Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1353 | 4282;4283;4284 | chr2:178779025;178779024;178779023 | chr2:179643752;179643751;179643750 |
| N2AB | 1353 | 4282;4283;4284 | chr2:178779025;178779024;178779023 | chr2:179643752;179643751;179643750 |
| N2A | 1353 | 4282;4283;4284 | chr2:178779025;178779024;178779023 | chr2:179643752;179643751;179643750 |
| N2B | 1307 | 4144;4145;4146 | chr2:178779025;178779024;178779023 | chr2:179643752;179643751;179643750 |
| Novex-1 | 1307 | 4144;4145;4146 | chr2:178779025;178779024;178779023 | chr2:179643752;179643751;179643750 |
| Novex-2 | 1307 | 4144;4145;4146 | chr2:178779025;178779024;178779023 | chr2:179643752;179643751;179643750 |
| Novex-3 | 1353 | 4282;4283;4284 | chr2:178779025;178779024;178779023 | chr2:179643752;179643751;179643750 |
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/L | rs36062108  |
-0.262 | 0.008 | N | 0.244 | 0.079 | 0.177238962908 | gnomAD-2.1.1 | 3.99E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.85E-06 | 0 |
| V/L | rs36062108 |
-0.262 | 0.008 | N | 0.244 | 0.079 | 0.177238962908 | gnomAD-3.1.2 | 6.62E-06 | None | None | None | None | I | None | 2.44E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/L | rs36062108 |
-0.262 | 0.008 | N | 0.244 | 0.079 | 0.177238962908 | gnomAD-4.0.0 | 2.7281E-05 | None | None | None | None | I | None | 2.68492E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 3.56049E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.32 | likely_benign | 0.3486 | ambiguous | -0.96 | Destabilizing | 0.517 | D | 0.457 | neutral | N | 0.365338544 | None | None | I |
| V/C | 0.8884 | likely_pathogenic | 0.8905 | pathogenic | -0.83 | Destabilizing | 0.996 | D | 0.57 | neutral | None | None | None | None | I |
| V/D | 0.7139 | likely_pathogenic | 0.7344 | pathogenic | -0.491 | Destabilizing | 0.901 | D | 0.681 | prob.neutral | N | 0.317374548 | None | None | I |
| V/E | 0.538 | ambiguous | 0.5641 | pathogenic | -0.546 | Destabilizing | 0.858 | D | 0.535 | neutral | None | None | None | None | I |
| V/F | 0.3115 | likely_benign | 0.333 | benign | -0.799 | Destabilizing | 0.901 | D | 0.52 | neutral | N | 0.426426392 | None | None | I |
| V/G | 0.5133 | ambiguous | 0.5507 | ambiguous | -1.196 | Destabilizing | 0.949 | D | 0.619 | neutral | N | 0.355557913 | None | None | I |
| V/H | 0.7756 | likely_pathogenic | 0.7934 | pathogenic | -0.633 | Destabilizing | 0.989 | D | 0.687 | prob.neutral | None | None | None | None | I |
| V/I | 0.1026 | likely_benign | 0.1071 | benign | -0.45 | Destabilizing | 0.008 | N | 0.329 | neutral | N | 0.442821883 | None | None | I |
| V/K | 0.6097 | likely_pathogenic | 0.6391 | pathogenic | -0.834 | Destabilizing | 0.858 | D | 0.546 | neutral | None | None | None | None | I |
| V/L | 0.3095 | likely_benign | 0.3455 | ambiguous | -0.45 | Destabilizing | 0.008 | N | 0.244 | neutral | N | 0.442646312 | None | None | I |
| V/M | 0.2165 | likely_benign | 0.2389 | benign | -0.445 | Destabilizing | 0.923 | D | 0.477 | neutral | None | None | None | None | I |
| V/N | 0.521 | ambiguous | 0.5398 | ambiguous | -0.602 | Destabilizing | 0.961 | D | 0.685 | prob.neutral | None | None | None | None | I |
| V/P | 0.9347 | likely_pathogenic | 0.938 | pathogenic | -0.583 | Destabilizing | 0.987 | D | 0.646 | neutral | None | None | None | None | I |
| V/Q | 0.5317 | ambiguous | 0.5562 | ambiguous | -0.797 | Destabilizing | 0.415 | N | 0.436 | neutral | None | None | None | None | I |
| V/R | 0.5136 | ambiguous | 0.5446 | ambiguous | -0.294 | Destabilizing | 0.923 | D | 0.687 | prob.neutral | None | None | None | None | I |
| V/S | 0.3923 | ambiguous | 0.4178 | ambiguous | -1.096 | Destabilizing | 0.923 | D | 0.547 | neutral | None | None | None | None | I |
| V/T | 0.2863 | likely_benign | 0.3096 | benign | -1.04 | Destabilizing | 0.775 | D | 0.457 | neutral | None | None | None | None | I |
| V/W | 0.9294 | likely_pathogenic | 0.9418 | pathogenic | -0.897 | Destabilizing | 0.996 | D | 0.739 | prob.delet. | None | None | None | None | I |
| V/Y | 0.7299 | likely_pathogenic | 0.7608 | pathogenic | -0.622 | Destabilizing | 0.961 | D | 0.52 | 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.