Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15866 | 47821;47822;47823 | chr2:178617489;178617488;178617487 | chr2:179482216;179482215;179482214 |
| N2AB | 14225 | 42898;42899;42900 | chr2:178617489;178617488;178617487 | chr2:179482216;179482215;179482214 |
| N2A | 13298 | 40117;40118;40119 | chr2:178617489;178617488;178617487 | chr2:179482216;179482215;179482214 |
| N2B | 6801 | 20626;20627;20628 | chr2:178617489;178617488;178617487 | chr2:179482216;179482215;179482214 |
| Novex-1 | 6926 | 21001;21002;21003 | chr2:178617489;178617488;178617487 | chr2:179482216;179482215;179482214 |
| Novex-2 | 6993 | 21202;21203;21204 | chr2:178617489;178617488;178617487 | chr2:179482216;179482215;179482214 |
| 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/P | rs756488211  |
-1.925 | 1.0 | N | 0.887 | 0.59 | 0.852106192891 | gnomAD-2.1.1 | 4.5E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 4.02E-05 | None | 0 | 0 | 0 |
| L/P | rs756488211 |
-1.925 | 1.0 | N | 0.887 | 0.59 | 0.852106192891 | gnomAD-4.0.0 | 1.65055E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.56182E-05 | 0 |
| L/V | rs1248132383 |
-1.525 | 0.999 | N | 0.699 | 0.317 | 0.504907739247 | gnomAD-2.1.1 | 4.5E-06 | None | None | None | None | N | None | 0 | 3.6E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| L/V | rs1248132383 |
-1.525 | 0.999 | N | 0.699 | 0.317 | 0.504907739247 | gnomAD-4.0.0 | 1.65108E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.91106E-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 | 0.7374 | likely_pathogenic | 0.7992 | pathogenic | -2.448 | Highly Destabilizing | 0.999 | D | 0.795 | deleterious | None | None | None | None | N |
| L/C | 0.7015 | likely_pathogenic | 0.7658 | pathogenic | -1.94 | Destabilizing | 1.0 | D | 0.793 | deleterious | None | None | None | None | N |
| L/D | 0.9893 | likely_pathogenic | 0.9927 | pathogenic | -2.746 | Highly Destabilizing | 1.0 | D | 0.887 | deleterious | None | None | None | None | N |
| L/E | 0.958 | likely_pathogenic | 0.9705 | pathogenic | -2.578 | Highly Destabilizing | 1.0 | D | 0.875 | deleterious | None | None | None | None | N |
| L/F | 0.3051 | likely_benign | 0.3407 | ambiguous | -1.51 | Destabilizing | 1.0 | D | 0.839 | deleterious | None | None | None | None | N |
| L/G | 0.9333 | likely_pathogenic | 0.9543 | pathogenic | -2.943 | Highly Destabilizing | 1.0 | D | 0.873 | deleterious | None | None | None | None | N |
| L/H | 0.8923 | likely_pathogenic | 0.9202 | pathogenic | -2.392 | Highly Destabilizing | 1.0 | D | 0.846 | deleterious | None | None | None | None | N |
| L/I | 0.1195 | likely_benign | 0.1435 | benign | -1.044 | Destabilizing | 0.999 | D | 0.696 | prob.neutral | D | 0.528698587 | None | None | N |
| L/K | 0.9129 | likely_pathogenic | 0.9405 | pathogenic | -1.829 | Destabilizing | 1.0 | D | 0.857 | deleterious | None | None | None | None | N |
| L/M | 0.2105 | likely_benign | 0.2426 | benign | -1.094 | Destabilizing | 1.0 | D | 0.807 | deleterious | None | None | None | None | N |
| L/N | 0.936 | likely_pathogenic | 0.9542 | pathogenic | -2.035 | Highly Destabilizing | 1.0 | D | 0.889 | deleterious | None | None | None | None | N |
| L/P | 0.6322 | likely_pathogenic | 0.7123 | pathogenic | -1.49 | Destabilizing | 1.0 | D | 0.887 | deleterious | N | 0.501238233 | None | None | N |
| L/Q | 0.8612 | likely_pathogenic | 0.8963 | pathogenic | -1.993 | Destabilizing | 1.0 | D | 0.876 | deleterious | D | 0.687962826 | None | None | N |
| L/R | 0.8752 | likely_pathogenic | 0.9063 | pathogenic | -1.491 | Destabilizing | 1.0 | D | 0.873 | deleterious | D | 0.746929239 | None | None | N |
| L/S | 0.9244 | likely_pathogenic | 0.952 | pathogenic | -2.712 | Highly Destabilizing | 1.0 | D | 0.853 | deleterious | None | None | None | None | N |
| L/T | 0.7251 | likely_pathogenic | 0.7867 | pathogenic | -2.407 | Highly Destabilizing | 1.0 | D | 0.849 | deleterious | None | None | None | None | N |
| L/V | 0.1359 | likely_benign | 0.158 | benign | -1.49 | Destabilizing | 0.999 | D | 0.699 | prob.neutral | N | 0.491838309 | None | None | N |
| L/W | 0.8084 | likely_pathogenic | 0.8422 | pathogenic | -1.843 | Destabilizing | 1.0 | D | 0.774 | deleterious | None | None | None | None | N |
| L/Y | 0.825 | likely_pathogenic | 0.8621 | pathogenic | -1.573 | Destabilizing | 1.0 | D | 0.839 | 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.