Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 6298 | 19117;19118;19119 | chr2:178729146;178729145;178729144 | chr2:179593873;179593872;179593871 |
| N2AB | 5981 | 18166;18167;18168 | chr2:178729146;178729145;178729144 | chr2:179593873;179593872;179593871 |
| N2A | 5054 | 15385;15386;15387 | chr2:178729146;178729145;178729144 | chr2:179593873;179593872;179593871 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/K | None | None | 0.984 | N | 0.833 | 0.477 | 0.777716587133 | gnomAD-4.0.0 | 7.64784E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.99164E-06 | 0 | 0 |
| I/R | rs375571785  |
-0.852 | 0.984 | N | 0.837 | 0.484 | 0.770724495559 | gnomAD-2.1.1 | 4.44E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 3.98E-05 | None | 0 | 0 | 0 |
| I/R | rs375571785 |
-0.852 | 0.984 | N | 0.837 | 0.484 | 0.770724495559 | gnomAD-4.0.0 | 6.95258E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.2239E-05 | 0 |
| I/T | rs375571785 |
-1.749 | 0.946 | N | 0.687 | 0.29 | None | gnomAD-2.1.1 | 5.45E-05 | None | None | None | None | I | None | 1.6899E-04 | 0 | None | 0 | 1.59557E-04 | None | 0 | None | 0 | 5.9E-05 | 0 |
| I/T | rs375571785 |
-1.749 | 0.946 | N | 0.687 | 0.29 | None | gnomAD-3.1.2 | 7.23E-05 | None | None | None | None | I | None | 2.17003E-04 | 0 | 0 | 0 | 1.92901E-04 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| I/T | rs375571785 |
-1.749 | 0.946 | N | 0.687 | 0.29 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | I | None | 0 | 0 | None | None | 1E-03 | 0 | None | None | None | 0 | None |
| I/T | rs375571785 |
-1.749 | 0.946 | N | 0.687 | 0.29 | None | gnomAD-4.0.0 | 3.08056E-05 | None | None | None | None | I | None | 1.348E-04 | 0 | None | 0 | 6.73461E-05 | None | 0 | 0 | 2.73754E-05 | 1.15567E-05 | 4.87948E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.4569 | ambiguous | 0.4735 | ambiguous | -2.114 | Highly Destabilizing | 0.919 | D | 0.599 | neutral | None | None | None | None | I |
| I/C | 0.9245 | likely_pathogenic | 0.94 | pathogenic | -1.422 | Destabilizing | 0.999 | D | 0.713 | prob.delet. | None | None | None | None | I |
| I/D | 0.9854 | likely_pathogenic | 0.987 | pathogenic | -1.759 | Destabilizing | 0.996 | D | 0.824 | deleterious | None | None | None | None | I |
| I/E | 0.9638 | likely_pathogenic | 0.9621 | pathogenic | -1.621 | Destabilizing | 0.996 | D | 0.83 | deleterious | None | None | None | None | I |
| I/F | 0.5133 | ambiguous | 0.5663 | pathogenic | -1.244 | Destabilizing | 0.976 | D | 0.61 | neutral | None | None | None | None | I |
| I/G | 0.9043 | likely_pathogenic | 0.9137 | pathogenic | -2.581 | Highly Destabilizing | 0.996 | D | 0.833 | deleterious | None | None | None | None | I |
| I/H | 0.9742 | likely_pathogenic | 0.9791 | pathogenic | -1.864 | Destabilizing | 0.999 | D | 0.815 | deleterious | None | None | None | None | I |
| I/K | 0.9494 | likely_pathogenic | 0.9523 | pathogenic | -1.427 | Destabilizing | 0.984 | D | 0.833 | deleterious | N | 0.480544319 | None | None | I |
| I/L | 0.1095 | likely_benign | 0.1398 | benign | -0.821 | Destabilizing | 0.011 | N | 0.197 | neutral | N | 0.349440794 | None | None | I |
| I/M | 0.1101 | likely_benign | 0.1176 | benign | -0.772 | Destabilizing | 0.968 | D | 0.592 | neutral | N | 0.487627459 | None | None | I |
| I/N | 0.841 | likely_pathogenic | 0.8636 | pathogenic | -1.498 | Destabilizing | 0.996 | D | 0.837 | deleterious | None | None | None | None | I |
| I/P | 0.7388 | likely_pathogenic | 0.736 | pathogenic | -1.226 | Destabilizing | 0.996 | D | 0.837 | deleterious | None | None | None | None | I |
| I/Q | 0.9338 | likely_pathogenic | 0.9404 | pathogenic | -1.495 | Destabilizing | 0.996 | D | 0.837 | deleterious | None | None | None | None | I |
| I/R | 0.922 | likely_pathogenic | 0.9324 | pathogenic | -1.047 | Destabilizing | 0.984 | D | 0.837 | deleterious | N | 0.468934524 | None | None | I |
| I/S | 0.7461 | likely_pathogenic | 0.7732 | pathogenic | -2.247 | Highly Destabilizing | 0.988 | D | 0.747 | deleterious | None | None | None | None | I |
| I/T | 0.3517 | ambiguous | 0.3606 | ambiguous | -1.973 | Destabilizing | 0.946 | D | 0.687 | prob.neutral | N | 0.50621322 | None | None | I |
| I/V | 0.1195 | likely_benign | 0.1191 | benign | -1.226 | Destabilizing | 0.437 | N | 0.4 | neutral | N | 0.494918791 | None | None | I |
| I/W | 0.9671 | likely_pathogenic | 0.9749 | pathogenic | -1.473 | Destabilizing | 0.999 | D | 0.791 | deleterious | None | None | None | None | I |
| I/Y | 0.9395 | likely_pathogenic | 0.9525 | pathogenic | -1.196 | Destabilizing | 0.988 | D | 0.727 | prob.delet. | 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.