Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 4776 | 14551;14552;14553 | chr2:178738127;178738126;178738125 | chr2:179602854;179602853;179602852 |
| N2AB | 4459 | 13600;13601;13602 | chr2:178738127;178738126;178738125 | chr2:179602854;179602853;179602852 |
| N2A | 3532 | 10819;10820;10821 | chr2:178738127;178738126;178738125 | chr2:179602854;179602853;179602852 |
| N2B | 4413 | 13462;13463;13464 | chr2:178738127;178738126;178738125 | chr2:179602854;179602853;179602852 |
| Novex-1 | 4538 | 13837;13838;13839 | chr2:178738127;178738126;178738125 | chr2:179602854;179602853;179602852 |
| Novex-2 | 4605 | 14038;14039;14040 | chr2:178738127;178738126;178738125 | chr2:179602854;179602853;179602852 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/D | rs727505309  |
-1.175 | 0.999 | N | 0.599 | 0.562 | 0.302459207581 | 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 |
| N/D | rs727505309 |
-1.175 | 0.999 | N | 0.599 | 0.562 | 0.302459207581 | gnomAD-4.0.0 | 1.36847E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.31873E-05 | 0 |
| N/K | rs952268172 |
None | 1.0 | N | 0.74 | 0.439 | 0.191931220699 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| N/K | rs952268172 |
None | 1.0 | N | 0.74 | 0.439 | 0.191931220699 | gnomAD-4.0.0 | 6.5716E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.47007E-05 | 0 | 0 |
| N/S | rs369669941 |
-0.609 | 0.999 | N | 0.563 | 0.565 | None | gnomAD-2.1.1 | 3.18E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 6.48E-05 | 0 |
| N/S | rs369669941 |
-0.609 | 0.999 | N | 0.563 | 0.565 | None | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| N/S | rs369669941 |
-0.609 | 0.999 | N | 0.563 | 0.565 | None | gnomAD-4.0.0 | 9.91508E-06 | None | None | None | None | I | None | 2.66909E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 1.18667E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/A | 0.9691 | likely_pathogenic | 0.9835 | pathogenic | -1.024 | Destabilizing | 1.0 | D | 0.75 | deleterious | None | None | None | None | I |
| N/C | 0.9174 | likely_pathogenic | 0.9385 | pathogenic | -0.269 | Destabilizing | 1.0 | D | 0.687 | prob.neutral | None | None | None | None | I |
| N/D | 0.812 | likely_pathogenic | 0.9002 | pathogenic | -1.342 | Destabilizing | 0.999 | D | 0.599 | neutral | N | 0.470119228 | None | None | I |
| N/E | 0.9917 | likely_pathogenic | 0.9943 | pathogenic | -1.209 | Destabilizing | 0.999 | D | 0.719 | prob.delet. | None | None | None | None | I |
| N/F | 0.9971 | likely_pathogenic | 0.9983 | pathogenic | -0.812 | Destabilizing | 1.0 | D | 0.72 | prob.delet. | None | None | None | None | I |
| N/G | 0.9273 | likely_pathogenic | 0.9526 | pathogenic | -1.378 | Destabilizing | 0.999 | D | 0.541 | neutral | None | None | None | None | I |
| N/H | 0.9126 | likely_pathogenic | 0.9397 | pathogenic | -1.124 | Destabilizing | 1.0 | D | 0.755 | deleterious | N | 0.471572814 | None | None | I |
| N/I | 0.9811 | likely_pathogenic | 0.991 | pathogenic | -0.109 | Destabilizing | 1.0 | D | 0.691 | prob.neutral | N | 0.471958289 | None | None | I |
| N/K | 0.9922 | likely_pathogenic | 0.9945 | pathogenic | -0.331 | Destabilizing | 1.0 | D | 0.74 | deleterious | N | 0.47101129 | None | None | I |
| N/L | 0.9453 | likely_pathogenic | 0.9638 | pathogenic | -0.109 | Destabilizing | 1.0 | D | 0.708 | prob.delet. | None | None | None | None | I |
| N/M | 0.9758 | likely_pathogenic | 0.9853 | pathogenic | 0.389 | Stabilizing | 1.0 | D | 0.725 | prob.delet. | None | None | None | None | I |
| N/P | 0.9896 | likely_pathogenic | 0.991 | pathogenic | -0.385 | Destabilizing | 1.0 | D | 0.716 | prob.delet. | None | None | None | None | I |
| N/Q | 0.9912 | likely_pathogenic | 0.9941 | pathogenic | -1.084 | Destabilizing | 1.0 | D | 0.759 | deleterious | None | None | None | None | I |
| N/R | 0.9865 | likely_pathogenic | 0.9892 | pathogenic | -0.353 | Destabilizing | 1.0 | D | 0.775 | deleterious | None | None | None | None | I |
| N/S | 0.372 | ambiguous | 0.5021 | ambiguous | -1.093 | Destabilizing | 0.999 | D | 0.563 | neutral | N | 0.375948407 | None | None | I |
| N/T | 0.7872 | likely_pathogenic | 0.8635 | pathogenic | -0.772 | Destabilizing | 0.999 | D | 0.708 | prob.delet. | N | 0.470264749 | None | None | I |
| N/V | 0.9658 | likely_pathogenic | 0.9818 | pathogenic | -0.385 | Destabilizing | 1.0 | D | 0.703 | prob.neutral | None | None | None | None | I |
| N/W | 0.9985 | likely_pathogenic | 0.9991 | pathogenic | -0.602 | Destabilizing | 1.0 | D | 0.693 | prob.neutral | None | None | None | None | I |
| N/Y | 0.9713 | likely_pathogenic | 0.9842 | pathogenic | -0.337 | Destabilizing | 1.0 | D | 0.72 | prob.delet. | N | 0.471572814 | 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.