Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16624 | 50095;50096;50097 | chr2:178612851;178612850;178612849 | chr2:179477578;179477577;179477576 |
| N2AB | 14983 | 45172;45173;45174 | chr2:178612851;178612850;178612849 | chr2:179477578;179477577;179477576 |
| N2A | 14056 | 42391;42392;42393 | chr2:178612851;178612850;178612849 | chr2:179477578;179477577;179477576 |
| N2B | 7559 | 22900;22901;22902 | chr2:178612851;178612850;178612849 | chr2:179477578;179477577;179477576 |
| Novex-1 | 7684 | 23275;23276;23277 | chr2:178612851;178612850;178612849 | chr2:179477578;179477577;179477576 |
| Novex-2 | 7751 | 23476;23477;23478 | chr2:178612851;178612850;178612849 | chr2:179477578;179477577;179477576 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/Q | rs367566671  |
-0.991 | 1.0 | D | 0.776 | 0.507 | None | gnomAD-2.1.1 | 1.64992E-04 | None | None | None | None | N | None | 8.28089E-04 | 0 | None | 0 | 0 | None | 8.50563E-04 | None | 0 | 0 | 0 |
| R/Q | rs367566671 |
-0.991 | 1.0 | D | 0.776 | 0.507 | None | gnomAD-3.1.2 | 1.44815E-04 | None | None | None | None | N | None | 4.10509E-04 | 6.56E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 8.285E-04 | 0 |
| R/Q | rs367566671 |
-0.991 | 1.0 | D | 0.776 | 0.507 | None | 1000 genomes | 5.99042E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 3.1E-03 | None |
| R/Q | rs367566671 |
-0.991 | 1.0 | D | 0.776 | 0.507 | None | gnomAD-4.0.0 | 7.62793E-05 | None | None | None | None | N | None | 6.53839E-04 | 1.66956E-05 | None | 0 | 0 | None | 0 | 0 | 5.08824E-06 | 6.70079E-04 | 9.61508E-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 | 0.9698 | likely_pathogenic | 0.9866 | pathogenic | -1.838 | Destabilizing | 0.999 | D | 0.602 | neutral | None | None | None | None | N |
| R/C | 0.6294 | likely_pathogenic | 0.7748 | pathogenic | -1.729 | Destabilizing | 1.0 | D | 0.797 | deleterious | None | None | None | None | N |
| R/D | 0.9981 | likely_pathogenic | 0.9992 | pathogenic | -0.973 | Destabilizing | 1.0 | D | 0.779 | deleterious | None | None | None | None | N |
| R/E | 0.9687 | likely_pathogenic | 0.9853 | pathogenic | -0.769 | Destabilizing | 0.999 | D | 0.665 | neutral | None | None | None | None | N |
| R/F | 0.9853 | likely_pathogenic | 0.9942 | pathogenic | -1.073 | Destabilizing | 1.0 | D | 0.837 | deleterious | None | None | None | None | N |
| R/G | 0.9718 | likely_pathogenic | 0.9887 | pathogenic | -2.146 | Highly Destabilizing | 1.0 | D | 0.708 | prob.delet. | D | 0.773346589 | None | None | N |
| R/H | 0.5848 | likely_pathogenic | 0.7482 | pathogenic | -2.163 | Highly Destabilizing | 1.0 | D | 0.813 | deleterious | None | None | None | None | N |
| R/I | 0.9318 | likely_pathogenic | 0.9739 | pathogenic | -0.946 | Destabilizing | 1.0 | D | 0.821 | deleterious | None | None | None | None | N |
| R/K | 0.6496 | likely_pathogenic | 0.7283 | pathogenic | -1.191 | Destabilizing | 0.998 | D | 0.64 | neutral | None | None | None | None | N |
| R/L | 0.8889 | likely_pathogenic | 0.9529 | pathogenic | -0.946 | Destabilizing | 1.0 | D | 0.708 | prob.delet. | D | 0.638994716 | None | None | N |
| R/M | 0.9538 | likely_pathogenic | 0.9833 | pathogenic | -1.504 | Destabilizing | 1.0 | D | 0.797 | deleterious | None | None | None | None | N |
| R/N | 0.9902 | likely_pathogenic | 0.9964 | pathogenic | -1.16 | Destabilizing | 1.0 | D | 0.771 | deleterious | None | None | None | None | N |
| R/P | 0.9989 | likely_pathogenic | 0.9995 | pathogenic | -1.233 | Destabilizing | 1.0 | D | 0.796 | deleterious | D | 0.774633957 | None | None | N |
| R/Q | 0.4551 | ambiguous | 0.6168 | pathogenic | -0.966 | Destabilizing | 1.0 | D | 0.776 | deleterious | D | 0.613851779 | None | None | N |
| R/S | 0.9818 | likely_pathogenic | 0.9931 | pathogenic | -1.93 | Destabilizing | 1.0 | D | 0.717 | prob.delet. | None | None | None | None | N |
| R/T | 0.9664 | likely_pathogenic | 0.9895 | pathogenic | -1.535 | Destabilizing | 1.0 | D | 0.717 | prob.delet. | None | None | None | None | N |
| R/V | 0.9394 | likely_pathogenic | 0.9746 | pathogenic | -1.233 | Destabilizing | 1.0 | D | 0.791 | deleterious | None | None | None | None | N |
| R/W | 0.8548 | likely_pathogenic | 0.934 | pathogenic | -0.73 | Destabilizing | 1.0 | D | 0.776 | deleterious | None | None | None | None | N |
| R/Y | 0.9674 | likely_pathogenic | 0.9856 | pathogenic | -0.556 | Destabilizing | 1.0 | D | 0.828 | 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.