Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21728 | 65407;65408;65409 | chr2:178584369;178584368;178584367 | chr2:179449096;179449095;179449094 |
| N2AB | 20087 | 60484;60485;60486 | chr2:178584369;178584368;178584367 | chr2:179449096;179449095;179449094 |
| N2A | 19160 | 57703;57704;57705 | chr2:178584369;178584368;178584367 | chr2:179449096;179449095;179449094 |
| N2B | 12663 | 38212;38213;38214 | chr2:178584369;178584368;178584367 | chr2:179449096;179449095;179449094 |
| Novex-1 | 12788 | 38587;38588;38589 | chr2:178584369;178584368;178584367 | chr2:179449096;179449095;179449094 |
| Novex-2 | 12855 | 38788;38789;38790 | chr2:178584369;178584368;178584367 | chr2:179449096;179449095;179449094 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/V | rs781121273  |
-1.343 | 0.767 | N | 0.341 | 0.183 | None | gnomAD-2.1.1 | 1.79E-05 | None | None | None | None | N | None | 0 | 5.66E-05 | None | 0 | 0 | None | 0 | None | 0 | 2.35E-05 | 0 |
| L/V | rs781121273 |
-1.343 | 0.767 | N | 0.341 | 0.183 | None | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| L/V | rs781121273 |
-1.343 | 0.767 | N | 0.341 | 0.183 | None | gnomAD-4.0.0 | 1.79779E-05 | None | None | None | None | N | None | 0 | 1.66789E-05 | None | 0 | 0 | None | 0 | 0 | 2.37398E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.8029 | likely_pathogenic | 0.6994 | pathogenic | -1.734 | Destabilizing | 0.997 | D | 0.537 | neutral | None | None | None | None | N |
| L/C | 0.8785 | likely_pathogenic | 0.8218 | pathogenic | -0.97 | Destabilizing | 1.0 | D | 0.707 | prob.neutral | None | None | None | None | N |
| L/D | 0.9871 | likely_pathogenic | 0.9739 | pathogenic | -1.182 | Destabilizing | 1.0 | D | 0.749 | deleterious | None | None | None | None | N |
| L/E | 0.9117 | likely_pathogenic | 0.8505 | pathogenic | -1.17 | Destabilizing | 1.0 | D | 0.741 | deleterious | None | None | None | None | N |
| L/F | 0.7063 | likely_pathogenic | 0.5829 | pathogenic | -1.212 | Destabilizing | 0.999 | D | 0.741 | deleterious | N | 0.50774452 | None | None | N |
| L/G | 0.9454 | likely_pathogenic | 0.9004 | pathogenic | -2.07 | Highly Destabilizing | 1.0 | D | 0.733 | prob.delet. | None | None | None | None | N |
| L/H | 0.8595 | likely_pathogenic | 0.7669 | pathogenic | -1.22 | Destabilizing | 1.0 | D | 0.739 | prob.delet. | N | 0.492852425 | None | None | N |
| L/I | 0.2614 | likely_benign | 0.2173 | benign | -0.879 | Destabilizing | 0.992 | D | 0.469 | neutral | N | 0.475882818 | None | None | N |
| L/K | 0.8172 | likely_pathogenic | 0.727 | pathogenic | -1.177 | Destabilizing | 1.0 | D | 0.733 | prob.delet. | None | None | None | None | N |
| L/M | 0.2697 | likely_benign | 0.2314 | benign | -0.633 | Destabilizing | 1.0 | D | 0.745 | deleterious | None | None | None | None | N |
| L/N | 0.8777 | likely_pathogenic | 0.8065 | pathogenic | -1.006 | Destabilizing | 1.0 | D | 0.755 | deleterious | None | None | None | None | N |
| L/P | 0.9898 | likely_pathogenic | 0.9794 | pathogenic | -1.133 | Destabilizing | 1.0 | D | 0.748 | deleterious | N | 0.492751496 | None | None | N |
| L/Q | 0.685 | likely_pathogenic | 0.5666 | pathogenic | -1.181 | Destabilizing | 1.0 | D | 0.755 | deleterious | None | None | None | None | N |
| L/R | 0.7371 | likely_pathogenic | 0.6214 | pathogenic | -0.542 | Destabilizing | 1.0 | D | 0.747 | deleterious | N | 0.470396853 | None | None | N |
| L/S | 0.907 | likely_pathogenic | 0.8333 | pathogenic | -1.624 | Destabilizing | 1.0 | D | 0.749 | deleterious | None | None | None | None | N |
| L/T | 0.7733 | likely_pathogenic | 0.65 | pathogenic | -1.495 | Destabilizing | 0.999 | D | 0.721 | prob.delet. | None | None | None | None | N |
| L/V | 0.3283 | likely_benign | 0.2607 | benign | -1.133 | Destabilizing | 0.767 | D | 0.341 | neutral | N | 0.467031261 | None | None | N |
| L/W | 0.8326 | likely_pathogenic | 0.7378 | pathogenic | -1.29 | Destabilizing | 1.0 | D | 0.695 | prob.neutral | None | None | None | None | N |
| L/Y | 0.8915 | likely_pathogenic | 0.8287 | pathogenic | -1.073 | Destabilizing | 1.0 | D | 0.752 | 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.