Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21420 | 64483;64484;64485 | chr2:178586643;178586642;178586641 | chr2:179451370;179451369;179451368 |
| N2AB | 19779 | 59560;59561;59562 | chr2:178586643;178586642;178586641 | chr2:179451370;179451369;179451368 |
| N2A | 18852 | 56779;56780;56781 | chr2:178586643;178586642;178586641 | chr2:179451370;179451369;179451368 |
| N2B | 12355 | 37288;37289;37290 | chr2:178586643;178586642;178586641 | chr2:179451370;179451369;179451368 |
| Novex-1 | 12480 | 37663;37664;37665 | chr2:178586643;178586642;178586641 | chr2:179451370;179451369;179451368 |
| Novex-2 | 12547 | 37864;37865;37866 | chr2:178586643;178586642;178586641 | chr2:179451370;179451369;179451368 |
| 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/A | rs765213969  |
-0.537 | 0.645 | N | 0.507 | 0.229 | 0.561599553422 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 6.46E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| V/A | rs765213969 |
-0.537 | 0.645 | N | 0.507 | 0.229 | 0.561599553422 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 2.42E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/A | rs765213969 |
-0.537 | 0.645 | N | 0.507 | 0.229 | 0.561599553422 | gnomAD-4.0.0 | 6.58007E-06 | None | None | None | None | I | None | 2.41558E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/L | None | None | 0.114 | N | 0.405 | 0.122 | 0.446913017954 | gnomAD-4.0.0 | 1.59254E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.861E-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 | 0.2955 | likely_benign | 0.2477 | benign | -0.693 | Destabilizing | 0.645 | D | 0.507 | neutral | N | 0.468036913 | None | None | I |
| V/C | 0.8119 | likely_pathogenic | 0.7778 | pathogenic | -0.792 | Destabilizing | 0.995 | D | 0.699 | prob.neutral | None | None | None | None | I |
| V/D | 0.6861 | likely_pathogenic | 0.5973 | pathogenic | -0.087 | Destabilizing | 0.945 | D | 0.777 | deleterious | None | None | None | None | I |
| V/E | 0.4943 | ambiguous | 0.3975 | ambiguous | -0.167 | Destabilizing | 0.928 | D | 0.761 | deleterious | N | 0.435137847 | None | None | I |
| V/F | 0.3093 | likely_benign | 0.2702 | benign | -0.678 | Destabilizing | 0.894 | D | 0.736 | prob.delet. | None | None | None | None | I |
| V/G | 0.539 | ambiguous | 0.4828 | ambiguous | -0.876 | Destabilizing | 0.928 | D | 0.771 | deleterious | N | 0.487182821 | None | None | I |
| V/H | 0.7023 | likely_pathogenic | 0.6324 | pathogenic | -0.331 | Destabilizing | 0.995 | D | 0.769 | deleterious | None | None | None | None | I |
| V/I | 0.087 | likely_benign | 0.083 | benign | -0.346 | Destabilizing | 0.007 | N | 0.239 | neutral | None | None | None | None | I |
| V/K | 0.5338 | ambiguous | 0.4399 | ambiguous | -0.53 | Destabilizing | 0.945 | D | 0.763 | deleterious | None | None | None | None | I |
| V/L | 0.273 | likely_benign | 0.222 | benign | -0.346 | Destabilizing | 0.114 | N | 0.405 | neutral | N | 0.447602925 | None | None | I |
| V/M | 0.1942 | likely_benign | 0.1654 | benign | -0.4 | Destabilizing | 0.864 | D | 0.653 | neutral | N | 0.521834112 | None | None | I |
| V/N | 0.4786 | ambiguous | 0.4131 | ambiguous | -0.351 | Destabilizing | 0.981 | D | 0.774 | deleterious | None | None | None | None | I |
| V/P | 0.8413 | likely_pathogenic | 0.7706 | pathogenic | -0.425 | Destabilizing | 0.981 | D | 0.767 | deleterious | None | None | None | None | I |
| V/Q | 0.4664 | ambiguous | 0.3973 | ambiguous | -0.552 | Destabilizing | 0.981 | D | 0.762 | deleterious | None | None | None | None | I |
| V/R | 0.4816 | ambiguous | 0.3909 | ambiguous | -0.042 | Destabilizing | 0.945 | D | 0.772 | deleterious | None | None | None | None | I |
| V/S | 0.3776 | ambiguous | 0.3297 | benign | -0.831 | Destabilizing | 0.945 | D | 0.755 | deleterious | None | None | None | None | I |
| V/T | 0.2047 | likely_benign | 0.1868 | benign | -0.801 | Destabilizing | 0.707 | D | 0.629 | neutral | None | None | None | None | I |
| V/W | 0.8871 | likely_pathogenic | 0.856 | pathogenic | -0.745 | Destabilizing | 0.995 | D | 0.791 | deleterious | None | None | None | None | I |
| V/Y | 0.7136 | likely_pathogenic | 0.6518 | pathogenic | -0.453 | Destabilizing | 0.945 | D | 0.746 | 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.