Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16989 | 51190;51191;51192 | chr2:178611164;178611163;178611162 | chr2:179475891;179475890;179475889 |
| N2AB | 15348 | 46267;46268;46269 | chr2:178611164;178611163;178611162 | chr2:179475891;179475890;179475889 |
| N2A | 14421 | 43486;43487;43488 | chr2:178611164;178611163;178611162 | chr2:179475891;179475890;179475889 |
| N2B | 7924 | 23995;23996;23997 | chr2:178611164;178611163;178611162 | chr2:179475891;179475890;179475889 |
| Novex-1 | 8049 | 24370;24371;24372 | chr2:178611164;178611163;178611162 | chr2:179475891;179475890;179475889 |
| Novex-2 | 8116 | 24571;24572;24573 | chr2:178611164;178611163;178611162 | chr2:179475891;179475890;179475889 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| H/L | rs2056241727  |
None | 1.0 | N | 0.718 | 0.475 | 0.514240282655 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.06954E-04 | 0 |
| H/L | rs2056241727 |
None | 1.0 | N | 0.718 | 0.475 | 0.514240282655 | gnomAD-4.0.0 | 6.57886E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.06954E-04 | 0 |
| H/Q | rs1187588369 |
-0.653 | 1.0 | N | 0.728 | 0.218 | 0.17258766438 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 2.91E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| H/Q | rs1187588369 |
-0.653 | 1.0 | N | 0.728 | 0.218 | 0.17258766438 | gnomAD-4.0.0 | 1.5934E-06 | None | None | None | None | N | None | 0 | 2.28896E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| H/A | 0.3627 | ambiguous | 0.365 | ambiguous | -1.115 | Destabilizing | 0.999 | D | 0.642 | neutral | None | None | None | None | N |
| H/C | 0.1615 | likely_benign | 0.1615 | benign | -0.593 | Destabilizing | 1.0 | D | 0.75 | deleterious | None | None | None | None | N |
| H/D | 0.3623 | ambiguous | 0.3709 | ambiguous | -0.379 | Destabilizing | 1.0 | D | 0.713 | prob.delet. | N | 0.448076751 | None | None | N |
| H/E | 0.2979 | likely_benign | 0.2928 | benign | -0.31 | Destabilizing | 0.999 | D | 0.509 | neutral | None | None | None | None | N |
| H/F | 0.2542 | likely_benign | 0.2736 | benign | -0.452 | Destabilizing | 1.0 | D | 0.773 | deleterious | None | None | None | None | N |
| H/G | 0.4453 | ambiguous | 0.4371 | ambiguous | -1.423 | Destabilizing | 0.999 | D | 0.675 | prob.neutral | None | None | None | None | N |
| H/I | 0.2874 | likely_benign | 0.2906 | benign | -0.284 | Destabilizing | 1.0 | D | 0.753 | deleterious | None | None | None | None | N |
| H/K | 0.1961 | likely_benign | 0.1875 | benign | -0.898 | Destabilizing | 1.0 | D | 0.711 | prob.delet. | None | None | None | None | N |
| H/L | 0.1292 | likely_benign | 0.1285 | benign | -0.284 | Destabilizing | 1.0 | D | 0.718 | prob.delet. | N | 0.386696254 | None | None | N |
| H/M | 0.3828 | ambiguous | 0.3915 | ambiguous | -0.38 | Destabilizing | 1.0 | D | 0.757 | deleterious | None | None | None | None | N |
| H/N | 0.1435 | likely_benign | 0.1455 | benign | -0.774 | Destabilizing | 0.999 | D | 0.503 | neutral | N | 0.448229931 | None | None | N |
| H/P | 0.9341 | likely_pathogenic | 0.9048 | pathogenic | -0.541 | Destabilizing | 1.0 | D | 0.747 | deleterious | N | 0.437439162 | None | None | N |
| H/Q | 0.1455 | likely_benign | 0.145 | benign | -0.666 | Destabilizing | 1.0 | D | 0.728 | prob.delet. | N | 0.433351486 | None | None | N |
| H/R | 0.1089 | likely_benign | 0.1051 | benign | -0.938 | Destabilizing | 1.0 | D | 0.681 | prob.neutral | N | 0.438397837 | None | None | N |
| H/S | 0.2691 | likely_benign | 0.2777 | benign | -1.071 | Destabilizing | 1.0 | D | 0.704 | prob.neutral | None | None | None | None | N |
| H/T | 0.2574 | likely_benign | 0.2568 | benign | -0.906 | Destabilizing | 1.0 | D | 0.742 | deleterious | None | None | None | None | N |
| H/V | 0.2458 | likely_benign | 0.243 | benign | -0.541 | Destabilizing | 1.0 | D | 0.737 | prob.delet. | None | None | None | None | N |
| H/W | 0.3752 | ambiguous | 0.3902 | ambiguous | -0.169 | Destabilizing | 1.0 | D | 0.757 | deleterious | None | None | None | None | N |
| H/Y | 0.1055 | likely_benign | 0.1156 | benign | 0.095 | Stabilizing | 0.999 | D | 0.514 | neutral | N | 0.414729915 | 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.