Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19539 | 58840;58841;58842 | chr2:178593685;178593684;178593683 | chr2:179458412;179458411;179458410 |
| N2AB | 17898 | 53917;53918;53919 | chr2:178593685;178593684;178593683 | chr2:179458412;179458411;179458410 |
| N2A | 16971 | 51136;51137;51138 | chr2:178593685;178593684;178593683 | chr2:179458412;179458411;179458410 |
| N2B | 10474 | 31645;31646;31647 | chr2:178593685;178593684;178593683 | chr2:179458412;179458411;179458410 |
| Novex-1 | 10599 | 32020;32021;32022 | chr2:178593685;178593684;178593683 | chr2:179458412;179458411;179458410 |
| Novex-2 | 10666 | 32221;32222;32223 | chr2:178593685;178593684;178593683 | chr2:179458412;179458411;179458410 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| C/F | rs539868284  |
-1.027 | 1.0 | N | 0.853 | 0.424 | 0.746742446189 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.67E-05 | 0 |
| C/F | rs539868284 |
-1.027 | 1.0 | N | 0.853 | 0.424 | 0.746742446189 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| C/F | rs539868284 |
-1.027 | 1.0 | N | 0.853 | 0.424 | 0.746742446189 | gnomAD-4.0.0 | 6.81905E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.32535E-06 | 0 | 0 |
| C/R | rs753678261 |
-0.431 | 1.0 | N | 0.875 | 0.545 | 0.825775482533 | gnomAD-2.1.1 | 2.82E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 3.92773E-04 | None | 0 | None | 0 | 0 | 0 |
| C/R | rs753678261 |
-0.431 | 1.0 | N | 0.875 | 0.545 | 0.825775482533 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 5.82072E-04 | None | 0 | 0 | 0 | 0 | 0 |
| C/R | rs753678261 |
-0.431 | 1.0 | N | 0.875 | 0.545 | 0.825775482533 | gnomAD-4.0.0 | 1.05377E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 3.5775E-04 | None | 0 | 0 | 0 | 0 | 1.60149E-05 |
| C/S | rs753678261 |
-1.141 | 1.0 | N | 0.689 | 0.546 | 0.694136321851 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.91E-06 | 0 |
| C/S | rs753678261 |
-1.141 | 1.0 | N | 0.689 | 0.546 | 0.694136321851 | gnomAD-4.0.0 | 1.36875E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79915E-06 | 0 | 0 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| C/A | 0.6024 | likely_pathogenic | 0.6065 | pathogenic | -1.156 | Destabilizing | 0.998 | D | 0.574 | neutral | None | None | None | None | N |
| C/D | 0.9573 | likely_pathogenic | 0.9663 | pathogenic | 0.475 | Stabilizing | 1.0 | D | 0.845 | deleterious | None | None | None | None | N |
| C/E | 0.9523 | likely_pathogenic | 0.9619 | pathogenic | 0.575 | Stabilizing | 1.0 | D | 0.873 | deleterious | None | None | None | None | N |
| C/F | 0.2373 | likely_benign | 0.2697 | benign | -0.679 | Destabilizing | 1.0 | D | 0.853 | deleterious | N | 0.433476048 | None | None | N |
| C/G | 0.4789 | ambiguous | 0.5062 | ambiguous | -1.437 | Destabilizing | 1.0 | D | 0.789 | deleterious | N | 0.478521581 | None | None | N |
| C/H | 0.761 | likely_pathogenic | 0.8064 | pathogenic | -1.362 | Destabilizing | 1.0 | D | 0.872 | deleterious | None | None | None | None | N |
| C/I | 0.5808 | likely_pathogenic | 0.5848 | pathogenic | -0.457 | Destabilizing | 1.0 | D | 0.734 | prob.delet. | None | None | None | None | N |
| C/K | 0.9635 | likely_pathogenic | 0.9662 | pathogenic | -0.216 | Destabilizing | 1.0 | D | 0.837 | deleterious | None | None | None | None | N |
| C/L | 0.5339 | ambiguous | 0.5355 | ambiguous | -0.457 | Destabilizing | 0.999 | D | 0.509 | neutral | None | None | None | None | N |
| C/M | 0.6522 | likely_pathogenic | 0.6693 | pathogenic | 0.182 | Stabilizing | 1.0 | D | 0.805 | deleterious | None | None | None | None | N |
| C/N | 0.8303 | likely_pathogenic | 0.8707 | pathogenic | -0.362 | Destabilizing | 1.0 | D | 0.875 | deleterious | None | None | None | None | N |
| C/P | 0.9962 | likely_pathogenic | 0.9968 | pathogenic | -0.664 | Destabilizing | 1.0 | D | 0.873 | deleterious | None | None | None | None | N |
| C/Q | 0.8511 | likely_pathogenic | 0.8782 | pathogenic | -0.18 | Destabilizing | 1.0 | D | 0.872 | deleterious | None | None | None | None | N |
| C/R | 0.8281 | likely_pathogenic | 0.8342 | pathogenic | -0.21 | Destabilizing | 1.0 | D | 0.875 | deleterious | N | 0.486915372 | None | None | N |
| C/S | 0.549 | ambiguous | 0.586 | pathogenic | -0.88 | Destabilizing | 1.0 | D | 0.689 | prob.neutral | N | 0.482053527 | None | None | N |
| C/T | 0.6528 | likely_pathogenic | 0.6845 | pathogenic | -0.589 | Destabilizing | 1.0 | D | 0.679 | prob.neutral | None | None | None | None | N |
| C/V | 0.4936 | ambiguous | 0.4987 | ambiguous | -0.664 | Destabilizing | 0.999 | D | 0.602 | neutral | None | None | None | None | N |
| C/W | 0.6827 | likely_pathogenic | 0.7085 | pathogenic | -0.712 | Destabilizing | 1.0 | D | 0.843 | deleterious | N | 0.482307016 | None | None | N |
| C/Y | 0.3882 | ambiguous | 0.4493 | ambiguous | -0.619 | Destabilizing | 1.0 | D | 0.861 | deleterious | N | 0.459966429 | 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.