Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15179 | 45760;45761;45762 | chr2:178621183;178621182;178621181 | chr2:179485910;179485909;179485908 |
| N2AB | 13538 | 40837;40838;40839 | chr2:178621183;178621182;178621181 | chr2:179485910;179485909;179485908 |
| N2A | 12611 | 38056;38057;38058 | chr2:178621183;178621182;178621181 | chr2:179485910;179485909;179485908 |
| N2B | 6114 | 18565;18566;18567 | chr2:178621183;178621182;178621181 | chr2:179485910;179485909;179485908 |
| Novex-1 | 6239 | 18940;18941;18942 | chr2:178621183;178621182;178621181 | chr2:179485910;179485909;179485908 |
| Novex-2 | 6306 | 19141;19142;19143 | chr2:178621183;178621182;178621181 | chr2:179485910;179485909;179485908 |
| 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/E | rs1559877046  |
None | 0.98 | N | 0.485 | 0.366 | 0.354610295913 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.92E-06 | 0 |
| K/E | rs1559877046 |
None | 0.98 | N | 0.485 | 0.366 | 0.354610295913 | 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 |
| K/E | rs1559877046 |
None | 0.98 | N | 0.485 | 0.366 | 0.354610295913 | gnomAD-4.0.0 | 9.3023E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.27198E-05 | 0 | 0 |
| K/N | rs762005432 |
-1.052 | 0.4 | N | 0.221 | 0.158 | 0.198526703765 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| K/N | rs762005432 |
-1.052 | 0.4 | N | 0.221 | 0.158 | 0.198526703765 | gnomAD-4.0.0 | 2.73863E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 4.64005E-05 | 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 | 0.7611 | likely_pathogenic | 0.6844 | pathogenic | -0.643 | Destabilizing | 0.985 | D | 0.497 | neutral | None | None | None | None | N |
| K/C | 0.9186 | likely_pathogenic | 0.8728 | pathogenic | -0.712 | Destabilizing | 1.0 | D | 0.679 | prob.neutral | None | None | None | None | N |
| K/D | 0.9043 | likely_pathogenic | 0.8675 | pathogenic | -0.405 | Destabilizing | 0.971 | D | 0.557 | neutral | None | None | None | None | N |
| K/E | 0.4615 | ambiguous | 0.4249 | ambiguous | -0.269 | Destabilizing | 0.98 | D | 0.485 | neutral | N | 0.505384125 | None | None | N |
| K/F | 0.9539 | likely_pathogenic | 0.9321 | pathogenic | -0.259 | Destabilizing | 0.999 | D | 0.686 | prob.neutral | None | None | None | None | N |
| K/G | 0.7971 | likely_pathogenic | 0.7354 | pathogenic | -1.044 | Destabilizing | 0.985 | D | 0.583 | neutral | None | None | None | None | N |
| K/H | 0.5135 | ambiguous | 0.4456 | ambiguous | -1.438 | Destabilizing | 0.999 | D | 0.613 | neutral | None | None | None | None | N |
| K/I | 0.7856 | likely_pathogenic | 0.7145 | pathogenic | 0.414 | Stabilizing | 0.994 | D | 0.695 | prob.neutral | D | 0.574037384 | None | None | N |
| K/L | 0.7008 | likely_pathogenic | 0.6267 | pathogenic | 0.414 | Stabilizing | 0.985 | D | 0.579 | neutral | None | None | None | None | N |
| K/M | 0.5787 | likely_pathogenic | 0.4981 | ambiguous | 0.318 | Stabilizing | 1.0 | D | 0.607 | neutral | None | None | None | None | N |
| K/N | 0.6787 | likely_pathogenic | 0.6159 | pathogenic | -0.727 | Destabilizing | 0.4 | N | 0.221 | neutral | N | 0.512583404 | None | None | N |
| K/P | 0.9516 | likely_pathogenic | 0.9295 | pathogenic | 0.092 | Stabilizing | 0.999 | D | 0.631 | neutral | None | None | None | None | N |
| K/Q | 0.2741 | likely_benign | 0.2486 | benign | -0.749 | Destabilizing | 0.997 | D | 0.56 | neutral | N | 0.507816148 | None | None | N |
| K/R | 0.0999 | likely_benign | 0.095 | benign | -0.81 | Destabilizing | 0.99 | D | 0.491 | neutral | N | 0.503651326 | None | None | N |
| K/S | 0.7659 | likely_pathogenic | 0.7017 | pathogenic | -1.365 | Destabilizing | 0.971 | D | 0.449 | neutral | None | None | None | None | N |
| K/T | 0.4618 | ambiguous | 0.3763 | ambiguous | -1.009 | Destabilizing | 0.4 | N | 0.274 | neutral | N | 0.504414832 | None | None | N |
| K/V | 0.7659 | likely_pathogenic | 0.6804 | pathogenic | 0.092 | Stabilizing | 0.996 | D | 0.593 | neutral | None | None | None | None | N |
| K/W | 0.9205 | likely_pathogenic | 0.8863 | pathogenic | -0.163 | Destabilizing | 1.0 | D | 0.67 | neutral | None | None | None | None | N |
| K/Y | 0.8781 | likely_pathogenic | 0.8379 | pathogenic | 0.147 | Stabilizing | 0.999 | D | 0.667 | neutral | None | None | 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.