Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24546 | 73861;73862;73863 | chr2:178572496;178572495;178572494 | chr2:179437223;179437222;179437221 |
| N2AB | 22905 | 68938;68939;68940 | chr2:178572496;178572495;178572494 | chr2:179437223;179437222;179437221 |
| N2A | 21978 | 66157;66158;66159 | chr2:178572496;178572495;178572494 | chr2:179437223;179437222;179437221 |
| N2B | 15481 | 46666;46667;46668 | chr2:178572496;178572495;178572494 | chr2:179437223;179437222;179437221 |
| Novex-1 | 15606 | 47041;47042;47043 | chr2:178572496;178572495;178572494 | chr2:179437223;179437222;179437221 |
| Novex-2 | 15673 | 47242;47243;47244 | chr2:178572496;178572495;178572494 | chr2:179437223;179437222;179437221 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/E | None | None | 0.486 | N | 0.458 | 0.234 | 0.255777322467 | gnomAD-4.0.0 | 6.84409E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99632E-07 | 0 | 0 |
| D/H | rs1051495269  |
-1.052 | 0.997 | D | 0.75 | 0.448 | 0.454238212503 | gnomAD-2.1.1 | 1.07E-05 | None | None | None | None | I | None | 1.24018E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| D/H | rs1051495269 |
-1.052 | 0.997 | D | 0.75 | 0.448 | 0.454238212503 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | I | None | 7.24E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| D/H | rs1051495269 |
-1.052 | 0.997 | D | 0.75 | 0.448 | 0.454238212503 | gnomAD-4.0.0 | 3.71946E-06 | None | None | None | None | I | None | 8.01303E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| D/V | rs769744030 |
0.091 | 0.974 | N | 0.739 | 0.542 | 0.513112959101 | gnomAD-2.1.1 | 2.15E-05 | None | None | None | None | I | None | 0 | 5.67E-05 | None | 0 | 0 | None | 0 | None | 0 | 2.35E-05 | 1.40924E-04 |
| D/V | rs769744030 |
0.091 | 0.974 | N | 0.739 | 0.542 | 0.513112959101 | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 5.88E-05 | 0 | 0 |
| D/V | rs769744030 |
0.091 | 0.974 | N | 0.739 | 0.542 | 0.513112959101 | gnomAD-4.0.0 | 1.42577E-05 | None | None | None | None | I | None | 0 | 6.67111E-05 | None | 0 | 0 | None | 0 | 0 | 1.61078E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.9583 | likely_pathogenic | 0.9189 | pathogenic | -0.598 | Destabilizing | 0.967 | D | 0.675 | neutral | N | 0.503097524 | None | None | I |
| D/C | 0.9888 | likely_pathogenic | 0.9783 | pathogenic | -0.08 | Destabilizing | 0.996 | D | 0.723 | prob.delet. | None | None | None | None | I |
| D/E | 0.8817 | likely_pathogenic | 0.8377 | pathogenic | -0.617 | Destabilizing | 0.486 | N | 0.458 | neutral | N | 0.499285636 | None | None | I |
| D/F | 0.9931 | likely_pathogenic | 0.9884 | pathogenic | -0.589 | Destabilizing | 1.0 | D | 0.733 | prob.delet. | None | None | None | None | I |
| D/G | 0.9468 | likely_pathogenic | 0.9094 | pathogenic | -0.873 | Destabilizing | 0.753 | D | 0.642 | neutral | D | 0.526014399 | None | None | I |
| D/H | 0.9682 | likely_pathogenic | 0.949 | pathogenic | -0.899 | Destabilizing | 0.997 | D | 0.75 | deleterious | D | 0.522620584 | None | None | I |
| D/I | 0.9891 | likely_pathogenic | 0.9807 | pathogenic | 0.104 | Stabilizing | 0.996 | D | 0.749 | deleterious | None | None | None | None | I |
| D/K | 0.9925 | likely_pathogenic | 0.9877 | pathogenic | -0.103 | Destabilizing | 0.993 | D | 0.685 | prob.neutral | None | None | None | None | I |
| D/L | 0.9792 | likely_pathogenic | 0.9662 | pathogenic | 0.104 | Stabilizing | 0.996 | D | 0.737 | prob.delet. | None | None | None | None | I |
| D/M | 0.9953 | likely_pathogenic | 0.9917 | pathogenic | 0.571 | Stabilizing | 0.999 | D | 0.718 | prob.delet. | None | None | None | None | I |
| D/N | 0.576 | likely_pathogenic | 0.5115 | ambiguous | -0.432 | Destabilizing | 0.026 | N | 0.261 | neutral | N | 0.471421691 | None | None | I |
| D/P | 0.993 | likely_pathogenic | 0.9854 | pathogenic | -0.106 | Destabilizing | 0.945 | D | 0.782 | deleterious | None | None | None | None | I |
| D/Q | 0.9825 | likely_pathogenic | 0.97 | pathogenic | -0.364 | Destabilizing | 0.981 | D | 0.772 | deleterious | None | None | None | None | I |
| D/R | 0.989 | likely_pathogenic | 0.9809 | pathogenic | -0.106 | Destabilizing | 0.993 | D | 0.758 | deleterious | None | None | None | None | I |
| D/S | 0.8358 | likely_pathogenic | 0.7653 | pathogenic | -0.616 | Destabilizing | 0.848 | D | 0.637 | neutral | None | None | None | None | I |
| D/T | 0.9504 | likely_pathogenic | 0.926 | pathogenic | -0.391 | Destabilizing | 0.946 | D | 0.685 | prob.neutral | None | None | None | None | I |
| D/V | 0.9704 | likely_pathogenic | 0.9492 | pathogenic | -0.106 | Destabilizing | 0.974 | D | 0.739 | prob.delet. | N | 0.517999002 | None | None | I |
| D/W | 0.998 | likely_pathogenic | 0.9962 | pathogenic | -0.464 | Destabilizing | 1.0 | D | 0.725 | prob.delet. | None | None | None | None | I |
| D/Y | 0.9455 | likely_pathogenic | 0.9155 | pathogenic | -0.357 | Destabilizing | 1.0 | D | 0.727 | prob.delet. | D | 0.555474959 | 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.