Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1861 | 5806;5807;5808 | chr2:178776283;178776282;178776281 | chr2:179641010;179641009;179641008 |
| N2AB | 1861 | 5806;5807;5808 | chr2:178776283;178776282;178776281 | chr2:179641010;179641009;179641008 |
| N2A | 1861 | 5806;5807;5808 | chr2:178776283;178776282;178776281 | chr2:179641010;179641009;179641008 |
| N2B | 1815 | 5668;5669;5670 | chr2:178776283;178776282;178776281 | chr2:179641010;179641009;179641008 |
| Novex-1 | 1815 | 5668;5669;5670 | chr2:178776283;178776282;178776281 | chr2:179641010;179641009;179641008 |
| Novex-2 | 1815 | 5668;5669;5670 | chr2:178776283;178776282;178776281 | chr2:179641010;179641009;179641008 |
| Novex-3 | 1861 | 5806;5807;5808 | chr2:178776283;178776282;178776281 | chr2:179641010;179641009;179641008 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/C | rs532733393  |
-0.926 | 1.0 | N | 0.761 | 0.698 | 0.84442553596 | gnomAD-2.1.1 | 6.01E-05 | None | None | None | None | I | None | 4.01E-05 | 1.69348E-04 | None | 9.65E-05 | 5.02E-05 | None | 0 | None | 7.98E-05 | 3.87E-05 | 1.38351E-04 |
| R/C | rs532733393 |
-0.926 | 1.0 | N | 0.761 | 0.698 | 0.84442553596 | gnomAD-3.1.2 | 3.94E-05 | None | None | None | None | I | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 4.1511E-04 | 0 |
| R/C | rs532733393 |
-0.926 | 1.0 | N | 0.761 | 0.698 | 0.84442553596 | 1000 genomes | 1.99681E-04 | None | None | None | None | I | None | 8E-04 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| R/C | rs532733393 |
-0.926 | 1.0 | N | 0.761 | 0.698 | 0.84442553596 | gnomAD-4.0.0 | 3.5935E-05 | None | None | None | None | I | None | 2.66581E-05 | 9.99767E-05 | None | 0 | 2.22836E-05 | None | 6.25254E-05 | 0 | 2.96613E-05 | 5.49016E-05 | 7.99949E-05 |
| R/H | rs140914855 |
-1.616 | 1.0 | N | 0.736 | 0.546 | None | gnomAD-2.1.1 | 8.49E-05 | None | None | None | None | I | None | 4.01E-05 | 5.65E-05 | None | 0 | 0 | None | 0 | None | 0 | 1.39476E-04 | 4.15053E-04 |
| R/H | rs140914855 |
-1.616 | 1.0 | N | 0.736 | 0.546 | None | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | I | None | 0 | 6.55E-05 | 0 | 2.88184E-04 | 1.9253E-04 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| R/H | rs140914855 |
-1.616 | 1.0 | N | 0.736 | 0.546 | None | gnomAD-4.0.0 | 7.99232E-05 | None | None | None | None | I | None | 1.19939E-04 | 9.997E-05 | None | 3.37815E-05 | 6.68419E-05 | None | 0 | 4.9505E-04 | 8.81366E-05 | 0 | 4.79985E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.9587 | likely_pathogenic | 0.9621 | pathogenic | -1.307 | Destabilizing | 0.999 | D | 0.63 | neutral | None | None | None | None | I |
| R/C | 0.7117 | likely_pathogenic | 0.7228 | pathogenic | -1.26 | Destabilizing | 1.0 | D | 0.761 | deleterious | N | 0.511506893 | None | None | I |
| R/D | 0.9925 | likely_pathogenic | 0.9931 | pathogenic | -0.639 | Destabilizing | 1.0 | D | 0.766 | deleterious | None | None | None | None | I |
| R/E | 0.9471 | likely_pathogenic | 0.9509 | pathogenic | -0.412 | Destabilizing | 0.999 | D | 0.613 | neutral | None | None | None | None | I |
| R/F | 0.9658 | likely_pathogenic | 0.9657 | pathogenic | -0.459 | Destabilizing | 1.0 | D | 0.759 | deleterious | None | None | None | None | I |
| R/G | 0.9545 | likely_pathogenic | 0.9565 | pathogenic | -1.707 | Destabilizing | 1.0 | D | 0.719 | prob.delet. | D | 0.556359018 | None | None | I |
| R/H | 0.4693 | ambiguous | 0.4669 | ambiguous | -1.633 | Destabilizing | 1.0 | D | 0.736 | prob.delet. | N | 0.50260898 | None | None | I |
| R/I | 0.8773 | likely_pathogenic | 0.8708 | pathogenic | -0.172 | Destabilizing | 1.0 | D | 0.768 | deleterious | None | None | None | None | I |
| R/K | 0.477 | ambiguous | 0.5015 | ambiguous | -0.981 | Destabilizing | 0.998 | D | 0.502 | neutral | None | None | None | None | I |
| R/L | 0.8379 | likely_pathogenic | 0.8332 | pathogenic | -0.172 | Destabilizing | 1.0 | D | 0.719 | prob.delet. | N | 0.510423236 | None | None | I |
| R/M | 0.9422 | likely_pathogenic | 0.9422 | pathogenic | -0.713 | Destabilizing | 1.0 | D | 0.786 | deleterious | None | None | None | None | I |
| R/N | 0.9837 | likely_pathogenic | 0.9845 | pathogenic | -1.051 | Destabilizing | 1.0 | D | 0.732 | prob.delet. | None | None | None | None | I |
| R/P | 0.9916 | likely_pathogenic | 0.9925 | pathogenic | -0.534 | Destabilizing | 1.0 | D | 0.755 | deleterious | N | 0.501007487 | None | None | I |
| R/Q | 0.4853 | ambiguous | 0.4905 | ambiguous | -0.901 | Destabilizing | 1.0 | D | 0.727 | prob.delet. | None | None | None | None | I |
| R/S | 0.9562 | likely_pathogenic | 0.9587 | pathogenic | -1.801 | Destabilizing | 1.0 | D | 0.77 | deleterious | N | 0.495595166 | None | None | I |
| R/T | 0.9222 | likely_pathogenic | 0.9277 | pathogenic | -1.343 | Destabilizing | 1.0 | D | 0.764 | deleterious | None | None | None | None | I |
| R/V | 0.9017 | likely_pathogenic | 0.9023 | pathogenic | -0.534 | Destabilizing | 1.0 | D | 0.766 | deleterious | None | None | None | None | I |
| R/W | 0.8027 | likely_pathogenic | 0.7896 | pathogenic | -0.016 | Destabilizing | 1.0 | D | 0.757 | deleterious | None | None | None | None | I |
| R/Y | 0.9219 | likely_pathogenic | 0.9223 | pathogenic | 0.13 | Stabilizing | 1.0 | D | 0.775 | deleterious | 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.