Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14284 | 43075;43076;43077 | chr2:178633509;178633508;178633507 | chr2:179498236;179498235;179498234 |
| N2AB | 12643 | 38152;38153;38154 | chr2:178633509;178633508;178633507 | chr2:179498236;179498235;179498234 |
| N2A | 11716 | 35371;35372;35373 | chr2:178633509;178633508;178633507 | chr2:179498236;179498235;179498234 |
| N2B | 5219 | 15880;15881;15882 | chr2:178633509;178633508;178633507 | chr2:179498236;179498235;179498234 |
| Novex-1 | 5344 | 16255;16256;16257 | chr2:178633509;178633508;178633507 | chr2:179498236;179498235;179498234 |
| Novex-2 | 5411 | 16456;16457;16458 | chr2:178633509;178633508;178633507 | chr2:179498236;179498235;179498234 |
| 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 | rs760157467  |
-2.097 | 1.0 | N | 0.891 | 0.322 | None | gnomAD-2.1.1 | 1.61E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 9.81E-05 | None | 0 | 8.9E-06 | 0 |
| R/C | rs760157467 |
-2.097 | 1.0 | N | 0.891 | 0.322 | None | gnomAD-4.0.0 | 6.84399E-06 | None | None | None | None | N | None | 2.98989E-05 | 0 | None | 0 | 2.52678E-05 | None | 0 | 0 | 2.69877E-06 | 5.79724E-05 | 0 |
| R/H | rs368572799 |
-2.277 | 1.0 | N | 0.77 | 0.375 | None | gnomAD-2.1.1 | 3.93E-05 | None | None | None | None | N | None | 1.23987E-04 | 0 | None | 0 | 3.61757E-04 | None | 0 | None | 0 | 7.82E-06 | 0 |
| R/H | rs368572799 |
-2.277 | 1.0 | N | 0.77 | 0.375 | None | gnomAD-3.1.2 | 7.23E-05 | None | None | None | None | N | None | 1.93143E-04 | 0 | 0 | 0 | 3.86399E-04 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/H | rs368572799 |
-2.277 | 1.0 | N | 0.77 | 0.375 | None | gnomAD-4.0.0 | 3.22356E-05 | None | None | None | None | N | None | 1.46925E-04 | 0 | None | 0 | 2.01135E-04 | None | 0 | 0 | 7.62981E-06 | 2.19611E-05 | 3.36431E-04 |
| R/L | rs368572799 |
-1.0 | 1.0 | N | 0.806 | 0.425 | 0.479744053436 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | N | None | 1.14758E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| R/L | rs368572799 |
-1.0 | 1.0 | N | 0.806 | 0.425 | 0.479744053436 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/L | rs368572799 |
-1.0 | 1.0 | N | 0.806 | 0.425 | 0.479744053436 | gnomAD-4.0.0 | 1.23983E-06 | None | None | None | None | N | None | 2.67137E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 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 | 0.875 | likely_pathogenic | 0.8677 | pathogenic | -1.761 | Destabilizing | 0.999 | D | 0.663 | neutral | None | None | None | None | N |
| R/C | 0.3406 | ambiguous | 0.329 | benign | -1.941 | Destabilizing | 1.0 | D | 0.891 | deleterious | N | 0.446535237 | None | None | N |
| R/D | 0.9748 | likely_pathogenic | 0.9701 | pathogenic | -1.02 | Destabilizing | 1.0 | D | 0.868 | deleterious | None | None | None | None | N |
| R/E | 0.8567 | likely_pathogenic | 0.8307 | pathogenic | -0.821 | Destabilizing | 0.999 | D | 0.587 | neutral | None | None | None | None | N |
| R/F | 0.9095 | likely_pathogenic | 0.9021 | pathogenic | -1.208 | Destabilizing | 1.0 | D | 0.891 | deleterious | None | None | None | None | N |
| R/G | 0.7407 | likely_pathogenic | 0.7148 | pathogenic | -2.108 | Highly Destabilizing | 1.0 | D | 0.806 | deleterious | N | 0.513447085 | None | None | N |
| R/H | 0.1694 | likely_benign | 0.1823 | benign | -1.997 | Destabilizing | 1.0 | D | 0.77 | deleterious | N | 0.447482526 | None | None | N |
| R/I | 0.8185 | likely_pathogenic | 0.784 | pathogenic | -0.772 | Destabilizing | 1.0 | D | 0.897 | deleterious | None | None | None | None | N |
| R/K | 0.2831 | likely_benign | 0.2951 | benign | -1.48 | Destabilizing | 0.998 | D | 0.618 | neutral | None | None | None | None | N |
| R/L | 0.7273 | likely_pathogenic | 0.7229 | pathogenic | -0.772 | Destabilizing | 1.0 | D | 0.806 | deleterious | N | 0.510070206 | None | None | N |
| R/M | 0.7859 | likely_pathogenic | 0.7655 | pathogenic | -1.225 | Destabilizing | 1.0 | D | 0.851 | deleterious | None | None | None | None | N |
| R/N | 0.9035 | likely_pathogenic | 0.8925 | pathogenic | -1.405 | Destabilizing | 1.0 | D | 0.712 | prob.delet. | None | None | None | None | N |
| R/P | 0.9896 | likely_pathogenic | 0.9876 | pathogenic | -1.088 | Destabilizing | 1.0 | D | 0.881 | deleterious | D | 0.610343338 | None | None | N |
| R/Q | 0.2216 | likely_benign | 0.2271 | benign | -1.32 | Destabilizing | 1.0 | D | 0.726 | prob.delet. | None | None | None | None | N |
| R/S | 0.8885 | likely_pathogenic | 0.8825 | pathogenic | -2.258 | Highly Destabilizing | 1.0 | D | 0.785 | deleterious | N | 0.428758868 | None | None | N |
| R/T | 0.7895 | likely_pathogenic | 0.7806 | pathogenic | -1.845 | Destabilizing | 1.0 | D | 0.781 | deleterious | None | None | None | None | N |
| R/V | 0.8292 | likely_pathogenic | 0.8203 | pathogenic | -1.088 | Destabilizing | 1.0 | D | 0.872 | deleterious | None | None | None | None | N |
| R/W | 0.4542 | ambiguous | 0.4546 | ambiguous | -0.775 | Destabilizing | 1.0 | D | 0.879 | deleterious | None | None | None | None | N |
| R/Y | 0.6573 | likely_pathogenic | 0.6569 | pathogenic | -0.545 | Destabilizing | 1.0 | D | 0.893 | 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.