Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20245 | 60958;60959;60960 | chr2:178590992;178590991;178590990 | chr2:179455719;179455718;179455717 |
| N2AB | 18604 | 56035;56036;56037 | chr2:178590992;178590991;178590990 | chr2:179455719;179455718;179455717 |
| N2A | 17677 | 53254;53255;53256 | chr2:178590992;178590991;178590990 | chr2:179455719;179455718;179455717 |
| N2B | 11180 | 33763;33764;33765 | chr2:178590992;178590991;178590990 | chr2:179455719;179455718;179455717 |
| Novex-1 | 11305 | 34138;34139;34140 | chr2:178590992;178590991;178590990 | chr2:179455719;179455718;179455717 |
| Novex-2 | 11372 | 34339;34340;34341 | chr2:178590992;178590991;178590990 | chr2:179455719;179455718;179455717 |
| 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/Q | rs575837567  |
-0.952 | 1.0 | N | 0.793 | 0.498 | None | gnomAD-2.1.1 | 6.09E-05 | None | None | None | None | N | None | 4.1377E-04 | 8.49E-05 | None | 0 | 1.02722E-04 | None | 0 | None | 0 | 1.57E-05 | 0 |
| R/Q | rs575837567 |
-0.952 | 1.0 | N | 0.793 | 0.498 | None | gnomAD-3.1.2 | 1.51272E-04 | None | None | None | None | N | None | 5.3117E-04 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/Q | rs575837567 |
-0.952 | 1.0 | N | 0.793 | 0.498 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 8E-04 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| R/Q | rs575837567 |
-0.952 | 1.0 | N | 0.793 | 0.498 | None | gnomAD-4.0.0 | 3.53281E-05 | None | None | None | None | N | None | 5.06788E-04 | 4.99983E-05 | None | 0 | 4.4619E-05 | None | 0 | 0 | 8.47781E-06 | 4.39223E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.9585 | likely_pathogenic | 0.9878 | pathogenic | -1.776 | Destabilizing | 0.999 | D | 0.66 | neutral | None | None | None | None | N |
| R/C | 0.452 | ambiguous | 0.6868 | pathogenic | -1.751 | Destabilizing | 1.0 | D | 0.831 | deleterious | None | None | None | None | N |
| R/D | 0.9971 | likely_pathogenic | 0.9992 | pathogenic | -1.016 | Destabilizing | 1.0 | D | 0.813 | deleterious | None | None | None | None | N |
| R/E | 0.9453 | likely_pathogenic | 0.9803 | pathogenic | -0.803 | Destabilizing | 0.999 | D | 0.694 | prob.neutral | None | None | None | None | N |
| R/F | 0.9836 | likely_pathogenic | 0.9959 | pathogenic | -0.897 | Destabilizing | 1.0 | D | 0.858 | deleterious | None | None | None | None | N |
| R/G | 0.9483 | likely_pathogenic | 0.9883 | pathogenic | -2.115 | Highly Destabilizing | 1.0 | D | 0.756 | deleterious | D | 0.538348664 | None | None | N |
| R/H | 0.3351 | likely_benign | 0.5292 | ambiguous | -2.077 | Highly Destabilizing | 1.0 | D | 0.821 | deleterious | None | None | None | None | N |
| R/I | 0.9244 | likely_pathogenic | 0.9787 | pathogenic | -0.793 | Destabilizing | 1.0 | D | 0.847 | deleterious | None | None | None | None | N |
| R/K | 0.3837 | ambiguous | 0.5651 | pathogenic | -1.399 | Destabilizing | 0.998 | D | 0.678 | prob.neutral | None | None | None | None | N |
| R/L | 0.8858 | likely_pathogenic | 0.9668 | pathogenic | -0.793 | Destabilizing | 1.0 | D | 0.756 | deleterious | N | 0.513914533 | None | None | N |
| R/M | 0.9259 | likely_pathogenic | 0.9804 | pathogenic | -1.327 | Destabilizing | 1.0 | D | 0.815 | deleterious | None | None | None | None | N |
| R/N | 0.987 | likely_pathogenic | 0.9965 | pathogenic | -1.411 | Destabilizing | 1.0 | D | 0.791 | deleterious | None | None | None | None | N |
| R/P | 0.9982 | likely_pathogenic | 0.9997 | pathogenic | -1.11 | Destabilizing | 1.0 | D | 0.825 | deleterious | D | 0.550211948 | None | None | N |
| R/Q | 0.325 | likely_benign | 0.53 | ambiguous | -1.168 | Destabilizing | 1.0 | D | 0.793 | deleterious | N | 0.495503882 | None | None | N |
| R/S | 0.9674 | likely_pathogenic | 0.991 | pathogenic | -2.152 | Highly Destabilizing | 1.0 | D | 0.751 | deleterious | None | None | None | None | N |
| R/T | 0.9289 | likely_pathogenic | 0.9849 | pathogenic | -1.738 | Destabilizing | 1.0 | D | 0.757 | deleterious | None | None | None | None | N |
| R/V | 0.9435 | likely_pathogenic | 0.9824 | pathogenic | -1.11 | Destabilizing | 1.0 | D | 0.823 | deleterious | None | None | None | None | N |
| R/W | 0.7714 | likely_pathogenic | 0.9237 | pathogenic | -0.533 | Destabilizing | 1.0 | D | 0.81 | deleterious | None | None | None | None | N |
| R/Y | 0.9539 | likely_pathogenic | 0.9864 | pathogenic | -0.378 | Destabilizing | 1.0 | D | 0.849 | 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.