Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31581 | 94966;94967;94968 | chr2:178546687;178546686;178546685 | chr2:179411414;179411413;179411412 |
| N2AB | 29940 | 90043;90044;90045 | chr2:178546687;178546686;178546685 | chr2:179411414;179411413;179411412 |
| N2A | 29013 | 87262;87263;87264 | chr2:178546687;178546686;178546685 | chr2:179411414;179411413;179411412 |
| N2B | 22516 | 67771;67772;67773 | chr2:178546687;178546686;178546685 | chr2:179411414;179411413;179411412 |
| Novex-1 | 22641 | 68146;68147;68148 | chr2:178546687;178546686;178546685 | chr2:179411414;179411413;179411412 |
| Novex-2 | 22708 | 68347;68348;68349 | chr2:178546687;178546686;178546685 | chr2:179411414;179411413;179411412 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| E/A | rs1321907057  |
-1.559 | 0.998 | N | 0.664 | 0.496 | 0.459282285925 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.91E-06 | 0 |
| E/A | rs1321907057 |
-1.559 | 0.998 | N | 0.664 | 0.496 | 0.459282285925 | gnomAD-4.0.0 | 3.18272E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.71706E-06 | 0 | 0 |
| E/K | rs1417917395 |
None | 0.998 | N | 0.607 | 0.401 | 0.345175991111 | gnomAD-4.0.0 | 4.78956E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.39696E-06 | 0 | 1.65662E-05 |
| E/Q | None | None | 0.999 | N | 0.68 | 0.352 | 0.248417906384 | gnomAD-4.0.0 | 6.84223E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99494E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| E/A | 0.5766 | likely_pathogenic | 0.5669 | pathogenic | -1.491 | Destabilizing | 0.998 | D | 0.664 | neutral | N | 0.490362093 | None | None | N |
| E/C | 0.9543 | likely_pathogenic | 0.9445 | pathogenic | -0.641 | Destabilizing | 1.0 | D | 0.811 | deleterious | None | None | None | None | N |
| E/D | 0.5928 | likely_pathogenic | 0.5854 | pathogenic | -1.484 | Destabilizing | 0.434 | N | 0.337 | neutral | N | 0.516097431 | None | None | N |
| E/F | 0.9701 | likely_pathogenic | 0.9662 | pathogenic | -1.132 | Destabilizing | 1.0 | D | 0.809 | deleterious | None | None | None | None | N |
| E/G | 0.8332 | likely_pathogenic | 0.8098 | pathogenic | -1.912 | Destabilizing | 0.999 | D | 0.723 | prob.delet. | N | 0.51556992 | None | None | N |
| E/H | 0.9007 | likely_pathogenic | 0.9014 | pathogenic | -1.06 | Destabilizing | 1.0 | D | 0.723 | prob.delet. | None | None | None | None | N |
| E/I | 0.7966 | likely_pathogenic | 0.798 | pathogenic | -0.278 | Destabilizing | 1.0 | D | 0.813 | deleterious | None | None | None | None | N |
| E/K | 0.7964 | likely_pathogenic | 0.7996 | pathogenic | -1.295 | Destabilizing | 0.998 | D | 0.607 | neutral | N | 0.501511981 | None | None | N |
| E/L | 0.8739 | likely_pathogenic | 0.8802 | pathogenic | -0.278 | Destabilizing | 1.0 | D | 0.753 | deleterious | None | None | None | None | N |
| E/M | 0.8399 | likely_pathogenic | 0.8345 | pathogenic | 0.498 | Stabilizing | 1.0 | D | 0.776 | deleterious | None | None | None | None | N |
| E/N | 0.827 | likely_pathogenic | 0.8113 | pathogenic | -1.583 | Destabilizing | 0.999 | D | 0.712 | prob.delet. | None | None | None | None | N |
| E/P | 0.9983 | likely_pathogenic | 0.9981 | pathogenic | -0.668 | Destabilizing | 1.0 | D | 0.748 | deleterious | None | None | None | None | N |
| E/Q | 0.3555 | ambiguous | 0.3633 | ambiguous | -1.267 | Destabilizing | 0.999 | D | 0.68 | prob.neutral | N | 0.476634966 | None | None | N |
| E/R | 0.8406 | likely_pathogenic | 0.8426 | pathogenic | -1.167 | Destabilizing | 1.0 | D | 0.732 | prob.delet. | None | None | None | None | N |
| E/S | 0.6456 | likely_pathogenic | 0.6229 | pathogenic | -2.27 | Highly Destabilizing | 0.997 | D | 0.615 | neutral | None | None | None | None | N |
| E/T | 0.7351 | likely_pathogenic | 0.7278 | pathogenic | -1.864 | Destabilizing | 1.0 | D | 0.723 | prob.delet. | None | None | None | None | N |
| E/V | 0.6332 | likely_pathogenic | 0.6251 | pathogenic | -0.668 | Destabilizing | 1.0 | D | 0.735 | prob.delet. | N | 0.47042096 | None | None | N |
| E/W | 0.9905 | likely_pathogenic | 0.9899 | pathogenic | -1.156 | Destabilizing | 1.0 | D | 0.82 | deleterious | None | None | None | None | N |
| E/Y | 0.9432 | likely_pathogenic | 0.9381 | pathogenic | -0.912 | Destabilizing | 1.0 | D | 0.779 | 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.