Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23800 | 71623;71624;71625 | chr2:178574734;178574733;178574732 | chr2:179439461;179439460;179439459 |
| N2AB | 22159 | 66700;66701;66702 | chr2:178574734;178574733;178574732 | chr2:179439461;179439460;179439459 |
| N2A | 21232 | 63919;63920;63921 | chr2:178574734;178574733;178574732 | chr2:179439461;179439460;179439459 |
| N2B | 14735 | 44428;44429;44430 | chr2:178574734;178574733;178574732 | chr2:179439461;179439460;179439459 |
| Novex-1 | 14860 | 44803;44804;44805 | chr2:178574734;178574733;178574732 | chr2:179439461;179439460;179439459 |
| Novex-2 | 14927 | 45004;45005;45006 | chr2:178574734;178574733;178574732 | chr2:179439461;179439460;179439459 |
| 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 | rs760839756  |
-1.686 | 1.0 | D | 0.827 | 0.613 | 0.80880172226 | gnomAD-2.1.1 | 8.07E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.59E-05 | None | 0 | None | 0 | 8.92E-06 | 0 |
| R/C | rs760839756 |
-1.686 | 1.0 | D | 0.827 | 0.613 | 0.80880172226 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/H | rs537705563 |
-2.2 | 1.0 | D | 0.811 | 0.66 | None | gnomAD-2.1.1 | 3.94E-05 | None | None | None | None | N | None | 1.65371E-04 | 2.83E-05 | None | 0 | 0 | None | 1.31208E-04 | None | 0 | 1.57E-05 | 0 |
| R/H | rs537705563 |
-2.2 | 1.0 | D | 0.811 | 0.66 | None | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | N | None | 1.20709E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/H | rs537705563 |
-2.2 | 1.0 | D | 0.811 | 0.66 | None | gnomAD-4.0.0 | 2.5419E-05 | None | None | None | None | N | None | 2.00331E-04 | 1.66856E-05 | None | 0 | 2.23334E-05 | None | 0 | 1.64582E-04 | 1.01741E-05 | 8.79411E-05 | 4.80569E-05 |
| R/S | rs760839756 |
-2.249 | 1.0 | N | 0.727 | 0.555 | 0.576874179423 | gnomAD-2.1.1 | 8.07E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.11869E-04 | None | 0 | None | 0 | 0 | 0 |
| R/S | rs760839756 |
-2.249 | 1.0 | N | 0.727 | 0.555 | 0.576874179423 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 1.94175E-04 | None | 0 | 0 | 0 | 0 | 0 |
| R/S | rs760839756 |
-2.249 | 1.0 | N | 0.727 | 0.555 | 0.576874179423 | gnomAD-4.0.0 | 1.23994E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.23334E-05 | None | 0 | 0 | 0 | 1.09924E-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 | 0.9207 | likely_pathogenic | 0.8658 | pathogenic | -1.87 | Destabilizing | 0.999 | D | 0.631 | neutral | None | None | None | None | N |
| R/C | 0.3301 | likely_benign | 0.2634 | benign | -1.835 | Destabilizing | 1.0 | D | 0.827 | deleterious | D | 0.537614648 | None | None | N |
| R/D | 0.9916 | likely_pathogenic | 0.9861 | pathogenic | -0.861 | Destabilizing | 1.0 | D | 0.797 | deleterious | None | None | None | None | N |
| R/E | 0.8978 | likely_pathogenic | 0.8535 | pathogenic | -0.649 | Destabilizing | 0.999 | D | 0.665 | neutral | None | None | None | None | N |
| R/F | 0.9446 | likely_pathogenic | 0.9165 | pathogenic | -1.107 | Destabilizing | 1.0 | D | 0.861 | deleterious | None | None | None | None | N |
| R/G | 0.9281 | likely_pathogenic | 0.8761 | pathogenic | -2.224 | Highly Destabilizing | 1.0 | D | 0.737 | prob.delet. | D | 0.548717464 | None | None | N |
| R/H | 0.2569 | likely_benign | 0.226 | benign | -2.095 | Highly Destabilizing | 1.0 | D | 0.811 | deleterious | D | 0.548970954 | None | None | N |
| R/I | 0.7284 | likely_pathogenic | 0.6512 | pathogenic | -0.849 | Destabilizing | 1.0 | D | 0.853 | deleterious | None | None | None | None | N |
| R/K | 0.2449 | likely_benign | 0.2006 | benign | -1.444 | Destabilizing | 0.998 | D | 0.651 | neutral | None | None | None | None | N |
| R/L | 0.6923 | likely_pathogenic | 0.6094 | pathogenic | -0.849 | Destabilizing | 1.0 | D | 0.737 | prob.delet. | N | 0.509470761 | None | None | N |
| R/M | 0.7526 | likely_pathogenic | 0.6818 | pathogenic | -1.342 | Destabilizing | 1.0 | D | 0.806 | deleterious | None | None | None | None | N |
| R/N | 0.9559 | likely_pathogenic | 0.9377 | pathogenic | -1.358 | Destabilizing | 1.0 | D | 0.772 | deleterious | None | None | None | None | N |
| R/P | 0.9993 | likely_pathogenic | 0.9985 | pathogenic | -1.177 | Destabilizing | 1.0 | D | 0.823 | deleterious | D | 0.549224443 | None | None | N |
| R/Q | 0.2246 | likely_benign | 0.1898 | benign | -1.238 | Destabilizing | 1.0 | D | 0.775 | deleterious | None | None | None | None | N |
| R/S | 0.9333 | likely_pathogenic | 0.8962 | pathogenic | -2.244 | Highly Destabilizing | 1.0 | D | 0.727 | prob.delet. | N | 0.50921359 | None | None | N |
| R/T | 0.8275 | likely_pathogenic | 0.7637 | pathogenic | -1.819 | Destabilizing | 1.0 | D | 0.733 | prob.delet. | None | None | None | None | N |
| R/V | 0.7905 | likely_pathogenic | 0.7094 | pathogenic | -1.177 | Destabilizing | 1.0 | D | 0.819 | deleterious | None | None | None | None | N |
| R/W | 0.661 | likely_pathogenic | 0.5977 | pathogenic | -0.619 | Destabilizing | 1.0 | D | 0.815 | deleterious | None | None | None | None | N |
| R/Y | 0.8654 | likely_pathogenic | 0.8242 | pathogenic | -0.471 | Destabilizing | 1.0 | D | 0.851 | 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.