Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 9385 | 28378;28379;28380 | chr2:178711083;178711082;178711081 | chr2:179575810;179575809;179575808 |
| N2AB | 9068 | 27427;27428;27429 | chr2:178711083;178711082;178711081 | chr2:179575810;179575809;179575808 |
| N2A | 8141 | 24646;24647;24648 | chr2:178711083;178711082;178711081 | chr2:179575810;179575809;179575808 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/N | rs945228543  |
-0.185 | None | None | 0.219 | 0.12 | 0.264081493735 | gnomAD-2.1.1 | 4.25E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 9.26E-06 | 0 |
| S/N | rs945228543 |
-0.185 | None | None | 0.219 | 0.12 | 0.264081493735 | 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 |
| S/N | rs945228543 |
-0.185 | None | None | 0.219 | 0.12 | 0.264081493735 | gnomAD-4.0.0 | 4.39068E-06 | None | None | None | None | N | None | 0 | 1.75439E-05 | None | 0 | 0 | None | 0 | 0 | 5.12615E-06 | 0 | 0 |
| S/R | rs2076586234 |
None | None | None | 0.283 | 0.185 | 0.292423486923 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.1152 | likely_benign | 0.1055 | benign | -0.568 | Destabilizing | 0.016 | N | 0.388 | neutral | None | None | None | None | N |
| S/C | 0.2532 | likely_benign | 0.2508 | benign | -0.314 | Destabilizing | 0.828 | D | 0.592 | neutral | None | None | None | None | N |
| S/D | 0.5621 | ambiguous | 0.4984 | ambiguous | -0.162 | Destabilizing | 0.038 | N | 0.459 | neutral | None | None | None | None | N |
| S/E | 0.629 | likely_pathogenic | 0.5861 | pathogenic | -0.249 | Destabilizing | 0.072 | N | 0.461 | neutral | None | None | None | None | N |
| S/F | 0.229 | likely_benign | 0.2174 | benign | -1.178 | Destabilizing | None | N | 0.516 | neutral | None | None | None | None | N |
| S/G | 0.1655 | likely_benign | 0.1258 | benign | -0.683 | Destabilizing | None | N | 0.22 | neutral | None | None | None | None | N |
| S/H | 0.3584 | ambiguous | 0.3638 | ambiguous | -1.293 | Destabilizing | 0.214 | N | 0.606 | neutral | None | None | None | None | N |
| S/I | 0.2253 | likely_benign | 0.2165 | benign | -0.386 | Destabilizing | 0.171 | N | 0.691 | prob.neutral | None | None | None | None | N |
| S/K | 0.6899 | likely_pathogenic | 0.6584 | pathogenic | -0.479 | Destabilizing | 0.016 | N | 0.432 | neutral | None | None | None | None | N |
| S/L | 0.1395 | likely_benign | 0.1306 | benign | -0.386 | Destabilizing | 0.038 | N | 0.596 | neutral | None | None | None | None | N |
| S/M | 0.2551 | likely_benign | 0.2478 | benign | 0.082 | Stabilizing | 0.628 | D | 0.604 | neutral | None | None | None | None | N |
| S/N | 0.1815 | likely_benign | 0.1522 | benign | -0.231 | Destabilizing | None | N | 0.219 | neutral | None | None | None | None | N |
| S/P | 0.671 | likely_pathogenic | 0.6941 | pathogenic | -0.419 | Destabilizing | 0.356 | N | 0.63 | neutral | None | None | None | None | N |
| S/Q | 0.5286 | ambiguous | 0.5046 | ambiguous | -0.578 | Destabilizing | 0.072 | N | 0.566 | neutral | None | None | None | None | N |
| S/R | 0.6011 | likely_pathogenic | 0.5652 | pathogenic | -0.254 | Destabilizing | None | N | 0.283 | neutral | None | None | None | None | N |
| S/T | 0.0903 | likely_benign | 0.0823 | benign | -0.339 | Destabilizing | 0.024 | N | 0.457 | neutral | None | None | None | None | N |
| S/V | 0.2193 | likely_benign | 0.2065 | benign | -0.419 | Destabilizing | 0.072 | N | 0.652 | neutral | None | None | None | None | N |
| S/W | 0.4831 | ambiguous | 0.491 | ambiguous | -1.126 | Destabilizing | 0.864 | D | 0.682 | prob.neutral | None | None | None | None | N |
| S/Y | 0.2485 | likely_benign | 0.2518 | benign | -0.856 | Destabilizing | 0.12 | N | 0.689 | 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.