Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23302 | 70129;70130;70131 | chr2:178576228;178576227;178576226 | chr2:179440955;179440954;179440953 |
| N2AB | 21661 | 65206;65207;65208 | chr2:178576228;178576227;178576226 | chr2:179440955;179440954;179440953 |
| N2A | 20734 | 62425;62426;62427 | chr2:178576228;178576227;178576226 | chr2:179440955;179440954;179440953 |
| N2B | 14237 | 42934;42935;42936 | chr2:178576228;178576227;178576226 | chr2:179440955;179440954;179440953 |
| Novex-1 | 14362 | 43309;43310;43311 | chr2:178576228;178576227;178576226 | chr2:179440955;179440954;179440953 |
| Novex-2 | 14429 | 43510;43511;43512 | chr2:178576228;178576227;178576226 | chr2:179440955;179440954;179440953 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/I | rs190421400  |
-0.191 | 0.383 | N | 0.437 | 0.093 | None | gnomAD-2.1.1 | 1.50721E-04 | None | None | None | None | I | None | 1.24121E-03 | 5.68E-05 | None | 0 | 1.55119E-04 | None | 6.56E-05 | None | 0 | 3.15E-05 | 1.41084E-04 |
| V/I | rs190421400 |
-0.191 | 0.383 | N | 0.437 | 0.093 | None | gnomAD-3.1.2 | 3.55128E-04 | None | None | None | None | I | None | 1.18249E-03 | 0 | 0 | 0 | 0 | None | 0 | 0 | 7.35E-05 | 0 | 0 |
| V/I | rs190421400 |
-0.191 | 0.383 | N | 0.437 | 0.093 | None | 1000 genomes | 7.98722E-04 | None | None | None | None | I | None | 3E-03 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| V/I | rs190421400 |
-0.191 | 0.383 | N | 0.437 | 0.093 | None | gnomAD-4.0.0 | 7.75029E-05 | None | None | None | None | I | None | 9.33582E-04 | 5.00684E-05 | None | 0 | 8.94374E-05 | None | 0 | 0 | 2.11978E-05 | 4.39773E-05 | 3.04263E-04 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.4056 | ambiguous | 0.3728 | ambiguous | -0.992 | Destabilizing | 0.805 | D | 0.506 | neutral | N | 0.496066089 | None | None | I |
| V/C | 0.8728 | likely_pathogenic | 0.8568 | pathogenic | -0.951 | Destabilizing | 0.999 | D | 0.657 | neutral | None | None | None | None | I |
| V/D | 0.6246 | likely_pathogenic | 0.5975 | pathogenic | -0.372 | Destabilizing | 0.967 | D | 0.761 | deleterious | N | 0.474406978 | None | None | I |
| V/E | 0.4649 | ambiguous | 0.4357 | ambiguous | -0.376 | Destabilizing | 0.95 | D | 0.68 | prob.neutral | None | None | None | None | I |
| V/F | 0.4541 | ambiguous | 0.4181 | ambiguous | -0.723 | Destabilizing | 0.993 | D | 0.683 | prob.neutral | N | 0.521617894 | None | None | I |
| V/G | 0.6426 | likely_pathogenic | 0.6149 | pathogenic | -1.27 | Destabilizing | 0.967 | D | 0.723 | prob.delet. | N | 0.475927915 | None | None | I |
| V/H | 0.7787 | likely_pathogenic | 0.7581 | pathogenic | -0.639 | Destabilizing | 0.997 | D | 0.745 | deleterious | None | None | None | None | I |
| V/I | 0.0957 | likely_benign | 0.0898 | benign | -0.353 | Destabilizing | 0.383 | N | 0.437 | neutral | N | 0.520500387 | None | None | I |
| V/K | 0.6653 | likely_pathogenic | 0.6276 | pathogenic | -0.781 | Destabilizing | 0.073 | N | 0.488 | neutral | None | None | None | None | I |
| V/L | 0.3999 | ambiguous | 0.3605 | ambiguous | -0.353 | Destabilizing | 0.812 | D | 0.452 | neutral | N | 0.48188607 | None | None | I |
| V/M | 0.2873 | likely_benign | 0.2596 | benign | -0.5 | Destabilizing | 0.987 | D | 0.576 | neutral | None | None | None | None | I |
| V/N | 0.5254 | ambiguous | 0.4883 | ambiguous | -0.716 | Destabilizing | 0.975 | D | 0.763 | deleterious | None | None | None | None | I |
| V/P | 0.9106 | likely_pathogenic | 0.9045 | pathogenic | -0.53 | Destabilizing | 0.987 | D | 0.733 | prob.delet. | None | None | None | None | I |
| V/Q | 0.5656 | likely_pathogenic | 0.5341 | ambiguous | -0.807 | Destabilizing | 0.975 | D | 0.735 | prob.delet. | None | None | None | None | I |
| V/R | 0.595 | likely_pathogenic | 0.5694 | pathogenic | -0.345 | Destabilizing | 0.95 | D | 0.757 | deleterious | None | None | None | None | I |
| V/S | 0.4305 | ambiguous | 0.4007 | ambiguous | -1.26 | Destabilizing | 0.975 | D | 0.678 | prob.neutral | None | None | None | None | I |
| V/T | 0.1815 | likely_benign | 0.1701 | benign | -1.135 | Destabilizing | 0.916 | D | 0.524 | neutral | None | None | None | None | I |
| V/W | 0.9522 | likely_pathogenic | 0.9493 | pathogenic | -0.856 | Destabilizing | 0.999 | D | 0.693 | prob.neutral | None | None | None | None | I |
| V/Y | 0.8226 | likely_pathogenic | 0.804 | pathogenic | -0.551 | Destabilizing | 0.996 | D | 0.687 | prob.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.