Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 4745 | 14458;14459;14460 | chr2:178738220;178738219;178738218 | chr2:179602947;179602946;179602945 |
| N2AB | 4428 | 13507;13508;13509 | chr2:178738220;178738219;178738218 | chr2:179602947;179602946;179602945 |
| N2A | 3501 | 10726;10727;10728 | chr2:178738220;178738219;178738218 | chr2:179602947;179602946;179602945 |
| N2B | 4382 | 13369;13370;13371 | chr2:178738220;178738219;178738218 | chr2:179602947;179602946;179602945 |
| Novex-1 | 4507 | 13744;13745;13746 | chr2:178738220;178738219;178738218 | chr2:179602947;179602946;179602945 |
| Novex-2 | 4574 | 13945;13946;13947 | chr2:178738220;178738219;178738218 | chr2:179602947;179602946;179602945 |
| 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 | None | None | 1.0 | N | 0.703 | 0.399 | 0.252162846088 | gnomAD-4.0.0 | 1.59166E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85847E-06 | 0 | 0 |
| K/N | rs756868442  |
None | 1.0 | N | 0.728 | 0.237 | 0.154104182512 | gnomAD-4.0.0 | 6.8428E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99489E-07 | 0 | 0 |
| K/R | rs778762576 |
-0.18 | 0.999 | N | 0.522 | 0.244 | 0.188950314367 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.61E-05 | None | 0 | None | 0 | 0 | 0 |
| K/R | rs778762576 |
-0.18 | 0.999 | N | 0.522 | 0.244 | 0.188950314367 | gnomAD-4.0.0 | 1.59166E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.78071E-05 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/A | 0.8816 | likely_pathogenic | 0.913 | pathogenic | -0.146 | Destabilizing | 0.999 | D | 0.61 | neutral | None | None | None | None | N |
| K/C | 0.9583 | likely_pathogenic | 0.9661 | pathogenic | -0.143 | Destabilizing | 1.0 | D | 0.717 | prob.delet. | None | None | None | None | N |
| K/D | 0.9388 | likely_pathogenic | 0.9528 | pathogenic | 0.344 | Stabilizing | 1.0 | D | 0.731 | prob.delet. | None | None | None | None | N |
| K/E | 0.8342 | likely_pathogenic | 0.8561 | pathogenic | 0.399 | Stabilizing | 0.999 | D | 0.509 | neutral | N | 0.448671421 | None | None | N |
| K/F | 0.9744 | likely_pathogenic | 0.9783 | pathogenic | -0.096 | Destabilizing | 1.0 | D | 0.738 | prob.delet. | None | None | None | None | N |
| K/G | 0.9141 | likely_pathogenic | 0.9325 | pathogenic | -0.437 | Destabilizing | 1.0 | D | 0.687 | prob.neutral | None | None | None | None | N |
| K/H | 0.6703 | likely_pathogenic | 0.6981 | pathogenic | -0.806 | Destabilizing | 1.0 | D | 0.706 | prob.neutral | None | None | None | None | N |
| K/I | 0.8736 | likely_pathogenic | 0.876 | pathogenic | 0.563 | Stabilizing | 1.0 | D | 0.736 | prob.delet. | None | None | None | None | N |
| K/L | 0.8393 | likely_pathogenic | 0.8635 | pathogenic | 0.563 | Stabilizing | 1.0 | D | 0.687 | prob.neutral | None | None | None | None | N |
| K/M | 0.8198 | likely_pathogenic | 0.8257 | pathogenic | 0.41 | Stabilizing | 1.0 | D | 0.703 | prob.neutral | N | 0.450851459 | None | None | N |
| K/N | 0.8814 | likely_pathogenic | 0.9062 | pathogenic | 0.204 | Stabilizing | 1.0 | D | 0.728 | prob.delet. | N | 0.435256329 | None | None | N |
| K/P | 0.9794 | likely_pathogenic | 0.9844 | pathogenic | 0.358 | Stabilizing | 1.0 | D | 0.708 | prob.delet. | None | None | None | None | N |
| K/Q | 0.5727 | likely_pathogenic | 0.6156 | pathogenic | 0.074 | Stabilizing | 1.0 | D | 0.703 | prob.neutral | N | 0.449348932 | None | None | N |
| K/R | 0.121 | likely_benign | 0.1326 | benign | -0.17 | Destabilizing | 0.999 | D | 0.522 | neutral | N | 0.433315355 | None | None | N |
| K/S | 0.9013 | likely_pathogenic | 0.928 | pathogenic | -0.415 | Destabilizing | 0.999 | D | 0.611 | neutral | None | None | None | None | N |
| K/T | 0.702 | likely_pathogenic | 0.7305 | pathogenic | -0.177 | Destabilizing | 1.0 | D | 0.718 | prob.delet. | N | 0.448671421 | None | None | N |
| K/V | 0.8487 | likely_pathogenic | 0.8656 | pathogenic | 0.358 | Stabilizing | 1.0 | D | 0.706 | prob.neutral | None | None | None | None | N |
| K/W | 0.9625 | likely_pathogenic | 0.9682 | pathogenic | -0.028 | Destabilizing | 1.0 | D | 0.729 | prob.delet. | None | None | None | None | N |
| K/Y | 0.9085 | likely_pathogenic | 0.9228 | pathogenic | 0.297 | Stabilizing | 1.0 | D | 0.71 | prob.delet. | 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.