Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 13734 | 41425;41426;41427 | chr2:178636527;178636526;178636525 | chr2:179501254;179501253;179501252 |
| N2AB | 12093 | 36502;36503;36504 | chr2:178636527;178636526;178636525 | chr2:179501254;179501253;179501252 |
| N2A | 11166 | 33721;33722;33723 | chr2:178636527;178636526;178636525 | chr2:179501254;179501253;179501252 |
| N2B | 4669 | 14230;14231;14232 | chr2:178636527;178636526;178636525 | chr2:179501254;179501253;179501252 |
| Novex-1 | 4794 | 14605;14606;14607 | chr2:178636527;178636526;178636525 | chr2:179501254;179501253;179501252 |
| Novex-2 | 4861 | 14806;14807;14808 | chr2:178636527;178636526;178636525 | chr2:179501254;179501253;179501252 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/L | None | None | 0.999 | N | 0.582 | 0.489 | 0.522717468363 | gnomAD-4.0.0 | 1.5919E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.77716E-05 | None | 0 | 0 | 0 | 0 | 0 |
| F/Y | rs764467205  |
-0.452 | 0.999 | N | 0.579 | 0.325 | 0.683432127188 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.59E-05 | None | 0 | None | 0 | 0 | 0 |
| F/Y | rs764467205 |
-0.452 | 0.999 | N | 0.579 | 0.325 | 0.683432127188 | gnomAD-4.0.0 | 1.5919E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.77716E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/A | 0.9855 | likely_pathogenic | 0.9905 | pathogenic | -2.539 | Highly Destabilizing | 1.0 | D | 0.765 | deleterious | None | None | None | None | N |
| F/C | 0.9508 | likely_pathogenic | 0.9571 | pathogenic | -1.397 | Destabilizing | 1.0 | D | 0.846 | deleterious | D | 0.694405423 | None | None | N |
| F/D | 0.9974 | likely_pathogenic | 0.998 | pathogenic | -2.158 | Highly Destabilizing | 1.0 | D | 0.851 | deleterious | None | None | None | None | N |
| F/E | 0.9958 | likely_pathogenic | 0.9967 | pathogenic | -2.005 | Highly Destabilizing | 1.0 | D | 0.844 | deleterious | None | None | None | None | N |
| F/G | 0.9948 | likely_pathogenic | 0.9966 | pathogenic | -2.94 | Highly Destabilizing | 1.0 | D | 0.842 | deleterious | None | None | None | None | N |
| F/H | 0.9669 | likely_pathogenic | 0.9739 | pathogenic | -1.247 | Destabilizing | 1.0 | D | 0.831 | deleterious | None | None | None | None | N |
| F/I | 0.7218 | likely_pathogenic | 0.7417 | pathogenic | -1.272 | Destabilizing | 1.0 | D | 0.765 | deleterious | N | 0.484889987 | None | None | N |
| F/K | 0.9958 | likely_pathogenic | 0.9957 | pathogenic | -1.675 | Destabilizing | 1.0 | D | 0.85 | deleterious | None | None | None | None | N |
| F/L | 0.9795 | likely_pathogenic | 0.9839 | pathogenic | -1.272 | Destabilizing | 0.999 | D | 0.582 | neutral | N | 0.501457605 | None | None | N |
| F/M | 0.8773 | likely_pathogenic | 0.8797 | pathogenic | -0.881 | Destabilizing | 1.0 | D | 0.797 | deleterious | None | None | None | None | N |
| F/N | 0.9817 | likely_pathogenic | 0.9861 | pathogenic | -1.936 | Destabilizing | 1.0 | D | 0.854 | deleterious | None | None | None | None | N |
| F/P | 0.9993 | likely_pathogenic | 0.9996 | pathogenic | -1.698 | Destabilizing | 1.0 | D | 0.855 | deleterious | None | None | None | None | N |
| F/Q | 0.9893 | likely_pathogenic | 0.991 | pathogenic | -1.959 | Destabilizing | 1.0 | D | 0.858 | deleterious | None | None | None | None | N |
| F/R | 0.9902 | likely_pathogenic | 0.9906 | pathogenic | -1.083 | Destabilizing | 1.0 | D | 0.853 | deleterious | None | None | None | None | N |
| F/S | 0.9798 | likely_pathogenic | 0.9874 | pathogenic | -2.666 | Highly Destabilizing | 1.0 | D | 0.827 | deleterious | D | 0.573257311 | None | None | N |
| F/T | 0.9796 | likely_pathogenic | 0.9849 | pathogenic | -2.409 | Highly Destabilizing | 1.0 | D | 0.831 | deleterious | None | None | None | None | N |
| F/V | 0.7801 | likely_pathogenic | 0.8247 | pathogenic | -1.698 | Destabilizing | 1.0 | D | 0.771 | deleterious | N | 0.491389827 | None | None | N |
| F/W | 0.8713 | likely_pathogenic | 0.9074 | pathogenic | -0.367 | Destabilizing | 1.0 | D | 0.775 | deleterious | None | None | None | None | N |
| F/Y | 0.3727 | ambiguous | 0.4524 | ambiguous | -0.668 | Destabilizing | 0.999 | D | 0.579 | neutral | N | 0.512203247 | 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.