Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22975 | 69148;69149;69150 | chr2:178577412;178577411;178577410 | chr2:179442139;179442138;179442137 |
| N2AB | 21334 | 64225;64226;64227 | chr2:178577412;178577411;178577410 | chr2:179442139;179442138;179442137 |
| N2A | 20407 | 61444;61445;61446 | chr2:178577412;178577411;178577410 | chr2:179442139;179442138;179442137 |
| N2B | 13910 | 41953;41954;41955 | chr2:178577412;178577411;178577410 | chr2:179442139;179442138;179442137 |
| Novex-1 | 14035 | 42328;42329;42330 | chr2:178577412;178577411;178577410 | chr2:179442139;179442138;179442137 |
| Novex-2 | 14102 | 42529;42530;42531 | chr2:178577412;178577411;178577410 | chr2:179442139;179442138;179442137 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/H | rs778464451  |
-0.558 | 1.0 | D | 0.787 | 0.761 | None | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | I | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 8.9E-06 | 1.66834E-04 |
| P/H | rs778464451 |
-0.558 | 1.0 | D | 0.787 | 0.761 | None | gnomAD-3.1.2 | 6.6E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| P/H | rs778464451 |
-0.558 | 1.0 | D | 0.787 | 0.761 | None | gnomAD-4.0.0 | 9.92482E-06 | None | None | None | None | I | None | 0 | 1.67023E-05 | None | 0 | 0 | None | 0 | 1.64636E-04 | 1.10237E-05 | 0 | 1.60231E-05 |
| P/L | None | None | 1.0 | D | 0.762 | 0.738 | 0.874729657411 | gnomAD-4.0.0 | 6.847E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99795E-07 | 0 | 0 |
| P/R | rs778464451 |
None | 1.0 | D | 0.797 | 0.782 | 0.806807560233 | gnomAD-3.1.2 | 6.6E-06 | None | None | None | None | I | None | 2.42E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| P/R | rs778464451 |
None | 1.0 | D | 0.797 | 0.782 | 0.806807560233 | gnomAD-4.0.0 | 6.59517E-06 | None | None | None | None | I | None | 2.42272E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| P/T | rs1218001244 |
-0.72 | 1.0 | D | 0.736 | 0.762 | 0.764784440165 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| P/T | rs1218001244 |
-0.72 | 1.0 | D | 0.736 | 0.762 | 0.764784440165 | gnomAD-4.0.0 | 1.5939E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43365E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.9518 | likely_pathogenic | 0.9633 | pathogenic | -0.972 | Destabilizing | 1.0 | D | 0.71 | prob.delet. | D | 0.565076741 | None | None | I |
| P/C | 0.9955 | likely_pathogenic | 0.996 | pathogenic | -0.65 | Destabilizing | 1.0 | D | 0.789 | deleterious | None | None | None | None | I |
| P/D | 0.9881 | likely_pathogenic | 0.9897 | pathogenic | -0.538 | Destabilizing | 1.0 | D | 0.734 | prob.delet. | None | None | None | None | I |
| P/E | 0.9851 | likely_pathogenic | 0.9883 | pathogenic | -0.563 | Destabilizing | 1.0 | D | 0.737 | prob.delet. | None | None | None | None | I |
| P/F | 0.9969 | likely_pathogenic | 0.9973 | pathogenic | -0.787 | Destabilizing | 1.0 | D | 0.814 | deleterious | None | None | None | None | I |
| P/G | 0.9819 | likely_pathogenic | 0.9824 | pathogenic | -1.224 | Destabilizing | 1.0 | D | 0.75 | deleterious | None | None | None | None | I |
| P/H | 0.9798 | likely_pathogenic | 0.9833 | pathogenic | -0.652 | Destabilizing | 1.0 | D | 0.787 | deleterious | D | 0.616653889 | None | None | I |
| P/I | 0.9711 | likely_pathogenic | 0.9786 | pathogenic | -0.407 | Destabilizing | 1.0 | D | 0.815 | deleterious | None | None | None | None | I |
| P/K | 0.9884 | likely_pathogenic | 0.99 | pathogenic | -0.772 | Destabilizing | 1.0 | D | 0.735 | prob.delet. | None | None | None | None | I |
| P/L | 0.9423 | likely_pathogenic | 0.9536 | pathogenic | -0.407 | Destabilizing | 1.0 | D | 0.762 | deleterious | D | 0.616653889 | None | None | I |
| P/M | 0.9847 | likely_pathogenic | 0.9881 | pathogenic | -0.435 | Destabilizing | 1.0 | D | 0.783 | deleterious | None | None | None | None | I |
| P/N | 0.9834 | likely_pathogenic | 0.9866 | pathogenic | -0.572 | Destabilizing | 1.0 | D | 0.789 | deleterious | None | None | None | None | I |
| P/Q | 0.9797 | likely_pathogenic | 0.9834 | pathogenic | -0.716 | Destabilizing | 1.0 | D | 0.777 | deleterious | None | None | None | None | I |
| P/R | 0.9752 | likely_pathogenic | 0.9782 | pathogenic | -0.287 | Destabilizing | 1.0 | D | 0.797 | deleterious | D | 0.625536867 | None | None | I |
| P/S | 0.9833 | likely_pathogenic | 0.987 | pathogenic | -1.04 | Destabilizing | 1.0 | D | 0.743 | deleterious | D | 0.576090652 | None | None | I |
| P/T | 0.9529 | likely_pathogenic | 0.9659 | pathogenic | -0.952 | Destabilizing | 1.0 | D | 0.736 | prob.delet. | D | 0.625536867 | None | None | I |
| P/V | 0.9511 | likely_pathogenic | 0.9627 | pathogenic | -0.56 | Destabilizing | 1.0 | D | 0.753 | deleterious | None | None | None | None | I |
| P/W | 0.9983 | likely_pathogenic | 0.9985 | pathogenic | -0.936 | Destabilizing | 1.0 | D | 0.791 | deleterious | None | None | None | None | I |
| P/Y | 0.9916 | likely_pathogenic | 0.9931 | pathogenic | -0.637 | Destabilizing | 1.0 | D | 0.827 | 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.