Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1319 | 4180;4181;4182 | chr2:178779237;178779236;178779235 | chr2:179643964;179643963;179643962 |
| N2AB | 1319 | 4180;4181;4182 | chr2:178779237;178779236;178779235 | chr2:179643964;179643963;179643962 |
| N2A | 1319 | 4180;4181;4182 | chr2:178779237;178779236;178779235 | chr2:179643964;179643963;179643962 |
| N2B | 1273 | 4042;4043;4044 | chr2:178779237;178779236;178779235 | chr2:179643964;179643963;179643962 |
| Novex-1 | 1273 | 4042;4043;4044 | chr2:178779237;178779236;178779235 | chr2:179643964;179643963;179643962 |
| Novex-2 | 1273 | 4042;4043;4044 | chr2:178779237;178779236;178779235 | chr2:179643964;179643963;179643962 |
| Novex-3 | 1319 | 4180;4181;4182 | chr2:178779237;178779236;178779235 | chr2:179643964;179643963;179643962 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/I | rs376633286  |
-0.205 | 0.239 | N | 0.551 | 0.057 | None | gnomAD-2.1.1 | 1.6E-05 | None | None | None | None | I | None | 2.55689E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| L/I | rs376633286 |
-0.205 | 0.239 | N | 0.551 | 0.057 | None | gnomAD-3.1.2 | 3.94E-05 | None | None | None | None | I | None | 1.20697E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| L/I | rs376633286 |
-0.205 | 0.239 | N | 0.551 | 0.057 | None | 1000 genomes | 5.99042E-04 | None | None | None | None | I | None | 2.3E-03 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| L/I | rs376633286 |
-0.205 | 0.239 | N | 0.551 | 0.057 | None | gnomAD-4.0.0 | 8.96689E-06 | None | None | None | None | I | None | 8.44167E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 2.3923E-06 | 0 | 2.84042E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.437 | ambiguous | 0.459 | ambiguous | -1.526 | Destabilizing | 0.547 | D | 0.626 | neutral | None | None | None | None | I |
| L/C | 0.8696 | likely_pathogenic | 0.8659 | pathogenic | -0.766 | Destabilizing | 0.985 | D | 0.656 | neutral | None | None | None | None | I |
| L/D | 0.9195 | likely_pathogenic | 0.925 | pathogenic | -0.632 | Destabilizing | 0.894 | D | 0.738 | prob.delet. | None | None | None | None | I |
| L/E | 0.6842 | likely_pathogenic | 0.7033 | pathogenic | -0.618 | Destabilizing | 0.894 | D | 0.733 | prob.delet. | None | None | None | None | I |
| L/F | 0.3559 | ambiguous | 0.3547 | ambiguous | -1.029 | Destabilizing | 0.864 | D | 0.674 | neutral | N | 0.500697758 | None | None | I |
| L/G | 0.8788 | likely_pathogenic | 0.8831 | pathogenic | -1.862 | Destabilizing | 0.809 | D | 0.693 | prob.neutral | None | None | None | None | I |
| L/H | 0.5896 | likely_pathogenic | 0.5924 | pathogenic | -1.158 | Destabilizing | 0.985 | D | 0.721 | prob.delet. | None | None | None | None | I |
| L/I | 0.1509 | likely_benign | 0.1529 | benign | -0.676 | Destabilizing | 0.239 | N | 0.551 | neutral | N | 0.430965665 | None | None | I |
| L/K | 0.4896 | ambiguous | 0.5008 | ambiguous | -0.935 | Destabilizing | 0.809 | D | 0.711 | prob.delet. | None | None | None | None | I |
| L/M | 0.1923 | likely_benign | 0.2008 | benign | -0.496 | Destabilizing | 0.894 | D | 0.649 | neutral | None | None | None | None | I |
| L/N | 0.7184 | likely_pathogenic | 0.7248 | pathogenic | -0.681 | Destabilizing | 0.809 | D | 0.739 | prob.delet. | None | None | None | None | I |
| L/P | 0.4565 | ambiguous | 0.4787 | ambiguous | -0.927 | Destabilizing | 0.945 | D | 0.738 | prob.delet. | None | None | None | None | I |
| L/Q | 0.3693 | ambiguous | 0.387 | ambiguous | -0.803 | Destabilizing | 0.894 | D | 0.725 | prob.delet. | None | None | None | None | I |
| L/R | 0.4615 | ambiguous | 0.4679 | ambiguous | -0.462 | Destabilizing | 0.894 | D | 0.724 | prob.delet. | None | None | None | None | I |
| L/S | 0.5682 | likely_pathogenic | 0.5791 | pathogenic | -1.332 | Destabilizing | 0.053 | N | 0.415 | neutral | N | 0.444843382 | None | None | I |
| L/T | 0.4543 | ambiguous | 0.4693 | ambiguous | -1.195 | Destabilizing | 0.547 | D | 0.66 | neutral | None | None | None | None | I |
| L/V | 0.1461 | likely_benign | 0.1519 | benign | -0.927 | Destabilizing | 0.006 | N | 0.325 | neutral | N | 0.465151884 | None | None | I |
| L/W | 0.7045 | likely_pathogenic | 0.6981 | pathogenic | -1.122 | Destabilizing | 0.995 | D | 0.718 | prob.delet. | None | None | None | None | I |
| L/Y | 0.6769 | likely_pathogenic | 0.6724 | pathogenic | -0.889 | Destabilizing | 0.945 | D | 0.675 | prob.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.