Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31592 | 94999;95000;95001 | chr2:178546654;178546653;178546652 | chr2:179411381;179411380;179411379 |
| N2AB | 29951 | 90076;90077;90078 | chr2:178546654;178546653;178546652 | chr2:179411381;179411380;179411379 |
| N2A | 29024 | 87295;87296;87297 | chr2:178546654;178546653;178546652 | chr2:179411381;179411380;179411379 |
| N2B | 22527 | 67804;67805;67806 | chr2:178546654;178546653;178546652 | chr2:179411381;179411380;179411379 |
| Novex-1 | 22652 | 68179;68180;68181 | chr2:178546654;178546653;178546652 | chr2:179411381;179411380;179411379 |
| Novex-2 | 22719 | 68380;68381;68382 | chr2:178546654;178546653;178546652 | chr2:179411381;179411380;179411379 |
| 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/I | rs370918800  |
-0.13 | 0.127 | N | 0.267 | 0.058 | None | gnomAD-2.1.1 | 3.58E-05 | None | None | None | None | I | None | 1.24018E-04 | 0 | None | 0 | 5.14E-05 | None | 0 | None | 0 | 4.7E-05 | 0 |
| V/I | rs370918800 |
-0.13 | 0.127 | N | 0.267 | 0.058 | None | gnomAD-3.1.2 | 5.91E-05 | None | None | None | None | I | None | 9.65E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 7.35E-05 | 0 | 0 |
| V/I | rs370918800 |
-0.13 | 0.127 | N | 0.267 | 0.058 | None | gnomAD-4.0.0 | 5.20593E-05 | None | None | None | None | I | None | 1.46874E-04 | 0 | None | 0 | 2.22906E-05 | None | 0 | 0 | 6.01851E-05 | 0 | 1.60128E-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 | 0.3138 | likely_benign | 0.2615 | benign | -0.849 | Destabilizing | 0.63 | D | 0.386 | neutral | N | 0.457441491 | None | None | I |
| V/C | 0.7683 | likely_pathogenic | 0.7342 | pathogenic | -0.773 | Destabilizing | 0.999 | D | 0.414 | neutral | None | None | None | None | I |
| V/D | 0.6981 | likely_pathogenic | 0.6683 | pathogenic | -0.269 | Destabilizing | 0.975 | D | 0.637 | neutral | None | None | None | None | I |
| V/E | 0.5983 | likely_pathogenic | 0.5692 | pathogenic | -0.359 | Destabilizing | 0.967 | D | 0.514 | neutral | N | 0.501963059 | None | None | I |
| V/F | 0.2301 | likely_benign | 0.2012 | benign | -0.954 | Destabilizing | 0.975 | D | 0.355 | neutral | None | None | None | None | I |
| V/G | 0.3855 | ambiguous | 0.3248 | benign | -1.029 | Destabilizing | 0.967 | D | 0.593 | neutral | N | 0.492539184 | None | None | I |
| V/H | 0.7573 | likely_pathogenic | 0.7243 | pathogenic | -0.548 | Destabilizing | 0.999 | D | 0.66 | neutral | None | None | None | None | I |
| V/I | 0.0796 | likely_benign | 0.0738 | benign | -0.507 | Destabilizing | 0.127 | N | 0.267 | neutral | N | 0.455150547 | None | None | I |
| V/K | 0.6916 | likely_pathogenic | 0.6696 | pathogenic | -0.52 | Destabilizing | 0.975 | D | 0.534 | neutral | None | None | None | None | I |
| V/L | 0.313 | likely_benign | 0.2677 | benign | -0.507 | Destabilizing | 0.598 | D | 0.375 | neutral | N | 0.438778372 | None | None | I |
| V/M | 0.2002 | likely_benign | 0.1658 | benign | -0.402 | Destabilizing | 0.975 | D | 0.368 | neutral | None | None | None | None | I |
| V/N | 0.3718 | ambiguous | 0.3255 | benign | -0.264 | Destabilizing | 0.975 | D | 0.623 | neutral | None | None | None | None | I |
| V/P | 0.9774 | likely_pathogenic | 0.9679 | pathogenic | -0.585 | Destabilizing | 0.987 | D | 0.519 | neutral | None | None | None | None | I |
| V/Q | 0.5418 | ambiguous | 0.5068 | ambiguous | -0.524 | Destabilizing | 0.987 | D | 0.534 | neutral | None | None | None | None | I |
| V/R | 0.6315 | likely_pathogenic | 0.6096 | pathogenic | -0.02 | Destabilizing | 0.987 | D | 0.625 | neutral | None | None | None | None | I |
| V/S | 0.3536 | ambiguous | 0.289 | benign | -0.756 | Destabilizing | 0.496 | N | 0.359 | neutral | None | None | None | None | I |
| V/T | 0.2928 | likely_benign | 0.2489 | benign | -0.741 | Destabilizing | 0.845 | D | 0.392 | neutral | None | None | None | None | I |
| V/W | 0.9177 | likely_pathogenic | 0.8971 | pathogenic | -0.996 | Destabilizing | 0.999 | D | 0.694 | prob.neutral | None | None | None | None | I |
| V/Y | 0.6764 | likely_pathogenic | 0.6284 | pathogenic | -0.691 | Destabilizing | 0.987 | D | 0.362 | neutral | None | None | None | None | I |
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.