Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2320 | 7183;7184;7185 | chr2:178774306;178774305;178774304 | chr2:179639033;179639032;179639031 |
| N2AB | 2320 | 7183;7184;7185 | chr2:178774306;178774305;178774304 | chr2:179639033;179639032;179639031 |
| N2A | 2320 | 7183;7184;7185 | chr2:178774306;178774305;178774304 | chr2:179639033;179639032;179639031 |
| N2B | 2274 | 7045;7046;7047 | chr2:178774306;178774305;178774304 | chr2:179639033;179639032;179639031 |
| Novex-1 | 2274 | 7045;7046;7047 | chr2:178774306;178774305;178774304 | chr2:179639033;179639032;179639031 |
| Novex-2 | 2274 | 7045;7046;7047 | chr2:178774306;178774305;178774304 | chr2:179639033;179639032;179639031 |
| Novex-3 | 2320 | 7183;7184;7185 | chr2:178774306;178774305;178774304 | chr2:179639033;179639032;179639031 |
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 | rs776478343  |
-0.649 | 1.0 | N | 0.737 | 0.529 | None | gnomAD-2.1.1 | 2.79E-05 | None | None | None | None | N | None | 0 | 2.89E-05 | None | 0 | 0 | None | 1.30659E-04 | None | 0 | 1.77E-05 | 0 |
| R/C | rs776478343 |
-0.649 | 1.0 | N | 0.737 | 0.529 | None | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | N | None | 7.24E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| R/C | rs776478343 |
-0.649 | 1.0 | N | 0.737 | 0.529 | None | gnomAD-4.0.0 | 3.09808E-05 | None | None | None | None | N | None | 1.33543E-04 | 3.33433E-05 | None | 0 | 2.22757E-05 | None | 0 | 0 | 1.35597E-05 | 2.08599E-04 | 3.20092E-05 |
| R/G | None | None | 1.0 | N | 0.705 | 0.57 | 0.726536768148 | gnomAD-4.0.0 | 6.84089E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99329E-07 | 0 | 0 |
| R/H | rs374615369 |
-1.285 | 1.0 | N | 0.72 | 0.568 | None | gnomAD-2.1.1 | 7.44E-05 | None | None | None | None | N | None | 1.20173E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.39825E-04 | 0 |
| R/H | rs374615369 |
-1.285 | 1.0 | N | 0.72 | 0.568 | None | gnomAD-3.1.2 | 7.89E-05 | None | None | None | None | N | None | 9.66E-05 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 1.0289E-04 | 0 | 0 |
| R/H | rs374615369 |
-1.285 | 1.0 | N | 0.72 | 0.568 | None | gnomAD-4.0.0 | 8.54974E-05 | None | None | None | None | N | None | 1.06644E-04 | 1.66628E-05 | None | 0 | 0 | None | 0 | 3.29924E-04 | 1.05935E-04 | 0 | 3.19959E-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 | 0.7357 | likely_pathogenic | 0.7738 | pathogenic | -1.004 | Destabilizing | 0.999 | D | 0.655 | neutral | None | None | None | None | N |
| R/C | 0.2522 | likely_benign | 0.2999 | benign | -0.999 | Destabilizing | 1.0 | D | 0.737 | prob.delet. | N | 0.505032843 | None | None | N |
| R/D | 0.9095 | likely_pathogenic | 0.9231 | pathogenic | -0.289 | Destabilizing | 1.0 | D | 0.765 | deleterious | None | None | None | None | N |
| R/E | 0.6148 | likely_pathogenic | 0.6576 | pathogenic | -0.177 | Destabilizing | 0.999 | D | 0.653 | neutral | None | None | None | None | N |
| R/F | 0.6193 | likely_pathogenic | 0.6509 | pathogenic | -0.961 | Destabilizing | 1.0 | D | 0.739 | prob.delet. | None | None | None | None | N |
| R/G | 0.6304 | likely_pathogenic | 0.6689 | pathogenic | -1.3 | Destabilizing | 1.0 | D | 0.705 | prob.neutral | N | 0.512818854 | None | None | N |
| R/H | 0.1323 | likely_benign | 0.1366 | benign | -1.542 | Destabilizing | 1.0 | D | 0.72 | prob.delet. | N | 0.512818854 | None | None | N |
| R/I | 0.3126 | likely_benign | 0.3415 | ambiguous | -0.212 | Destabilizing | 1.0 | D | 0.773 | deleterious | None | None | None | None | N |
| R/K | 0.1379 | likely_benign | 0.1423 | benign | -1.1 | Destabilizing | 0.998 | D | 0.49 | neutral | None | None | None | None | N |
| R/L | 0.3853 | ambiguous | 0.4083 | ambiguous | -0.212 | Destabilizing | 1.0 | D | 0.705 | prob.neutral | N | 0.50341418 | None | None | N |
| R/M | 0.4216 | ambiguous | 0.4572 | ambiguous | -0.424 | Destabilizing | 1.0 | D | 0.723 | prob.delet. | None | None | None | None | N |
| R/N | 0.7631 | likely_pathogenic | 0.7906 | pathogenic | -0.516 | Destabilizing | 1.0 | D | 0.733 | prob.delet. | None | None | None | None | N |
| R/P | 0.9697 | likely_pathogenic | 0.9733 | pathogenic | -0.456 | Destabilizing | 1.0 | D | 0.749 | deleterious | N | 0.509395126 | None | None | N |
| R/Q | 0.1415 | likely_benign | 0.1497 | benign | -0.742 | Destabilizing | 1.0 | D | 0.741 | deleterious | None | None | None | None | N |
| R/S | 0.764 | likely_pathogenic | 0.7916 | pathogenic | -1.318 | Destabilizing | 1.0 | D | 0.747 | deleterious | N | 0.505400675 | None | None | N |
| R/T | 0.5118 | ambiguous | 0.5518 | ambiguous | -1.03 | Destabilizing | 1.0 | D | 0.735 | prob.delet. | None | None | None | None | N |
| R/V | 0.4612 | ambiguous | 0.4939 | ambiguous | -0.456 | Destabilizing | 1.0 | D | 0.773 | deleterious | None | None | None | None | N |
| R/W | 0.2744 | likely_benign | 0.2946 | benign | -0.593 | Destabilizing | 1.0 | D | 0.732 | prob.delet. | None | None | None | None | N |
| R/Y | 0.4748 | ambiguous | 0.5076 | ambiguous | -0.291 | Destabilizing | 1.0 | D | 0.76 | 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.