Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31699 | 95320;95321;95322 | chr2:178546236;178546235;178546234 | chr2:179410963;179410962;179410961 |
| N2AB | 30058 | 90397;90398;90399 | chr2:178546236;178546235;178546234 | chr2:179410963;179410962;179410961 |
| N2A | 29131 | 87616;87617;87618 | chr2:178546236;178546235;178546234 | chr2:179410963;179410962;179410961 |
| N2B | 22634 | 68125;68126;68127 | chr2:178546236;178546235;178546234 | chr2:179410963;179410962;179410961 |
| Novex-1 | 22759 | 68500;68501;68502 | chr2:178546236;178546235;178546234 | chr2:179410963;179410962;179410961 |
| Novex-2 | 22826 | 68701;68702;68703 | chr2:178546236;178546235;178546234 | chr2:179410963;179410962;179410961 |
| 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/M | rs751420355  |
-0.48 | 0.988 | N | 0.607 | 0.3 | 0.626087153395 | gnomAD-2.1.1 | 3.23E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.12E-05 | None | 1.6481E-04 | None | 0 | 2.35E-05 | 0 |
| V/M | rs751420355 |
-0.48 | 0.988 | N | 0.607 | 0.3 | 0.626087153395 | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 1.92604E-04 | None | 0 | 0 | 2.94E-05 | 2.06868E-04 | 4.77555E-04 |
| V/M | rs751420355 |
-0.48 | 0.988 | N | 0.607 | 0.3 | 0.626087153395 | gnomAD-4.0.0 | 2.66854E-05 | None | None | None | None | N | None | 0 | 0 | None | 3.39029E-05 | 4.45891E-05 | None | 0 | 0 | 2.54654E-05 | 9.90535E-05 | 1.60292E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.165 | likely_benign | 0.1633 | benign | -0.539 | Destabilizing | 0.002 | N | 0.137 | neutral | N | 0.409303614 | None | None | N |
| V/C | 0.742 | likely_pathogenic | 0.7467 | pathogenic | -0.809 | Destabilizing | 0.998 | D | 0.634 | neutral | None | None | None | None | N |
| V/D | 0.6656 | likely_pathogenic | 0.6709 | pathogenic | -0.049 | Destabilizing | 0.949 | D | 0.711 | prob.delet. | None | None | None | None | N |
| V/E | 0.5123 | ambiguous | 0.5184 | ambiguous | -0.124 | Destabilizing | 0.801 | D | 0.657 | neutral | N | 0.514991071 | None | None | N |
| V/F | 0.2179 | likely_benign | 0.2129 | benign | -0.569 | Destabilizing | 0.949 | D | 0.663 | neutral | None | None | None | None | N |
| V/G | 0.3551 | ambiguous | 0.358 | ambiguous | -0.712 | Destabilizing | 0.669 | D | 0.622 | neutral | N | 0.481187929 | None | None | N |
| V/H | 0.7659 | likely_pathogenic | 0.7763 | pathogenic | -0.197 | Destabilizing | 0.998 | D | 0.699 | prob.neutral | None | None | None | None | N |
| V/I | 0.0834 | likely_benign | 0.0831 | benign | -0.217 | Destabilizing | 0.016 | N | 0.223 | neutral | None | None | None | None | N |
| V/K | 0.6212 | likely_pathogenic | 0.6293 | pathogenic | -0.464 | Destabilizing | 0.842 | D | 0.665 | neutral | None | None | None | None | N |
| V/L | 0.2156 | likely_benign | 0.2106 | benign | -0.217 | Destabilizing | 0.679 | D | 0.448 | neutral | D | 0.530403241 | None | None | N |
| V/M | 0.1664 | likely_benign | 0.1627 | benign | -0.429 | Destabilizing | 0.988 | D | 0.607 | neutral | N | 0.485238711 | None | None | N |
| V/N | 0.5582 | ambiguous | 0.5396 | ambiguous | -0.315 | Destabilizing | 0.949 | D | 0.713 | prob.delet. | None | None | None | None | N |
| V/P | 0.95 | likely_pathogenic | 0.9534 | pathogenic | -0.289 | Destabilizing | 0.974 | D | 0.69 | prob.neutral | None | None | None | None | N |
| V/Q | 0.5295 | ambiguous | 0.5425 | ambiguous | -0.473 | Destabilizing | 0.974 | D | 0.689 | prob.neutral | None | None | None | None | N |
| V/R | 0.5671 | likely_pathogenic | 0.5807 | pathogenic | -0.02 | Destabilizing | 0.974 | D | 0.719 | prob.delet. | None | None | None | None | N |
| V/S | 0.3317 | likely_benign | 0.3297 | benign | -0.758 | Destabilizing | 0.172 | N | 0.471 | neutral | None | None | None | None | N |
| V/T | 0.2435 | likely_benign | 0.2385 | benign | -0.716 | Destabilizing | 0.728 | D | 0.481 | neutral | None | None | None | None | N |
| V/W | 0.9134 | likely_pathogenic | 0.9164 | pathogenic | -0.659 | Destabilizing | 0.998 | D | 0.739 | prob.delet. | None | None | None | None | N |
| V/Y | 0.6931 | likely_pathogenic | 0.6876 | pathogenic | -0.361 | Destabilizing | 0.991 | D | 0.655 | 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.