 0.3115 | benign | -0.23 | Destabilizing | 0.628 | D | 0.376 | neutral | None | None | None | None | I |
| I/K | 0.2188 | likely_benign | 0.2607 | benign | -0.37 | Destabilizing | 0.072 | N | 0.404 | neutral | None | None | None | None | I |
| I/L | 0.0873 | likely_benign | 0.0987 | benign | -0.402 | Destabilizing | None | N | 0.167 | neutral | N | 0.465333042 | None | None | I |
| I/M | 0.0753 | likely_benign | 0.0858 | benign | -0.325 | Destabilizing | 0.171 | N | 0.244 | neutral | N | 0.479051701 | None | None | I |
| I/N | 0.1158 | likely_benign | 0.1333 | benign | -0.123 | Destabilizing | 0.055 | N | 0.441 | neutral | N | 0.461215302 | None | None | I |
| I/P | 0.7018 | likely_pathogenic | 0.8264 | pathogenic | -0.476 | Destabilizing | 0.136 | N | 0.477 | neutral | None | None | None | None | I |
| I/Q | 0.2063 | likely_benign | 0.2417 | benign | -0.38 | Destabilizing | 0.356 | N | 0.457 | neutral | None | None | None | None | I |
| I/R | 0.1882 | likely_benign | 0.2284 | benign | 0.213 | Stabilizing | 0.136 | N | 0.454 | neutral | None | None | None | None | I |
| I/S | 0.121 | likely_benign | 0.1428 | benign | -0.574 | Destabilizing | 0.001 | N | 0.183 | neutral | N | 0.433044479 | None | None | I |
| I/T | 0.0968 | likely_benign | 0.1151 | benign | -0.566 | Destabilizing | None | N | 0.142 | neutral | N | 0.459252432 | None | None | I |
| I/V | 0.0562 | likely_benign | 0.0653 | benign | -0.476 | Destabilizing | None | N | 0.142 | neutral | N | 0.41909932 | None | None | I |
| I/W | 0.6141 | likely_pathogenic | 0.6989 | pathogenic | -0.795 | Destabilizing | 0.864 | D | 0.379 | neutral | None | None | None | None | I |
| I/Y | 0.3266 | likely_benign | 0.3968 | ambiguous | -0.539 | Destabilizing | 0.356 | N | 0.376 | 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.