Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16250 | 48973;48974;48975 | chr2:178614859;178614858;178614857 | chr2:179479586;179479585;179479584 |
| N2AB | 14609 | 44050;44051;44052 | chr2:178614859;178614858;178614857 | chr2:179479586;179479585;179479584 |
| N2A | 13682 | 41269;41270;41271 | chr2:178614859;178614858;178614857 | chr2:179479586;179479585;179479584 |
| N2B | 7185 | 21778;21779;21780 | chr2:178614859;178614858;178614857 | chr2:179479586;179479585;179479584 |
| Novex-1 | 7310 | 22153;22154;22155 | chr2:178614859;178614858;178614857 | chr2:179479586;179479585;179479584 |
| Novex-2 | 7377 | 22354;22355;22356 | chr2:178614859;178614858;178614857 | chr2:179479586;179479585;179479584 |
| 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/M | rs1051281754  |
None | 0.004 | N | 0.366 | 0.064 | 0.278968121808 | gnomAD-2.1.1 | 5.38E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.29E-05 | 0 |
| V/M | rs1051281754 |
None | 0.004 | N | 0.366 | 0.064 | 0.278968121808 | gnomAD-4.0.0 | 3.40664E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 6.10575E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.1944 | likely_benign | 0.2325 | benign | -1.155 | Destabilizing | 0.012 | N | 0.281 | neutral | N | 0.493264297 | None | None | N |
| V/C | 0.6791 | likely_pathogenic | 0.7645 | pathogenic | -1.155 | Destabilizing | 0.869 | D | 0.32 | neutral | None | None | None | None | N |
| V/D | 0.6132 | likely_pathogenic | 0.703 | pathogenic | -1.549 | Destabilizing | 0.221 | N | 0.657 | prob.neutral | None | None | None | None | N |
| V/E | 0.3601 | ambiguous | 0.4137 | ambiguous | -1.619 | Destabilizing | 0.177 | N | 0.557 | neutral | N | 0.480254007 | None | None | N |
| V/F | 0.2547 | likely_benign | 0.2987 | benign | -1.361 | Destabilizing | 0.221 | N | 0.44 | neutral | None | None | None | None | N |
| V/G | 0.3386 | likely_benign | 0.3823 | ambiguous | -1.346 | Destabilizing | 0.177 | N | 0.584 | neutral | N | 0.477985068 | None | None | N |
| V/H | 0.614 | likely_pathogenic | 0.7022 | pathogenic | -0.809 | Destabilizing | 0.869 | D | 0.541 | neutral | None | None | None | None | N |
| V/I | 0.0736 | likely_benign | 0.0828 | benign | -0.757 | Destabilizing | None | N | 0.181 | neutral | None | None | None | None | N |
| V/K | 0.2836 | likely_benign | 0.3268 | benign | -0.826 | Destabilizing | 0.221 | N | 0.511 | neutral | None | None | None | None | N |
| V/L | 0.2086 | likely_benign | 0.2607 | benign | -0.757 | Destabilizing | None | N | 0.159 | neutral | N | 0.471325082 | None | None | N |
| V/M | 0.139 | likely_benign | 0.1623 | benign | -0.588 | Destabilizing | 0.004 | N | 0.366 | neutral | N | 0.491259173 | None | None | N |
| V/N | 0.3613 | ambiguous | 0.4812 | ambiguous | -0.73 | Destabilizing | 0.221 | N | 0.602 | neutral | None | None | None | None | N |
| V/P | 0.9374 | likely_pathogenic | 0.956 | pathogenic | -0.857 | Destabilizing | 0.366 | N | 0.609 | neutral | None | None | None | None | N |
| V/Q | 0.3052 | likely_benign | 0.3587 | ambiguous | -1.079 | Destabilizing | 0.366 | N | 0.526 | neutral | None | None | None | None | N |
| V/R | 0.2856 | likely_benign | 0.3299 | benign | -0.241 | Destabilizing | 0.221 | N | 0.6 | neutral | None | None | None | None | N |
| V/S | 0.2682 | likely_benign | 0.3401 | ambiguous | -1.126 | Destabilizing | 0.039 | N | 0.465 | neutral | None | None | None | None | N |
| V/T | 0.1423 | likely_benign | 0.1706 | benign | -1.104 | Destabilizing | 0.003 | N | 0.193 | neutral | None | None | None | None | N |
| V/W | 0.8735 | likely_pathogenic | 0.9016 | pathogenic | -1.422 | Destabilizing | 0.869 | D | 0.646 | neutral | None | None | None | None | N |
| V/Y | 0.67 | likely_pathogenic | 0.7553 | pathogenic | -1.079 | Destabilizing | 0.366 | N | 0.358 | neutral | 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.