Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 33475 | 100648;100649;100650 | chr2:178536324;178536323;178536322 | chr2:179401051;179401050;179401049 |
| N2AB | 31834 | 95725;95726;95727 | chr2:178536324;178536323;178536322 | chr2:179401051;179401050;179401049 |
| N2A | 30907 | 92944;92945;92946 | chr2:178536324;178536323;178536322 | chr2:179401051;179401050;179401049 |
| N2B | 24410 | 73453;73454;73455 | chr2:178536324;178536323;178536322 | chr2:179401051;179401050;179401049 |
| Novex-1 | 24535 | 73828;73829;73830 | chr2:178536324;178536323;178536322 | chr2:179401051;179401050;179401049 |
| Novex-2 | 24602 | 74029;74030;74031 | chr2:178536324;178536323;178536322 | chr2:179401051;179401050;179401049 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| E/K | rs377287413  |
-0.749 | 0.999 | N | 0.755 | 0.41 | None | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 1.29349E-04 | 2.91E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| E/K | rs377287413 |
-0.749 | 0.999 | N | 0.755 | 0.41 | None | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | N | None | 9.65E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| E/K | rs377287413 |
-0.749 | 0.999 | N | 0.755 | 0.41 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 8E-04 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| E/K | rs377287413 |
-0.749 | 0.999 | N | 0.755 | 0.41 | None | gnomAD-4.0.0 | 9.91537E-06 | None | None | None | None | N | None | 9.32935E-05 | 3.33489E-05 | None | 0 | 0 | None | 1.56406E-05 | 0 | 4.23822E-06 | 0 | 1.60087E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| E/A | 0.1899 | likely_benign | 0.1835 | benign | -0.918 | Destabilizing | 0.999 | D | 0.723 | prob.delet. | N | 0.451464376 | None | None | N |
| E/C | 0.8791 | likely_pathogenic | 0.8668 | pathogenic | -0.46 | Destabilizing | 1.0 | D | 0.783 | deleterious | None | None | None | None | N |
| E/D | 0.2348 | likely_benign | 0.1998 | benign | -0.945 | Destabilizing | 0.999 | D | 0.607 | neutral | N | 0.470396853 | None | None | N |
| E/F | 0.7557 | likely_pathogenic | 0.7473 | pathogenic | -0.389 | Destabilizing | 1.0 | D | 0.801 | deleterious | None | None | None | None | N |
| E/G | 0.3154 | likely_benign | 0.307 | benign | -1.239 | Destabilizing | 1.0 | D | 0.766 | deleterious | N | 0.508357809 | None | None | N |
| E/H | 0.6999 | likely_pathogenic | 0.6962 | pathogenic | -0.514 | Destabilizing | 1.0 | D | 0.777 | deleterious | None | None | None | None | N |
| E/I | 0.3045 | likely_benign | 0.2969 | benign | -0.054 | Destabilizing | 1.0 | D | 0.804 | deleterious | None | None | None | None | N |
| E/K | 0.25 | likely_benign | 0.2699 | benign | -0.442 | Destabilizing | 0.999 | D | 0.755 | deleterious | N | 0.431243819 | None | None | N |
| E/L | 0.4654 | ambiguous | 0.4517 | ambiguous | -0.054 | Destabilizing | 1.0 | D | 0.801 | deleterious | None | None | None | None | N |
| E/M | 0.5071 | ambiguous | 0.4811 | ambiguous | 0.353 | Stabilizing | 1.0 | D | 0.791 | deleterious | None | None | None | None | N |
| E/N | 0.3977 | ambiguous | 0.3614 | ambiguous | -0.939 | Destabilizing | 1.0 | D | 0.803 | deleterious | None | None | None | None | N |
| E/P | 0.5571 | ambiguous | 0.5611 | ambiguous | -0.322 | Destabilizing | 1.0 | D | 0.775 | deleterious | None | None | None | None | N |
| E/Q | 0.2243 | likely_benign | 0.2206 | benign | -0.84 | Destabilizing | 1.0 | D | 0.737 | prob.delet. | N | 0.408617676 | None | None | N |
| E/R | 0.455 | ambiguous | 0.4842 | ambiguous | -0.125 | Destabilizing | 1.0 | D | 0.803 | deleterious | None | None | None | None | N |
| E/S | 0.3007 | likely_benign | 0.2868 | benign | -1.192 | Destabilizing | 0.999 | D | 0.775 | deleterious | None | None | None | None | N |
| E/T | 0.284 | likely_benign | 0.271 | benign | -0.922 | Destabilizing | 1.0 | D | 0.771 | deleterious | None | None | None | None | N |
| E/V | 0.2093 | likely_benign | 0.1998 | benign | -0.322 | Destabilizing | 1.0 | D | 0.808 | deleterious | N | 0.423200339 | None | None | N |
| E/W | 0.9433 | likely_pathogenic | 0.9436 | pathogenic | -0.084 | Destabilizing | 1.0 | D | 0.785 | deleterious | None | None | None | None | N |
| E/Y | 0.7221 | likely_pathogenic | 0.7233 | pathogenic | -0.128 | Destabilizing | 1.0 | D | 0.797 | 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.