Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24501 | 73726;73727;73728 | chr2:178572631;178572630;178572629 | chr2:179437358;179437357;179437356 |
| N2AB | 22860 | 68803;68804;68805 | chr2:178572631;178572630;178572629 | chr2:179437358;179437357;179437356 |
| N2A | 21933 | 66022;66023;66024 | chr2:178572631;178572630;178572629 | chr2:179437358;179437357;179437356 |
| N2B | 15436 | 46531;46532;46533 | chr2:178572631;178572630;178572629 | chr2:179437358;179437357;179437356 |
| Novex-1 | 15561 | 46906;46907;46908 | chr2:178572631;178572630;178572629 | chr2:179437358;179437357;179437356 |
| Novex-2 | 15628 | 47107;47108;47109 | chr2:178572631;178572630;178572629 | chr2:179437358;179437357;179437356 |
| 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 | rs1400873497  |
-1.891 | None | N | 0.311 | 0.293 | 0.453772157364 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.91E-06 | 0 |
| V/A | rs1400873497 |
-1.891 | None | N | 0.311 | 0.293 | 0.453772157364 | gnomAD-4.0.0 | 1.59243E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85992E-06 | 0 | 0 |
| V/I | rs774708126 |
-0.681 | None | N | 0.224 | 0.146 | None | gnomAD-2.1.1 | 1.61E-05 | None | None | None | None | I | None | 0 | 2.91E-05 | None | 0 | 0 | None | 3.28E-05 | None | 0 | 1.78E-05 | 0 |
| V/I | rs774708126 |
-0.681 | None | N | 0.224 | 0.146 | None | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| V/I | rs774708126 |
-0.681 | None | N | 0.224 | 0.146 | None | gnomAD-4.0.0 | 7.43863E-06 | None | None | None | None | I | None | 0 | 1.66767E-05 | None | 0 | 2.23244E-05 | None | 0 | 0 | 6.78244E-06 | 2.19761E-05 | 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 | 0.3413 | ambiguous | 0.29 | benign | -1.704 | Destabilizing | None | N | 0.311 | neutral | N | 0.412626347 | None | None | I |
| V/C | 0.9019 | likely_pathogenic | 0.8809 | pathogenic | -1.464 | Destabilizing | 0.824 | D | 0.693 | prob.neutral | None | None | None | None | I |
| V/D | 0.9942 | likely_pathogenic | 0.9941 | pathogenic | -1.705 | Destabilizing | 0.555 | D | 0.779 | deleterious | None | None | None | None | I |
| V/E | 0.9817 | likely_pathogenic | 0.982 | pathogenic | -1.683 | Destabilizing | 0.317 | N | 0.736 | prob.delet. | N | 0.518785238 | None | None | I |
| V/F | 0.7692 | likely_pathogenic | 0.7585 | pathogenic | -1.383 | Destabilizing | 0.38 | N | 0.729 | prob.delet. | None | None | None | None | I |
| V/G | 0.7835 | likely_pathogenic | 0.7675 | pathogenic | -2.054 | Highly Destabilizing | 0.062 | N | 0.735 | prob.delet. | D | 0.524888352 | None | None | I |
| V/H | 0.9965 | likely_pathogenic | 0.9963 | pathogenic | -1.615 | Destabilizing | 0.935 | D | 0.755 | deleterious | None | None | None | None | I |
| V/I | 0.0724 | likely_benign | 0.0727 | benign | -0.827 | Destabilizing | None | N | 0.224 | neutral | N | 0.497565678 | None | None | I |
| V/K | 0.9913 | likely_pathogenic | 0.991 | pathogenic | -1.429 | Destabilizing | 0.38 | N | 0.735 | prob.delet. | None | None | None | None | I |
| V/L | 0.1848 | likely_benign | 0.195 | benign | -0.827 | Destabilizing | None | N | 0.289 | neutral | N | 0.425705579 | None | None | I |
| V/M | 0.3136 | likely_benign | 0.2935 | benign | -0.726 | Destabilizing | 0.38 | N | 0.627 | neutral | None | None | None | None | I |
| V/N | 0.9763 | likely_pathogenic | 0.9769 | pathogenic | -1.306 | Destabilizing | 0.555 | D | 0.78 | deleterious | None | None | None | None | I |
| V/P | 0.986 | likely_pathogenic | 0.9856 | pathogenic | -1.085 | Destabilizing | 0.555 | D | 0.753 | deleterious | None | None | None | None | I |
| V/Q | 0.9815 | likely_pathogenic | 0.9795 | pathogenic | -1.465 | Destabilizing | 0.555 | D | 0.743 | deleterious | None | None | None | None | I |
| V/R | 0.9841 | likely_pathogenic | 0.9825 | pathogenic | -0.935 | Destabilizing | 0.555 | D | 0.783 | deleterious | None | None | None | None | I |
| V/S | 0.8321 | likely_pathogenic | 0.8173 | pathogenic | -1.879 | Destabilizing | 0.081 | N | 0.698 | prob.neutral | None | None | None | None | I |
| V/T | 0.5851 | likely_pathogenic | 0.5542 | ambiguous | -1.737 | Destabilizing | 0.149 | N | 0.563 | neutral | None | None | None | None | I |
| V/W | 0.9963 | likely_pathogenic | 0.996 | pathogenic | -1.579 | Destabilizing | 0.935 | D | 0.756 | deleterious | None | None | None | None | I |
| V/Y | 0.9865 | likely_pathogenic | 0.9847 | pathogenic | -1.28 | Destabilizing | 0.555 | D | 0.738 | prob.delet. | 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.