Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1518 | 4777;4778;4779 | chr2:178777513;178777512;178777511 | chr2:179642240;179642239;179642238 |
| N2AB | 1518 | 4777;4778;4779 | chr2:178777513;178777512;178777511 | chr2:179642240;179642239;179642238 |
| N2A | 1518 | 4777;4778;4779 | chr2:178777513;178777512;178777511 | chr2:179642240;179642239;179642238 |
| N2B | 1472 | 4639;4640;4641 | chr2:178777513;178777512;178777511 | chr2:179642240;179642239;179642238 |
| Novex-1 | 1472 | 4639;4640;4641 | chr2:178777513;178777512;178777511 | chr2:179642240;179642239;179642238 |
| Novex-2 | 1472 | 4639;4640;4641 | chr2:178777513;178777512;178777511 | chr2:179642240;179642239;179642238 |
| Novex-3 | 1518 | 4777;4778;4779 | chr2:178777513;178777512;178777511 | chr2:179642240;179642239;179642238 |
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 | rs752482916  |
-0.71 | 0.334 | N | 0.441 | 0.229 | None | gnomAD-4.0.0 | 1.2448E-04 | None | None | None | None | N | None | 0 | 4.59664E-05 | None | 9.54198E-05 | 3.06629E-04 | None | 8.38447E-04 | 2.41429E-04 | 4.86718E-05 | 0 | 3.03453E-05 |
| V/F | rs755962102 |
-0.85 | 0.638 | N | 0.647 | 0.29 | 0.809845328503 | gnomAD-2.1.1 | 3.99E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.84E-06 | 0 |
| V/F | rs755962102 |
-0.85 | 0.638 | N | 0.647 | 0.29 | 0.809845328503 | gnomAD-4.0.0 | 1.59128E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85722E-06 | 0 | 0 |
| V/I | None | -0.206 | 0.002 | N | 0.231 | 0.069 | 0.528260413467 | gnomAD-2.1.1 | 7.1E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.56E-05 | 0 |
| V/I | None | -0.206 | 0.002 | N | 0.231 | 0.069 | 0.528260413467 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 4.41E-05 | 0 | 0 |
| V/I | None | -0.206 | 0.002 | N | 0.231 | 0.069 | 0.528260413467 | gnomAD-4.0.0 | 6.40553E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.19609E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.6511 | likely_pathogenic | 0.6241 | pathogenic | -1.11 | Destabilizing | 0.334 | N | 0.441 | neutral | N | 0.491879087 | None | None | N |
| V/C | 0.945 | likely_pathogenic | 0.9379 | pathogenic | -0.873 | Destabilizing | 0.982 | D | 0.622 | neutral | None | None | None | None | N |
| V/D | 0.9446 | likely_pathogenic | 0.9243 | pathogenic | -0.657 | Destabilizing | 0.781 | D | 0.699 | prob.neutral | N | 0.471166709 | None | None | N |
| V/E | 0.8737 | likely_pathogenic | 0.8518 | pathogenic | -0.72 | Destabilizing | 0.826 | D | 0.634 | neutral | None | None | None | None | N |
| V/F | 0.5059 | ambiguous | 0.4374 | ambiguous | -1.056 | Destabilizing | 0.638 | D | 0.647 | neutral | N | 0.509489816 | None | None | N |
| V/G | 0.7702 | likely_pathogenic | 0.7433 | pathogenic | -1.342 | Destabilizing | 0.781 | D | 0.69 | prob.neutral | N | 0.509746559 | None | None | N |
| V/H | 0.9485 | likely_pathogenic | 0.9335 | pathogenic | -0.835 | Destabilizing | 0.982 | D | 0.658 | neutral | None | None | None | None | N |
| V/I | 0.1302 | likely_benign | 0.1083 | benign | -0.61 | Destabilizing | 0.002 | N | 0.231 | neutral | N | 0.489462684 | None | None | N |
| V/K | 0.9335 | likely_pathogenic | 0.9183 | pathogenic | -0.778 | Destabilizing | 0.826 | D | 0.637 | neutral | None | None | None | None | N |
| V/L | 0.5467 | ambiguous | 0.4618 | ambiguous | -0.61 | Destabilizing | 0.034 | N | 0.373 | neutral | N | 0.483697973 | None | None | N |
| V/M | 0.4607 | ambiguous | 0.4162 | ambiguous | -0.472 | Destabilizing | 0.7 | D | 0.629 | neutral | None | None | None | None | N |
| V/N | 0.8228 | likely_pathogenic | 0.7835 | pathogenic | -0.509 | Destabilizing | 0.935 | D | 0.691 | prob.neutral | None | None | None | None | N |
| V/P | 0.973 | likely_pathogenic | 0.9538 | pathogenic | -0.74 | Destabilizing | 0.935 | D | 0.654 | neutral | None | None | None | None | N |
| V/Q | 0.8404 | likely_pathogenic | 0.814 | pathogenic | -0.762 | Destabilizing | 0.935 | D | 0.643 | neutral | None | None | None | None | N |
| V/R | 0.8833 | likely_pathogenic | 0.8514 | pathogenic | -0.253 | Destabilizing | 0.826 | D | 0.689 | prob.neutral | None | None | None | None | N |
| V/S | 0.5747 | likely_pathogenic | 0.5742 | pathogenic | -1.027 | Destabilizing | 0.826 | D | 0.643 | neutral | None | None | None | None | N |
| V/T | 0.5825 | likely_pathogenic | 0.5712 | pathogenic | -0.985 | Destabilizing | 0.399 | N | 0.558 | neutral | None | None | None | None | N |
| V/W | 0.9866 | likely_pathogenic | 0.9799 | pathogenic | -1.123 | Destabilizing | 0.982 | D | 0.678 | prob.neutral | None | None | None | None | N |
| V/Y | 0.9209 | likely_pathogenic | 0.8975 | pathogenic | -0.831 | Destabilizing | 0.826 | D | 0.657 | 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.