Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29498 | 88717;88718;88719 | chr2:178554967;178554966;178554965 | chr2:179419694;179419693;179419692 |
| N2AB | 27857 | 83794;83795;83796 | chr2:178554967;178554966;178554965 | chr2:179419694;179419693;179419692 |
| N2A | 26930 | 81013;81014;81015 | chr2:178554967;178554966;178554965 | chr2:179419694;179419693;179419692 |
| N2B | 20433 | 61522;61523;61524 | chr2:178554967;178554966;178554965 | chr2:179419694;179419693;179419692 |
| Novex-1 | 20558 | 61897;61898;61899 | chr2:178554967;178554966;178554965 | chr2:179419694;179419693;179419692 |
| Novex-2 | 20625 | 62098;62099;62100 | chr2:178554967;178554966;178554965 | chr2:179419694;179419693;179419692 |
| 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 | rs762766139  |
-3.044 | 0.062 | N | 0.741 | 0.319 | 0.431490205687 | gnomAD-2.1.1 | 8.05E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.78E-05 | 0 |
| I/T | rs762766139 |
-3.044 | 0.062 | N | 0.741 | 0.319 | 0.431490205687 | gnomAD-4.0.0 | 2.73696E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.52525E-05 | None | 0 | 0 | 2.69835E-06 | 0 | 0 |
| I/V | rs1559235133 |
None | None | N | 0.236 | 0.065 | 0.185906805712 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.61E-05 | None | 0 | None | 0 | 0 | 0 |
| I/V | rs1559235133 |
None | None | N | 0.236 | 0.065 | 0.185906805712 | gnomAD-4.0.0 | 3.18286E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.78009E-05 | None | 0 | 0 | 0 | 1.43283E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.8089 | likely_pathogenic | 0.8064 | pathogenic | -2.721 | Highly Destabilizing | 0.035 | N | 0.716 | prob.delet. | None | None | None | None | N |
| I/C | 0.8515 | likely_pathogenic | 0.8519 | pathogenic | -2.015 | Highly Destabilizing | 0.824 | D | 0.789 | deleterious | None | None | None | None | N |
| I/D | 0.9973 | likely_pathogenic | 0.9965 | pathogenic | -3.547 | Highly Destabilizing | 0.555 | D | 0.855 | deleterious | None | None | None | None | N |
| I/E | 0.9945 | likely_pathogenic | 0.9935 | pathogenic | -3.219 | Highly Destabilizing | 0.555 | D | 0.83 | deleterious | None | None | None | None | N |
| I/F | 0.4023 | ambiguous | 0.3598 | ambiguous | -1.683 | Destabilizing | 0.38 | N | 0.694 | prob.neutral | None | None | None | None | N |
| I/G | 0.9772 | likely_pathogenic | 0.9744 | pathogenic | -3.323 | Highly Destabilizing | 0.555 | D | 0.834 | deleterious | None | None | None | None | N |
| I/H | 0.9849 | likely_pathogenic | 0.9795 | pathogenic | -3.131 | Highly Destabilizing | 0.935 | D | 0.859 | deleterious | None | None | None | None | N |
| I/K | 0.9883 | likely_pathogenic | 0.9837 | pathogenic | -2.214 | Highly Destabilizing | 0.484 | N | 0.834 | deleterious | N | 0.481837637 | None | None | N |
| I/L | 0.112 | likely_benign | 0.1097 | benign | -0.897 | Destabilizing | None | N | 0.286 | neutral | N | 0.272125577 | None | None | N |
| I/M | 0.2293 | likely_benign | 0.2195 | benign | -1.13 | Destabilizing | 0.317 | N | 0.626 | neutral | N | 0.451168013 | None | None | N |
| I/N | 0.971 | likely_pathogenic | 0.9641 | pathogenic | -2.982 | Highly Destabilizing | 0.791 | D | 0.861 | deleterious | None | None | None | None | N |
| I/P | 0.9938 | likely_pathogenic | 0.9922 | pathogenic | -1.498 | Destabilizing | 0.555 | D | 0.857 | deleterious | None | None | None | None | N |
| I/Q | 0.9859 | likely_pathogenic | 0.9828 | pathogenic | -2.592 | Highly Destabilizing | 0.791 | D | 0.859 | deleterious | None | None | None | None | N |
| I/R | 0.9787 | likely_pathogenic | 0.9708 | pathogenic | -2.338 | Highly Destabilizing | 0.484 | N | 0.86 | deleterious | N | 0.481837637 | None | None | N |
| I/S | 0.9447 | likely_pathogenic | 0.9369 | pathogenic | -3.476 | Highly Destabilizing | 0.38 | N | 0.813 | deleterious | None | None | None | None | N |
| I/T | 0.9156 | likely_pathogenic | 0.9154 | pathogenic | -2.981 | Highly Destabilizing | 0.062 | N | 0.741 | deleterious | N | 0.463251876 | None | None | N |
| I/V | 0.0809 | likely_benign | 0.0893 | benign | -1.498 | Destabilizing | None | N | 0.236 | neutral | N | 0.390754273 | None | None | N |
| I/W | 0.9829 | likely_pathogenic | 0.976 | pathogenic | -2.095 | Highly Destabilizing | 0.935 | D | 0.853 | deleterious | None | None | None | None | N |
| I/Y | 0.9118 | likely_pathogenic | 0.8725 | pathogenic | -1.902 | Destabilizing | 0.555 | D | 0.793 | deleterious | 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.