Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 34172 | 102739;102740;102741 | chr2:178534101;178534100;178534099 | chr2:179398828;179398827;179398826 |
| N2AB | 32531 | 97816;97817;97818 | chr2:178534101;178534100;178534099 | chr2:179398828;179398827;179398826 |
| N2A | 31604 | 95035;95036;95037 | chr2:178534101;178534100;178534099 | chr2:179398828;179398827;179398826 |
| N2B | 25107 | 75544;75545;75546 | chr2:178534101;178534100;178534099 | chr2:179398828;179398827;179398826 |
| Novex-1 | 25232 | 75919;75920;75921 | chr2:178534101;178534100;178534099 | chr2:179398828;179398827;179398826 |
| Novex-2 | 25299 | 76120;76121;76122 | chr2:178534101;178534100;178534099 | chr2:179398828;179398827;179398826 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/I | None | None | 0.959 | N | 0.526 | 0.22 | 0.412980791724 | gnomAD-4.0.0 | 1.59097E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.8577E-06 | 0 | 0 |
| F/L | None | None | 0.826 | N | 0.482 | 0.202 | 0.168933306366 | gnomAD-4.0.0 | 1.59102E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.77269E-05 | None | 0 | 0 | 0 | 0 | 0 |
| F/S | rs757435628  |
None | 0.959 | N | 0.563 | 0.231 | 0.377451072189 | gnomAD-4.0.0 | 2.73665E-06 | None | None | None | None | N | None | 2.98757E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99421E-07 | 1.15934E-05 | 1.65645E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/A | 0.7569 | likely_pathogenic | 0.7935 | pathogenic | -2.193 | Highly Destabilizing | 0.863 | D | 0.525 | neutral | None | None | None | None | N |
| F/C | 0.4874 | ambiguous | 0.5896 | pathogenic | -1.212 | Destabilizing | 0.077 | N | 0.444 | neutral | N | 0.450263936 | None | None | N |
| F/D | 0.9525 | likely_pathogenic | 0.9628 | pathogenic | -1.0 | Destabilizing | 0.991 | D | 0.667 | neutral | None | None | None | None | N |
| F/E | 0.9483 | likely_pathogenic | 0.9571 | pathogenic | -0.852 | Destabilizing | 0.939 | D | 0.636 | neutral | None | None | None | None | N |
| F/G | 0.9287 | likely_pathogenic | 0.9382 | pathogenic | -2.583 | Highly Destabilizing | 0.969 | D | 0.607 | neutral | None | None | None | None | N |
| F/H | 0.6204 | likely_pathogenic | 0.6742 | pathogenic | -0.877 | Destabilizing | 0.02 | N | 0.267 | neutral | None | None | None | None | N |
| F/I | 0.5871 | likely_pathogenic | 0.65 | pathogenic | -0.991 | Destabilizing | 0.959 | D | 0.526 | neutral | N | 0.457208551 | None | None | N |
| F/K | 0.8376 | likely_pathogenic | 0.8562 | pathogenic | -1.18 | Destabilizing | 0.991 | D | 0.668 | neutral | None | None | None | None | N |
| F/L | 0.919 | likely_pathogenic | 0.9264 | pathogenic | -0.991 | Destabilizing | 0.826 | D | 0.482 | neutral | N | 0.466942756 | None | None | N |
| F/M | 0.7322 | likely_pathogenic | 0.7438 | pathogenic | -0.787 | Destabilizing | 0.997 | D | 0.565 | neutral | None | None | None | None | N |
| F/N | 0.836 | likely_pathogenic | 0.8661 | pathogenic | -1.333 | Destabilizing | 0.982 | D | 0.665 | neutral | None | None | None | None | N |
| F/P | 0.9989 | likely_pathogenic | 0.999 | pathogenic | -1.39 | Destabilizing | 0.997 | D | 0.676 | prob.neutral | None | None | None | None | N |
| F/Q | 0.8383 | likely_pathogenic | 0.8562 | pathogenic | -1.323 | Destabilizing | 0.991 | D | 0.672 | neutral | None | None | None | None | N |
| F/R | 0.7064 | likely_pathogenic | 0.7476 | pathogenic | -0.685 | Destabilizing | 0.991 | D | 0.669 | neutral | None | None | None | None | N |
| F/S | 0.6973 | likely_pathogenic | 0.7558 | pathogenic | -2.197 | Highly Destabilizing | 0.959 | D | 0.563 | neutral | N | 0.476141029 | None | None | N |
| F/T | 0.8014 | likely_pathogenic | 0.8295 | pathogenic | -1.949 | Destabilizing | 0.969 | D | 0.577 | neutral | None | None | None | None | N |
| F/V | 0.5131 | ambiguous | 0.573 | pathogenic | -1.39 | Destabilizing | 0.92 | D | 0.531 | neutral | N | 0.486664667 | None | None | N |
| F/W | 0.6332 | likely_pathogenic | 0.6673 | pathogenic | -0.009 | Destabilizing | 0.999 | D | 0.553 | neutral | None | None | None | None | N |
| F/Y | 0.1494 | likely_benign | 0.1802 | benign | -0.289 | Destabilizing | 0.92 | D | 0.528 | neutral | N | 0.449570503 | 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.