Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30432 | 91519;91520;91521 | chr2:178551237;178551236;178551235 | chr2:179415964;179415963;179415962 |
| N2AB | 28791 | 86596;86597;86598 | chr2:178551237;178551236;178551235 | chr2:179415964;179415963;179415962 |
| N2A | 27864 | 83815;83816;83817 | chr2:178551237;178551236;178551235 | chr2:179415964;179415963;179415962 |
| N2B | 21367 | 64324;64325;64326 | chr2:178551237;178551236;178551235 | chr2:179415964;179415963;179415962 |
| Novex-1 | 21492 | 64699;64700;64701 | chr2:178551237;178551236;178551235 | chr2:179415964;179415963;179415962 |
| Novex-2 | 21559 | 64900;64901;64902 | chr2:178551237;178551236;178551235 | chr2:179415964;179415963;179415962 |
| 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/T | None | None | 0.989 | N | 0.626 | 0.322 | 0.594197360623 | gnomAD-4.0.0 | 2.05359E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.77117E-05 | 0 | 8.99633E-07 | 0 | 0 |
| I/V | rs766841800  |
-0.498 | 0.333 | N | 0.195 | 0.092 | 0.436671004673 | gnomAD-4.0.0 | 1.59297E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43349E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.3626 | ambiguous | 0.4402 | ambiguous | -1.22 | Destabilizing | 0.992 | D | 0.522 | neutral | None | None | None | None | N |
| I/C | 0.8001 | likely_pathogenic | 0.8256 | pathogenic | -0.68 | Destabilizing | 1.0 | D | 0.654 | neutral | None | None | None | None | N |
| I/D | 0.914 | likely_pathogenic | 0.9401 | pathogenic | -0.358 | Destabilizing | 1.0 | D | 0.743 | deleterious | None | None | None | None | N |
| I/E | 0.7726 | likely_pathogenic | 0.8087 | pathogenic | -0.383 | Destabilizing | 1.0 | D | 0.743 | deleterious | None | None | None | None | N |
| I/F | 0.3498 | ambiguous | 0.3924 | ambiguous | -0.864 | Destabilizing | 0.998 | D | 0.593 | neutral | N | 0.496490163 | None | None | N |
| I/G | 0.8239 | likely_pathogenic | 0.8701 | pathogenic | -1.498 | Destabilizing | 1.0 | D | 0.741 | deleterious | None | None | None | None | N |
| I/H | 0.7808 | likely_pathogenic | 0.8298 | pathogenic | -0.655 | Destabilizing | 1.0 | D | 0.719 | prob.delet. | None | None | None | None | N |
| I/K | 0.6452 | likely_pathogenic | 0.7219 | pathogenic | -0.649 | Destabilizing | 1.0 | D | 0.741 | deleterious | None | None | None | None | N |
| I/L | 0.1489 | likely_benign | 0.1609 | benign | -0.559 | Destabilizing | 0.889 | D | 0.264 | neutral | N | 0.393997727 | None | None | N |
| I/M | 0.1285 | likely_benign | 0.1421 | benign | -0.465 | Destabilizing | 0.998 | D | 0.568 | neutral | N | 0.476210892 | None | None | N |
| I/N | 0.6287 | likely_pathogenic | 0.7079 | pathogenic | -0.429 | Destabilizing | 0.999 | D | 0.747 | deleterious | N | 0.472027121 | None | None | N |
| I/P | 0.9544 | likely_pathogenic | 0.9675 | pathogenic | -0.746 | Destabilizing | 1.0 | D | 0.751 | deleterious | None | None | None | None | N |
| I/Q | 0.6709 | likely_pathogenic | 0.7133 | pathogenic | -0.605 | Destabilizing | 1.0 | D | 0.733 | prob.delet. | None | None | None | None | N |
| I/R | 0.5195 | ambiguous | 0.6031 | pathogenic | -0.098 | Destabilizing | 1.0 | D | 0.747 | deleterious | None | None | None | None | N |
| I/S | 0.4298 | ambiguous | 0.5167 | ambiguous | -1.036 | Destabilizing | 0.998 | D | 0.689 | prob.neutral | N | 0.443132894 | None | None | N |
| I/T | 0.1203 | likely_benign | 0.162 | benign | -0.941 | Destabilizing | 0.989 | D | 0.626 | neutral | N | 0.397131246 | None | None | N |
| I/V | 0.0774 | likely_benign | 0.0883 | benign | -0.746 | Destabilizing | 0.333 | N | 0.195 | neutral | N | 0.440154091 | None | None | N |
| I/W | 0.8716 | likely_pathogenic | 0.8847 | pathogenic | -0.893 | Destabilizing | 1.0 | D | 0.694 | prob.neutral | None | None | None | None | N |
| I/Y | 0.7737 | likely_pathogenic | 0.8054 | pathogenic | -0.659 | 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.