Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27414 | 82465;82466;82467 | chr2:178563892;178563891;178563890 | chr2:179428619;179428618;179428617 |
| N2AB | 25773 | 77542;77543;77544 | chr2:178563892;178563891;178563890 | chr2:179428619;179428618;179428617 |
| N2A | 24846 | 74761;74762;74763 | chr2:178563892;178563891;178563890 | chr2:179428619;179428618;179428617 |
| N2B | 18349 | 55270;55271;55272 | chr2:178563892;178563891;178563890 | chr2:179428619;179428618;179428617 |
| Novex-1 | 18474 | 55645;55646;55647 | chr2:178563892;178563891;178563890 | chr2:179428619;179428618;179428617 |
| Novex-2 | 18541 | 55846;55847;55848 | chr2:178563892;178563891;178563890 | chr2:179428619;179428618;179428617 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/Q | rs763336230  |
-0.098 | 0.997 | N | 0.397 | 0.24 | 0.238096912614 | gnomAD-2.1.1 | 4.64E-05 | None | None | None | None | N | None | 4.13E-05 | 1.41443E-04 | None | 0 | 5.13E-05 | None | 9.8E-05 | None | 0 | 2.35E-05 | 0 |
| R/Q | rs763336230 |
-0.098 | 0.997 | N | 0.397 | 0.24 | 0.238096912614 | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | N | None | 0 | 6.55E-05 | 0 | 0 | 3.86997E-04 | None | 0 | 0 | 1.47E-05 | 2.07555E-04 | 0 |
| R/Q | rs763336230 |
-0.098 | 0.997 | N | 0.397 | 0.24 | 0.238096912614 | gnomAD-4.0.0 | 2.54092E-05 | None | None | None | None | N | None | 1.33518E-05 | 1.00027E-04 | None | 0 | 6.69045E-05 | None | 0 | 0 | 2.03434E-05 | 7.68656E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.9652 | likely_pathogenic | 0.9837 | pathogenic | -0.642 | Destabilizing | 0.845 | D | 0.439 | neutral | None | None | None | None | N |
| R/C | 0.6607 | likely_pathogenic | 0.8254 | pathogenic | -0.639 | Destabilizing | 0.999 | D | 0.593 | neutral | None | None | None | None | N |
| R/D | 0.9897 | likely_pathogenic | 0.9947 | pathogenic | -0.05 | Destabilizing | 0.975 | D | 0.437 | neutral | None | None | None | None | N |
| R/E | 0.9494 | likely_pathogenic | 0.9741 | pathogenic | 0.01 | Stabilizing | 0.916 | D | 0.357 | neutral | None | None | None | None | N |
| R/F | 0.9583 | likely_pathogenic | 0.9792 | pathogenic | -0.877 | Destabilizing | 0.987 | D | 0.564 | neutral | None | None | None | None | N |
| R/G | 0.929 | likely_pathogenic | 0.9684 | pathogenic | -0.847 | Destabilizing | 0.954 | D | 0.365 | neutral | N | 0.507661588 | None | None | N |
| R/H | 0.3167 | likely_benign | 0.5353 | ambiguous | -1.153 | Destabilizing | 0.999 | D | 0.387 | neutral | None | None | None | None | N |
| R/I | 0.9347 | likely_pathogenic | 0.9666 | pathogenic | -0.125 | Destabilizing | 0.975 | D | 0.55 | neutral | None | None | None | None | N |
| R/K | 0.5501 | ambiguous | 0.7151 | pathogenic | -0.582 | Destabilizing | 0.818 | D | 0.404 | neutral | None | None | None | None | N |
| R/L | 0.8364 | likely_pathogenic | 0.9168 | pathogenic | -0.125 | Destabilizing | 0.913 | D | 0.395 | neutral | N | 0.49889988 | None | None | N |
| R/M | 0.9305 | likely_pathogenic | 0.9709 | pathogenic | -0.275 | Destabilizing | 0.999 | D | 0.416 | neutral | None | None | None | None | N |
| R/N | 0.9727 | likely_pathogenic | 0.9863 | pathogenic | -0.07 | Destabilizing | 0.975 | D | 0.363 | neutral | None | None | None | None | N |
| R/P | 0.9914 | likely_pathogenic | 0.9945 | pathogenic | -0.278 | Destabilizing | 0.993 | D | 0.487 | neutral | N | 0.468514267 | None | None | N |
| R/Q | 0.5115 | ambiguous | 0.7193 | pathogenic | -0.357 | Destabilizing | 0.997 | D | 0.397 | neutral | N | 0.465854467 | None | None | N |
| R/S | 0.9663 | likely_pathogenic | 0.9828 | pathogenic | -0.766 | Destabilizing | 0.845 | D | 0.415 | neutral | None | None | None | None | N |
| R/T | 0.9475 | likely_pathogenic | 0.9778 | pathogenic | -0.564 | Destabilizing | 0.033 | N | 0.343 | neutral | None | None | None | None | N |
| R/V | 0.9476 | likely_pathogenic | 0.9727 | pathogenic | -0.278 | Destabilizing | 0.95 | D | 0.481 | neutral | None | None | None | None | N |
| R/W | 0.6697 | likely_pathogenic | 0.8089 | pathogenic | -0.692 | Destabilizing | 0.999 | D | 0.656 | neutral | None | None | None | None | N |
| R/Y | 0.8847 | likely_pathogenic | 0.9425 | pathogenic | -0.334 | Destabilizing | 0.996 | D | 0.487 | 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.