Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14861 | 44806;44807;44808 | chr2:178624699;178624698;178624697 | chr2:179489426;179489425;179489424 |
| N2AB | 13220 | 39883;39884;39885 | chr2:178624699;178624698;178624697 | chr2:179489426;179489425;179489424 |
| N2A | 12293 | 37102;37103;37104 | chr2:178624699;178624698;178624697 | chr2:179489426;179489425;179489424 |
| N2B | 5796 | 17611;17612;17613 | chr2:178624699;178624698;178624697 | chr2:179489426;179489425;179489424 |
| Novex-1 | 5921 | 17986;17987;17988 | chr2:178624699;178624698;178624697 | chr2:179489426;179489425;179489424 |
| Novex-2 | 5988 | 18187;18188;18189 | chr2:178624699;178624698;178624697 | chr2:179489426;179489425;179489424 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/N | rs1044788441  |
0.39 | 1.0 | N | 0.635 | 0.433 | 0.459370960843 | gnomAD-2.1.1 | 8.08E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.79E-05 | 0 |
| D/N | rs1044788441 |
0.39 | 1.0 | N | 0.635 | 0.433 | 0.459370960843 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| D/N | rs1044788441 |
0.39 | 1.0 | N | 0.635 | 0.433 | 0.459370960843 | gnomAD-4.0.0 | 1.11648E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.18748E-05 | 0 | 6.41375E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.8317 | likely_pathogenic | 0.797 | pathogenic | 0.005 | Stabilizing | 1.0 | D | 0.739 | prob.delet. | D | 0.597122429 | None | None | N |
| D/C | 0.9797 | likely_pathogenic | 0.9784 | pathogenic | 0.343 | Stabilizing | 1.0 | D | 0.722 | prob.delet. | None | None | None | None | N |
| D/E | 0.7593 | likely_pathogenic | 0.7338 | pathogenic | -0.285 | Destabilizing | 1.0 | D | 0.433 | neutral | D | 0.565886696 | None | None | N |
| D/F | 0.9799 | likely_pathogenic | 0.9778 | pathogenic | -0.321 | Destabilizing | 1.0 | D | 0.745 | deleterious | None | None | None | None | N |
| D/G | 0.7303 | likely_pathogenic | 0.6893 | pathogenic | -0.153 | Destabilizing | 1.0 | D | 0.741 | deleterious | D | 0.652433845 | None | None | N |
| D/H | 0.9125 | likely_pathogenic | 0.9111 | pathogenic | -0.31 | Destabilizing | 1.0 | D | 0.703 | prob.neutral | D | 0.630968016 | None | None | N |
| D/I | 0.9631 | likely_pathogenic | 0.9593 | pathogenic | 0.357 | Stabilizing | 1.0 | D | 0.747 | deleterious | None | None | None | None | N |
| D/K | 0.9407 | likely_pathogenic | 0.9451 | pathogenic | 0.393 | Stabilizing | 1.0 | D | 0.762 | deleterious | None | None | None | None | N |
| D/L | 0.9552 | likely_pathogenic | 0.9524 | pathogenic | 0.357 | Stabilizing | 1.0 | D | 0.759 | deleterious | None | None | None | None | N |
| D/M | 0.981 | likely_pathogenic | 0.9794 | pathogenic | 0.531 | Stabilizing | 1.0 | D | 0.726 | prob.delet. | None | None | None | None | N |
| D/N | 0.3294 | likely_benign | 0.3288 | benign | 0.399 | Stabilizing | 1.0 | D | 0.635 | neutral | N | 0.511978713 | None | None | N |
| D/P | 0.9209 | likely_pathogenic | 0.9163 | pathogenic | 0.262 | Stabilizing | 1.0 | D | 0.749 | deleterious | None | None | None | None | N |
| D/Q | 0.9492 | likely_pathogenic | 0.9469 | pathogenic | 0.38 | Stabilizing | 1.0 | D | 0.673 | neutral | None | None | None | None | N |
| D/R | 0.9609 | likely_pathogenic | 0.9621 | pathogenic | 0.396 | Stabilizing | 1.0 | D | 0.749 | deleterious | None | None | None | None | N |
| D/S | 0.6385 | likely_pathogenic | 0.6006 | pathogenic | 0.268 | Stabilizing | 1.0 | D | 0.659 | neutral | None | None | None | None | N |
| D/T | 0.8928 | likely_pathogenic | 0.8817 | pathogenic | 0.372 | Stabilizing | 1.0 | D | 0.765 | deleterious | None | None | None | None | N |
| D/V | 0.9091 | likely_pathogenic | 0.898 | pathogenic | 0.262 | Stabilizing | 1.0 | D | 0.759 | deleterious | D | 0.635217178 | None | None | N |
| D/W | 0.9954 | likely_pathogenic | 0.9954 | pathogenic | -0.356 | Destabilizing | 1.0 | D | 0.718 | prob.delet. | None | None | None | None | N |
| D/Y | 0.8478 | likely_pathogenic | 0.8331 | pathogenic | -0.123 | Destabilizing | 1.0 | D | 0.739 | prob.delet. | D | 0.736063715 | 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.