Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30233 | 90922;90923;90924 | chr2:178552203;178552202;178552201 | chr2:179416930;179416929;179416928 |
| N2AB | 28592 | 85999;86000;86001 | chr2:178552203;178552202;178552201 | chr2:179416930;179416929;179416928 |
| N2A | 27665 | 83218;83219;83220 | chr2:178552203;178552202;178552201 | chr2:179416930;179416929;179416928 |
| N2B | 21168 | 63727;63728;63729 | chr2:178552203;178552202;178552201 | chr2:179416930;179416929;179416928 |
| Novex-1 | 21293 | 64102;64103;64104 | chr2:178552203;178552202;178552201 | chr2:179416930;179416929;179416928 |
| Novex-2 | 21360 | 64303;64304;64305 | chr2:178552203;178552202;178552201 | chr2:179416930;179416929;179416928 |
| 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 | rs757438306  |
-0.523 | 0.275 | N | 0.337 | 0.078 | 0.110078149338 | gnomAD-2.1.1 | 3.58E-05 | None | None | None | None | N | None | 0 | 2.83E-05 | None | 0 | 2.05128E-04 | None | 0 | None | 4.01E-05 | 3.14E-05 | 0 |
| R/Q | rs757438306 |
-0.523 | 0.275 | N | 0.337 | 0.078 | 0.110078149338 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/Q | rs757438306 |
-0.523 | 0.275 | N | 0.337 | 0.078 | 0.110078149338 | gnomAD-4.0.0 | 1.54951E-05 | None | None | None | None | N | None | 2.67037E-05 | 3.33634E-05 | None | 0 | 1.11418E-04 | None | 3.12647E-05 | 0 | 9.32442E-06 | 0 | 4.80477E-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 | 0.4554 | ambiguous | 0.3333 | benign | -0.566 | Destabilizing | 0.59 | D | 0.564 | neutral | None | None | None | None | N |
| R/C | 0.1331 | likely_benign | 0.1112 | benign | -0.557 | Destabilizing | 0.996 | D | 0.661 | neutral | None | None | None | None | N |
| R/D | 0.7114 | likely_pathogenic | 0.6164 | pathogenic | 0.066 | Stabilizing | 0.742 | D | 0.616 | neutral | None | None | None | None | N |
| R/E | 0.41 | ambiguous | 0.3308 | benign | 0.176 | Stabilizing | 0.373 | N | 0.52 | neutral | None | None | None | None | N |
| R/F | 0.5171 | ambiguous | 0.4318 | ambiguous | -0.541 | Destabilizing | 0.953 | D | 0.629 | neutral | None | None | None | None | N |
| R/G | 0.4039 | ambiguous | 0.3106 | benign | -0.849 | Destabilizing | 0.846 | D | 0.595 | neutral | N | 0.475118221 | None | None | N |
| R/H | 0.0851 | likely_benign | 0.0755 | benign | -1.219 | Destabilizing | 0.02 | N | 0.345 | neutral | None | None | None | None | N |
| R/I | 0.2161 | likely_benign | 0.1643 | benign | 0.176 | Stabilizing | 0.953 | D | 0.645 | neutral | None | None | None | None | N |
| R/K | 0.1126 | likely_benign | 0.0993 | benign | -0.524 | Destabilizing | 0.009 | N | 0.203 | neutral | None | None | None | None | N |
| R/L | 0.2379 | likely_benign | 0.1764 | benign | 0.176 | Stabilizing | 0.846 | D | 0.597 | neutral | N | 0.47537171 | None | None | N |
| R/M | 0.3154 | likely_benign | 0.2424 | benign | -0.176 | Destabilizing | 0.987 | D | 0.593 | neutral | None | None | None | None | N |
| R/N | 0.5251 | ambiguous | 0.4259 | ambiguous | -0.056 | Destabilizing | 0.742 | D | 0.531 | neutral | None | None | None | None | N |
| R/P | 0.9429 | likely_pathogenic | 0.912 | pathogenic | -0.05 | Destabilizing | 0.975 | D | 0.641 | neutral | N | 0.485095401 | None | None | N |
| R/Q | 0.0979 | likely_benign | 0.0845 | benign | -0.226 | Destabilizing | 0.275 | N | 0.337 | neutral | N | 0.488542684 | None | None | N |
| R/S | 0.4837 | ambiguous | 0.3676 | ambiguous | -0.762 | Destabilizing | 0.59 | D | 0.544 | neutral | None | None | None | None | N |
| R/T | 0.2471 | likely_benign | 0.1746 | benign | -0.476 | Destabilizing | 0.742 | D | 0.587 | neutral | None | None | None | None | N |
| R/V | 0.291 | likely_benign | 0.2194 | benign | -0.05 | Destabilizing | 0.91 | D | 0.625 | neutral | None | None | None | None | N |
| R/W | 0.2258 | likely_benign | 0.1814 | benign | -0.291 | Destabilizing | 0.996 | D | 0.695 | prob.neutral | None | None | None | None | N |
| R/Y | 0.3311 | likely_benign | 0.2845 | benign | 0.042 | Stabilizing | 0.91 | D | 0.639 | neutral | 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.