Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 6235 | 18928;18929;18930 | chr2:178729453;178729452;178729451 | chr2:179594180;179594179;179594178 |
| N2AB | 5918 | 17977;17978;17979 | chr2:178729453;178729452;178729451 | chr2:179594180;179594179;179594178 |
| N2A | 4991 | 15196;15197;15198 | chr2:178729453;178729452;178729451 | chr2:179594180;179594179;179594178 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/K | rs766055257  |
0.35 | 0.92 | N | 0.331 | 0.229 | 0.134241683229 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.91E-06 | 0 |
| N/K | rs766055257 |
0.35 | 0.92 | N | 0.331 | 0.229 | 0.134241683229 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| N/K | rs766055257 |
0.35 | 0.92 | N | 0.331 | 0.229 | 0.134241683229 | gnomAD-4.0.0 | 3.71877E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.23866E-06 | 0 | 1.60133E-05 |
| N/S | rs2079993234 |
None | 0.704 | N | 0.381 | 0.224 | 0.158396225186 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| N/S | rs2079993234 |
None | 0.704 | N | 0.381 | 0.224 | 0.158396225186 | gnomAD-4.0.0 | 2.56265E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.78758E-06 | 0 | 0 |
| N/Y | None | None | 0.996 | N | 0.442 | 0.41 | 0.517655672 | gnomAD-4.0.0 | 2.05287E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 3.47802E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/A | 0.4069 | ambiguous | 0.4367 | ambiguous | -0.696 | Destabilizing | 0.17 | N | 0.245 | neutral | None | None | None | None | N |
| N/C | 0.5563 | ambiguous | 0.581 | pathogenic | 0.218 | Stabilizing | 0.999 | D | 0.458 | neutral | None | None | None | None | N |
| N/D | 0.1121 | likely_benign | 0.1138 | benign | -0.04 | Destabilizing | 0.005 | N | 0.12 | neutral | N | 0.409281319 | None | None | N |
| N/E | 0.4591 | ambiguous | 0.4913 | ambiguous | -0.016 | Destabilizing | 0.759 | D | 0.341 | neutral | None | None | None | None | N |
| N/F | 0.7494 | likely_pathogenic | 0.7753 | pathogenic | -0.727 | Destabilizing | 0.997 | D | 0.463 | neutral | None | None | None | None | N |
| N/G | 0.2774 | likely_benign | 0.2999 | benign | -0.96 | Destabilizing | 0.863 | D | 0.358 | neutral | None | None | None | None | N |
| N/H | 0.2195 | likely_benign | 0.2228 | benign | -0.87 | Destabilizing | 0.996 | D | 0.365 | neutral | N | 0.495199669 | None | None | N |
| N/I | 0.6152 | likely_pathogenic | 0.6367 | pathogenic | -0.06 | Destabilizing | 0.988 | D | 0.472 | neutral | N | 0.513810903 | None | None | N |
| N/K | 0.5272 | ambiguous | 0.5169 | ambiguous | -0.192 | Destabilizing | 0.92 | D | 0.331 | neutral | N | 0.459698721 | None | None | N |
| N/L | 0.5294 | ambiguous | 0.5582 | ambiguous | -0.06 | Destabilizing | 0.939 | D | 0.478 | neutral | None | None | None | None | N |
| N/M | 0.5581 | ambiguous | 0.5797 | pathogenic | 0.338 | Stabilizing | 0.999 | D | 0.439 | neutral | None | None | None | None | N |
| N/P | 0.953 | likely_pathogenic | 0.9627 | pathogenic | -0.243 | Destabilizing | 0.991 | D | 0.424 | neutral | None | None | None | None | N |
| N/Q | 0.4613 | ambiguous | 0.4793 | ambiguous | -0.605 | Destabilizing | 0.991 | D | 0.324 | neutral | None | None | None | None | N |
| N/R | 0.5729 | likely_pathogenic | 0.5714 | pathogenic | -0.196 | Destabilizing | 0.991 | D | 0.316 | neutral | None | None | None | None | N |
| N/S | 0.1409 | likely_benign | 0.1461 | benign | -0.523 | Destabilizing | 0.704 | D | 0.381 | neutral | N | 0.461268884 | None | None | N |
| N/T | 0.3677 | ambiguous | 0.3822 | ambiguous | -0.327 | Destabilizing | 0.92 | D | 0.326 | neutral | N | 0.501947619 | None | None | N |
| N/V | 0.596 | likely_pathogenic | 0.6197 | pathogenic | -0.243 | Destabilizing | 0.939 | D | 0.473 | neutral | None | None | None | None | N |
| N/W | 0.854 | likely_pathogenic | 0.8655 | pathogenic | -0.584 | Destabilizing | 0.999 | D | 0.553 | neutral | None | None | None | None | N |
| N/Y | 0.2743 | likely_benign | 0.2851 | benign | -0.388 | Destabilizing | 0.996 | D | 0.442 | neutral | N | 0.502454598 | 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.