Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32963 | 99112;99113;99114 | chr2:178539048;178539047;178539046 | chr2:179403775;179403774;179403773 |
| N2AB | 31322 | 94189;94190;94191 | chr2:178539048;178539047;178539046 | chr2:179403775;179403774;179403773 |
| N2A | 30395 | 91408;91409;91410 | chr2:178539048;178539047;178539046 | chr2:179403775;179403774;179403773 |
| N2B | 23898 | 71917;71918;71919 | chr2:178539048;178539047;178539046 | chr2:179403775;179403774;179403773 |
| Novex-1 | 24023 | 72292;72293;72294 | chr2:178539048;178539047;178539046 | chr2:179403775;179403774;179403773 |
| Novex-2 | 24090 | 72493;72494;72495 | chr2:178539048;178539047;178539046 | chr2:179403775;179403774;179403773 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | rs762929989  |
-0.966 | 0.948 | N | 0.358 | 0.241 | 0.605642446472 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.88E-06 | 0 |
| V/A | rs762929989 |
-0.966 | 0.948 | N | 0.358 | 0.241 | 0.605642446472 | gnomAD-4.0.0 | 1.32035E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.44375E-05 | 0 | 0 |
| V/I | rs745608832 |
None | 0.198 | N | 0.163 | 0.187 | 0.352910780287 | gnomAD-4.0.0 | 1.36845E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99505E-07 | 0 | 1.65678E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.5115 | ambiguous | 0.5363 | ambiguous | -0.909 | Destabilizing | 0.948 | D | 0.358 | neutral | N | 0.460990723 | None | None | N |
| V/C | 0.8902 | likely_pathogenic | 0.8853 | pathogenic | -0.738 | Destabilizing | 1.0 | D | 0.558 | neutral | None | None | None | None | N |
| V/D | 0.8157 | likely_pathogenic | 0.8168 | pathogenic | -0.427 | Destabilizing | 0.999 | D | 0.735 | prob.delet. | N | 0.479115124 | None | None | N |
| V/E | 0.6887 | likely_pathogenic | 0.7036 | pathogenic | -0.484 | Destabilizing | 0.999 | D | 0.663 | neutral | None | None | None | None | N |
| V/F | 0.3579 | ambiguous | 0.3726 | ambiguous | -0.835 | Destabilizing | 0.997 | D | 0.545 | neutral | N | 0.478269762 | None | None | N |
| V/G | 0.5908 | likely_pathogenic | 0.6039 | pathogenic | -1.136 | Destabilizing | 0.999 | D | 0.721 | prob.delet. | N | 0.470052111 | None | None | N |
| V/H | 0.8351 | likely_pathogenic | 0.8491 | pathogenic | -0.55 | Destabilizing | 1.0 | D | 0.719 | prob.delet. | None | None | None | None | N |
| V/I | 0.0989 | likely_benign | 0.0993 | benign | -0.427 | Destabilizing | 0.198 | N | 0.163 | neutral | N | 0.410236616 | None | None | N |
| V/K | 0.7264 | likely_pathogenic | 0.7348 | pathogenic | -0.687 | Destabilizing | 0.999 | D | 0.67 | neutral | None | None | None | None | N |
| V/L | 0.2915 | likely_benign | 0.3013 | benign | -0.427 | Destabilizing | 0.9 | D | 0.333 | neutral | N | 0.455256829 | None | None | N |
| V/M | 0.2972 | likely_benign | 0.3096 | benign | -0.441 | Destabilizing | 0.998 | D | 0.484 | neutral | None | None | None | None | N |
| V/N | 0.6496 | likely_pathogenic | 0.6689 | pathogenic | -0.428 | Destabilizing | 0.999 | D | 0.733 | prob.delet. | None | None | None | None | N |
| V/P | 0.8693 | likely_pathogenic | 0.8963 | pathogenic | -0.551 | Destabilizing | 0.999 | D | 0.662 | neutral | None | None | None | None | N |
| V/Q | 0.6276 | likely_pathogenic | 0.6437 | pathogenic | -0.621 | Destabilizing | 0.999 | D | 0.665 | neutral | None | None | None | None | N |
| V/R | 0.677 | likely_pathogenic | 0.6861 | pathogenic | -0.16 | Destabilizing | 0.999 | D | 0.726 | prob.delet. | None | None | None | None | N |
| V/S | 0.5241 | ambiguous | 0.5467 | ambiguous | -0.912 | Destabilizing | 0.999 | D | 0.599 | neutral | None | None | None | None | N |
| V/T | 0.4561 | ambiguous | 0.469 | ambiguous | -0.853 | Destabilizing | 0.992 | D | 0.383 | neutral | None | None | None | None | N |
| V/W | 0.9483 | likely_pathogenic | 0.9525 | pathogenic | -0.922 | Destabilizing | 1.0 | D | 0.731 | prob.delet. | None | None | None | None | N |
| V/Y | 0.7993 | likely_pathogenic | 0.8121 | pathogenic | -0.635 | Destabilizing | 0.999 | D | 0.548 | 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.