Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 7007 | 21244;21245;21246 | chr2:178724356;178724355;178724354 | chr2:179589083;179589082;179589081 |
| N2AB | 6690 | 20293;20294;20295 | chr2:178724356;178724355;178724354 | chr2:179589083;179589082;179589081 |
| N2A | 5763 | 17512;17513;17514 | chr2:178724356;178724355;178724354 | chr2:179589083;179589082;179589081 |
| 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/F | rs114626713  |
-1.91 | 1.0 | N | 0.803 | 0.586 | None | gnomAD-2.1.1 | 1.52088E-03 | None | None | None | None | N | None | 1.67866E-02 | 4.24785E-04 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 2.34E-05 | 1.40568E-04 |
| I/F | rs114626713 |
-1.91 | 1.0 | N | 0.803 | 0.586 | None | gnomAD-3.1.2 | 4.51493E-03 | None | None | None | None | N | None | 1.61376E-02 | 5.89468E-04 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 3.34288E-03 |
| I/F | rs114626713 |
-1.91 | 1.0 | N | 0.803 | 0.586 | None | 1000 genomes | 3.99361E-03 | None | None | None | None | N | None | 1.51E-02 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| I/F | rs114626713 |
-1.91 | 1.0 | N | 0.803 | 0.586 | None | gnomAD-4.0.0 | 8.13706E-04 | None | None | None | None | N | None | 1.60082E-02 | 4.8343E-04 | None | 0 | 0 | None | 0 | 3.3036E-04 | 5.93404E-06 | 3.2941E-05 | 1.13666E-03 |
| I/T | rs773611280 |
-3.553 | 1.0 | D | 0.813 | 0.828 | 0.856322546766 | gnomAD-2.1.1 | 1.43E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 3.12E-05 | 0 |
| I/T | rs773611280 |
-3.553 | 1.0 | D | 0.813 | 0.828 | 0.856322546766 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 4.41E-05 | 0 | 0 |
| I/T | rs773611280 |
-3.553 | 1.0 | D | 0.813 | 0.828 | 0.856322546766 | gnomAD-4.0.0 | 2.60315E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.47567E-05 | 0 | 1.60149E-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 | 0.9639 | likely_pathogenic | 0.944 | pathogenic | -3.194 | Highly Destabilizing | 0.999 | D | 0.712 | prob.delet. | None | None | None | None | N |
| I/C | 0.9541 | likely_pathogenic | 0.9337 | pathogenic | -2.583 | Highly Destabilizing | 1.0 | D | 0.824 | deleterious | None | None | None | None | N |
| I/D | 0.9911 | likely_pathogenic | 0.9904 | pathogenic | -3.779 | Highly Destabilizing | 1.0 | D | 0.862 | deleterious | None | None | None | None | N |
| I/E | 0.9879 | likely_pathogenic | 0.9856 | pathogenic | -3.488 | Highly Destabilizing | 1.0 | D | 0.861 | deleterious | None | None | None | None | N |
| I/F | 0.2578 | likely_benign | 0.2495 | benign | -1.877 | Destabilizing | 1.0 | D | 0.803 | deleterious | N | 0.51891794 | None | None | N |
| I/G | 0.9861 | likely_pathogenic | 0.9806 | pathogenic | -3.803 | Highly Destabilizing | 1.0 | D | 0.859 | deleterious | None | None | None | None | N |
| I/H | 0.9511 | likely_pathogenic | 0.9456 | pathogenic | -3.255 | Highly Destabilizing | 1.0 | D | 0.873 | deleterious | None | None | None | None | N |
| I/K | 0.9631 | likely_pathogenic | 0.9575 | pathogenic | -2.587 | Highly Destabilizing | 1.0 | D | 0.861 | deleterious | None | None | None | None | N |
| I/L | 0.182 | likely_benign | 0.1486 | benign | -1.375 | Destabilizing | 0.993 | D | 0.415 | neutral | N | 0.48614523 | None | None | N |
| I/M | 0.224 | likely_benign | 0.2004 | benign | -1.465 | Destabilizing | 1.0 | D | 0.752 | deleterious | D | 0.547243787 | None | None | N |
| I/N | 0.9014 | likely_pathogenic | 0.902 | pathogenic | -3.16 | Highly Destabilizing | 1.0 | D | 0.887 | deleterious | D | 0.59021389 | None | None | N |
| I/P | 0.9929 | likely_pathogenic | 0.9907 | pathogenic | -1.97 | Destabilizing | 1.0 | D | 0.881 | deleterious | None | None | None | None | N |
| I/Q | 0.9648 | likely_pathogenic | 0.9605 | pathogenic | -2.903 | Highly Destabilizing | 1.0 | D | 0.893 | deleterious | None | None | None | None | N |
| I/R | 0.9466 | likely_pathogenic | 0.9401 | pathogenic | -2.353 | Highly Destabilizing | 1.0 | D | 0.886 | deleterious | None | None | None | None | N |
| I/S | 0.9466 | likely_pathogenic | 0.9358 | pathogenic | -3.84 | Highly Destabilizing | 1.0 | D | 0.851 | deleterious | D | 0.59021389 | None | None | N |
| I/T | 0.9715 | likely_pathogenic | 0.9579 | pathogenic | -3.391 | Highly Destabilizing | 1.0 | D | 0.813 | deleterious | D | 0.606061807 | None | None | N |
| I/V | 0.2385 | likely_benign | 0.1784 | benign | -1.97 | Destabilizing | 0.993 | D | 0.397 | neutral | N | 0.520693002 | None | None | N |
| I/W | 0.9305 | likely_pathogenic | 0.9237 | pathogenic | -2.314 | Highly Destabilizing | 1.0 | D | 0.871 | deleterious | None | None | None | None | N |
| I/Y | 0.7725 | likely_pathogenic | 0.7655 | pathogenic | -2.137 | Highly Destabilizing | 1.0 | D | 0.831 | deleterious | 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.