Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25293 | 76102;76103;76104 | chr2:178570255;178570254;178570253 | chr2:179434982;179434981;179434980 |
| N2AB | 23652 | 71179;71180;71181 | chr2:178570255;178570254;178570253 | chr2:179434982;179434981;179434980 |
| N2A | 22725 | 68398;68399;68400 | chr2:178570255;178570254;178570253 | chr2:179434982;179434981;179434980 |
| N2B | 16228 | 48907;48908;48909 | chr2:178570255;178570254;178570253 | chr2:179434982;179434981;179434980 |
| Novex-1 | 16353 | 49282;49283;49284 | chr2:178570255;178570254;178570253 | chr2:179434982;179434981;179434980 |
| Novex-2 | 16420 | 49483;49484;49485 | chr2:178570255;178570254;178570253 | chr2:179434982;179434981;179434980 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/C | rs186240800  |
-0.393 | 0.049 | D | 0.581 | 0.425 | None | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 5.61E-05 | None | 0 | None | 0 | 0 | 0 |
| S/C | rs186240800 |
-0.393 | 0.049 | D | 0.581 | 0.425 | None | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 1.93498E-04 | None | 0 | 0 | 0 | 0 | 0 |
| S/C | rs186240800 |
-0.393 | 0.049 | D | 0.581 | 0.425 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | I | None | 0 | 0 | None | None | 1E-03 | 0 | None | None | None | 0 | None |
| S/C | rs186240800 |
-0.393 | 0.049 | D | 0.581 | 0.425 | None | gnomAD-4.0.0 | 8.97098E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 1.70283E-04 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.2684 | likely_benign | 0.2514 | benign | -0.557 | Destabilizing | 0.595 | D | 0.502 | neutral | N | 0.508246674 | None | None | I |
| S/C | 0.3114 | likely_benign | 0.2923 | benign | -0.371 | Destabilizing | 0.049 | N | 0.581 | neutral | D | 0.540798335 | None | None | I |
| S/D | 0.9536 | likely_pathogenic | 0.9566 | pathogenic | -0.522 | Destabilizing | 0.995 | D | 0.629 | neutral | None | None | None | None | I |
| S/E | 0.982 | likely_pathogenic | 0.9804 | pathogenic | -0.406 | Destabilizing | 0.995 | D | 0.627 | neutral | None | None | None | None | I |
| S/F | 0.9329 | likely_pathogenic | 0.9161 | pathogenic | -0.446 | Destabilizing | 0.981 | D | 0.69 | prob.delet. | D | 0.540544845 | None | None | I |
| S/G | 0.2942 | likely_benign | 0.2954 | benign | -0.913 | Destabilizing | 0.95 | D | 0.591 | neutral | None | None | None | None | I |
| S/H | 0.9618 | likely_pathogenic | 0.9582 | pathogenic | -1.314 | Destabilizing | 0.999 | D | 0.641 | neutral | None | None | None | None | I |
| S/I | 0.8436 | likely_pathogenic | 0.8116 | pathogenic | 0.314 | Stabilizing | 0.971 | D | 0.629 | neutral | None | None | None | None | I |
| S/K | 0.9952 | likely_pathogenic | 0.9949 | pathogenic | -0.338 | Destabilizing | 0.985 | D | 0.625 | neutral | None | None | None | None | I |
| S/L | 0.5536 | ambiguous | 0.5193 | ambiguous | 0.314 | Stabilizing | 0.825 | D | 0.633 | neutral | None | None | None | None | I |
| S/M | 0.6273 | likely_pathogenic | 0.5824 | pathogenic | 0.223 | Stabilizing | 0.999 | D | 0.634 | neutral | None | None | None | None | I |
| S/N | 0.8308 | likely_pathogenic | 0.8161 | pathogenic | -0.69 | Destabilizing | 0.995 | D | 0.626 | neutral | None | None | None | None | I |
| S/P | 0.9772 | likely_pathogenic | 0.9798 | pathogenic | 0.06 | Stabilizing | 0.994 | D | 0.607 | neutral | N | 0.509767611 | None | None | I |
| S/Q | 0.9787 | likely_pathogenic | 0.9752 | pathogenic | -0.572 | Destabilizing | 0.995 | D | 0.589 | neutral | None | None | None | None | I |
| S/R | 0.9938 | likely_pathogenic | 0.9929 | pathogenic | -0.557 | Destabilizing | 0.995 | D | 0.61 | neutral | None | None | None | None | I |
| S/T | 0.1152 | likely_benign | 0.1134 | benign | -0.504 | Destabilizing | 0.877 | D | 0.644 | neutral | N | 0.521855542 | None | None | I |
| S/V | 0.7224 | likely_pathogenic | 0.679 | pathogenic | 0.06 | Stabilizing | 0.971 | D | 0.629 | neutral | None | None | None | None | I |
| S/W | 0.9489 | likely_pathogenic | 0.9378 | pathogenic | -0.603 | Destabilizing | 0.999 | D | 0.78 | deleterious | None | None | None | None | I |
| S/Y | 0.9172 | likely_pathogenic | 0.9011 | pathogenic | -0.201 | Destabilizing | 0.994 | D | 0.703 | prob.delet. | D | 0.551647661 | 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.