Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 8776 | 26551;26552;26553 | chr2:178714448;178714447;178714446 | chr2:179579175;179579174;179579173 |
| N2AB | 8459 | 25600;25601;25602 | chr2:178714448;178714447;178714446 | chr2:179579175;179579174;179579173 |
| N2A | 7532 | 22819;22820;22821 | chr2:178714448;178714447;178714446 | chr2:179579175;179579174;179579173 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/L | rs746071731  |
-0.022 | None | N | 0.337 | 0.176 | 0.0666544352282 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.57E-05 | None | 0 | None | 0 | 0 | 0 |
| I/L | rs746071731 |
-0.022 | None | N | 0.337 | 0.176 | 0.0666544352282 | gnomAD-4.0.0 | 1.59158E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.77285E-05 | None | 0 | 0 | 0 | 0 | 0 |
| I/M | None | None | 0.005 | N | 0.376 | 0.216 | 0.0884992946249 | gnomAD-4.0.0 | 6.84287E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99536E-07 | 0 | 0 |
| I/V | rs746071731 |
-0.562 | None | N | 0.192 | 0.144 | 0.119812018005 | gnomAD-2.1.1 | 8.07E-06 | None | None | None | None | N | None | 0 | 5.8E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/V | rs746071731 |
-0.562 | None | N | 0.192 | 0.144 | 0.119812018005 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | rs746071731 |
-0.562 | None | N | 0.192 | 0.144 | 0.119812018005 | gnomAD-4.0.0 | 5.1251E-06 | None | None | None | None | N | None | 0 | 6.78104E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.1553 | likely_benign | 0.2376 | benign | -1.289 | Destabilizing | 0.064 | N | 0.571 | neutral | None | None | None | None | N |
| I/C | 0.6506 | likely_pathogenic | 0.782 | pathogenic | -0.836 | Destabilizing | 0.899 | D | 0.667 | neutral | None | None | None | None | N |
| I/D | 0.5146 | ambiguous | 0.7333 | pathogenic | -0.627 | Destabilizing | 0.702 | D | 0.749 | deleterious | None | None | None | None | N |
| I/E | 0.3815 | ambiguous | 0.5965 | pathogenic | -0.616 | Destabilizing | 0.635 | D | 0.74 | deleterious | None | None | None | None | N |
| I/F | 0.1246 | likely_benign | 0.1934 | benign | -0.785 | Destabilizing | 0.259 | N | 0.569 | neutral | N | 0.518445026 | None | None | N |
| I/G | 0.4547 | ambiguous | 0.6659 | pathogenic | -1.592 | Destabilizing | 0.702 | D | 0.723 | prob.delet. | None | None | None | None | N |
| I/H | 0.4432 | ambiguous | 0.6339 | pathogenic | -0.676 | Destabilizing | 0.918 | D | 0.758 | deleterious | None | None | None | None | N |
| I/K | 0.315 | likely_benign | 0.5131 | ambiguous | -0.861 | Destabilizing | 0.033 | N | 0.732 | prob.delet. | None | None | None | None | N |
| I/L | 0.097 | likely_benign | 0.1341 | benign | -0.54 | Destabilizing | None | N | 0.337 | neutral | N | 0.492922288 | None | None | N |
| I/M | 0.0726 | likely_benign | 0.0995 | benign | -0.559 | Destabilizing | 0.005 | N | 0.376 | neutral | N | 0.495225436 | None | None | N |
| I/N | 0.2264 | likely_benign | 0.3751 | ambiguous | -0.777 | Destabilizing | 0.64 | D | 0.768 | deleterious | D | 0.535281834 | None | None | N |
| I/P | 0.3694 | ambiguous | 0.5482 | ambiguous | -0.758 | Destabilizing | 0.878 | D | 0.763 | deleterious | None | None | None | None | N |
| I/Q | 0.34 | ambiguous | 0.5527 | ambiguous | -0.902 | Destabilizing | 0.495 | N | 0.769 | deleterious | None | None | None | None | N |
| I/R | 0.2258 | likely_benign | 0.407 | ambiguous | -0.307 | Destabilizing | 0.317 | N | 0.765 | deleterious | None | None | None | None | N |
| I/S | 0.2083 | likely_benign | 0.3468 | ambiguous | -1.362 | Destabilizing | 0.468 | N | 0.689 | prob.neutral | N | 0.504553826 | None | None | N |
| I/T | 0.1094 | likely_benign | 0.1607 | benign | -1.23 | Destabilizing | 0.036 | N | 0.599 | neutral | N | 0.487463529 | None | None | N |
| I/V | 0.0647 | likely_benign | 0.0716 | benign | -0.758 | Destabilizing | None | N | 0.192 | neutral | N | 0.48080114 | None | None | N |
| I/W | 0.5903 | likely_pathogenic | 0.7556 | pathogenic | -0.856 | Destabilizing | 0.976 | D | 0.759 | deleterious | None | None | None | None | N |
| I/Y | 0.3709 | ambiguous | 0.5371 | ambiguous | -0.621 | Destabilizing | 0.099 | N | 0.688 | prob.neutral | 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.