Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1531 | 4816;4817;4818 | chr2:178777474;178777473;178777472 | chr2:179642201;179642200;179642199 |
| N2AB | 1531 | 4816;4817;4818 | chr2:178777474;178777473;178777472 | chr2:179642201;179642200;179642199 |
| N2A | 1531 | 4816;4817;4818 | chr2:178777474;178777473;178777472 | chr2:179642201;179642200;179642199 |
| N2B | 1485 | 4678;4679;4680 | chr2:178777474;178777473;178777472 | chr2:179642201;179642200;179642199 |
| Novex-1 | 1485 | 4678;4679;4680 | chr2:178777474;178777473;178777472 | chr2:179642201;179642200;179642199 |
| Novex-2 | 1485 | 4678;4679;4680 | chr2:178777474;178777473;178777472 | chr2:179642201;179642200;179642199 |
| Novex-3 | 1531 | 4816;4817;4818 | chr2:178777474;178777473;178777472 | chr2:179642201;179642200;179642199 |
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/D | rs794727429  |
None | 0.879 | D | 0.867 | 0.582 | 0.875277342448 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 6.17284E-04 | 0 | 0 | 0 |
| V/F | None | None | 0.782 | D | 0.809 | 0.352 | 0.719773709958 | gnomAD-4.0.0 | 6.84176E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.9935E-07 | 0 | 0 |
| V/I | rs1246164291 |
-0.332 | 0.001 | N | 0.275 | 0.053 | 0.349870743963 | gnomAD-2.1.1 | 3.99E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.83E-06 | 0 |
| V/I | rs1246164291 |
-0.332 | 0.001 | N | 0.275 | 0.053 | 0.349870743963 | gnomAD-4.0.0 | 6.84176E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.9935E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.3235 | likely_benign | 0.4176 | ambiguous | -1.489 | Destabilizing | 0.296 | N | 0.615 | neutral | D | 0.6056504 | None | None | I |
| V/C | 0.8566 | likely_pathogenic | 0.8925 | pathogenic | -0.923 | Destabilizing | 0.991 | D | 0.771 | deleterious | None | None | None | None | I |
| V/D | 0.7257 | likely_pathogenic | 0.8189 | pathogenic | -1.5 | Destabilizing | 0.879 | D | 0.867 | deleterious | D | 0.66966045 | None | None | I |
| V/E | 0.4683 | ambiguous | 0.5616 | ambiguous | -1.279 | Destabilizing | 0.906 | D | 0.832 | deleterious | None | None | None | None | I |
| V/F | 0.2496 | likely_benign | 0.309 | benign | -0.738 | Destabilizing | 0.782 | D | 0.809 | deleterious | D | 0.608852116 | None | None | I |
| V/G | 0.6112 | likely_pathogenic | 0.7148 | pathogenic | -2.013 | Highly Destabilizing | 0.879 | D | 0.838 | deleterious | D | 0.730569947 | None | None | I |
| V/H | 0.7491 | likely_pathogenic | 0.8262 | pathogenic | -1.799 | Destabilizing | 0.991 | D | 0.835 | deleterious | None | None | None | None | I |
| V/I | 0.0648 | likely_benign | 0.0674 | benign | -0.04 | Destabilizing | 0.001 | N | 0.275 | neutral | N | 0.489641733 | None | None | I |
| V/K | 0.614 | likely_pathogenic | 0.7171 | pathogenic | -0.883 | Destabilizing | 0.906 | D | 0.837 | deleterious | None | None | None | None | I |
| V/L | 0.2081 | likely_benign | 0.2574 | benign | -0.04 | Destabilizing | 0.031 | N | 0.454 | neutral | N | 0.513741068 | None | None | I |
| V/M | 0.1444 | likely_benign | 0.1739 | benign | -0.226 | Destabilizing | 0.826 | D | 0.721 | prob.delet. | None | None | None | None | I |
| V/N | 0.5572 | ambiguous | 0.6751 | pathogenic | -1.15 | Destabilizing | 0.967 | D | 0.865 | deleterious | None | None | None | None | I |
| V/P | 0.9873 | likely_pathogenic | 0.9937 | pathogenic | -0.495 | Destabilizing | 0.967 | D | 0.823 | deleterious | None | None | None | None | I |
| V/Q | 0.5185 | ambiguous | 0.6092 | pathogenic | -0.949 | Destabilizing | 0.967 | D | 0.816 | deleterious | None | None | None | None | I |
| V/R | 0.5503 | ambiguous | 0.6504 | pathogenic | -0.946 | Destabilizing | 0.906 | D | 0.861 | deleterious | None | None | None | None | I |
| V/S | 0.4305 | ambiguous | 0.5359 | ambiguous | -1.822 | Destabilizing | 0.906 | D | 0.795 | deleterious | None | None | None | None | I |
| V/T | 0.2336 | likely_benign | 0.2947 | benign | -1.454 | Destabilizing | 0.575 | D | 0.649 | neutral | None | None | None | None | I |
| V/W | 0.8908 | likely_pathogenic | 0.9253 | pathogenic | -1.207 | Destabilizing | 0.991 | D | 0.811 | deleterious | None | None | None | None | I |
| V/Y | 0.7066 | likely_pathogenic | 0.7712 | pathogenic | -0.763 | Destabilizing | 0.906 | D | 0.811 | deleterious | None | None | None | None | I |
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.