Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17198 | 51817;51818;51819 | chr2:178609831;178609830;178609829 | chr2:179474558;179474557;179474556 |
| N2AB | 15557 | 46894;46895;46896 | chr2:178609831;178609830;178609829 | chr2:179474558;179474557;179474556 |
| N2A | 14630 | 44113;44114;44115 | chr2:178609831;178609830;178609829 | chr2:179474558;179474557;179474556 |
| N2B | 8133 | 24622;24623;24624 | chr2:178609831;178609830;178609829 | chr2:179474558;179474557;179474556 |
| Novex-1 | 8258 | 24997;24998;24999 | chr2:178609831;178609830;178609829 | chr2:179474558;179474557;179474556 |
| Novex-2 | 8325 | 25198;25199;25200 | chr2:178609831;178609830;178609829 | chr2:179474558;179474557;179474556 |
| 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/S | rs766535854  |
-1.164 | 0.999 | N | 0.592 | 0.31 | 0.256793551483 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 1.65618E-04 |
| N/S | rs766535854 |
-1.164 | 0.999 | N | 0.592 | 0.31 | 0.256793551483 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 0 | 1.31337E-04 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| N/S | rs766535854 |
-1.164 | 0.999 | N | 0.592 | 0.31 | 0.256793551483 | gnomAD-4.0.0 | 5.58023E-06 | None | None | None | None | N | None | 0 | 3.33667E-05 | None | 0 | 0 | None | 1.56206E-05 | 0 | 4.23994E-06 | 1.09832E-05 | 0 |
| N/T | None | None | 0.999 | N | 0.687 | 0.371 | 0.306053231325 | gnomAD-4.0.0 | 6.84471E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99802E-07 | 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 | 0.7492 | likely_pathogenic | 0.7923 | pathogenic | -0.96 | Destabilizing | 1.0 | D | 0.669 | neutral | None | None | None | None | N |
| N/C | 0.6134 | likely_pathogenic | 0.6155 | pathogenic | -0.08 | Destabilizing | 1.0 | D | 0.735 | prob.delet. | None | None | None | None | N |
| N/D | 0.7686 | likely_pathogenic | 0.849 | pathogenic | -0.876 | Destabilizing | 0.999 | D | 0.631 | neutral | N | 0.521887253 | None | None | N |
| N/E | 0.952 | likely_pathogenic | 0.9685 | pathogenic | -0.687 | Destabilizing | 0.999 | D | 0.703 | prob.neutral | None | None | None | None | N |
| N/F | 0.9812 | likely_pathogenic | 0.9845 | pathogenic | -0.5 | Destabilizing | 1.0 | D | 0.771 | deleterious | None | None | None | None | N |
| N/G | 0.7007 | likely_pathogenic | 0.7603 | pathogenic | -1.37 | Destabilizing | 0.999 | D | 0.578 | neutral | None | None | None | None | N |
| N/H | 0.7015 | likely_pathogenic | 0.7835 | pathogenic | -0.924 | Destabilizing | 1.0 | D | 0.762 | deleterious | N | 0.504707002 | None | None | N |
| N/I | 0.8325 | likely_pathogenic | 0.8499 | pathogenic | 0.125 | Stabilizing | 1.0 | D | 0.763 | deleterious | N | 0.498626392 | None | None | N |
| N/K | 0.9745 | likely_pathogenic | 0.985 | pathogenic | -0.203 | Destabilizing | 1.0 | D | 0.724 | prob.delet. | N | 0.52063646 | None | None | N |
| N/L | 0.831 | likely_pathogenic | 0.8467 | pathogenic | 0.125 | Stabilizing | 1.0 | D | 0.751 | deleterious | None | None | None | None | N |
| N/M | 0.8726 | likely_pathogenic | 0.8822 | pathogenic | 0.432 | Stabilizing | 1.0 | D | 0.731 | prob.delet. | None | None | None | None | N |
| N/P | 0.9252 | likely_pathogenic | 0.9332 | pathogenic | -0.207 | Destabilizing | 1.0 | D | 0.753 | deleterious | None | None | None | None | N |
| N/Q | 0.9251 | likely_pathogenic | 0.9413 | pathogenic | -0.748 | Destabilizing | 1.0 | D | 0.77 | deleterious | None | None | None | None | N |
| N/R | 0.9557 | likely_pathogenic | 0.9662 | pathogenic | -0.399 | Destabilizing | 1.0 | D | 0.75 | deleterious | None | None | None | None | N |
| N/S | 0.1591 | likely_benign | 0.2011 | benign | -1.077 | Destabilizing | 0.999 | D | 0.592 | neutral | N | 0.484598302 | None | None | N |
| N/T | 0.3349 | likely_benign | 0.3685 | ambiguous | -0.676 | Destabilizing | 0.999 | D | 0.687 | prob.neutral | N | 0.483539509 | None | None | N |
| N/V | 0.7152 | likely_pathogenic | 0.7133 | pathogenic | -0.207 | Destabilizing | 1.0 | D | 0.76 | deleterious | None | None | None | None | N |
| N/W | 0.9935 | likely_pathogenic | 0.9945 | pathogenic | -0.292 | Destabilizing | 1.0 | D | 0.721 | prob.delet. | None | None | None | None | N |
| N/Y | 0.9052 | likely_pathogenic | 0.9316 | pathogenic | -0.019 | Destabilizing | 1.0 | D | 0.751 | deleterious | D | 0.52327412 | 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.