Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23211 | 69856;69857;69858 | chr2:178576613;178576612;178576611 | chr2:179441340;179441339;179441338 |
| N2AB | 21570 | 64933;64934;64935 | chr2:178576613;178576612;178576611 | chr2:179441340;179441339;179441338 |
| N2A | 20643 | 62152;62153;62154 | chr2:178576613;178576612;178576611 | chr2:179441340;179441339;179441338 |
| N2B | 14146 | 42661;42662;42663 | chr2:178576613;178576612;178576611 | chr2:179441340;179441339;179441338 |
| Novex-1 | 14271 | 43036;43037;43038 | chr2:178576613;178576612;178576611 | chr2:179441340;179441339;179441338 |
| Novex-2 | 14338 | 43237;43238;43239 | chr2:178576613;178576612;178576611 | chr2:179441340;179441339;179441338 |
| 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 | rs1215669622  |
-1.39 | 1.0 | N | 0.583 | 0.369 | 0.326881540566 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.9E-06 | 0 |
| E/K | rs1215669622 |
-1.39 | 1.0 | N | 0.583 | 0.369 | 0.326881540566 | gnomAD-4.0.0 | 9.58008E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.04236E-05 | None | 0 | 1.73491E-04 | 8.99564E-06 | 1.15945E-05 | 0 |
| E/Q | rs1215669622 |
None | 1.0 | N | 0.657 | 0.267 | 0.353974658523 | gnomAD-4.0.0 | 6.84291E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99564E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| E/A | 0.3097 | likely_benign | 0.3596 | ambiguous | -1.921 | Destabilizing | 0.999 | D | 0.651 | neutral | N | 0.4882225 | None | None | N |
| E/C | 0.876 | likely_pathogenic | 0.8978 | pathogenic | -1.134 | Destabilizing | 1.0 | D | 0.789 | deleterious | None | None | None | None | N |
| E/D | 0.5054 | ambiguous | 0.5157 | ambiguous | -1.715 | Destabilizing | 0.999 | D | 0.528 | neutral | N | 0.487995463 | None | None | N |
| E/F | 0.8821 | likely_pathogenic | 0.8894 | pathogenic | -1.71 | Destabilizing | 1.0 | D | 0.821 | deleterious | None | None | None | None | N |
| E/G | 0.5616 | ambiguous | 0.6215 | pathogenic | -2.302 | Highly Destabilizing | 1.0 | D | 0.727 | prob.delet. | N | 0.511126148 | None | None | N |
| E/H | 0.7181 | likely_pathogenic | 0.732 | pathogenic | -1.569 | Destabilizing | 1.0 | D | 0.675 | prob.neutral | None | None | None | None | N |
| E/I | 0.4623 | ambiguous | 0.4847 | ambiguous | -0.827 | Destabilizing | 1.0 | D | 0.825 | deleterious | None | None | None | None | N |
| E/K | 0.4408 | ambiguous | 0.483 | ambiguous | -1.598 | Destabilizing | 1.0 | D | 0.583 | neutral | N | 0.503397493 | None | None | N |
| E/L | 0.5821 | likely_pathogenic | 0.6435 | pathogenic | -0.827 | Destabilizing | 1.0 | D | 0.794 | deleterious | None | None | None | None | N |
| E/M | 0.562 | ambiguous | 0.5921 | pathogenic | -0.087 | Destabilizing | 1.0 | D | 0.741 | deleterious | None | None | None | None | N |
| E/N | 0.697 | likely_pathogenic | 0.7219 | pathogenic | -1.789 | Destabilizing | 1.0 | D | 0.719 | prob.delet. | None | None | None | None | N |
| E/P | 0.9944 | likely_pathogenic | 0.9962 | pathogenic | -1.178 | Destabilizing | 1.0 | D | 0.735 | prob.delet. | None | None | None | None | N |
| E/Q | 0.1466 | likely_benign | 0.1555 | benign | -1.569 | Destabilizing | 1.0 | D | 0.657 | neutral | N | 0.490910985 | None | None | N |
| E/R | 0.5225 | ambiguous | 0.5761 | pathogenic | -1.376 | Destabilizing | 1.0 | D | 0.721 | prob.delet. | None | None | None | None | N |
| E/S | 0.3824 | ambiguous | 0.4223 | ambiguous | -2.503 | Highly Destabilizing | 0.999 | D | 0.635 | neutral | None | None | None | None | N |
| E/T | 0.4049 | ambiguous | 0.4435 | ambiguous | -2.132 | Highly Destabilizing | 1.0 | D | 0.742 | deleterious | None | None | None | None | N |
| E/V | 0.3171 | likely_benign | 0.3443 | ambiguous | -1.178 | Destabilizing | 1.0 | D | 0.733 | prob.delet. | N | 0.515692 | None | None | N |
| E/W | 0.9716 | likely_pathogenic | 0.9734 | pathogenic | -1.67 | Destabilizing | 1.0 | D | 0.789 | deleterious | None | None | None | None | N |
| E/Y | 0.8382 | likely_pathogenic | 0.8493 | pathogenic | -1.476 | Destabilizing | 1.0 | D | 0.751 | 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.