Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22042 | 66349;66350;66351 | chr2:178582332;178582331;178582330 | chr2:179447059;179447058;179447057 |
| N2AB | 20401 | 61426;61427;61428 | chr2:178582332;178582331;178582330 | chr2:179447059;179447058;179447057 |
| N2A | 19474 | 58645;58646;58647 | chr2:178582332;178582331;178582330 | chr2:179447059;179447058;179447057 |
| N2B | 12977 | 39154;39155;39156 | chr2:178582332;178582331;178582330 | chr2:179447059;179447058;179447057 |
| Novex-1 | 13102 | 39529;39530;39531 | chr2:178582332;178582331;178582330 | chr2:179447059;179447058;179447057 |
| Novex-2 | 13169 | 39730;39731;39732 | chr2:178582332;178582331;178582330 | chr2:179447059;179447058;179447057 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/L | rs764678997  |
-0.134 | 0.001 | N | 0.395 | 0.06 | 0.237489013734 | gnomAD-2.1.1 | 4.13E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.47E-05 | None | 0 | 0 | 0 |
| V/L | rs764678997 |
-0.134 | 0.001 | N | 0.395 | 0.06 | 0.237489013734 | gnomAD-4.0.0 | 1.61948E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.47545E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.2257 | likely_benign | 0.1778 | benign | -1.726 | Destabilizing | None | N | 0.161 | neutral | N | 0.421037973 | None | None | N |
| V/C | 0.5615 | ambiguous | 0.498 | ambiguous | -1.08 | Destabilizing | 0.204 | N | 0.526 | neutral | None | None | None | None | N |
| V/D | 0.6426 | likely_pathogenic | 0.5923 | pathogenic | -2.131 | Highly Destabilizing | 0.026 | N | 0.705 | prob.delet. | N | 0.487766244 | None | None | N |
| V/E | 0.5149 | ambiguous | 0.4758 | ambiguous | -1.946 | Destabilizing | 0.035 | N | 0.625 | neutral | None | None | None | None | N |
| V/F | 0.2421 | likely_benign | 0.233 | benign | -0.994 | Destabilizing | 0.087 | N | 0.667 | prob.neutral | N | 0.518201948 | None | None | N |
| V/G | 0.368 | ambiguous | 0.2858 | benign | -2.227 | Highly Destabilizing | 0.013 | N | 0.605 | neutral | N | 0.478779555 | None | None | N |
| V/H | 0.6766 | likely_pathogenic | 0.623 | pathogenic | -2.012 | Highly Destabilizing | 0.439 | N | 0.683 | prob.neutral | None | None | None | None | N |
| V/I | 0.0606 | likely_benign | 0.0601 | benign | -0.357 | Destabilizing | None | N | 0.099 | neutral | N | 0.444184192 | None | None | N |
| V/K | 0.5372 | ambiguous | 0.4782 | ambiguous | -1.478 | Destabilizing | 0.018 | N | 0.595 | neutral | None | None | None | None | N |
| V/L | 0.1261 | likely_benign | 0.1041 | benign | -0.357 | Destabilizing | 0.001 | N | 0.395 | neutral | N | 0.370030363 | None | None | N |
| V/M | 0.1403 | likely_benign | 0.1286 | benign | -0.295 | Destabilizing | 0.112 | N | 0.488 | neutral | None | None | None | None | N |
| V/N | 0.3872 | ambiguous | 0.328 | benign | -1.665 | Destabilizing | 0.112 | N | 0.717 | prob.delet. | None | None | None | None | N |
| V/P | 0.9186 | likely_pathogenic | 0.8909 | pathogenic | -0.784 | Destabilizing | 0.204 | N | 0.675 | prob.neutral | None | None | None | None | N |
| V/Q | 0.4589 | ambiguous | 0.4056 | ambiguous | -1.552 | Destabilizing | 0.112 | N | 0.677 | prob.neutral | None | None | None | None | N |
| V/R | 0.4653 | ambiguous | 0.3864 | ambiguous | -1.295 | Destabilizing | None | N | 0.651 | prob.neutral | None | None | None | None | N |
| V/S | 0.3009 | likely_benign | 0.2331 | benign | -2.251 | Highly Destabilizing | 0.007 | N | 0.565 | neutral | None | None | None | None | N |
| V/T | 0.2358 | likely_benign | 0.2022 | benign | -1.931 | Destabilizing | None | N | 0.187 | neutral | None | None | None | None | N |
| V/W | 0.8791 | likely_pathogenic | 0.8633 | pathogenic | -1.521 | Destabilizing | 0.747 | D | 0.743 | deleterious | None | None | None | None | N |
| V/Y | 0.6206 | likely_pathogenic | 0.5879 | pathogenic | -1.087 | Destabilizing | 0.204 | N | 0.626 | 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.