Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31089 | 93490;93491;93492 | chr2:178548361;178548360;178548359 | chr2:179413088;179413087;179413086 |
| N2AB | 29448 | 88567;88568;88569 | chr2:178548361;178548360;178548359 | chr2:179413088;179413087;179413086 |
| N2A | 28521 | 85786;85787;85788 | chr2:178548361;178548360;178548359 | chr2:179413088;179413087;179413086 |
| N2B | 22024 | 66295;66296;66297 | chr2:178548361;178548360;178548359 | chr2:179413088;179413087;179413086 |
| Novex-1 | 22149 | 66670;66671;66672 | chr2:178548361;178548360;178548359 | chr2:179413088;179413087;179413086 |
| Novex-2 | 22216 | 66871;66872;66873 | chr2:178548361;178548360;178548359 | chr2:179413088;179413087;179413086 |
| 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 | rs766670903  |
-1.548 | 1.0 | D | 0.726 | 0.543 | 0.766564822981 | gnomAD-2.1.1 | 1.61E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.30719E-04 | None | 0 | 0 | 0 |
| R/C | rs766670903 |
-1.548 | 1.0 | D | 0.726 | 0.543 | 0.766564822981 | gnomAD-4.0.0 | 1.16312E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.69832E-06 | 1.15931E-04 | 6.62581E-05 |
| R/H | rs367993101 |
-2.054 | 1.0 | D | 0.603 | 0.66 | None | gnomAD-2.1.1 | 2.86E-05 | None | None | None | None | N | None | 0 | 8.48E-05 | None | 0 | 0 | None | 9.8E-05 | None | 0 | 1.57E-05 | 0 |
| R/H | rs367993101 |
-2.054 | 1.0 | D | 0.603 | 0.66 | None | gnomAD-3.1.2 | 3.94E-05 | None | None | None | None | N | None | 0 | 1.31044E-04 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 6.23182E-04 | 0 |
| R/H | rs367993101 |
-2.054 | 1.0 | D | 0.603 | 0.66 | None | gnomAD-4.0.0 | 1.79713E-05 | None | None | None | None | N | None | 2.66994E-05 | 8.33556E-05 | None | 0 | 0 | None | 0 | 0 | 5.0855E-06 | 1.75685E-04 | 0 |
| R/S | None | None | 0.998 | D | 0.544 | 0.478 | 0.519837540645 | gnomAD-4.0.0 | 6.8419E-07 | None | None | None | None | N | None | 2.98739E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 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 | 0.9085 | likely_pathogenic | 0.89 | pathogenic | -1.7 | Destabilizing | 0.992 | D | 0.563 | neutral | None | None | None | None | N |
| R/C | 0.3792 | ambiguous | 0.3963 | ambiguous | -1.646 | Destabilizing | 1.0 | D | 0.726 | prob.delet. | D | 0.54880637 | None | None | N |
| R/D | 0.995 | likely_pathogenic | 0.9931 | pathogenic | -0.86 | Destabilizing | 1.0 | D | 0.68 | prob.neutral | None | None | None | None | N |
| R/E | 0.9342 | likely_pathogenic | 0.9162 | pathogenic | -0.654 | Destabilizing | 0.999 | D | 0.564 | neutral | None | None | None | None | N |
| R/F | 0.9662 | likely_pathogenic | 0.9635 | pathogenic | -0.896 | Destabilizing | 0.998 | D | 0.727 | prob.delet. | None | None | None | None | N |
| R/G | 0.8908 | likely_pathogenic | 0.8568 | pathogenic | -2.034 | Highly Destabilizing | 0.998 | D | 0.588 | neutral | D | 0.566657135 | None | None | N |
| R/H | 0.3386 | likely_benign | 0.3331 | benign | -1.939 | Destabilizing | 1.0 | D | 0.603 | neutral | D | 0.54403343 | None | None | N |
| R/I | 0.8822 | likely_pathogenic | 0.8642 | pathogenic | -0.739 | Destabilizing | 0.995 | D | 0.682 | prob.neutral | None | None | None | None | N |
| R/K | 0.2637 | likely_benign | 0.267 | benign | -1.169 | Destabilizing | 0.99 | D | 0.617 | neutral | None | None | None | None | N |
| R/L | 0.7938 | likely_pathogenic | 0.7645 | pathogenic | -0.739 | Destabilizing | 0.991 | D | 0.599 | neutral | D | 0.534816718 | None | None | N |
| R/M | 0.845 | likely_pathogenic | 0.827 | pathogenic | -1.288 | Destabilizing | 0.96 | D | 0.558 | neutral | None | None | None | None | N |
| R/N | 0.9752 | likely_pathogenic | 0.9713 | pathogenic | -1.13 | Destabilizing | 1.0 | D | 0.546 | neutral | None | None | None | None | N |
| R/P | 0.9986 | likely_pathogenic | 0.9973 | pathogenic | -1.048 | Destabilizing | 1.0 | D | 0.689 | prob.neutral | D | 0.567164114 | None | None | N |
| R/Q | 0.278 | likely_benign | 0.2597 | benign | -0.962 | Destabilizing | 0.999 | D | 0.562 | neutral | None | None | None | None | N |
| R/S | 0.9287 | likely_pathogenic | 0.9259 | pathogenic | -1.933 | Destabilizing | 0.998 | D | 0.544 | neutral | D | 0.527153261 | None | None | N |
| R/T | 0.8876 | likely_pathogenic | 0.8709 | pathogenic | -1.527 | Destabilizing | 0.996 | D | 0.545 | neutral | None | None | None | None | N |
| R/V | 0.8938 | likely_pathogenic | 0.8828 | pathogenic | -1.048 | Destabilizing | 0.983 | D | 0.637 | neutral | None | None | None | None | N |
| R/W | 0.7484 | likely_pathogenic | 0.7289 | pathogenic | -0.508 | Destabilizing | 1.0 | D | 0.709 | prob.delet. | None | None | None | None | N |
| R/Y | 0.9141 | likely_pathogenic | 0.9143 | pathogenic | -0.33 | Destabilizing | 1.0 | D | 0.7 | 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.