Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17228 | 51907;51908;51909 | chr2:178609741;178609740;178609739 | chr2:179474468;179474467;179474466 |
| N2AB | 15587 | 46984;46985;46986 | chr2:178609741;178609740;178609739 | chr2:179474468;179474467;179474466 |
| N2A | 14660 | 44203;44204;44205 | chr2:178609741;178609740;178609739 | chr2:179474468;179474467;179474466 |
| N2B | 8163 | 24712;24713;24714 | chr2:178609741;178609740;178609739 | chr2:179474468;179474467;179474466 |
| Novex-1 | 8288 | 25087;25088;25089 | chr2:178609741;178609740;178609739 | chr2:179474468;179474467;179474466 |
| Novex-2 | 8355 | 25288;25289;25290 | chr2:178609741;178609740;178609739 | chr2:179474468;179474467;179474466 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/T | rs369150143  |
-0.331 | 1.0 | N | 0.783 | 0.351 | None | gnomAD-2.1.1 | 1.32616E-04 | None | None | None | None | I | None | 4.14E-05 | 2.54914E-04 | None | 0 | 0 | None | 3.28E-05 | None | 8.05E-05 | 1.88389E-04 | 0 |
| A/T | rs369150143 |
-0.331 | 1.0 | N | 0.783 | 0.351 | None | gnomAD-3.1.2 | 3.95E-05 | None | None | None | None | I | None | 0 | 1.31251E-04 | 0 | 0 | 0 | None | 0 | 0 | 5.89E-05 | 0 | 0 |
| A/T | rs369150143 |
-0.331 | 1.0 | N | 0.783 | 0.351 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | I | None | 0 | 1.4E-03 | None | None | 0 | 0 | None | None | None | 0 | None |
| A/T | rs369150143 |
-0.331 | 1.0 | N | 0.783 | 0.351 | None | gnomAD-4.0.0 | 4.52814E-05 | None | None | None | None | I | None | 1.33461E-05 | 1.66795E-04 | None | 0 | 0 | None | 7.81861E-05 | 0 | 3.39345E-05 | 1.09992E-05 | 2.56394E-04 |
| A/V | rs370644359 |
-0.13 | 1.0 | N | 0.717 | 0.247 | None | gnomAD-2.1.1 | 7.88E-05 | None | None | None | None | I | None | 4.14E-05 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 8.04E-05 | 1.25537E-04 | 2.82008E-04 |
| A/V | rs370644359 |
-0.13 | 1.0 | N | 0.717 | 0.247 | None | gnomAD-3.1.2 | 1.58003E-04 | None | None | None | None | I | None | 2.42E-05 | 3.2817E-04 | 0 | 0 | 0 | None | 9.44E-05 | 0 | 2.50265E-04 | 0 | 0 |
| A/V | rs370644359 |
-0.13 | 1.0 | N | 0.717 | 0.247 | None | gnomAD-4.0.0 | 1.0918E-04 | None | None | None | None | I | None | 2.67394E-05 | 1.33467E-04 | None | 0 | 2.23394E-05 | None | 7.81983E-05 | 0 | 1.25558E-04 | 4.39889E-05 | 1.28226E-04 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.583 | likely_pathogenic | 0.5286 | ambiguous | -0.797 | Destabilizing | 1.0 | D | 0.815 | deleterious | None | None | None | None | I |
| A/D | 0.9179 | likely_pathogenic | 0.8624 | pathogenic | -0.443 | Destabilizing | 1.0 | D | 0.872 | deleterious | None | None | None | None | I |
| A/E | 0.8304 | likely_pathogenic | 0.7394 | pathogenic | -0.603 | Destabilizing | 1.0 | D | 0.809 | deleterious | N | 0.471609047 | None | None | I |
| A/F | 0.6121 | likely_pathogenic | 0.4815 | ambiguous | -0.856 | Destabilizing | 1.0 | D | 0.885 | deleterious | None | None | None | None | I |
| A/G | 0.3861 | ambiguous | 0.3361 | benign | -0.202 | Destabilizing | 1.0 | D | 0.618 | neutral | N | 0.473165983 | None | None | I |
| A/H | 0.8643 | likely_pathogenic | 0.8075 | pathogenic | -0.144 | Destabilizing | 1.0 | D | 0.856 | deleterious | None | None | None | None | I |
| A/I | 0.4618 | ambiguous | 0.3837 | ambiguous | -0.345 | Destabilizing | 1.0 | D | 0.806 | deleterious | None | None | None | None | I |
| A/K | 0.9489 | likely_pathogenic | 0.9182 | pathogenic | -0.465 | Destabilizing | 1.0 | D | 0.809 | deleterious | None | None | None | None | I |
| A/L | 0.4532 | ambiguous | 0.3926 | ambiguous | -0.345 | Destabilizing | 1.0 | D | 0.735 | prob.delet. | None | None | None | None | I |
| A/M | 0.4774 | ambiguous | 0.3941 | ambiguous | -0.425 | Destabilizing | 1.0 | D | 0.816 | deleterious | None | None | None | None | I |
| A/N | 0.728 | likely_pathogenic | 0.6698 | pathogenic | -0.196 | Destabilizing | 1.0 | D | 0.887 | deleterious | None | None | None | None | I |
| A/P | 0.963 | likely_pathogenic | 0.9514 | pathogenic | -0.263 | Destabilizing | 1.0 | D | 0.82 | deleterious | N | 0.511428863 | None | None | I |
| A/Q | 0.7763 | likely_pathogenic | 0.7139 | pathogenic | -0.491 | Destabilizing | 1.0 | D | 0.828 | deleterious | None | None | None | None | I |
| A/R | 0.8845 | likely_pathogenic | 0.8333 | pathogenic | 0.012 | Stabilizing | 1.0 | D | 0.826 | deleterious | None | None | None | None | I |
| A/S | 0.1734 | likely_benign | 0.1583 | benign | -0.393 | Destabilizing | 1.0 | D | 0.622 | neutral | N | 0.473383474 | None | None | I |
| A/T | 0.2805 | likely_benign | 0.2218 | benign | -0.476 | Destabilizing | 1.0 | D | 0.783 | deleterious | N | 0.485727284 | None | None | I |
| A/V | 0.2045 | likely_benign | 0.1628 | benign | -0.263 | Destabilizing | 1.0 | D | 0.717 | prob.delet. | N | 0.467071334 | None | None | I |
| A/W | 0.9467 | likely_pathogenic | 0.9123 | pathogenic | -0.952 | Destabilizing | 1.0 | D | 0.865 | deleterious | None | None | None | None | I |
| A/Y | 0.8305 | likely_pathogenic | 0.7544 | pathogenic | -0.615 | Destabilizing | 1.0 | D | 0.883 | deleterious | 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.