Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20677 | 62254;62255;62256 | chr2:178589696;178589695;178589694 | chr2:179454423;179454422;179454421 |
| N2AB | 19036 | 57331;57332;57333 | chr2:178589696;178589695;178589694 | chr2:179454423;179454422;179454421 |
| N2A | 18109 | 54550;54551;54552 | chr2:178589696;178589695;178589694 | chr2:179454423;179454422;179454421 |
| N2B | 11612 | 35059;35060;35061 | chr2:178589696;178589695;178589694 | chr2:179454423;179454422;179454421 |
| Novex-1 | 11737 | 35434;35435;35436 | chr2:178589696;178589695;178589694 | chr2:179454423;179454422;179454421 |
| Novex-2 | 11804 | 35635;35636;35637 | chr2:178589696;178589695;178589694 | chr2:179454423;179454422;179454421 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/N | None | None | 0.996 | N | 0.728 | 0.47 | 0.807339971026 | gnomAD-4.0.0 | 2.05293E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.69876E-06 | 0 | 0 |
| I/T | rs558670891  |
-2.805 | 0.92 | N | 0.572 | 0.307 | None | gnomAD-2.1.1 | 4.84E-05 | None | None | None | None | N | None | 6.46E-05 | 0 | None | 0 | 0 | None | 3.26861E-04 | None | 0 | 8.92E-06 | 0 |
| I/T | rs558670891 |
-2.805 | 0.92 | N | 0.572 | 0.307 | None | gnomAD-3.1.2 | 3.95E-05 | None | None | None | None | N | None | 9.65E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 4.14422E-04 | 0 |
| I/T | rs558670891 |
-2.805 | 0.92 | N | 0.572 | 0.307 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 1E-03 | None |
| I/T | rs558670891 |
-2.805 | 0.92 | N | 0.572 | 0.307 | None | gnomAD-4.0.0 | 3.59465E-05 | None | None | None | None | N | None | 6.66542E-05 | 1.66689E-05 | None | 0 | 0 | None | 0 | 0 | 2.37369E-05 | 2.30597E-04 | 4.80231E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.7672 | likely_pathogenic | 0.7308 | pathogenic | -2.242 | Highly Destabilizing | 0.079 | N | 0.294 | neutral | None | None | None | None | N |
| I/C | 0.9052 | likely_pathogenic | 0.8959 | pathogenic | -1.277 | Destabilizing | 0.999 | D | 0.624 | neutral | None | None | None | None | N |
| I/D | 0.9886 | likely_pathogenic | 0.983 | pathogenic | -2.196 | Highly Destabilizing | 0.991 | D | 0.726 | prob.delet. | None | None | None | None | N |
| I/E | 0.9608 | likely_pathogenic | 0.9452 | pathogenic | -2.073 | Highly Destabilizing | 0.991 | D | 0.721 | prob.delet. | None | None | None | None | N |
| I/F | 0.4796 | ambiguous | 0.4249 | ambiguous | -1.442 | Destabilizing | 0.988 | D | 0.583 | neutral | N | 0.510648752 | None | None | N |
| I/G | 0.9755 | likely_pathogenic | 0.9691 | pathogenic | -2.678 | Highly Destabilizing | 0.939 | D | 0.697 | prob.neutral | None | None | None | None | N |
| I/H | 0.9506 | likely_pathogenic | 0.9408 | pathogenic | -1.885 | Destabilizing | 0.999 | D | 0.709 | prob.delet. | None | None | None | None | N |
| I/K | 0.9273 | likely_pathogenic | 0.9001 | pathogenic | -1.714 | Destabilizing | 0.991 | D | 0.721 | prob.delet. | None | None | None | None | N |
| I/L | 0.2506 | likely_benign | 0.2522 | benign | -1.034 | Destabilizing | 0.509 | D | 0.424 | neutral | N | 0.437633861 | None | None | N |
| I/M | 0.2721 | likely_benign | 0.2631 | benign | -0.751 | Destabilizing | 0.988 | D | 0.569 | neutral | N | 0.478093962 | None | None | N |
| I/N | 0.9078 | likely_pathogenic | 0.8799 | pathogenic | -1.754 | Destabilizing | 0.996 | D | 0.728 | prob.delet. | N | 0.478854431 | None | None | N |
| I/P | 0.9129 | likely_pathogenic | 0.8914 | pathogenic | -1.413 | Destabilizing | 0.991 | D | 0.727 | prob.delet. | None | None | None | None | N |
| I/Q | 0.9366 | likely_pathogenic | 0.9214 | pathogenic | -1.795 | Destabilizing | 0.997 | D | 0.735 | prob.delet. | None | None | None | None | N |
| I/R | 0.9069 | likely_pathogenic | 0.8766 | pathogenic | -1.197 | Destabilizing | 0.991 | D | 0.729 | prob.delet. | None | None | None | None | N |
| I/S | 0.8512 | likely_pathogenic | 0.8159 | pathogenic | -2.374 | Highly Destabilizing | 0.852 | D | 0.623 | neutral | D | 0.524023481 | None | None | N |
| I/T | 0.5954 | likely_pathogenic | 0.5328 | ambiguous | -2.121 | Highly Destabilizing | 0.92 | D | 0.572 | neutral | N | 0.471599502 | None | None | N |
| I/V | 0.0919 | likely_benign | 0.0905 | benign | -1.413 | Destabilizing | 0.061 | N | 0.155 | neutral | N | 0.403902502 | None | None | N |
| I/W | 0.9548 | likely_pathogenic | 0.9485 | pathogenic | -1.673 | Destabilizing | 0.999 | D | 0.737 | prob.delet. | None | None | None | None | N |
| I/Y | 0.8713 | likely_pathogenic | 0.8506 | pathogenic | -1.419 | Destabilizing | 0.997 | D | 0.643 | 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.