Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32382 | 97369;97370;97371 | chr2:178542710;178542709;178542708 | chr2:179407437;179407436;179407435 |
| N2AB | 30741 | 92446;92447;92448 | chr2:178542710;178542709;178542708 | chr2:179407437;179407436;179407435 |
| N2A | 29814 | 89665;89666;89667 | chr2:178542710;178542709;178542708 | chr2:179407437;179407436;179407435 |
| N2B | 23317 | 70174;70175;70176 | chr2:178542710;178542709;178542708 | chr2:179407437;179407436;179407435 |
| Novex-1 | 23442 | 70549;70550;70551 | chr2:178542710;178542709;178542708 | chr2:179407437;179407436;179407435 |
| Novex-2 | 23509 | 70750;70751;70752 | chr2:178542710;178542709;178542708 | chr2:179407437;179407436;179407435 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/M | rs748057827  |
0.457 | 1.0 | N | 0.679 | 0.62 | 0.482357354261 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| K/M | rs748057827 |
0.457 | 1.0 | N | 0.679 | 0.62 | 0.482357354261 | gnomAD-4.0.0 | 1.59129E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43291E-05 | 0 |
| K/N | rs781006271 |
0.09 | 1.0 | D | 0.773 | 0.328 | 0.268211541103 | gnomAD-2.1.1 | 8.04E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 6.54E-05 | None | 0 | 0 | 0 |
| K/N | rs781006271 |
0.09 | 1.0 | D | 0.773 | 0.328 | 0.268211541103 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.07125E-04 | 0 |
| K/N | rs781006271 |
0.09 | 1.0 | D | 0.773 | 0.328 | 0.268211541103 | gnomAD-4.0.0 | 6.81677E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.20784E-04 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/A | 0.5827 | likely_pathogenic | 0.5344 | ambiguous | -0.253 | Destabilizing | 0.999 | D | 0.743 | deleterious | None | None | None | None | I |
| K/C | 0.6945 | likely_pathogenic | 0.6535 | pathogenic | -0.315 | Destabilizing | 1.0 | D | 0.741 | deleterious | None | None | None | None | I |
| K/D | 0.8375 | likely_pathogenic | 0.8179 | pathogenic | -0.017 | Destabilizing | 1.0 | D | 0.763 | deleterious | None | None | None | None | I |
| K/E | 0.3378 | likely_benign | 0.3205 | benign | 0.002 | Stabilizing | 0.999 | D | 0.734 | prob.delet. | N | 0.473317807 | None | None | I |
| K/F | 0.9057 | likely_pathogenic | 0.8868 | pathogenic | -0.446 | Destabilizing | 1.0 | D | 0.725 | prob.delet. | None | None | None | None | I |
| K/G | 0.6991 | likely_pathogenic | 0.6529 | pathogenic | -0.497 | Destabilizing | 1.0 | D | 0.729 | prob.delet. | None | None | None | None | I |
| K/H | 0.3328 | likely_benign | 0.3087 | benign | -0.957 | Destabilizing | 1.0 | D | 0.682 | prob.neutral | None | None | None | None | I |
| K/I | 0.603 | likely_pathogenic | 0.5788 | pathogenic | 0.325 | Stabilizing | 1.0 | D | 0.749 | deleterious | None | None | None | None | I |
| K/L | 0.6068 | likely_pathogenic | 0.5609 | ambiguous | 0.325 | Stabilizing | 1.0 | D | 0.729 | prob.delet. | None | None | None | None | I |
| K/M | 0.418 | ambiguous | 0.3739 | ambiguous | 0.387 | Stabilizing | 1.0 | D | 0.679 | prob.neutral | N | 0.497065996 | None | None | I |
| K/N | 0.6425 | likely_pathogenic | 0.6129 | pathogenic | 0.069 | Stabilizing | 1.0 | D | 0.773 | deleterious | D | 0.526941648 | None | None | I |
| K/P | 0.9722 | likely_pathogenic | 0.9671 | pathogenic | 0.162 | Stabilizing | 1.0 | D | 0.753 | deleterious | None | None | None | None | I |
| K/Q | 0.1421 | likely_benign | 0.1328 | benign | -0.203 | Destabilizing | 1.0 | D | 0.769 | deleterious | N | 0.498408253 | None | None | I |
| K/R | 0.0782 | likely_benign | 0.0746 | benign | -0.17 | Destabilizing | 0.999 | D | 0.667 | neutral | N | 0.496965458 | None | None | I |
| K/S | 0.5732 | likely_pathogenic | 0.5395 | ambiguous | -0.532 | Destabilizing | 0.999 | D | 0.772 | deleterious | None | None | None | None | I |
| K/T | 0.2739 | likely_benign | 0.2526 | benign | -0.349 | Destabilizing | 1.0 | D | 0.746 | deleterious | N | 0.448939438 | None | None | I |
| K/V | 0.5483 | ambiguous | 0.5178 | ambiguous | 0.162 | Stabilizing | 1.0 | D | 0.773 | deleterious | None | None | None | None | I |
| K/W | 0.8338 | likely_pathogenic | 0.7919 | pathogenic | -0.349 | Destabilizing | 1.0 | D | 0.737 | prob.delet. | None | None | None | None | I |
| K/Y | 0.8008 | likely_pathogenic | 0.7707 | pathogenic | 0.008 | Stabilizing | 1.0 | D | 0.737 | 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.