Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14964 | 45115;45116;45117 | chr2:178622693;178622692;178622691 | chr2:179487420;179487419;179487418 |
| N2AB | 13323 | 40192;40193;40194 | chr2:178622693;178622692;178622691 | chr2:179487420;179487419;179487418 |
| N2A | 12396 | 37411;37412;37413 | chr2:178622693;178622692;178622691 | chr2:179487420;179487419;179487418 |
| N2B | 5899 | 17920;17921;17922 | chr2:178622693;178622692;178622691 | chr2:179487420;179487419;179487418 |
| Novex-1 | 6024 | 18295;18296;18297 | chr2:178622693;178622692;178622691 | chr2:179487420;179487419;179487418 |
| Novex-2 | 6091 | 18496;18497;18498 | chr2:178622693;178622692;178622691 | chr2:179487420;179487419;179487418 |
| 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/D | None | None | 0.999 | D | 0.442 | 0.285 | 0.393006254552 | gnomAD-4.0.0 | 1.20041E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.31261E-06 | 0 | 0 |
| E/K | rs1259780221  |
None | 0.999 | N | 0.549 | 0.423 | 0.47185959272 | gnomAD-3.1.2 | 6.59E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 4.79846E-04 |
| E/K | rs1259780221 |
None | 0.999 | N | 0.549 | 0.423 | 0.47185959272 | gnomAD-4.0.0 | 2.58483E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.41095E-06 | 0 | 2.87092E-05 |
| E/Q | rs1259780221 |
-0.886 | 1.0 | D | 0.572 | 0.257 | 0.37550373646 | gnomAD-2.1.1 | 4.15E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 1.70882E-04 |
| E/Q | rs1259780221 |
-0.886 | 1.0 | D | 0.572 | 0.257 | 0.37550373646 | gnomAD-4.0.0 | 1.60764E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.05362E-05 |
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 | 0.3309 | likely_benign | 0.3109 | benign | -0.981 | Destabilizing | 0.999 | D | 0.667 | neutral | D | 0.602766267 | None | None | N |
| E/C | 0.9462 | likely_pathogenic | 0.9243 | pathogenic | -0.597 | Destabilizing | 1.0 | D | 0.725 | prob.delet. | None | None | None | None | N |
| E/D | 0.5196 | ambiguous | 0.4584 | ambiguous | -1.364 | Destabilizing | 0.999 | D | 0.442 | neutral | D | 0.596839423 | None | None | N |
| E/F | 0.8772 | likely_pathogenic | 0.8405 | pathogenic | -0.473 | Destabilizing | 1.0 | D | 0.759 | deleterious | None | None | None | None | N |
| E/G | 0.5267 | ambiguous | 0.461 | ambiguous | -1.379 | Destabilizing | 1.0 | D | 0.733 | prob.delet. | D | 0.651970533 | None | None | N |
| E/H | 0.701 | likely_pathogenic | 0.6642 | pathogenic | -0.802 | Destabilizing | 1.0 | D | 0.645 | neutral | None | None | None | None | N |
| E/I | 0.4827 | ambiguous | 0.4661 | ambiguous | 0.123 | Stabilizing | 1.0 | D | 0.783 | deleterious | None | None | None | None | N |
| E/K | 0.3174 | likely_benign | 0.2456 | benign | -0.931 | Destabilizing | 0.999 | D | 0.549 | neutral | N | 0.508417697 | None | None | N |
| E/L | 0.6268 | likely_pathogenic | 0.5871 | pathogenic | 0.123 | Stabilizing | 1.0 | D | 0.77 | deleterious | None | None | None | None | N |
| E/M | 0.641 | likely_pathogenic | 0.6143 | pathogenic | 0.668 | Stabilizing | 1.0 | D | 0.722 | prob.delet. | None | None | None | None | N |
| E/N | 0.6658 | likely_pathogenic | 0.6159 | pathogenic | -1.355 | Destabilizing | 1.0 | D | 0.711 | prob.delet. | None | None | None | None | N |
| E/P | 0.9701 | likely_pathogenic | 0.9525 | pathogenic | -0.224 | Destabilizing | 1.0 | D | 0.775 | deleterious | None | None | None | None | N |
| E/Q | 0.2004 | likely_benign | 0.1939 | benign | -1.192 | Destabilizing | 1.0 | D | 0.572 | neutral | D | 0.539288192 | None | None | N |
| E/R | 0.4666 | ambiguous | 0.4279 | ambiguous | -0.699 | Destabilizing | 1.0 | D | 0.711 | prob.delet. | None | None | None | None | N |
| E/S | 0.4397 | ambiguous | 0.4004 | ambiguous | -1.78 | Destabilizing | 0.999 | D | 0.589 | neutral | None | None | None | None | N |
| E/T | 0.3993 | ambiguous | 0.3754 | ambiguous | -1.441 | Destabilizing | 1.0 | D | 0.777 | deleterious | None | None | None | None | N |
| E/V | 0.3005 | likely_benign | 0.2903 | benign | -0.224 | Destabilizing | 1.0 | D | 0.758 | deleterious | D | 0.599142732 | None | None | N |
| E/W | 0.9735 | likely_pathogenic | 0.9625 | pathogenic | -0.297 | Destabilizing | 1.0 | D | 0.729 | prob.delet. | None | None | None | None | N |
| E/Y | 0.8297 | likely_pathogenic | 0.7989 | pathogenic | -0.231 | Destabilizing | 1.0 | D | 0.749 | 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.