Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21710 | 65353;65354;65355 | chr2:178584423;178584422;178584421 | chr2:179449150;179449149;179449148 |
| N2AB | 20069 | 60430;60431;60432 | chr2:178584423;178584422;178584421 | chr2:179449150;179449149;179449148 |
| N2A | 19142 | 57649;57650;57651 | chr2:178584423;178584422;178584421 | chr2:179449150;179449149;179449148 |
| N2B | 12645 | 38158;38159;38160 | chr2:178584423;178584422;178584421 | chr2:179449150;179449149;179449148 |
| Novex-1 | 12770 | 38533;38534;38535 | chr2:178584423;178584422;178584421 | chr2:179449150;179449149;179449148 |
| Novex-2 | 12837 | 38734;38735;38736 | chr2:178584423;178584422;178584421 | chr2:179449150;179449149;179449148 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/K | None | None | 1.0 | N | 0.729 | 0.367 | 0.137902524267 | gnomAD-4.0.0 | 1.16347E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.43944E-05 | 0 | 1.65728E-05 |
| N/S | rs756152181  |
-1.126 | 0.999 | D | 0.595 | 0.445 | 0.194818534648 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.91E-06 | 0 |
| N/S | rs756152181 |
-1.126 | 0.999 | D | 0.595 | 0.445 | 0.194818534648 | gnomAD-4.0.0 | 3.1845E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.7202E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/A | 0.8629 | likely_pathogenic | 0.823 | pathogenic | -1.022 | Destabilizing | 1.0 | D | 0.685 | prob.neutral | None | None | None | None | N |
| N/C | 0.7122 | likely_pathogenic | 0.645 | pathogenic | -0.117 | Destabilizing | 1.0 | D | 0.746 | deleterious | None | None | None | None | N |
| N/D | 0.86 | likely_pathogenic | 0.8191 | pathogenic | -0.77 | Destabilizing | 0.999 | D | 0.641 | neutral | N | 0.483205616 | None | None | N |
| N/E | 0.9845 | likely_pathogenic | 0.9803 | pathogenic | -0.598 | Destabilizing | 0.999 | D | 0.707 | prob.neutral | None | None | None | None | N |
| N/F | 0.9957 | likely_pathogenic | 0.9942 | pathogenic | -0.616 | Destabilizing | 1.0 | D | 0.791 | deleterious | None | None | None | None | N |
| N/G | 0.7932 | likely_pathogenic | 0.7452 | pathogenic | -1.423 | Destabilizing | 0.999 | D | 0.594 | neutral | None | None | None | None | N |
| N/H | 0.8452 | likely_pathogenic | 0.8234 | pathogenic | -0.975 | Destabilizing | 1.0 | D | 0.749 | deleterious | N | 0.474847824 | None | None | N |
| N/I | 0.9488 | likely_pathogenic | 0.9341 | pathogenic | 0.031 | Stabilizing | 1.0 | D | 0.787 | deleterious | N | 0.479940386 | None | None | N |
| N/K | 0.989 | likely_pathogenic | 0.9865 | pathogenic | -0.181 | Destabilizing | 1.0 | D | 0.729 | prob.delet. | N | 0.491092428 | None | None | N |
| N/L | 0.9341 | likely_pathogenic | 0.9231 | pathogenic | 0.031 | Stabilizing | 1.0 | D | 0.772 | deleterious | None | None | None | None | N |
| N/M | 0.947 | likely_pathogenic | 0.9367 | pathogenic | 0.397 | Stabilizing | 1.0 | D | 0.74 | deleterious | None | None | None | None | N |
| N/P | 0.9661 | likely_pathogenic | 0.9638 | pathogenic | -0.29 | Destabilizing | 1.0 | D | 0.769 | deleterious | None | None | None | None | N |
| N/Q | 0.9701 | likely_pathogenic | 0.9623 | pathogenic | -0.789 | Destabilizing | 1.0 | D | 0.764 | deleterious | None | None | None | None | N |
| N/R | 0.9794 | likely_pathogenic | 0.9738 | pathogenic | -0.323 | Destabilizing | 1.0 | D | 0.751 | deleterious | None | None | None | None | N |
| N/S | 0.1686 | likely_benign | 0.1503 | benign | -1.058 | Destabilizing | 0.999 | D | 0.595 | neutral | D | 0.522884544 | None | None | N |
| N/T | 0.416 | ambiguous | 0.3927 | ambiguous | -0.669 | Destabilizing | 0.999 | D | 0.694 | prob.neutral | N | 0.520460314 | None | None | N |
| N/V | 0.8947 | likely_pathogenic | 0.8644 | pathogenic | -0.29 | Destabilizing | 1.0 | D | 0.787 | deleterious | None | None | None | None | N |
| N/W | 0.9978 | likely_pathogenic | 0.997 | pathogenic | -0.354 | Destabilizing | 1.0 | D | 0.737 | prob.delet. | None | None | None | None | N |
| N/Y | 0.967 | likely_pathogenic | 0.9615 | pathogenic | -0.112 | Destabilizing | 1.0 | D | 0.772 | deleterious | N | 0.479433407 | 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.