Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32508 | 97747;97748;97749 | chr2:178541555;178541554;178541553 | chr2:179406282;179406281;179406280 |
| N2AB | 30867 | 92824;92825;92826 | chr2:178541555;178541554;178541553 | chr2:179406282;179406281;179406280 |
| N2A | 29940 | 90043;90044;90045 | chr2:178541555;178541554;178541553 | chr2:179406282;179406281;179406280 |
| N2B | 23443 | 70552;70553;70554 | chr2:178541555;178541554;178541553 | chr2:179406282;179406281;179406280 |
| Novex-1 | 23568 | 70927;70928;70929 | chr2:178541555;178541554;178541553 | chr2:179406282;179406281;179406280 |
| Novex-2 | 23635 | 71128;71129;71130 | chr2:178541555;178541554;178541553 | chr2:179406282;179406281;179406280 |
| 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/K | None | None | 0.896 | N | 0.68 | 0.493 | 0.693281465932 | gnomAD-4.0.0 | 2.40064E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.625E-06 | 0 | 0 |
| I/M | rs755848026  |
-0.45 | 0.81 | N | 0.573 | 0.159 | 0.463501289208 | gnomAD-2.1.1 | 3.25E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 7.2E-05 | 0 |
| I/M | rs755848026 |
-0.45 | 0.81 | N | 0.573 | 0.159 | 0.463501289208 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| I/M | rs755848026 |
-0.45 | 0.81 | N | 0.573 | 0.159 | 0.463501289208 | gnomAD-4.0.0 | 4.21894E-05 | None | None | None | None | I | None | 1.33593E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 5.68362E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.3907 | ambiguous | 0.3135 | benign | -2.273 | Highly Destabilizing | 0.009 | N | 0.305 | neutral | None | None | None | None | I |
| I/C | 0.6441 | likely_pathogenic | 0.5439 | ambiguous | -1.268 | Destabilizing | 0.977 | D | 0.606 | neutral | None | None | None | None | I |
| I/D | 0.8482 | likely_pathogenic | 0.8124 | pathogenic | -1.968 | Destabilizing | 0.92 | D | 0.674 | neutral | None | None | None | None | I |
| I/E | 0.8076 | likely_pathogenic | 0.7863 | pathogenic | -1.817 | Destabilizing | 0.92 | D | 0.677 | prob.neutral | None | None | None | None | I |
| I/F | 0.2778 | likely_benign | 0.27 | benign | -1.342 | Destabilizing | 0.85 | D | 0.581 | neutral | None | None | None | None | I |
| I/G | 0.675 | likely_pathogenic | 0.6041 | pathogenic | -2.757 | Highly Destabilizing | 0.617 | D | 0.647 | neutral | None | None | None | None | I |
| I/H | 0.774 | likely_pathogenic | 0.7068 | pathogenic | -2.073 | Highly Destabilizing | 0.992 | D | 0.639 | neutral | None | None | None | None | I |
| I/K | 0.7575 | likely_pathogenic | 0.7113 | pathogenic | -1.554 | Destabilizing | 0.896 | D | 0.68 | prob.neutral | N | 0.480740535 | None | None | I |
| I/L | 0.1516 | likely_benign | 0.1346 | benign | -0.911 | Destabilizing | 0.099 | N | 0.404 | neutral | N | 0.42847566 | None | None | I |
| I/M | 0.1708 | likely_benign | 0.1469 | benign | -0.671 | Destabilizing | 0.81 | D | 0.573 | neutral | N | 0.494124649 | None | None | I |
| I/N | 0.3952 | ambiguous | 0.3234 | benign | -1.576 | Destabilizing | 0.972 | D | 0.675 | neutral | None | None | None | None | I |
| I/P | 0.5606 | ambiguous | 0.5418 | ambiguous | -1.341 | Destabilizing | 0.92 | D | 0.666 | neutral | None | None | None | None | I |
| I/Q | 0.7376 | likely_pathogenic | 0.6907 | pathogenic | -1.556 | Destabilizing | 0.972 | D | 0.671 | neutral | None | None | None | None | I |
| I/R | 0.6802 | likely_pathogenic | 0.6232 | pathogenic | -1.186 | Destabilizing | 0.896 | D | 0.673 | neutral | N | 0.469384229 | None | None | I |
| I/S | 0.4259 | ambiguous | 0.3352 | benign | -2.3 | Highly Destabilizing | 0.447 | N | 0.574 | neutral | None | None | None | None | I |
| I/T | 0.3882 | ambiguous | 0.2758 | benign | -2.013 | Highly Destabilizing | 0.549 | D | 0.527 | neutral | N | 0.468978275 | None | None | I |
| I/V | 0.0739 | likely_benign | 0.0668 | benign | -1.341 | Destabilizing | 0.001 | N | 0.175 | neutral | N | 0.354340474 | None | None | I |
| I/W | 0.9006 | likely_pathogenic | 0.8853 | pathogenic | -1.613 | Destabilizing | 0.992 | D | 0.661 | neutral | None | None | None | None | I |
| I/Y | 0.6369 | likely_pathogenic | 0.6133 | pathogenic | -1.357 | Destabilizing | 0.92 | D | 0.627 | neutral | 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.