Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18291 | 55096;55097;55098 | chr2:178602531;178602530;178602529 | chr2:179467258;179467257;179467256 |
| N2AB | 16650 | 50173;50174;50175 | chr2:178602531;178602530;178602529 | chr2:179467258;179467257;179467256 |
| N2A | 15723 | 47392;47393;47394 | chr2:178602531;178602530;178602529 | chr2:179467258;179467257;179467256 |
| N2B | 9226 | 27901;27902;27903 | chr2:178602531;178602530;178602529 | chr2:179467258;179467257;179467256 |
| Novex-1 | 9351 | 28276;28277;28278 | chr2:178602531;178602530;178602529 | chr2:179467258;179467257;179467256 |
| Novex-2 | 9418 | 28477;28478;28479 | chr2:178602531;178602530;178602529 | chr2:179467258;179467257;179467256 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/I | None | None | 0.999 | N | 0.519 | 0.283 | 0.296679040009 | gnomAD-4.0.0 | 1.61793E-06 | None | None | None | None | N | None | 0 | 0 | None | 4.82067E-05 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| L/P | rs769159180  |
None | 1.0 | D | 0.93 | 0.631 | None | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.42E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| L/P | rs769159180 |
None | 1.0 | D | 0.93 | 0.631 | None | gnomAD-4.0.0 | 2.59576E-06 | None | None | None | None | N | None | 1.70085E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 2.87886E-05 |
| L/R | rs769159180 |
-2.035 | 1.0 | D | 0.9 | 0.567 | 0.785555827254 | gnomAD-2.1.1 | 2.55E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 2.05804E-04 | None | 0 | 0 | 0 |
| L/R | rs769159180 |
-2.035 | 1.0 | D | 0.9 | 0.567 | 0.785555827254 | gnomAD-4.0.0 | 8.08303E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 7.32257E-05 | 0 |
| L/V | None | None | 0.999 | N | 0.543 | 0.3 | 0.293502639404 | gnomAD-4.0.0 | 1.61793E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.90308E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.9436 | likely_pathogenic | 0.9215 | pathogenic | -2.402 | Highly Destabilizing | 0.999 | D | 0.659 | neutral | None | None | None | None | N |
| L/C | 0.9435 | likely_pathogenic | 0.9219 | pathogenic | -1.633 | Destabilizing | 1.0 | D | 0.803 | deleterious | None | None | None | None | N |
| L/D | 0.9994 | likely_pathogenic | 0.9994 | pathogenic | -2.994 | Highly Destabilizing | 1.0 | D | 0.925 | deleterious | None | None | None | None | N |
| L/E | 0.9957 | likely_pathogenic | 0.9956 | pathogenic | -2.669 | Highly Destabilizing | 1.0 | D | 0.91 | deleterious | None | None | None | None | N |
| L/F | 0.6405 | likely_pathogenic | 0.5147 | ambiguous | -1.417 | Destabilizing | 1.0 | D | 0.739 | prob.delet. | None | None | None | None | N |
| L/G | 0.9941 | likely_pathogenic | 0.9925 | pathogenic | -3.033 | Highly Destabilizing | 1.0 | D | 0.902 | deleterious | None | None | None | None | N |
| L/H | 0.9909 | likely_pathogenic | 0.9888 | pathogenic | -2.811 | Highly Destabilizing | 1.0 | D | 0.867 | deleterious | None | None | None | None | N |
| L/I | 0.1567 | likely_benign | 0.1391 | benign | -0.523 | Destabilizing | 0.999 | D | 0.519 | neutral | N | 0.464577474 | None | None | N |
| L/K | 0.9901 | likely_pathogenic | 0.9922 | pathogenic | -1.742 | Destabilizing | 1.0 | D | 0.892 | deleterious | None | None | None | None | N |
| L/M | 0.3635 | ambiguous | 0.3275 | benign | -0.661 | Destabilizing | 1.0 | D | 0.73 | prob.delet. | None | None | None | None | N |
| L/N | 0.9972 | likely_pathogenic | 0.9975 | pathogenic | -2.408 | Highly Destabilizing | 1.0 | D | 0.93 | deleterious | None | None | None | None | N |
| L/P | 0.9932 | likely_pathogenic | 0.9895 | pathogenic | -1.137 | Destabilizing | 1.0 | D | 0.93 | deleterious | D | 0.543598448 | None | None | N |
| L/Q | 0.9872 | likely_pathogenic | 0.9856 | pathogenic | -2.046 | Highly Destabilizing | 1.0 | D | 0.916 | deleterious | D | 0.543851938 | None | None | N |
| L/R | 0.9823 | likely_pathogenic | 0.9808 | pathogenic | -1.879 | Destabilizing | 1.0 | D | 0.9 | deleterious | D | 0.543598448 | None | None | N |
| L/S | 0.9936 | likely_pathogenic | 0.9915 | pathogenic | -3.03 | Highly Destabilizing | 1.0 | D | 0.89 | deleterious | None | None | None | None | N |
| L/T | 0.9474 | likely_pathogenic | 0.9351 | pathogenic | -2.529 | Highly Destabilizing | 1.0 | D | 0.815 | deleterious | None | None | None | None | N |
| L/V | 0.2224 | likely_benign | 0.1916 | benign | -1.137 | Destabilizing | 0.999 | D | 0.543 | neutral | N | 0.516163641 | None | None | N |
| L/W | 0.963 | likely_pathogenic | 0.9408 | pathogenic | -1.87 | Destabilizing | 1.0 | D | 0.832 | deleterious | None | None | None | None | N |
| L/Y | 0.9777 | likely_pathogenic | 0.9674 | pathogenic | -1.559 | Destabilizing | 1.0 | D | 0.81 | deleterious | None | None | None | None | N |
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.