Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21368 | 64327;64328;64329 | chr2:178586799;178586798;178586797 | chr2:179451526;179451525;179451524 |
| N2AB | 19727 | 59404;59405;59406 | chr2:178586799;178586798;178586797 | chr2:179451526;179451525;179451524 |
| N2A | 18800 | 56623;56624;56625 | chr2:178586799;178586798;178586797 | chr2:179451526;179451525;179451524 |
| N2B | 12303 | 37132;37133;37134 | chr2:178586799;178586798;178586797 | chr2:179451526;179451525;179451524 |
| Novex-1 | 12428 | 37507;37508;37509 | chr2:178586799;178586798;178586797 | chr2:179451526;179451525;179451524 |
| Novex-2 | 12495 | 37708;37709;37710 | chr2:178586799;178586798;178586797 | chr2:179451526;179451525;179451524 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/H | None | None | 1.0 | N | 0.877 | 0.401 | 0.490006198212 | gnomAD-4.0.0 | 6.85379E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.00153E-07 | 0 | 0 |
| D/N | rs1462401348  |
None | 1.0 | N | 0.843 | 0.395 | 0.423597194605 | gnomAD-4.0.0 | 6.85379E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 2.52461E-05 | None | 0 | 0 | 0 | 0 | 0 |
| D/Y | rs1462401348 |
-0.306 | 1.0 | N | 0.855 | 0.422 | 0.756051586483 | gnomAD-2.1.1 | 8.14E-06 | None | None | None | None | I | None | 0 | 5.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| D/Y | rs1462401348 |
-0.306 | 1.0 | N | 0.855 | 0.422 | 0.756051586483 | gnomAD-4.0.0 | 1.37076E-06 | None | None | None | None | I | None | 0 | 4.52039E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.7783 | likely_pathogenic | 0.7189 | pathogenic | -0.499 | Destabilizing | 1.0 | D | 0.843 | deleterious | N | 0.517630154 | None | None | I |
| D/C | 0.9818 | likely_pathogenic | 0.9711 | pathogenic | -0.391 | Destabilizing | 1.0 | D | 0.845 | deleterious | None | None | None | None | I |
| D/E | 0.8414 | likely_pathogenic | 0.7597 | pathogenic | -0.922 | Destabilizing | 1.0 | D | 0.661 | neutral | N | 0.517596154 | None | None | I |
| D/F | 0.9644 | likely_pathogenic | 0.9487 | pathogenic | -0.425 | Destabilizing | 1.0 | D | 0.857 | deleterious | None | None | None | None | I |
| D/G | 0.8198 | likely_pathogenic | 0.7835 | pathogenic | -0.851 | Destabilizing | 1.0 | D | 0.835 | deleterious | N | 0.480347275 | None | None | I |
| D/H | 0.9538 | likely_pathogenic | 0.9248 | pathogenic | -0.928 | Destabilizing | 1.0 | D | 0.877 | deleterious | N | 0.519911559 | None | None | I |
| D/I | 0.9854 | likely_pathogenic | 0.9694 | pathogenic | 0.432 | Stabilizing | 1.0 | D | 0.861 | deleterious | None | None | None | None | I |
| D/K | 0.9878 | likely_pathogenic | 0.9774 | pathogenic | -0.894 | Destabilizing | 1.0 | D | 0.874 | deleterious | None | None | None | None | I |
| D/L | 0.9291 | likely_pathogenic | 0.8936 | pathogenic | 0.432 | Stabilizing | 1.0 | D | 0.876 | deleterious | None | None | None | None | I |
| D/M | 0.9864 | likely_pathogenic | 0.9749 | pathogenic | 0.902 | Stabilizing | 1.0 | D | 0.813 | deleterious | None | None | None | None | I |
| D/N | 0.8148 | likely_pathogenic | 0.6976 | pathogenic | -1.115 | Destabilizing | 1.0 | D | 0.843 | deleterious | N | 0.486803695 | None | None | I |
| D/P | 0.9949 | likely_pathogenic | 0.9924 | pathogenic | 0.147 | Stabilizing | 1.0 | D | 0.889 | deleterious | None | None | None | None | I |
| D/Q | 0.9701 | likely_pathogenic | 0.95 | pathogenic | -0.948 | Destabilizing | 1.0 | D | 0.852 | deleterious | None | None | None | None | I |
| D/R | 0.9863 | likely_pathogenic | 0.9778 | pathogenic | -0.84 | Destabilizing | 1.0 | D | 0.883 | deleterious | None | None | None | None | I |
| D/S | 0.7069 | likely_pathogenic | 0.6152 | pathogenic | -1.447 | Destabilizing | 1.0 | D | 0.819 | deleterious | None | None | None | None | I |
| D/T | 0.9562 | likely_pathogenic | 0.9257 | pathogenic | -1.166 | Destabilizing | 1.0 | D | 0.874 | deleterious | None | None | None | None | I |
| D/V | 0.9583 | likely_pathogenic | 0.9222 | pathogenic | 0.147 | Stabilizing | 1.0 | D | 0.875 | deleterious | N | 0.51940458 | None | None | I |
| D/W | 0.9959 | likely_pathogenic | 0.9933 | pathogenic | -0.471 | Destabilizing | 1.0 | D | 0.859 | deleterious | None | None | None | None | I |
| D/Y | 0.8806 | likely_pathogenic | 0.8126 | pathogenic | -0.269 | Destabilizing | 1.0 | D | 0.855 | deleterious | N | 0.51965807 | None | None | I |
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.