Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29965 | 90118;90119;90120 | chr2:178553007;178553006;178553005 | chr2:179417734;179417733;179417732 |
| N2AB | 28324 | 85195;85196;85197 | chr2:178553007;178553006;178553005 | chr2:179417734;179417733;179417732 |
| N2A | 27397 | 82414;82415;82416 | chr2:178553007;178553006;178553005 | chr2:179417734;179417733;179417732 |
| N2B | 20900 | 62923;62924;62925 | chr2:178553007;178553006;178553005 | chr2:179417734;179417733;179417732 |
| Novex-1 | 21025 | 63298;63299;63300 | chr2:178553007;178553006;178553005 | chr2:179417734;179417733;179417732 |
| Novex-2 | 21092 | 63499;63500;63501 | chr2:178553007;178553006;178553005 | chr2:179417734;179417733;179417732 |
| 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/K | None | None | 0.984 | D | 0.797 | 0.584 | 0.874136450708 | gnomAD-4.0.0 | 1.59642E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43291E-05 | 0 |
| I/T | rs1409848812  |
None | 0.896 | N | 0.649 | 0.483 | 0.748136256137 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/T | rs1409848812 |
None | 0.896 | N | 0.649 | 0.483 | 0.748136256137 | gnomAD-4.0.0 | 6.57065E-06 | None | None | None | None | I | None | 0 | 6.54879E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | rs370135800 |
-1.596 | 0.004 | N | 0.14 | 0.079 | None | gnomAD-2.1.1 | 1.22E-05 | None | None | None | None | I | None | 6.46E-05 | 0 | None | 0 | 1.11995E-04 | None | 0 | None | 0 | 0 | 0 |
| I/V | rs370135800 |
-1.596 | 0.004 | N | 0.14 | 0.079 | None | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | I | None | 9.65E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | rs370135800 |
-1.596 | 0.004 | N | 0.14 | 0.079 | None | gnomAD-4.0.0 | 4.34328E-06 | None | None | None | None | I | None | 6.67183E-05 | 0 | None | 0 | 2.23085E-05 | None | 0 | 0 | 0 | 0 | 1.60164E-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 | 0.9344 | likely_pathogenic | 0.9236 | pathogenic | -2.418 | Highly Destabilizing | 0.702 | D | 0.585 | neutral | None | None | None | None | I |
| I/C | 0.9612 | likely_pathogenic | 0.9546 | pathogenic | -1.405 | Destabilizing | 0.999 | D | 0.709 | prob.delet. | None | None | None | None | I |
| I/D | 0.9968 | likely_pathogenic | 0.9966 | pathogenic | -2.583 | Highly Destabilizing | 0.996 | D | 0.805 | deleterious | None | None | None | None | I |
| I/E | 0.9914 | likely_pathogenic | 0.9907 | pathogenic | -2.469 | Highly Destabilizing | 0.988 | D | 0.8 | deleterious | None | None | None | None | I |
| I/F | 0.8933 | likely_pathogenic | 0.8687 | pathogenic | -1.621 | Destabilizing | 0.976 | D | 0.653 | neutral | None | None | None | None | I |
| I/G | 0.9905 | likely_pathogenic | 0.9884 | pathogenic | -2.858 | Highly Destabilizing | 0.988 | D | 0.809 | deleterious | None | None | None | None | I |
| I/H | 0.9919 | likely_pathogenic | 0.9908 | pathogenic | -2.244 | Highly Destabilizing | 0.999 | D | 0.786 | deleterious | None | None | None | None | I |
| I/K | 0.9807 | likely_pathogenic | 0.9793 | pathogenic | -1.888 | Destabilizing | 0.984 | D | 0.797 | deleterious | D | 0.539112813 | None | None | I |
| I/L | 0.3616 | ambiguous | 0.326 | benign | -1.195 | Destabilizing | 0.437 | N | 0.32 | neutral | N | 0.486175492 | None | None | I |
| I/M | 0.5062 | ambiguous | 0.4586 | ambiguous | -0.811 | Destabilizing | 0.984 | D | 0.66 | neutral | D | 0.53151549 | None | None | I |
| I/N | 0.9446 | likely_pathogenic | 0.9391 | pathogenic | -1.915 | Destabilizing | 0.996 | D | 0.817 | deleterious | None | None | None | None | I |
| I/P | 0.9529 | likely_pathogenic | 0.9609 | pathogenic | -1.579 | Destabilizing | 0.996 | D | 0.812 | deleterious | None | None | None | None | I |
| I/Q | 0.9846 | likely_pathogenic | 0.9831 | pathogenic | -1.97 | Destabilizing | 0.996 | D | 0.819 | deleterious | None | None | None | None | I |
| I/R | 0.9751 | likely_pathogenic | 0.9721 | pathogenic | -1.327 | Destabilizing | 0.984 | D | 0.819 | deleterious | D | 0.550633703 | None | None | I |
| I/S | 0.9589 | likely_pathogenic | 0.9546 | pathogenic | -2.519 | Highly Destabilizing | 0.988 | D | 0.776 | deleterious | None | None | None | None | I |
| I/T | 0.9112 | likely_pathogenic | 0.9018 | pathogenic | -2.288 | Highly Destabilizing | 0.896 | D | 0.649 | neutral | N | 0.52024809 | None | None | I |
| I/V | 0.0706 | likely_benign | 0.0685 | benign | -1.579 | Destabilizing | 0.004 | N | 0.14 | neutral | N | 0.455993122 | None | None | I |
| I/W | 0.9976 | likely_pathogenic | 0.997 | pathogenic | -1.948 | Destabilizing | 0.999 | D | 0.793 | deleterious | None | None | None | None | I |
| I/Y | 0.9856 | likely_pathogenic | 0.9816 | pathogenic | -1.702 | Destabilizing | 0.988 | D | 0.727 | prob.delet. | 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.