Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21028 | 63307;63308;63309 | chr2:178588643;178588642;178588641 | chr2:179453370;179453369;179453368 |
| N2AB | 19387 | 58384;58385;58386 | chr2:178588643;178588642;178588641 | chr2:179453370;179453369;179453368 |
| N2A | 18460 | 55603;55604;55605 | chr2:178588643;178588642;178588641 | chr2:179453370;179453369;179453368 |
| N2B | 11963 | 36112;36113;36114 | chr2:178588643;178588642;178588641 | chr2:179453370;179453369;179453368 |
| Novex-1 | 12088 | 36487;36488;36489 | chr2:178588643;178588642;178588641 | chr2:179453370;179453369;179453368 |
| Novex-2 | 12155 | 36688;36689;36690 | chr2:178588643;178588642;178588641 | chr2:179453370;179453369;179453368 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/F | rs756584422  |
-2.115 | 1.0 | D | 0.847 | 0.551 | 0.858883120336 | gnomAD-2.1.1 | 4.1E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 9.03E-06 | 0 |
| L/F | rs756584422 |
-2.115 | 1.0 | D | 0.847 | 0.551 | 0.858883120336 | gnomAD-4.0.0 | 1.60492E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.87512E-06 | 0 | 0 |
| L/V | None | None | 0.999 | D | 0.834 | 0.542 | 0.826222710811 | gnomAD-4.0.0 | 1.60492E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.87512E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.9707 | likely_pathogenic | 0.96 | pathogenic | -2.889 | Highly Destabilizing | 0.999 | D | 0.799 | deleterious | None | None | None | None | N |
| L/C | 0.9278 | likely_pathogenic | 0.9009 | pathogenic | -2.196 | Highly Destabilizing | 1.0 | D | 0.75 | deleterious | None | None | None | None | N |
| L/D | 0.9994 | likely_pathogenic | 0.999 | pathogenic | -3.513 | Highly Destabilizing | 1.0 | D | 0.825 | deleterious | None | None | None | None | N |
| L/E | 0.9979 | likely_pathogenic | 0.9963 | pathogenic | -3.293 | Highly Destabilizing | 1.0 | D | 0.825 | deleterious | None | None | None | None | N |
| L/F | 0.8928 | likely_pathogenic | 0.8134 | pathogenic | -1.818 | Destabilizing | 1.0 | D | 0.847 | deleterious | D | 0.64942121 | None | None | N |
| L/G | 0.9946 | likely_pathogenic | 0.991 | pathogenic | -3.432 | Highly Destabilizing | 1.0 | D | 0.814 | deleterious | None | None | None | None | N |
| L/H | 0.9924 | likely_pathogenic | 0.9868 | pathogenic | -2.919 | Highly Destabilizing | 1.0 | D | 0.787 | deleterious | D | 0.666247788 | None | None | N |
| L/I | 0.2579 | likely_benign | 0.2342 | benign | -1.306 | Destabilizing | 0.999 | D | 0.826 | deleterious | D | 0.648412189 | None | None | N |
| L/K | 0.9938 | likely_pathogenic | 0.9901 | pathogenic | -2.457 | Highly Destabilizing | 1.0 | D | 0.809 | deleterious | None | None | None | None | N |
| L/M | 0.5275 | ambiguous | 0.4631 | ambiguous | -1.172 | Destabilizing | 1.0 | D | 0.831 | deleterious | None | None | None | None | N |
| L/N | 0.9942 | likely_pathogenic | 0.9902 | pathogenic | -2.816 | Highly Destabilizing | 1.0 | D | 0.831 | deleterious | None | None | None | None | N |
| L/P | 0.9963 | likely_pathogenic | 0.9922 | pathogenic | -1.817 | Destabilizing | 1.0 | D | 0.822 | deleterious | D | 0.666247788 | None | None | N |
| L/Q | 0.9889 | likely_pathogenic | 0.9819 | pathogenic | -2.695 | Highly Destabilizing | 1.0 | D | 0.816 | deleterious | None | None | None | None | N |
| L/R | 0.9862 | likely_pathogenic | 0.9787 | pathogenic | -2.045 | Highly Destabilizing | 1.0 | D | 0.813 | deleterious | D | 0.650228427 | None | None | N |
| L/S | 0.9952 | likely_pathogenic | 0.9921 | pathogenic | -3.457 | Highly Destabilizing | 1.0 | D | 0.808 | deleterious | None | None | None | None | N |
| L/T | 0.9655 | likely_pathogenic | 0.9452 | pathogenic | -3.099 | Highly Destabilizing | 1.0 | D | 0.783 | deleterious | None | None | None | None | N |
| L/V | 0.3395 | likely_benign | 0.3082 | benign | -1.817 | Destabilizing | 0.999 | D | 0.834 | deleterious | D | 0.593499889 | None | None | N |
| L/W | 0.9924 | likely_pathogenic | 0.9835 | pathogenic | -2.291 | Highly Destabilizing | 1.0 | D | 0.727 | prob.delet. | None | None | None | None | N |
| L/Y | 0.9883 | likely_pathogenic | 0.9786 | pathogenic | -2.038 | Highly Destabilizing | 1.0 | D | 0.781 | 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.