Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 7518 | 22777;22778;22779 | chr2:178722111;178722110;178722109 | chr2:179586838;179586837;179586836 |
| N2AB | 7201 | 21826;21827;21828 | chr2:178722111;178722110;178722109 | chr2:179586838;179586837;179586836 |
| N2A | 6274 | 19045;19046;19047 | chr2:178722111;178722110;178722109 | chr2:179586838;179586837;179586836 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/E | None | None | 0.98 | N | 0.348 | 0.151 | 0.218112801441 | gnomAD-4.0.0 | 1.69609E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.59944E-05 | 0 |
| D/V | rs749008105  |
0.544 | 1.0 | N | 0.737 | 0.36 | 0.312001716656 | gnomAD-2.1.1 | 1.85E-05 | None | None | None | None | I | None | 0 | 7.14E-05 | None | 0 | 0 | None | 8.83E-05 | None | 0 | 0 | 0 |
| D/V | rs749008105 |
0.544 | 1.0 | N | 0.737 | 0.36 | 0.312001716656 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.06868E-04 | 0 |
| D/V | rs749008105 |
0.544 | 1.0 | N | 0.737 | 0.36 | 0.312001716656 | gnomAD-4.0.0 | 1.08031E-05 | None | None | None | None | I | None | 0 | 3.78172E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 8.9315E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.7837 | likely_pathogenic | 0.8497 | pathogenic | -0.519 | Destabilizing | 1.0 | D | 0.624 | neutral | N | 0.439892227 | None | None | I |
| D/C | 0.9856 | likely_pathogenic | 0.99 | pathogenic | -0.336 | Destabilizing | 1.0 | D | 0.763 | deleterious | None | None | None | None | I |
| D/E | 0.7169 | likely_pathogenic | 0.7762 | pathogenic | -0.587 | Destabilizing | 0.98 | D | 0.348 | neutral | N | 0.420845107 | None | None | I |
| D/F | 0.9572 | likely_pathogenic | 0.972 | pathogenic | 0.159 | Stabilizing | 1.0 | D | 0.767 | deleterious | None | None | None | None | I |
| D/G | 0.7827 | likely_pathogenic | 0.8612 | pathogenic | -0.912 | Destabilizing | 0.998 | D | 0.545 | neutral | N | 0.4873581 | None | None | I |
| D/H | 0.8462 | likely_pathogenic | 0.8926 | pathogenic | -0.138 | Destabilizing | 0.65 | D | 0.277 | neutral | N | 0.439142866 | None | None | I |
| D/I | 0.883 | likely_pathogenic | 0.9171 | pathogenic | 0.538 | Stabilizing | 1.0 | D | 0.767 | deleterious | None | None | None | None | I |
| D/K | 0.9477 | likely_pathogenic | 0.9639 | pathogenic | -0.759 | Destabilizing | 1.0 | D | 0.614 | neutral | None | None | None | None | I |
| D/L | 0.8737 | likely_pathogenic | 0.9117 | pathogenic | 0.538 | Stabilizing | 1.0 | D | 0.741 | deleterious | None | None | None | None | I |
| D/M | 0.9689 | likely_pathogenic | 0.9797 | pathogenic | 0.976 | Stabilizing | 1.0 | D | 0.748 | deleterious | None | None | None | None | I |
| D/N | 0.3958 | ambiguous | 0.5104 | ambiguous | -1.23 | Destabilizing | 0.995 | D | 0.459 | neutral | N | 0.464289239 | None | None | I |
| D/P | 0.9821 | likely_pathogenic | 0.9896 | pathogenic | 0.211 | Stabilizing | 0.999 | D | 0.641 | neutral | None | None | None | None | I |
| D/Q | 0.9095 | likely_pathogenic | 0.9381 | pathogenic | -1.015 | Destabilizing | 1.0 | D | 0.591 | neutral | None | None | None | None | I |
| D/R | 0.9337 | likely_pathogenic | 0.9541 | pathogenic | -0.461 | Destabilizing | 1.0 | D | 0.693 | prob.neutral | None | None | None | None | I |
| D/S | 0.5819 | likely_pathogenic | 0.6887 | pathogenic | -1.538 | Destabilizing | 0.999 | D | 0.471 | neutral | None | None | None | None | I |
| D/T | 0.7792 | likely_pathogenic | 0.848 | pathogenic | -1.214 | Destabilizing | 1.0 | D | 0.65 | neutral | None | None | None | None | I |
| D/V | 0.7587 | likely_pathogenic | 0.8214 | pathogenic | 0.211 | Stabilizing | 1.0 | D | 0.737 | prob.delet. | N | 0.360140577 | None | None | I |
| D/W | 0.993 | likely_pathogenic | 0.9944 | pathogenic | 0.331 | Stabilizing | 1.0 | D | 0.769 | deleterious | None | None | None | None | I |
| D/Y | 0.7949 | likely_pathogenic | 0.8522 | pathogenic | 0.367 | Stabilizing | 1.0 | D | 0.74 | deleterious | N | 0.47344744 | None | None | I |
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.