Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16197 | 48814;48815;48816 | chr2:178615356;178615355;178615354 | chr2:179480083;179480082;179480081 |
| N2AB | 14556 | 43891;43892;43893 | chr2:178615356;178615355;178615354 | chr2:179480083;179480082;179480081 |
| N2A | 13629 | 41110;41111;41112 | chr2:178615356;178615355;178615354 | chr2:179480083;179480082;179480081 |
| N2B | 7132 | 21619;21620;21621 | chr2:178615356;178615355;178615354 | chr2:179480083;179480082;179480081 |
| Novex-1 | 7257 | 21994;21995;21996 | chr2:178615356;178615355;178615354 | chr2:179480083;179480082;179480081 |
| Novex-2 | 7324 | 22195;22196;22197 | chr2:178615356;178615355;178615354 | chr2:179480083;179480082;179480081 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/C | rs748917057  |
-0.358 | 1.0 | D | 0.702 | 0.403 | 0.671359793744 | gnomAD-2.1.1 | 1.43E-05 | None | None | None | None | N | None | 8.28E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 7.83E-06 | 1.40647E-04 |
| R/C | rs748917057 |
-0.358 | 1.0 | D | 0.702 | 0.403 | 0.671359793744 | gnomAD-3.1.2 | 5.27E-05 | None | None | None | None | N | None | 7.25E-05 | 6.57E-05 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 9.5511E-04 |
| R/C | rs748917057 |
-0.358 | 1.0 | D | 0.702 | 0.403 | 0.671359793744 | gnomAD-4.0.0 | 1.30249E-05 | None | None | None | None | N | None | 5.34888E-05 | 5.00885E-05 | None | 0 | 0 | None | 0 | 0 | 6.78538E-06 | 1.099E-05 | 8.01462E-05 |
| R/G | rs748917057 |
-0.999 | 1.0 | N | 0.653 | 0.403 | 0.575644953977 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| R/G | rs748917057 |
-0.999 | 1.0 | N | 0.653 | 0.403 | 0.575644953977 | gnomAD-4.0.0 | 1.36949E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.32126E-05 | 0 |
| R/H | rs369826752 |
-1.545 | 1.0 | N | 0.673 | 0.395 | None | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 6.47E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| R/H | rs369826752 |
-1.545 | 1.0 | N | 0.673 | 0.395 | None | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.5412 | ambiguous | 0.5716 | pathogenic | -0.302 | Destabilizing | 0.999 | D | 0.644 | neutral | None | None | None | None | N |
| R/C | 0.436 | ambiguous | 0.4389 | ambiguous | -0.344 | Destabilizing | 1.0 | D | 0.702 | prob.neutral | D | 0.557606247 | None | None | N |
| R/D | 0.8801 | likely_pathogenic | 0.8842 | pathogenic | -0.003 | Destabilizing | 1.0 | D | 0.701 | prob.neutral | None | None | None | None | N |
| R/E | 0.5631 | ambiguous | 0.581 | pathogenic | 0.102 | Stabilizing | 0.999 | D | 0.682 | prob.neutral | None | None | None | None | N |
| R/F | 0.8074 | likely_pathogenic | 0.8236 | pathogenic | -0.382 | Destabilizing | 1.0 | D | 0.685 | prob.neutral | None | None | None | None | N |
| R/G | 0.5823 | likely_pathogenic | 0.5761 | pathogenic | -0.551 | Destabilizing | 1.0 | D | 0.653 | neutral | N | 0.464154005 | None | None | N |
| R/H | 0.2548 | likely_benign | 0.2457 | benign | -1.21 | Destabilizing | 1.0 | D | 0.673 | neutral | N | 0.480727346 | None | None | N |
| R/I | 0.487 | ambiguous | 0.5255 | ambiguous | 0.339 | Stabilizing | 1.0 | D | 0.7 | prob.neutral | None | None | None | None | N |
| R/K | 0.1597 | likely_benign | 0.1617 | benign | -0.228 | Destabilizing | 0.998 | D | 0.525 | neutral | None | None | None | None | N |
| R/L | 0.4338 | ambiguous | 0.4509 | ambiguous | 0.339 | Stabilizing | 1.0 | D | 0.653 | neutral | N | 0.460721406 | None | None | N |
| R/M | 0.5336 | ambiguous | 0.5416 | ambiguous | -0.141 | Destabilizing | 1.0 | D | 0.656 | neutral | None | None | None | None | N |
| R/N | 0.8235 | likely_pathogenic | 0.8402 | pathogenic | 0.033 | Stabilizing | 1.0 | D | 0.685 | prob.neutral | None | None | None | None | N |
| R/P | 0.6838 | likely_pathogenic | 0.6891 | pathogenic | 0.147 | Stabilizing | 1.0 | D | 0.681 | prob.neutral | N | 0.453314561 | None | None | N |
| R/Q | 0.1863 | likely_benign | 0.1812 | benign | -0.033 | Destabilizing | 1.0 | D | 0.677 | prob.neutral | None | None | None | None | N |
| R/S | 0.756 | likely_pathogenic | 0.7766 | pathogenic | -0.453 | Destabilizing | 1.0 | D | 0.667 | neutral | N | 0.460576876 | None | None | N |
| R/T | 0.5638 | ambiguous | 0.5727 | pathogenic | -0.18 | Destabilizing | 1.0 | D | 0.664 | neutral | None | None | None | None | N |
| R/V | 0.5489 | ambiguous | 0.5929 | pathogenic | 0.147 | Stabilizing | 1.0 | D | 0.693 | prob.neutral | None | None | None | None | N |
| R/W | 0.5037 | ambiguous | 0.4657 | ambiguous | -0.324 | Destabilizing | 1.0 | D | 0.705 | prob.neutral | None | None | None | None | N |
| R/Y | 0.6919 | likely_pathogenic | 0.7013 | pathogenic | 0.052 | Stabilizing | 1.0 | D | 0.691 | prob.neutral | None | None | 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.