Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26733 | 80422;80423;80424 | chr2:178565935;178565934;178565933 | chr2:179430662;179430661;179430660 |
| N2AB | 25092 | 75499;75500;75501 | chr2:178565935;178565934;178565933 | chr2:179430662;179430661;179430660 |
| N2A | 24165 | 72718;72719;72720 | chr2:178565935;178565934;178565933 | chr2:179430662;179430661;179430660 |
| N2B | 17668 | 53227;53228;53229 | chr2:178565935;178565934;178565933 | chr2:179430662;179430661;179430660 |
| Novex-1 | 17793 | 53602;53603;53604 | chr2:178565935;178565934;178565933 | chr2:179430662;179430661;179430660 |
| Novex-2 | 17860 | 53803;53804;53805 | chr2:178565935;178565934;178565933 | chr2:179430662;179430661;179430660 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/E | rs746813986  |
-1.069 | 0.998 | N | 0.791 | 0.577 | 0.805024126583 | gnomAD-2.1.1 | 1.61E-05 | None | None | None | None | N | None | 6.46E-05 | 0 | None | 0 | 1.67299E-04 | None | 0 | None | 0 | 0 | 0 |
| V/E | rs746813986 |
-1.069 | 0.998 | N | 0.791 | 0.577 | 0.805024126583 | gnomAD-4.0.0 | 2.05283E-06 | None | None | None | None | N | None | 5.97836E-05 | 0 | None | 0 | 2.5208E-05 | None | 0 | 0 | 0 | 0 | 0 |
| V/M | rs755876442 |
-0.551 | 0.998 | N | 0.723 | 0.38 | 0.47185959272 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.9E-06 | 0 |
| V/M | rs755876442 |
-0.551 | 0.998 | N | 0.723 | 0.38 | 0.47185959272 | gnomAD-4.0.0 | 1.5054E-05 | None | None | None | None | N | None | 2.989E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 1.88905E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.3843 | ambiguous | 0.4332 | ambiguous | -1.409 | Destabilizing | 0.983 | D | 0.476 | neutral | N | 0.48031878 | None | None | N |
| V/C | 0.813 | likely_pathogenic | 0.8664 | pathogenic | -1.189 | Destabilizing | 1.0 | D | 0.801 | deleterious | None | None | None | None | N |
| V/D | 0.9512 | likely_pathogenic | 0.9557 | pathogenic | -0.829 | Destabilizing | 1.0 | D | 0.827 | deleterious | None | None | None | None | N |
| V/E | 0.8999 | likely_pathogenic | 0.9028 | pathogenic | -0.782 | Destabilizing | 0.998 | D | 0.791 | deleterious | N | 0.503873403 | None | None | N |
| V/F | 0.4479 | ambiguous | 0.5006 | ambiguous | -1.019 | Destabilizing | 0.999 | D | 0.821 | deleterious | None | None | None | None | N |
| V/G | 0.7146 | likely_pathogenic | 0.7434 | pathogenic | -1.768 | Destabilizing | 1.0 | D | 0.798 | deleterious | N | 0.513680134 | None | None | N |
| V/H | 0.9515 | likely_pathogenic | 0.9596 | pathogenic | -1.223 | Destabilizing | 1.0 | D | 0.8 | deleterious | None | None | None | None | N |
| V/I | 0.076 | likely_benign | 0.079 | benign | -0.515 | Destabilizing | 0.136 | N | 0.267 | neutral | None | None | None | None | N |
| V/K | 0.9441 | likely_pathogenic | 0.9442 | pathogenic | -1.121 | Destabilizing | 0.999 | D | 0.796 | deleterious | None | None | None | None | N |
| V/L | 0.3965 | ambiguous | 0.4422 | ambiguous | -0.515 | Destabilizing | 0.647 | D | 0.421 | neutral | N | 0.520828461 | None | None | N |
| V/M | 0.3326 | likely_benign | 0.3864 | ambiguous | -0.53 | Destabilizing | 0.998 | D | 0.723 | prob.delet. | N | 0.508337763 | None | None | N |
| V/N | 0.8451 | likely_pathogenic | 0.8746 | pathogenic | -1.07 | Destabilizing | 0.995 | D | 0.824 | deleterious | None | None | None | None | N |
| V/P | 0.9734 | likely_pathogenic | 0.9752 | pathogenic | -0.777 | Destabilizing | 0.995 | D | 0.819 | deleterious | None | None | None | None | N |
| V/Q | 0.8731 | likely_pathogenic | 0.8891 | pathogenic | -1.115 | Destabilizing | 0.999 | D | 0.819 | deleterious | None | None | None | None | N |
| V/R | 0.922 | likely_pathogenic | 0.9219 | pathogenic | -0.729 | Destabilizing | 1.0 | D | 0.826 | deleterious | None | None | None | None | N |
| V/S | 0.6428 | likely_pathogenic | 0.7009 | pathogenic | -1.702 | Destabilizing | 0.999 | D | 0.784 | deleterious | None | None | None | None | N |
| V/T | 0.4749 | ambiguous | 0.5348 | ambiguous | -1.515 | Destabilizing | 0.984 | D | 0.602 | neutral | None | None | None | None | N |
| V/W | 0.9779 | likely_pathogenic | 0.9824 | pathogenic | -1.208 | Destabilizing | 1.0 | D | 0.789 | deleterious | None | None | None | None | N |
| V/Y | 0.8873 | likely_pathogenic | 0.9048 | pathogenic | -0.887 | Destabilizing | 1.0 | D | 0.83 | 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.