Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16486 | 49681;49682;49683 | chr2:178613827;178613826;178613825 | chr2:179478554;179478553;179478552 |
| N2AB | 14845 | 44758;44759;44760 | chr2:178613827;178613826;178613825 | chr2:179478554;179478553;179478552 |
| N2A | 13918 | 41977;41978;41979 | chr2:178613827;178613826;178613825 | chr2:179478554;179478553;179478552 |
| N2B | 7421 | 22486;22487;22488 | chr2:178613827;178613826;178613825 | chr2:179478554;179478553;179478552 |
| Novex-1 | 7546 | 22861;22862;22863 | chr2:178613827;178613826;178613825 | chr2:179478554;179478553;179478552 |
| Novex-2 | 7613 | 23062;23063;23064 | chr2:178613827;178613826;178613825 | chr2:179478554;179478553;179478552 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| W/R | None | None | 1.0 | N | 0.802 | 0.522 | 0.586174608782 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 1.95465E-04 | None | 0 | 0 | 0 | 0 | 0 |
| W/R | None | None | 1.0 | N | 0.802 | 0.522 | 0.586174608782 | gnomAD-4.0.0 | 6.58371E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 1.95465E-04 | None | 0 | 0 | 0 | 0 | 0 |
| W/S | rs774023517  |
-2.319 | 1.0 | N | 0.791 | 0.397 | 0.783064499603 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| W/S | rs774023517 |
-2.319 | 1.0 | N | 0.791 | 0.397 | 0.783064499603 | gnomAD-4.0.0 | 3.18725E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.86862E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| W/A | 0.9454 | likely_pathogenic | 0.9429 | pathogenic | -3.964 | Highly Destabilizing | 1.0 | D | 0.797 | deleterious | None | None | None | None | I |
| W/C | 0.9356 | likely_pathogenic | 0.9204 | pathogenic | -2.026 | Highly Destabilizing | 1.0 | D | 0.767 | deleterious | N | 0.477142519 | None | None | I |
| W/D | 0.9916 | likely_pathogenic | 0.9936 | pathogenic | -3.282 | Highly Destabilizing | 1.0 | D | 0.801 | deleterious | None | None | None | None | I |
| W/E | 0.9884 | likely_pathogenic | 0.9886 | pathogenic | -3.218 | Highly Destabilizing | 1.0 | D | 0.798 | deleterious | None | None | None | None | I |
| W/F | 0.4267 | ambiguous | 0.3853 | ambiguous | -2.508 | Highly Destabilizing | 1.0 | D | 0.825 | deleterious | None | None | None | None | I |
| W/G | 0.9556 | likely_pathogenic | 0.9574 | pathogenic | -4.144 | Highly Destabilizing | 1.0 | D | 0.787 | deleterious | N | 0.478402037 | None | None | I |
| W/H | 0.8373 | likely_pathogenic | 0.7899 | pathogenic | -2.487 | Highly Destabilizing | 1.0 | D | 0.775 | deleterious | None | None | None | None | I |
| W/I | 0.6848 | likely_pathogenic | 0.6516 | pathogenic | -3.247 | Highly Destabilizing | 1.0 | D | 0.799 | deleterious | None | None | None | None | I |
| W/K | 0.988 | likely_pathogenic | 0.9876 | pathogenic | -2.454 | Highly Destabilizing | 1.0 | D | 0.798 | deleterious | None | None | None | None | I |
| W/L | 0.6738 | likely_pathogenic | 0.6655 | pathogenic | -3.247 | Highly Destabilizing | 1.0 | D | 0.787 | deleterious | N | 0.444785063 | None | None | I |
| W/M | 0.8624 | likely_pathogenic | 0.8523 | pathogenic | -2.583 | Highly Destabilizing | 1.0 | D | 0.781 | deleterious | None | None | None | None | I |
| W/N | 0.97 | likely_pathogenic | 0.9715 | pathogenic | -2.798 | Highly Destabilizing | 1.0 | D | 0.792 | deleterious | None | None | None | None | I |
| W/P | 0.9994 | likely_pathogenic | 0.9994 | pathogenic | -3.512 | Highly Destabilizing | 1.0 | D | 0.794 | deleterious | None | None | None | None | I |
| W/Q | 0.9789 | likely_pathogenic | 0.9753 | pathogenic | -2.874 | Highly Destabilizing | 1.0 | D | 0.79 | deleterious | None | None | None | None | I |
| W/R | 0.9714 | likely_pathogenic | 0.9659 | pathogenic | -1.667 | Destabilizing | 1.0 | D | 0.802 | deleterious | N | 0.450334234 | None | None | I |
| W/S | 0.8985 | likely_pathogenic | 0.8969 | pathogenic | -3.138 | Highly Destabilizing | 1.0 | D | 0.791 | deleterious | N | 0.460376495 | None | None | I |
| W/T | 0.9027 | likely_pathogenic | 0.8975 | pathogenic | -3.023 | Highly Destabilizing | 1.0 | D | 0.79 | deleterious | None | None | None | None | I |
| W/V | 0.7514 | likely_pathogenic | 0.7168 | pathogenic | -3.512 | Highly Destabilizing | 1.0 | D | 0.793 | deleterious | None | None | None | None | I |
| W/Y | 0.6204 | likely_pathogenic | 0.5626 | ambiguous | -2.343 | Highly Destabilizing | 1.0 | D | 0.781 | deleterious | None | None | 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.