Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 3221 | 9886;9887;9888 | chr2:178766423;178766422;178766421 | chr2:179631150;179631149;179631148 |
| N2AB | 3221 | 9886;9887;9888 | chr2:178766423;178766422;178766421 | chr2:179631150;179631149;179631148 |
| N2A | 3221 | 9886;9887;9888 | chr2:178766423;178766422;178766421 | chr2:179631150;179631149;179631148 |
| N2B | 3175 | 9748;9749;9750 | chr2:178766423;178766422;178766421 | chr2:179631150;179631149;179631148 |
| Novex-1 | 3175 | 9748;9749;9750 | chr2:178766423;178766422;178766421 | chr2:179631150;179631149;179631148 |
| Novex-2 | 3175 | 9748;9749;9750 | chr2:178766423;178766422;178766421 | chr2:179631150;179631149;179631148 |
| Novex-3 | 3221 | 9886;9887;9888 | chr2:178766423;178766422;178766421 | chr2:179631150;179631149;179631148 |
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 | rs1445925686  |
-1.082 | 0.309 | N | 0.553 | 0.311 | 0.540788926979 | gnomAD-2.1.1 | 3.98E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.44E-05 | None | 0 | None | 0 | 0 | 0 |
| V/A | rs1445925686 |
-1.082 | 0.309 | N | 0.553 | 0.311 | 0.540788926979 | gnomAD-4.0.0 | 1.59053E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.77331E-05 | None | 0 | 0 | 0 | 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 | 0.3982 | ambiguous | 0.4635 | ambiguous | -1.735 | Destabilizing | 0.309 | N | 0.553 | neutral | N | 0.508711952 | None | None | N |
| V/C | 0.9242 | likely_pathogenic | 0.9198 | pathogenic | -1.061 | Destabilizing | 0.996 | D | 0.563 | neutral | None | None | None | None | N |
| V/D | 0.9052 | likely_pathogenic | 0.9036 | pathogenic | -2.13 | Highly Destabilizing | 0.91 | D | 0.693 | prob.neutral | None | None | None | None | N |
| V/E | 0.6978 | likely_pathogenic | 0.6758 | pathogenic | -1.926 | Destabilizing | 0.792 | D | 0.615 | neutral | N | 0.50646609 | None | None | N |
| V/F | 0.4958 | ambiguous | 0.4856 | ambiguous | -0.958 | Destabilizing | 0.02 | N | 0.389 | neutral | None | None | None | None | N |
| V/G | 0.7557 | likely_pathogenic | 0.7751 | pathogenic | -2.257 | Highly Destabilizing | 0.884 | D | 0.659 | neutral | D | 0.582495722 | None | None | N |
| V/H | 0.9033 | likely_pathogenic | 0.8918 | pathogenic | -2.094 | Highly Destabilizing | 0.987 | D | 0.667 | neutral | None | None | None | None | N |
| V/I | 0.1132 | likely_benign | 0.1094 | benign | -0.287 | Destabilizing | 0.004 | N | 0.245 | neutral | None | None | None | None | N |
| V/K | 0.8243 | likely_pathogenic | 0.8026 | pathogenic | -1.24 | Destabilizing | 0.009 | N | 0.506 | neutral | None | None | None | None | N |
| V/L | 0.4958 | ambiguous | 0.444 | ambiguous | -0.287 | Destabilizing | 0.164 | N | 0.373 | neutral | N | 0.512417193 | None | None | N |
| V/M | 0.3691 | ambiguous | 0.3504 | ambiguous | -0.288 | Destabilizing | 0.884 | D | 0.593 | neutral | D | 0.542451181 | None | None | N |
| V/N | 0.8327 | likely_pathogenic | 0.8346 | pathogenic | -1.466 | Destabilizing | 0.91 | D | 0.688 | prob.neutral | None | None | None | None | N |
| V/P | 0.9969 | likely_pathogenic | 0.996 | pathogenic | -0.742 | Destabilizing | 0.953 | D | 0.639 | neutral | None | None | None | None | N |
| V/Q | 0.6898 | likely_pathogenic | 0.6557 | pathogenic | -1.316 | Destabilizing | 0.91 | D | 0.643 | neutral | None | None | None | None | N |
| V/R | 0.741 | likely_pathogenic | 0.7154 | pathogenic | -1.164 | Destabilizing | 0.835 | D | 0.692 | prob.neutral | None | None | None | None | N |
| V/S | 0.5105 | ambiguous | 0.557 | ambiguous | -2.082 | Highly Destabilizing | 0.742 | D | 0.604 | neutral | None | None | None | None | N |
| V/T | 0.4015 | ambiguous | 0.4133 | ambiguous | -1.741 | Destabilizing | 0.742 | D | 0.575 | neutral | None | None | None | None | N |
| V/W | 0.9712 | likely_pathogenic | 0.9633 | pathogenic | -1.513 | Destabilizing | 0.996 | D | 0.683 | prob.neutral | None | None | None | None | N |
| V/Y | 0.8816 | likely_pathogenic | 0.8758 | pathogenic | -1.088 | Destabilizing | 0.835 | D | 0.584 | 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.