Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32750 | 98473;98474;98475 | chr2:178539817;178539816;178539815 | chr2:179404544;179404543;179404542 |
| N2AB | 31109 | 93550;93551;93552 | chr2:178539817;178539816;178539815 | chr2:179404544;179404543;179404542 |
| N2A | 30182 | 90769;90770;90771 | chr2:178539817;178539816;178539815 | chr2:179404544;179404543;179404542 |
| N2B | 23685 | 71278;71279;71280 | chr2:178539817;178539816;178539815 | chr2:179404544;179404543;179404542 |
| Novex-1 | 23810 | 71653;71654;71655 | chr2:178539817;178539816;178539815 | chr2:179404544;179404543;179404542 |
| Novex-2 | 23877 | 71854;71855;71856 | chr2:178539817;178539816;178539815 | chr2:179404544;179404543;179404542 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/I | None | None | 0.985 | N | 0.535 | 0.349 | 0.723745936845 | gnomAD-4.0.0 | 2.40064E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.625E-06 | 0 | 0 |
| M/V | rs771143872  |
0.15 | 0.985 | N | 0.47 | 0.397 | 0.709758000367 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.87E-06 | 0 |
| M/V | rs771143872 |
0.15 | 0.985 | N | 0.47 | 0.397 | 0.709758000367 | gnomAD-4.0.0 | 5.47356E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 7.19577E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.5774 | likely_pathogenic | 0.6098 | pathogenic | -0.73 | Destabilizing | 0.989 | D | 0.521 | neutral | None | None | None | None | N |
| M/C | 0.8369 | likely_pathogenic | 0.8433 | pathogenic | -0.706 | Destabilizing | 1.0 | D | 0.549 | neutral | None | None | None | None | N |
| M/D | 0.8921 | likely_pathogenic | 0.9067 | pathogenic | 0.141 | Stabilizing | 0.999 | D | 0.585 | neutral | None | None | None | None | N |
| M/E | 0.6907 | likely_pathogenic | 0.6962 | pathogenic | 0.117 | Stabilizing | 0.999 | D | 0.455 | neutral | None | None | None | None | N |
| M/F | 0.4892 | ambiguous | 0.5027 | ambiguous | -0.143 | Destabilizing | 0.999 | D | 0.45 | neutral | None | None | None | None | N |
| M/G | 0.8437 | likely_pathogenic | 0.858 | pathogenic | -0.951 | Destabilizing | 0.995 | D | 0.505 | neutral | None | None | None | None | N |
| M/H | 0.7017 | likely_pathogenic | 0.7221 | pathogenic | -0.083 | Destabilizing | 1.0 | D | 0.567 | neutral | None | None | None | None | N |
| M/I | 0.5212 | ambiguous | 0.5536 | ambiguous | -0.222 | Destabilizing | 0.985 | D | 0.535 | neutral | N | 0.457964353 | None | None | N |
| M/K | 0.4122 | ambiguous | 0.4079 | ambiguous | 0.106 | Stabilizing | 0.994 | D | 0.504 | neutral | N | 0.418923175 | None | None | N |
| M/L | 0.184 | likely_benign | 0.1868 | benign | -0.222 | Destabilizing | 0.927 | D | 0.326 | neutral | N | 0.47379781 | None | None | N |
| M/N | 0.7007 | likely_pathogenic | 0.7331 | pathogenic | 0.211 | Stabilizing | 0.999 | D | 0.553 | neutral | None | None | None | None | N |
| M/P | 0.9816 | likely_pathogenic | 0.9831 | pathogenic | -0.362 | Destabilizing | 0.999 | D | 0.551 | neutral | None | None | None | None | N |
| M/Q | 0.4044 | ambiguous | 0.3997 | ambiguous | 0.091 | Stabilizing | 0.999 | D | 0.448 | neutral | None | None | None | None | N |
| M/R | 0.4483 | ambiguous | 0.4473 | ambiguous | 0.6 | Stabilizing | 0.998 | D | 0.471 | neutral | N | 0.42840945 | None | None | N |
| M/S | 0.624 | likely_pathogenic | 0.651 | pathogenic | -0.28 | Destabilizing | 0.995 | D | 0.485 | neutral | None | None | None | None | N |
| M/T | 0.4462 | ambiguous | 0.4753 | ambiguous | -0.197 | Destabilizing | 0.994 | D | 0.501 | neutral | N | 0.432855264 | None | None | N |
| M/V | 0.1247 | likely_benign | 0.1293 | benign | -0.362 | Destabilizing | 0.985 | D | 0.47 | neutral | N | 0.449824872 | None | None | N |
| M/W | 0.8109 | likely_pathogenic | 0.8286 | pathogenic | -0.124 | Destabilizing | 1.0 | D | 0.566 | neutral | None | None | None | None | N |
| M/Y | 0.7295 | likely_pathogenic | 0.7542 | pathogenic | -0.028 | Destabilizing | 0.999 | D | 0.524 | 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.