Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25441 | 76546;76547;76548 | chr2:178569811;178569810;178569809 | chr2:179434538;179434537;179434536 |
| N2AB | 23800 | 71623;71624;71625 | chr2:178569811;178569810;178569809 | chr2:179434538;179434537;179434536 |
| N2A | 22873 | 68842;68843;68844 | chr2:178569811;178569810;178569809 | chr2:179434538;179434537;179434536 |
| N2B | 16376 | 49351;49352;49353 | chr2:178569811;178569810;178569809 | chr2:179434538;179434537;179434536 |
| Novex-1 | 16501 | 49726;49727;49728 | chr2:178569811;178569810;178569809 | chr2:179434538;179434537;179434536 |
| Novex-2 | 16568 | 49927;49928;49929 | chr2:178569811;178569810;178569809 | chr2:179434538;179434537;179434536 |
| 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/V | rs759489696  |
-1.487 | 0.333 | N | 0.255 | 0.044 | 0.416581338634 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.89E-06 | 0 |
| I/V | rs759489696 |
-1.487 | 0.333 | N | 0.255 | 0.044 | 0.416581338634 | 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 |
| I/V | rs759489696 |
-1.487 | 0.333 | N | 0.255 | 0.044 | 0.416581338634 | gnomAD-4.0.0 | 4.33889E-06 | None | None | None | None | N | None | 1.33522E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 2.54318E-06 | 2.19645E-05 | 1.60169E-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 | 0.3307 | likely_benign | 0.3774 | ambiguous | -2.7 | Highly Destabilizing | 0.992 | D | 0.593 | neutral | None | None | None | None | N |
| I/C | 0.6536 | likely_pathogenic | 0.7008 | pathogenic | -2.229 | Highly Destabilizing | 1.0 | D | 0.689 | prob.neutral | None | None | None | None | N |
| I/D | 0.8973 | likely_pathogenic | 0.9308 | pathogenic | -3.437 | Highly Destabilizing | 1.0 | D | 0.762 | deleterious | None | None | None | None | N |
| I/E | 0.7343 | likely_pathogenic | 0.8083 | pathogenic | -3.267 | Highly Destabilizing | 1.0 | D | 0.747 | deleterious | None | None | None | None | N |
| I/F | 0.1886 | likely_benign | 0.2214 | benign | -1.51 | Destabilizing | 0.998 | D | 0.65 | neutral | N | 0.510360751 | None | None | N |
| I/G | 0.8034 | likely_pathogenic | 0.8508 | pathogenic | -3.172 | Highly Destabilizing | 1.0 | D | 0.742 | deleterious | None | None | None | None | N |
| I/H | 0.5934 | likely_pathogenic | 0.6648 | pathogenic | -2.513 | Highly Destabilizing | 1.0 | D | 0.745 | deleterious | None | None | None | None | N |
| I/K | 0.4468 | ambiguous | 0.5577 | ambiguous | -2.147 | Highly Destabilizing | 1.0 | D | 0.747 | deleterious | None | None | None | None | N |
| I/L | 0.1103 | likely_benign | 0.1129 | benign | -1.34 | Destabilizing | 0.889 | D | 0.399 | neutral | N | 0.504376141 | None | None | N |
| I/M | 0.096 | likely_benign | 0.1012 | benign | -1.423 | Destabilizing | 0.998 | D | 0.674 | neutral | N | 0.467089597 | None | None | N |
| I/N | 0.4938 | ambiguous | 0.6056 | pathogenic | -2.437 | Highly Destabilizing | 0.999 | D | 0.767 | deleterious | N | 0.510224678 | None | None | N |
| I/P | 0.9854 | likely_pathogenic | 0.987 | pathogenic | -1.776 | Destabilizing | 1.0 | D | 0.767 | deleterious | None | None | None | None | N |
| I/Q | 0.5514 | ambiguous | 0.6442 | pathogenic | -2.384 | Highly Destabilizing | 1.0 | D | 0.761 | deleterious | None | None | None | None | N |
| I/R | 0.3317 | likely_benign | 0.4198 | ambiguous | -1.714 | Destabilizing | 1.0 | D | 0.763 | deleterious | None | None | None | None | N |
| I/S | 0.3788 | ambiguous | 0.456 | ambiguous | -3.019 | Highly Destabilizing | 0.998 | D | 0.695 | prob.neutral | N | 0.513398269 | None | None | N |
| I/T | 0.1746 | likely_benign | 0.2117 | benign | -2.728 | Highly Destabilizing | 0.989 | D | 0.625 | neutral | N | 0.487598534 | None | None | N |
| I/V | 0.0625 | likely_benign | 0.0676 | benign | -1.776 | Destabilizing | 0.333 | N | 0.255 | neutral | N | 0.440346092 | None | None | N |
| I/W | 0.8108 | likely_pathogenic | 0.8102 | pathogenic | -1.906 | Destabilizing | 1.0 | D | 0.694 | prob.neutral | None | None | None | None | N |
| I/Y | 0.5626 | ambiguous | 0.5971 | pathogenic | -1.73 | Destabilizing | 1.0 | D | 0.697 | 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.