Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16730 | 50413;50414;50415 | chr2:178612337;178612336;178612335 | chr2:179477064;179477063;179477062 |
| N2AB | 15089 | 45490;45491;45492 | chr2:178612337;178612336;178612335 | chr2:179477064;179477063;179477062 |
| N2A | 14162 | 42709;42710;42711 | chr2:178612337;178612336;178612335 | chr2:179477064;179477063;179477062 |
| N2B | 7665 | 23218;23219;23220 | chr2:178612337;178612336;178612335 | chr2:179477064;179477063;179477062 |
| Novex-1 | 7790 | 23593;23594;23595 | chr2:178612337;178612336;178612335 | chr2:179477064;179477063;179477062 |
| Novex-2 | 7857 | 23794;23795;23796 | chr2:178612337;178612336;178612335 | chr2:179477064;179477063;179477062 |
| 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 | None | None | 0.993 | N | 0.633 | 0.198 | 0.335414705075 | gnomAD-4.0.0 | 3.42348E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.49938E-06 | 0 | 0 |
| A/V | rs763483590  |
-0.03 | 0.955 | N | 0.417 | 0.213 | 0.483301346737 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 5.65E-05 | None | 0 | None | 0 | 0 | 0 |
| A/V | rs763483590 |
-0.03 | 0.955 | N | 0.417 | 0.213 | 0.483301346737 | gnomAD-4.0.0 | 1.59398E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 2.79111E-05 | 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 | 0.8257 | likely_pathogenic | 0.7953 | pathogenic | -0.762 | Destabilizing | 1.0 | D | 0.633 | neutral | None | None | None | None | I |
| A/D | 0.7947 | likely_pathogenic | 0.7895 | pathogenic | -0.535 | Destabilizing | 0.999 | D | 0.653 | neutral | N | 0.476029647 | None | None | I |
| A/E | 0.7513 | likely_pathogenic | 0.7373 | pathogenic | -0.699 | Destabilizing | 0.999 | D | 0.654 | neutral | None | None | None | None | I |
| A/F | 0.7768 | likely_pathogenic | 0.7455 | pathogenic | -0.927 | Destabilizing | 0.995 | D | 0.675 | neutral | None | None | None | None | I |
| A/G | 0.3899 | ambiguous | 0.3521 | ambiguous | -0.265 | Destabilizing | 0.996 | D | 0.505 | neutral | N | 0.461699487 | None | None | I |
| A/H | 0.8287 | likely_pathogenic | 0.8026 | pathogenic | -0.257 | Destabilizing | 1.0 | D | 0.657 | neutral | None | None | None | None | I |
| A/I | 0.6116 | likely_pathogenic | 0.5248 | ambiguous | -0.378 | Destabilizing | 0.289 | N | 0.437 | neutral | None | None | None | None | I |
| A/K | 0.8716 | likely_pathogenic | 0.8742 | pathogenic | -0.531 | Destabilizing | 0.998 | D | 0.655 | neutral | None | None | None | None | I |
| A/L | 0.4555 | ambiguous | 0.4063 | ambiguous | -0.378 | Destabilizing | 0.966 | D | 0.425 | neutral | None | None | None | None | I |
| A/M | 0.6026 | likely_pathogenic | 0.5302 | ambiguous | -0.367 | Destabilizing | 0.999 | D | 0.634 | neutral | None | None | None | None | I |
| A/N | 0.558 | ambiguous | 0.5301 | ambiguous | -0.243 | Destabilizing | 0.999 | D | 0.681 | prob.neutral | None | None | None | None | I |
| A/P | 0.6004 | likely_pathogenic | 0.5853 | pathogenic | -0.302 | Destabilizing | 0.999 | D | 0.646 | neutral | N | 0.485291615 | None | None | I |
| A/Q | 0.6926 | likely_pathogenic | 0.6525 | pathogenic | -0.559 | Destabilizing | 0.999 | D | 0.661 | neutral | None | None | None | None | I |
| A/R | 0.8078 | likely_pathogenic | 0.8103 | pathogenic | -0.031 | Destabilizing | 0.999 | D | 0.653 | neutral | None | None | None | None | I |
| A/S | 0.1612 | likely_benign | 0.1469 | benign | -0.424 | Destabilizing | 0.989 | D | 0.496 | neutral | N | 0.445372798 | None | None | I |
| A/T | 0.251 | likely_benign | 0.2032 | benign | -0.515 | Destabilizing | 0.993 | D | 0.633 | neutral | N | 0.479415763 | None | None | I |
| A/V | 0.3778 | ambiguous | 0.303 | benign | -0.302 | Destabilizing | 0.955 | D | 0.417 | neutral | N | 0.478417197 | None | None | I |
| A/W | 0.9742 | likely_pathogenic | 0.9686 | pathogenic | -1.033 | Destabilizing | 1.0 | D | 0.707 | prob.neutral | None | None | None | None | I |
| A/Y | 0.8686 | likely_pathogenic | 0.8511 | pathogenic | -0.69 | Destabilizing | 0.999 | D | 0.681 | prob.neutral | None | None | 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.