Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19909 | 59950;59951;59952 | chr2:178592179;178592178;178592177 | chr2:179456906;179456905;179456904 |
| N2AB | 18268 | 55027;55028;55029 | chr2:178592179;178592178;178592177 | chr2:179456906;179456905;179456904 |
| N2A | 17341 | 52246;52247;52248 | chr2:178592179;178592178;178592177 | chr2:179456906;179456905;179456904 |
| N2B | 10844 | 32755;32756;32757 | chr2:178592179;178592178;178592177 | chr2:179456906;179456905;179456904 |
| Novex-1 | 10969 | 33130;33131;33132 | chr2:178592179;178592178;178592177 | chr2:179456906;179456905;179456904 |
| Novex-2 | 11036 | 33331;33332;33333 | chr2:178592179;178592178;178592177 | chr2:179456906;179456905;179456904 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/T | rs775088892  |
-2.325 | 0.201 | D | 0.789 | 0.436 | 0.785508900599 | gnomAD-2.1.1 | 8.1E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.79E-05 | 0 |
| I/T | rs775088892 |
-2.325 | 0.201 | D | 0.789 | 0.436 | 0.785508900599 | 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 |
| I/T | rs775088892 |
-2.325 | 0.201 | D | 0.789 | 0.436 | 0.785508900599 | gnomAD-4.0.0 | 8.06124E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.10223E-05 | 0 | 0 |
| I/V | rs1060500484 |
-1.56 | 0.001 | N | 0.289 | 0.178 | 0.252681307341 | gnomAD-2.1.1 | 1.08E-05 | None | None | None | None | I | None | 1.24533E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/V | rs1060500484 |
-1.56 | 0.001 | N | 0.289 | 0.178 | 0.252681307341 | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | I | None | 9.65E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | rs1060500484 |
-1.56 | 0.001 | N | 0.289 | 0.178 | 0.252681307341 | gnomAD-4.0.0 | 5.58099E-06 | None | None | None | None | I | None | 1.06829E-04 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 1.60277E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.9414 | likely_pathogenic | 0.95 | pathogenic | -2.397 | Highly Destabilizing | 0.25 | N | 0.679 | prob.neutral | None | None | None | None | I |
| I/C | 0.9556 | likely_pathogenic | 0.9613 | pathogenic | -1.583 | Destabilizing | 0.947 | D | 0.726 | prob.delet. | None | None | None | None | I |
| I/D | 0.9963 | likely_pathogenic | 0.9977 | pathogenic | -2.549 | Highly Destabilizing | 0.826 | D | 0.799 | deleterious | None | None | None | None | I |
| I/E | 0.9885 | likely_pathogenic | 0.9917 | pathogenic | -2.461 | Highly Destabilizing | 0.826 | D | 0.799 | deleterious | None | None | None | None | I |
| I/F | 0.8626 | likely_pathogenic | 0.8918 | pathogenic | -1.726 | Destabilizing | 0.638 | D | 0.753 | deleterious | N | 0.51927013 | None | None | I |
| I/G | 0.9887 | likely_pathogenic | 0.9914 | pathogenic | -2.825 | Highly Destabilizing | 0.826 | D | 0.793 | deleterious | None | None | None | None | I |
| I/H | 0.9885 | likely_pathogenic | 0.9928 | pathogenic | -2.203 | Highly Destabilizing | 0.982 | D | 0.769 | deleterious | None | None | None | None | I |
| I/K | 0.9738 | likely_pathogenic | 0.9819 | pathogenic | -1.796 | Destabilizing | 0.826 | D | 0.801 | deleterious | None | None | None | None | I |
| I/L | 0.3418 | ambiguous | 0.3983 | ambiguous | -1.218 | Destabilizing | 0.043 | N | 0.515 | neutral | N | 0.486175492 | None | None | I |
| I/M | 0.5125 | ambiguous | 0.554 | ambiguous | -0.877 | Destabilizing | 0.638 | D | 0.713 | prob.delet. | D | 0.544682221 | None | None | I |
| I/N | 0.9278 | likely_pathogenic | 0.9571 | pathogenic | -1.81 | Destabilizing | 0.916 | D | 0.805 | deleterious | D | 0.545696179 | None | None | I |
| I/P | 0.9287 | likely_pathogenic | 0.937 | pathogenic | -1.586 | Destabilizing | 0.935 | D | 0.805 | deleterious | None | None | None | None | I |
| I/Q | 0.9792 | likely_pathogenic | 0.9851 | pathogenic | -1.904 | Destabilizing | 0.935 | D | 0.808 | deleterious | None | None | None | None | I |
| I/R | 0.9652 | likely_pathogenic | 0.9768 | pathogenic | -1.232 | Destabilizing | 0.826 | D | 0.808 | deleterious | None | None | None | None | I |
| I/S | 0.9533 | likely_pathogenic | 0.9659 | pathogenic | -2.436 | Highly Destabilizing | 0.638 | D | 0.761 | deleterious | D | 0.526831455 | None | None | I |
| I/T | 0.8843 | likely_pathogenic | 0.8983 | pathogenic | -2.225 | Highly Destabilizing | 0.201 | N | 0.789 | deleterious | D | 0.522058515 | None | None | I |
| I/V | 0.0947 | likely_benign | 0.0881 | benign | -1.586 | Destabilizing | 0.001 | N | 0.289 | neutral | N | 0.490471055 | None | None | I |
| I/W | 0.9953 | likely_pathogenic | 0.9963 | pathogenic | -2.0 | Highly Destabilizing | 0.982 | D | 0.733 | prob.delet. | None | None | None | None | I |
| I/Y | 0.9764 | likely_pathogenic | 0.984 | pathogenic | -1.762 | Destabilizing | 0.826 | D | 0.775 | 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.