Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20055 | 60388;60389;60390 | chr2:178591656;178591655;178591654 | chr2:179456383;179456382;179456381 |
| N2AB | 18414 | 55465;55466;55467 | chr2:178591656;178591655;178591654 | chr2:179456383;179456382;179456381 |
| N2A | 17487 | 52684;52685;52686 | chr2:178591656;178591655;178591654 | chr2:179456383;179456382;179456381 |
| N2B | 10990 | 33193;33194;33195 | chr2:178591656;178591655;178591654 | chr2:179456383;179456382;179456381 |
| Novex-1 | 11115 | 33568;33569;33570 | chr2:178591656;178591655;178591654 | chr2:179456383;179456382;179456381 |
| Novex-2 | 11182 | 33769;33770;33771 | chr2:178591656;178591655;178591654 | chr2:179456383;179456382;179456381 |
| 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/T | rs755318489  |
-0.232 | 0.92 | N | 0.437 | 0.198 | None | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 5.58E-05 | None | 0 | None | 0 | 0 | 0 |
| I/T | rs755318489 |
-0.232 | 0.92 | N | 0.437 | 0.198 | None | gnomAD-4.0.0 | 4.10596E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.49806E-06 | 0 | 1.65678E-05 |
| I/V | rs1445750788 |
-0.109 | 0.675 | N | 0.336 | 0.149 | 0.455081427078 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.89E-06 | 0 |
| I/V | rs1445750788 |
-0.109 | 0.675 | N | 0.336 | 0.149 | 0.455081427078 | 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/V | rs1445750788 |
-0.109 | 0.675 | N | 0.336 | 0.149 | 0.455081427078 | gnomAD-4.0.0 | 2.47928E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.39106E-05 | 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 | 0.1363 | likely_benign | 0.1599 | benign | -0.462 | Destabilizing | 0.028 | N | 0.178 | neutral | None | None | None | None | I |
| I/C | 0.6553 | likely_pathogenic | 0.73 | pathogenic | -0.715 | Destabilizing | 0.997 | D | 0.395 | neutral | None | None | None | None | I |
| I/D | 0.4738 | ambiguous | 0.5431 | ambiguous | -0.115 | Destabilizing | 0.991 | D | 0.475 | neutral | None | None | None | None | I |
| I/E | 0.3397 | likely_benign | 0.3919 | ambiguous | -0.22 | Destabilizing | 0.991 | D | 0.458 | neutral | None | None | None | None | I |
| I/F | 0.1969 | likely_benign | 0.2322 | benign | -0.595 | Destabilizing | 0.996 | D | 0.328 | neutral | N | 0.507397803 | None | None | I |
| I/G | 0.4545 | ambiguous | 0.5374 | ambiguous | -0.579 | Destabilizing | 0.884 | D | 0.482 | neutral | None | None | None | None | I |
| I/H | 0.3761 | ambiguous | 0.4519 | ambiguous | 0.057 | Stabilizing | 0.999 | D | 0.458 | neutral | None | None | None | None | I |
| I/K | 0.2265 | likely_benign | 0.2817 | benign | -0.247 | Destabilizing | 0.982 | D | 0.455 | neutral | None | None | None | None | I |
| I/L | 0.1128 | likely_benign | 0.1284 | benign | -0.288 | Destabilizing | 0.675 | D | 0.32 | neutral | N | 0.418336024 | None | None | I |
| I/M | 0.0868 | likely_benign | 0.0983 | benign | -0.386 | Destabilizing | 0.996 | D | 0.326 | neutral | N | 0.446792062 | None | None | I |
| I/N | 0.1958 | likely_benign | 0.2576 | benign | -0.127 | Destabilizing | 0.996 | D | 0.477 | neutral | N | 0.46533775 | None | None | I |
| I/P | 0.5155 | ambiguous | 0.5422 | ambiguous | -0.314 | Destabilizing | 0.991 | D | 0.483 | neutral | None | None | None | None | I |
| I/Q | 0.2785 | likely_benign | 0.3316 | benign | -0.344 | Destabilizing | 0.997 | D | 0.469 | neutral | None | None | None | None | I |
| I/R | 0.1822 | likely_benign | 0.221 | benign | 0.267 | Stabilizing | 0.991 | D | 0.481 | neutral | None | None | None | None | I |
| I/S | 0.1615 | likely_benign | 0.2033 | benign | -0.54 | Destabilizing | 0.852 | D | 0.455 | neutral | N | 0.387858401 | None | None | I |
| I/T | 0.1221 | likely_benign | 0.1464 | benign | -0.539 | Destabilizing | 0.92 | D | 0.437 | neutral | N | 0.442018173 | None | None | I |
| I/V | 0.0736 | likely_benign | 0.0793 | benign | -0.314 | Destabilizing | 0.675 | D | 0.336 | neutral | N | 0.409119108 | None | None | I |
| I/W | 0.7547 | likely_pathogenic | 0.7901 | pathogenic | -0.61 | Destabilizing | 0.999 | D | 0.572 | neutral | None | None | None | None | I |
| I/Y | 0.5011 | ambiguous | 0.5732 | pathogenic | -0.351 | Destabilizing | 0.997 | D | 0.414 | 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.