Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 13857 | 41794;41795;41796 | chr2:178636002;178636001;178636000 | chr2:179500729;179500728;179500727 |
| N2AB | 12216 | 36871;36872;36873 | chr2:178636002;178636001;178636000 | chr2:179500729;179500728;179500727 |
| N2A | 11289 | 34090;34091;34092 | chr2:178636002;178636001;178636000 | chr2:179500729;179500728;179500727 |
| N2B | 4792 | 14599;14600;14601 | chr2:178636002;178636001;178636000 | chr2:179500729;179500728;179500727 |
| Novex-1 | 4917 | 14974;14975;14976 | chr2:178636002;178636001;178636000 | chr2:179500729;179500728;179500727 |
| Novex-2 | 4984 | 15175;15176;15177 | chr2:178636002;178636001;178636000 | chr2:179500729;179500728;179500727 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/T | rs144963490  |
-1.79 | 0.919 | N | 0.498 | 0.086 | None | gnomAD-2.1.1 | 3.25E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.23839E-04 | None | 0 | None | 0 | 3.59E-05 | 0 |
| A/T | rs144963490 |
-1.79 | 0.919 | N | 0.498 | 0.086 | None | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 5.82072E-04 | None | 0 | 0 | 0 | 0 | 0 |
| A/T | rs144963490 |
-1.79 | 0.919 | N | 0.498 | 0.086 | None | 1000 genomes | 3.99361E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 2E-03 | 0 | None | None | None | 0 | None |
| A/T | rs144963490 |
-1.79 | 0.919 | N | 0.498 | 0.086 | None | gnomAD-4.0.0 | 3.60309E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.09669E-03 | None | 0 | 0 | 6.79656E-06 | 1.10297E-05 | 0 |
| A/V | rs1308553972 |
-0.394 | 0.005 | N | 0.093 | 0.099 | 0.247872288689 | gnomAD-2.1.1 | 4.05E-06 | None | None | None | None | N | None | 0 | 2.92E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| A/V | rs1308553972 |
-0.394 | 0.005 | N | 0.093 | 0.099 | 0.247872288689 | gnomAD-4.0.0 | 1.60055E-06 | None | None | None | None | N | None | 0 | 2.29495E-05 | None | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.706 | likely_pathogenic | 0.6622 | pathogenic | -0.702 | Destabilizing | 0.998 | D | 0.592 | neutral | None | None | None | None | N |
| A/D | 0.6344 | likely_pathogenic | 0.6622 | pathogenic | -0.775 | Destabilizing | 0.934 | D | 0.692 | prob.delet. | N | 0.346021327 | None | None | N |
| A/E | 0.6038 | likely_pathogenic | 0.6201 | pathogenic | -0.905 | Destabilizing | 0.842 | D | 0.654 | prob.neutral | None | None | None | None | N |
| A/F | 0.7409 | likely_pathogenic | 0.7279 | pathogenic | -0.929 | Destabilizing | 0.949 | D | 0.698 | prob.delet. | None | None | None | None | N |
| A/G | 0.2883 | likely_benign | 0.2764 | benign | -0.515 | Destabilizing | 0.669 | D | 0.521 | neutral | N | 0.348733631 | None | None | N |
| A/H | 0.8042 | likely_pathogenic | 0.7999 | pathogenic | -0.71 | Destabilizing | 0.998 | D | 0.655 | prob.neutral | None | None | None | None | N |
| A/I | 0.6338 | likely_pathogenic | 0.619 | pathogenic | -0.312 | Destabilizing | 0.029 | N | 0.316 | neutral | None | None | None | None | N |
| A/K | 0.8271 | likely_pathogenic | 0.8414 | pathogenic | -0.918 | Destabilizing | 0.842 | D | 0.648 | neutral | None | None | None | None | N |
| A/L | 0.5138 | ambiguous | 0.5144 | ambiguous | -0.312 | Destabilizing | 0.016 | N | 0.366 | neutral | None | None | None | None | N |
| A/M | 0.5888 | likely_pathogenic | 0.5777 | pathogenic | -0.354 | Destabilizing | 0.949 | D | 0.663 | prob.neutral | None | None | None | None | N |
| A/N | 0.6075 | likely_pathogenic | 0.6043 | pathogenic | -0.49 | Destabilizing | 0.949 | D | 0.707 | prob.delet. | None | None | None | None | N |
| A/P | 0.7753 | likely_pathogenic | 0.8239 | pathogenic | -0.308 | Destabilizing | 0.986 | D | 0.691 | prob.delet. | N | 0.349502197 | None | None | N |
| A/Q | 0.6487 | likely_pathogenic | 0.6455 | pathogenic | -0.748 | Destabilizing | 0.974 | D | 0.713 | prob.delet. | None | None | None | None | N |
| A/R | 0.7423 | likely_pathogenic | 0.7412 | pathogenic | -0.473 | Destabilizing | 0.949 | D | 0.688 | prob.delet. | None | None | None | None | N |
| A/S | 0.1457 | likely_benign | 0.1376 | benign | -0.664 | Destabilizing | 0.121 | N | 0.349 | neutral | N | 0.345226505 | None | None | N |
| A/T | 0.1824 | likely_benign | 0.1811 | benign | -0.715 | Destabilizing | 0.919 | D | 0.498 | neutral | N | 0.343129818 | None | None | N |
| A/V | 0.3222 | likely_benign | 0.3109 | benign | -0.308 | Destabilizing | 0.005 | N | 0.093 | neutral | N | 0.346973347 | None | None | N |
| A/W | 0.9429 | likely_pathogenic | 0.9387 | pathogenic | -1.136 | Destabilizing | 0.998 | D | 0.725 | deleterious | None | None | None | None | N |
| A/Y | 0.8201 | likely_pathogenic | 0.8178 | pathogenic | -0.779 | Destabilizing | 0.974 | D | 0.753 | deleterious | 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.