Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19731 | 59416;59417;59418 | chr2:178592928;178592927;178592926 | chr2:179457655;179457654;179457653 |
| N2AB | 18090 | 54493;54494;54495 | chr2:178592928;178592927;178592926 | chr2:179457655;179457654;179457653 |
| N2A | 17163 | 51712;51713;51714 | chr2:178592928;178592927;178592926 | chr2:179457655;179457654;179457653 |
| N2B | 10666 | 32221;32222;32223 | chr2:178592928;178592927;178592926 | chr2:179457655;179457654;179457653 |
| Novex-1 | 10791 | 32596;32597;32598 | chr2:178592928;178592927;178592926 | chr2:179457655;179457654;179457653 |
| Novex-2 | 10858 | 32797;32798;32799 | chr2:178592928;178592927;178592926 | chr2:179457655;179457654;179457653 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/K | rs774146313  |
-0.438 | 1.0 | N | 0.749 | 0.429 | 0.158396225186 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 1.65673E-04 |
| N/K | rs774146313 |
-0.438 | 1.0 | N | 0.749 | 0.429 | 0.158396225186 | gnomAD-4.0.0 | 1.59168E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.0248E-05 |
| N/S | rs879073304 |
None | 0.999 | N | 0.653 | 0.228 | None | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| N/S | rs879073304 |
None | 0.999 | N | 0.653 | 0.228 | None | gnomAD-4.0.0 | 6.81795E-06 | None | None | None | None | N | None | 4.00727E-05 | 1.66783E-05 | None | 0 | 0 | None | 0 | 1.64474E-04 | 5.08642E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/A | 0.8083 | likely_pathogenic | 0.8167 | pathogenic | -0.789 | Destabilizing | 1.0 | D | 0.718 | prob.delet. | None | None | None | None | N |
| N/C | 0.6569 | likely_pathogenic | 0.7175 | pathogenic | -0.219 | Destabilizing | 1.0 | D | 0.797 | deleterious | None | None | None | None | N |
| N/D | 0.8214 | likely_pathogenic | 0.8015 | pathogenic | -1.715 | Destabilizing | 0.999 | D | 0.681 | prob.neutral | N | 0.470914712 | None | None | N |
| N/E | 0.9702 | likely_pathogenic | 0.9693 | pathogenic | -1.499 | Destabilizing | 0.999 | D | 0.729 | prob.delet. | None | None | None | None | N |
| N/F | 0.9763 | likely_pathogenic | 0.9818 | pathogenic | -0.341 | Destabilizing | 1.0 | D | 0.819 | deleterious | None | None | None | None | N |
| N/G | 0.7837 | likely_pathogenic | 0.7941 | pathogenic | -1.198 | Destabilizing | 0.999 | D | 0.644 | neutral | None | None | None | None | N |
| N/H | 0.7623 | likely_pathogenic | 0.7847 | pathogenic | -0.944 | Destabilizing | 1.0 | D | 0.768 | deleterious | N | 0.48255096 | None | None | N |
| N/I | 0.7894 | likely_pathogenic | 0.8205 | pathogenic | 0.292 | Stabilizing | 1.0 | D | 0.804 | deleterious | N | 0.475447389 | None | None | N |
| N/K | 0.9818 | likely_pathogenic | 0.9805 | pathogenic | -0.281 | Destabilizing | 1.0 | D | 0.749 | deleterious | N | 0.483992538 | None | None | N |
| N/L | 0.8098 | likely_pathogenic | 0.8212 | pathogenic | 0.292 | Stabilizing | 1.0 | D | 0.789 | deleterious | None | None | None | None | N |
| N/M | 0.8891 | likely_pathogenic | 0.9062 | pathogenic | 0.604 | Stabilizing | 1.0 | D | 0.788 | deleterious | None | None | None | None | N |
| N/P | 0.94 | likely_pathogenic | 0.9257 | pathogenic | -0.039 | Destabilizing | 1.0 | D | 0.791 | deleterious | None | None | None | None | N |
| N/Q | 0.9509 | likely_pathogenic | 0.9536 | pathogenic | -0.917 | Destabilizing | 1.0 | D | 0.773 | deleterious | None | None | None | None | N |
| N/R | 0.9692 | likely_pathogenic | 0.9666 | pathogenic | -0.58 | Destabilizing | 1.0 | D | 0.757 | deleterious | None | None | None | None | N |
| N/S | 0.2247 | likely_benign | 0.2065 | benign | -1.186 | Destabilizing | 0.999 | D | 0.653 | neutral | N | 0.46689856 | None | None | N |
| N/T | 0.4278 | ambiguous | 0.4566 | ambiguous | -0.782 | Destabilizing | 0.999 | D | 0.712 | prob.delet. | N | 0.466631843 | None | None | N |
| N/V | 0.7009 | likely_pathogenic | 0.7407 | pathogenic | -0.039 | Destabilizing | 1.0 | D | 0.803 | deleterious | None | None | None | None | N |
| N/W | 0.9924 | likely_pathogenic | 0.9937 | pathogenic | -0.318 | Destabilizing | 1.0 | D | 0.773 | deleterious | None | None | None | None | N |
| N/Y | 0.8915 | likely_pathogenic | 0.9041 | pathogenic | 0.05 | Stabilizing | 1.0 | D | 0.797 | deleterious | N | 0.47936141 | 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.